PHILIPPINE CONSENSUS REPORT ON
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ASTHMA DIAGNOSIS
AND MANAGEMENT
2019
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PHILIPPINE COLLEGE OF CHEST PHYSICIANS
COUNCIL ON ASTHMA
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TABLE OF CONTENTS
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CHAPTER I – EPIDEMIOLOGY, DEFINITION, AND DIAGNOSIS................................1
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CHAPTER 2 – ASSESSMENT AND CLASSIFICATION OF ASTHMA.........................13
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CHAPTER 3 – RISK FACTORS FOR ASTHMA EXACERBATIONS.........................23
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How should we assess asthma?...................................................................................................15
What are the tools for assessing asthma symptom control?.........................................16
How do we assess future risk of adverse outcomes?.........................................................17
What is the role of lung function determination in the assessment
of future risk of adverse outcomes?...........................................................................................18
How do you differentiate poorly controlled asthma and
asthma exacerbations?....................................................................................................................18
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What is the burden of asthma globally and in the Philippines?.....................................3
How is asthma defined?..................................................................................................................6
How is asthma diagnosed?............................................................................................................6
What diseases may mimic asthma?............................................................................................9
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©2019 Philippine College of Chest Physicians Council on Asthma
Printed in the Philippines
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Editorial content. Although great care has been taken in compiling and
checking the information given in the publication to ensure that it is
accurate at press time, the authors and publishers shall not be
responsible and hereby disclaim from any liability to any party for any loss,
damage or disruptions caused by any errors, omissions or
inaccuracies in this document. Modifications, alterations and revisions to
this document will be regularly done as new information and
knowledge become available, and will appear in the Philippine College of
Chest Physicians’ (PCCP) website – www.philchest.org - as current
supplement to this document.
ISBN
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No part of this publication may be reproduced by any process in any
language without the written consent of the publisher and copyright
holder.
Tables and Figures..............................................................................................................viii
Preface...............................................................................................................................x
Philippine Consensus Report on Asthma Diagnosis and Management 2019
Update Project Committee...............................................................................................xii
Table A. Levels of Evidence (Adapted from GINA Guidelines)............................xiii
Aeroallergens.......................................................................................................................................25
What is the burden imposed by allergen exposure in asthma?.........................25
House Dust Mite (HDM) Allergens...................................................................................26
Is the association of house dust mite allergen exposure
and asthma established?.................................................................................................26
Are avoidance measures directed to house dust mite
beneficial to asthma patients?......................................................................................26
Molds and Fungi.........................................................................................................................27
What is the effect of indoor dampness and mold on asthma?........................27
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CHAPTER 4 – ASTHMA MEDICATIONS.........................................................................47
Can air pollution trigger asthma exacerbations?....................................................31
What avoidance measures reduce the impact of air pollution
exposure on asthma?..........................................................................................................31
Indoor Fuel Exposure..............................................................................................................31
What is the effect of indoor fuel exposure on asthma?......................................32
Tobacco Smoke.........................................................................................................................32
What is the effect of tobacco smoke on asthma?.................................................32
What is the effect of secondhand smoke (SHS) on asthma?...........................33
What are the benefits of smoking cessation and the
interventions that are needed?......................................................................................33
Climate Change and Global Warming....................................................................................34
What is the effect of climate change on asthma?....................................................34
Exercise-Induced Bronchoconstriction (EIB)......................................................................35
What is the effect of exercise on asthma?...................................................................35
How is exercise-induced bronchoconstriction (EIB) diagnosed?.....................35
What is the treatment and prevention of EIB?..........................................................36
Beta-blockers......................................................................................................................................37
Can beta-blockers be given to asthmatics?................................................................37
Respiratory Infections.....................................................................................................................37
What is the impact of viral respiratory infections on asthma.............................37
Are there effective treatment and preventive strategies for
virus-induced exacerbations?............................................................................................38
Should antibiotics be routinely used in the treatment of asthma
exacerbations?...........................................................................................................................38
Add-On Therapies.............................................................................................................................57
What is the mechanism of action of leukotriene modifiers?...............................57
What is the role of methylxanthines in asthma treatment?...........................58
Does tiotropium have a role in asthma management?..........................................59
What is the mechanism of action of omalizumab?.................................................59
Inhaler Therapy..................................................................................................................................60
Is there a difference between pressurized metered-dose inhalers
(pMDIs) and dry power inhalers (DPIs)?........................................................................61
What patient factors should be considered in the choice of
inhaler device?............................................................................................................................62
What strategies can ensure effective use of inhaler devices?.....................63
What is the role of nebulizers in asthma management?.......................................64
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How is an asthma exacerbation diagnosed?.........................................................................71
How is the severity of an asthma exacerbation evaluated?..........................................71
Why is it important to identify patients who are at risk for
asthma-related deaths?..................................................................................................................73
What is the ideal first-line therapy for symptom relief in asthma
exacerbations?...................................................................................................................................73
What is the first-line therapy for control of inflammation in asthma
exacerbations?....................................................................................................................................74
Is there a role for inhaled corticosteroids (ICS) in the management of
asthma exacerbations?...................................................................................................................75
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Controllers............................................................................................................................................49
What are the recommended controller medications for asthma?....................49
Are all inhaled corticosteroids (ICS) the same?.........................................................49
What are the recommended doses of ICS?...................................................................51
How safe is long term use of ICS?.....................................................................................52
What is the role of systemic corticosteroids?.......................................................53
Are all long–acting beta2-agonists (LABA) the same?..........................................54
What is the benefit of ICS–LABA combination in achieving
asthma control?.........................................................................................................................55
Relievers........................................................................................................................................56
What are the reliever medications for asthma?........................................................56
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Furry Animals.............................................................................................................................28
What are the effects of furry animal exposure on asthma?..............................28
What intervention strategies can be adopted?.....................................................28
Cockroach Allergens...............................................................................................................29
Does cockroach allergen exposure cause exacerbation of
asthma?....................................................................................................................................29
What intervention strategies can be adopted to minimize the
effects of cockroach allergens?....................................................................................29
Irritants and Pollutants...................................................................................................................30
Outdoor Air Pollution.............................................................................................................30
What are the effects of air pollution on asthma?..................................................30
Can air pollution cause the development of asthma?.........................................30
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What is the association of menstruation with asthma?..............................130
How common is pre-menstrual asthma (PMA)?..............................................130
What causes pre-menstrual asthma (PMA)?.....................................................130
How is pre-menstrual asthma (PMA) diagnosed?...........................................131
How is pre-menstrual asthma (PMA) treated?................................................132
Can pre-menstrual asthma (PMA) be prevented?..............................................132
Surgery and Asthma...........................................................................................................132
Are there increased perioperative risks of surgery among
asthmatic patients?.....................................................................................................132
What is the approach to the management of asthmatic
patients undergoing surgery?...................................................................................133
Sinus Disease and Asthma...............................................................................................134
Is there a relationship between asthma and allergic rhinitis (AR),
sinusitis, nasal polyps?................................................................................................134
What is the impact of treatment of sinonasal disease on
asthma outcomes?......................................................................................................136
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What is Guided Self-Management Education and its impact on
asthma outcomes?...........................................................................................................................113
What are the core components of Guided Self-Management
Education Program?........................................................................................................................114
What are the components of a written asthma action plan?........................................114
Who should deliver Asthma Education?...............................................................................116
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Chapter 7 – PATIENT EDUCATION.................................................................................111
Pregnancy and Asthma................................................................................................................125
How common Is asthma in pregnancy?.......................................................................125
What is the course of asthma during pregnancy?..................................................125
What are the possible adverse maternal and fetal outcomes in
pregnant asthmatics?............................................................................................................126
How is asthma diagnosed in pregnancy?....................................................................126
What medications can be prescribed for pregnant asthmatics?.....................127
What is the approach to the management of asthma
exacerbations in pregnancy?.............................................................................................128
When should pregnant asthmatics be hospitalized?.............................................129
What is the approach to the management of the pregnant
asthmatic during labor and delivery?............................................................................129
Menstruation and Asthma...........................................................................................................130
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What are the goals of chronic asthma management?.......................................................91
What is control-based asthma management?......................................................................91
What is the stepwise approach for adjusting asthma treatment
in adults?................................................................................................................................................92
How often should response to treatment be assessed and monitored?.................99
What are the guidelines for the escalation of asthma treatment?............................99
What are the guidelines for the de-escalation of asthma treatment?..................100
What are the strategies to reduce the risk of asthma exacerbations?...................101
What is the role of immunotherapy in asthma?.................................................................103
What is the role of vaccination among asthmatics?........................................................103
What are the non-pharmacological interventions for asthma?.................................103
Chapter 8 – SPECIAL CONSIDERATIONS...................................................................123
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Chapter 6 – CHRONIC ASTHMA MANAGEMENT......................................................87
What are the effective methods of asthma information delivery?.............................116
What are the effective strategies for asthma adherence management?..............117
What is the impact of information and communication technology
in the Guided Self-Management Education?.......................................................................119
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Is there a role for long–acting beta2–agonist – inhaled corticosteroid
(LABA-ICS) in the management of acute asthma?...........................................................76
What is the role of magnesium sulfate in the management of an
asthma exacerbations?..................................................................................................................76
What is the role of methylxanthines in the management of an
asthma exacerbations?..................................................................................................................76
How should asthma exacerbations be managed at home?...........................................76
How should asthma exacerbations be managed in the out-patient
setting?..................................................................................................................................................81
How should asthma exacerbation be managed in the
emergency room (ER)......................................................................................................................81
What are the indications for hospitalization?.......................................................................83
When do we discharge patients after being treated in the
emergency room (ER)?..................................................................................................................83
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What is the approach to the diagnosis of difficult-to-treat
asthma?......................................................................................................................................149
When should referral to a specialist or severe asthma clinic
be considered?........................................................................................................................150
What is the approach to the management of difficult-to-treat
asthma?......................................................................................................................................150
How is treatment response of difficult-to-treat asthma
assessed and addressed?...................................................................................................151
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What is the relationship of food allergy and anaphylaxis
among asthmatics?.....................................................................................................144
How is food allergy, anaphylaxis in asthma managed?................................145
Aspirin-Exaceberated Respiratory Disease (AERD)..............................................145
What is aspirin-exaceberated respiratory disease (AERD)?......................145
How is aspirin-exacerbated respiratory disease (AERD)
diagnosed?......................................................................................................................146
How is aspirin-exacerbated respiratory disease (AERD)
managed?....................................................................................................................................147
Stress and Asthma..........................................................................................................................147
Is there a relationship between stress and asthma?...............................................145
How is asthma worsened by stress managed?.........................................................148
Difficult-to-Treat Asthma............................................................................................................148
How is difficult-to-treat asthma differentiated
from severe asthma?.............................................................................................................148
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Work-Related Asthma (WRA)........................................................................................137
What is occupational asthma (OA) and how is it diagnosed?..................137
How is work-related asthma (WRA) managed?...............................................138
Work-exacerbated asthma (WEA).......................................................................139
What is work-exacerbated asthma (WEA) and how
is it recognized?.......................................................................................................139
How is work-exacerbated asthma (WEA) managed?...............................140
Obesity and Asthma............................................................................................................141
Is there a relationship between obesity and asthma?....................................141
How are obese asthmatics managed?...................................................................141
Gastroesophageal Reflux Disease (GERD)-Related Asthma.............................142
Is gastroesophageal reflux disease (GERD) more common
in patient with asthma?..............................................................................................142
What is gastroesophageal reflux disease (GERD)-related
asthma and what mechanisms are involved?...................................................142
How is gastroesophageal reflux disease (GERD)-related
asthma diagnosed?.......................................................................................................143
How is gastroesophageal reflux disease (GERD)-related
asthma managed?........................................................................................................143
Food Allergy, Anaphylaxis and Asthma.....................................................................144
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TABLES & FIGURES
CHAPTER 5 – MANAGEMENT OF ASTHMA EXACERBATIONS
CHAPTER 1 – EPIDEMIOLOGY, DEFINITION, AND DIAGNOSIS
Table 5.1.
Table 5.2.
Figure 5.1.
Figure 1.1.
Table 1.1.
Figure 1.2.
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The control-based asthma management cycle...................................................92
Stepwise approach to asthma treatment in Filipino adults............................93
Treating modifiable risk factors to reduce exacerbations............................102
Non-pharmacological interventions for asthma................................................104
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Figure 6.1.
Figure 6.2
Table 6.1.
Table 6.2.
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Poor medication adherence in asthma...................................................................118
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Table 7.1.
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Chapter 7 – PATIENT EDUCATION
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Relationship between glucocorticoid receptor binding affinity
and mid-range nominal therapeutic daily doses of inhaled
corticosteroids (ICS)..........................................................................................................50
Table 4.1. Inhaled corticosteroid (ICS) pharmacological characteristics.......................51
Table 4.2. Low, medium and high daily doses of inhaled
corticosteroids (ICS)..........................................................................................................52
Table 4.3. Common types of systemic corticosteroids and their relative
properties................................................................................................................................54
Table 4.4. Pharmacologic characteristics of long–acting
bronchodilators....................................................................................................................55
Table 4.5. Advantages and disadvantages between pressurized
metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs).................61
Figure 4.2. How to choose the right inhaler.................................................................................62
Table 4.6. Strategies to ensure effective use of inhaler devices.........................................63
viii
Chapter 6 – CHRONIC ASTHMA MANAGEMENT
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CHAPTER 4 – ASTHMA MEDICATIONS
Figure 4.1.
Table 5.3.
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Assessment of asthma in adults, adolescents and children
6-11 years....................................................................................................................................15
GINA assessment of asthma control in adults, adolescents and
children 6-11 years.................................................................................................................16
Risk factors for poor asthma outcomes.................................................................17
Investigating a patient with poor symptom control and/or
exacerbations despite treatment..................................................................................19
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Table 2.3.
Figure 2.1.
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Table 2.2.
Figure 5.3.
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CHAPTER 2 – ASSESSMENT AND CLASSIFICATION OF ASTHMA
Table 2.1.
Figure 5.2.
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Figure 1.3.
Disability adjusted life years (DALYs) attributed to asthma per
100,000 Population, 2010..................................................................................................4
Summary of prevalence studies for asthma in the Philippines.......................5
Age-standardized asthma mortality rates (all ages) 2001-2005 and
2011-2015 by country, ranked by 2011-2015 aged-standardized
mortality within World Bank 2014 income group.................................................5
Diagnostic flowchart for diagnosing asthma at initial presentation
in clinical practice...................................................................................................................8
Classification of severity of exacerbation................................................................72
Risk factors for asthma-related deaths....................................................................73
Self-management of worsening asthma in adults and
adolescents with action plan.........................................................................................78
Management of asthma exacerbations in the out-patient
setting.......................................................................................................................................80
Management of asthma exacerbation at the emergency
room (ER)...............................................................................................................................82
Discharge management after hospital or
emergency room care for asthma.............................................................................84
ix
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PREFACE
We acknowledge the Global Initiative on Asthma (GINA) documents as
major resources of this Report and we thank them for granting permission
to adopt major tables and figures. Our utmost gratitude to the support staff
of the Philippine College of Chest Physicians who assisted the Committee
in this endeavor and to AstraZeneca, Phil. who helped in facilitating the
printing of this document.
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Dina V. Diaz, M.D., FPCCP
Project Chairman
Philippine Consensus Report on Asthma Diagnosis and Management Update
Council on Asthma
Philippine College of Chest Physicians
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The Consensus Committee encourages the dissemination and implementation of the management strategies and recommendations of this updated
Philippine Asthma Consensus Report. We hope that it can further raise
awareness among our healthcare professionals on the value of adherence
to high standards of asthma care, instill a desire to seek new knowledge
and, for some, provide the much-needed motivation to embark on
researches that may help resolve some unanswered questions on asthma.
This Report may also be utilized as an additional scientific resource to assist
local health authorities in formulating more up-to-date, evidence- and
practice-based policies on asthma management in the Philippines.
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The Council on Asthma of the Philippine College of Chest Physicians then
decided to embark on this ambitious project to re-formulate a new version
of the local Asthma Consensus Report that will provide a comprehensive
treatise on the clinical approach to asthma management that is intended
both for generalists and specialists alike. This rejuvenated version deals
with various aspects on asthma such as the definition, epidemiology,
diagnosis and classification, risk factors, special considerations, as well as
treatment recommendations on asthma exacerbations and chronic
management. Although much of the content was adapted from the Global
Initiative on Asthma clinical practice guidelines (with permission), this
Report utilized the question and answer format similar to the 2004
Philippine Asthma Consensus Report. On the other hand, the chapter topics
and titles featured here were lifted from the 2009 Philippine Asthma
Consensus Report.
Epidemiology, Definition and Diagnosis
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The Philippine Consensus Report on Asthma Diagnosis and Management
was first published in 1996 and was followed by updated versions in 2004
and in 2009. It took a decade for this current report to be developed
because international asthma management guidelines such as the Global
Initiative on Asthma (GINA) as well as other clinical practice guidelines that
are regularly updated and easily accessed adequately filled the gap during
the interim.
The members of the Consensus Committee are solely responsible for the
statements presented in this publication. They did not receive any
honorarium to attend the review and deliberation meetings, and there was
no remuneration given for the time they devoted in poring over scientific
literature and in contributing substantively to the content of this Report.
Their truly commendable efforts, commitment and cooperation were
invaluable towards the successful completion of this Consensus Report.
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Medical literature reports that asthma continues to be an important global
health problem affecting over 300 million people of all age groups, with
increasing prevalence and rising treatment costs. As one of the most
common chronic conditions, asthma imposes a large burden on many
countries in the developing world such as the Philippines, where limited
healthcare resources are challenged by the affected population’s high
healthcare utilization, impact on quality of life, loss of productivity, and
increased morbidity and mortality.
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
As a practice guideline update, this aims to inform local practitioners on
current evidence-based practice on asthma management. As a consensus
document, it not only shows which of the strategies gathered from international guidelines may be considered relevant and feasible in the local
setting, but also presents some crucial caveats and innovations on
treatment recommendations. Some variation is inevitable in this era of
personalized medicine and is likely borne from the nuances of medical
practice unique to the Filipino physician who often draws on his or her own
experiences in making clinical decisions in the management of asthma
patients.
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
UPDATE PROJECT COMMITTEE
Council Chairman: Maria Bella R. Siasoco, M.D., FPCCP
Project Chairman: Dina V. Diaz, M.D., FPCCP
Table A. Levels of Evidence (adapted from GINA guidelines)
Project Secretary: Eloisa S. de Guia, M.D., FPCCP
EVIDENCE LEVEL
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Evidence is from outcomes of non-randomized or
uncontrolled trials or from observational studies.
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This is a panel consensus judgement based on clinical
experience or knowledge that does not meet the above
listed criteria. This category is used only in cases where the
provision of some guidance was deemed valuable but the
clinical literature addressing the subject was insufficient to
justify placement in one of the other categories.
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B
Evidence is from endpoints of intervention studies that
include only a limited number of patients, post hoc or
subgroup analysis of RCTs or meta-analysis of such RCTs.
In general, Category B pertains when few randomized trials
exist, they are small in size, they were undertaken in a
population that differs from the target population of the
recommendation, or the results are somewhat inconsistent.
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Evidence is from endpoints of well-designed randomized
controlled trials (RCTs) or meta-analyses of relevant studies
that provide a consistent pattern of findings in the
population for which the recommendation is made.
Category A requires substantial numbers of studies
involving substantial numbers of participants.
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xii
DESCRIPTION
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Members:
Twinkle T. Adiaz, M.D., FPCCP
Johann Paolo D. Almazar, M.D., FPCCP
Gene Philip Louie C. Ambrosio, M.D., FPCCP
Eileen G. Aniceto, M.D., FPCCP
Tito C. Atienza, M.D., FPCCP
Glynna O. Cabrera, M.D., FPCCP
Elizabeth V. Cadena, M.D., FPCCP
Maryanne Cristy T. Dadulla, M.D., FPCCP
Maria Charisma L. De la Trinidad, M.D., FPCCP
Virginia S. Delos Reyes, M.D., FPCCP
Paul Rilhelm M. Evangelista, M.D., FPCCP
Irene V. Felipe, M.D., FPCCP
Liza L. Garcia, M.D., FPCCP
Renato B. Herradura, M.D., FPCCP
Isaias A. Lanzona, M.D., FPCCP
Lalaine L. Mortera, M.D., FPCCP
Maria Piedad R. Natividad, M.D., FPCCP
Josephine B. Ramos, M.D., FPCCP
Camilo C. Roa, Jr., M.D., FPCCP
Oliver A. Tabag, M.D., FPCCP
Dennis C. Teo, M.D., FPCCP
Esther Fredelyn M. Tomas, M.D., FPCCP
Aileen D. Wang, M.D., FPCCP
Ricardo C. Zotomayor, M.D., FPCCP
xiii
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CHAPTER
1
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Epidemiology, Definition and Diagnosis
CHAPTER 1
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Bronchial asthma is now recognized as one of the most important
non-communicable threats to global health, social welfare and economic
development in all regions of the world, especially in low-to-middle income
countries. Focused and accelerated efforts are required to make asthma a
lung health priority.1
What is the burden of asthma globally and in the Philippines?
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Globally, asthma is ranked 28th among the leading causes of burden of the
disease and 16th among the leading causes of years lived with disability.2
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C
The prevalence of asthma symptoms in children is 14% while in young adults
aged 18 to 45-years old, it is pegged at 8.6%, according to the International
Study of Asthma and Allergies in Childhood (ISAAC) undertaken between
2000 and 2003. Of the young adults who participated in the survey, only
4.5% were diagnosed to have asthma or were taking treatment for asthma.3
A World Health Survey was conducted in 2002 to determine the prevalence
of asthma, involving 178,215 individuals aged 18 to 45-years old from
70 countries. Asthma was categorized as self-reported, doctor-diagnosed
or based on clinical (symptoms or treatment) and the prevalence was 4.3%,
4.5% and 8.6% respectively.4 The same survey showed that among those
with clinical/treated asthma, almost 24% were current smokers, half mostly
coming from South East Asia (57.9%) reported wheezing in the past 12
months, and 20% were treatment-naïve.
O
IG
N
PY
O
D
R
T
O
N
PY
O
D
O
C
C
P
P
C
Asthma was acknowledged as the most prevalent chronic respiratory
disease worldwide. In 2016, the Global Burden of Disease (GBD) study
estimated that there were 339.4 million people worldwide affected by
asthma. This represents a 3.6% increase in age-standardized prevalence
since 2006.2
In 2016, asthma, across all ages, contributed 23.7 million Disability-Adjusted
Life Years (DALYs) globally. This total burden of disease has remained
unchanged since 1990, despite the substantial increase in world population
over that time. Hence, the age-standardized rate (329·2 DALYs per 100,000
population in 2016) has decreased by 36% since 1990. Globally, asthma
ranked 28th among the leading causes of burden of disease and 27th in
low- and middle-income countries (LMICs). More than half (56%) of the
global burden attributable to asthma was due to 13.2 million Years Lived
with Disability (YLD). This represents a small (3.0%) increase in the
age-standardized rate of YLD due to asthma since 2006. In 2016, asthma
ranked 16th in the leading causes of YLD globally. Worldwide, there were 10.5
million Years of Life Lost (YLL) attributed to asthma-related premature
deaths. This represents an age-standardized rate of 148·5 YLL per 100,000
3
CHAPTER 1
CHAPTER 1
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Table 1.1. Summary of prevalence studies for asthma in the Philippines.
population, 26% lower in 2016 compared to 2006. In 2016, asthma ranked
23rd (global) and 31st (LMICs) among the leading causes of premature
mortality.2
On the other hand, premature deaths measured in YLL is highest in the
elderly (aged 75-79) (Figure 1.1.A). The burden is similar in males and
females below ages 30-34 years, but there is male predominance for
asthma burden at older age groups (Figure 1.1.B).
80+ yrs.
70-74 yrs.
75-79 yrs.
60-64 yrs.
65-69 yrs.
50-54 yrs.
55-59 yrs.
1-4 yrs.
0
200
400
600
800
1000
D
M
R
TE
A
IS
D
High-income
countries
U
IB
L-
IA
TR
-
TE
TE
In the Philippines, the overall prevalence of asthma based on wheezing for
the past 12 months was estimated at 8.7% (SE 0.4%), based on a survey
involving 7,202 adults at least 20-years old from 3,744 households,
79 provinces and 17 regions using pre-validated written questionnaire used
in the ISAAC Study. Males were reported to have higher prevalence at 9.4%
(SE 0.5%) compared to females at 8.2% (SE 0.5%). Wheezing at any time
was reported at 14.3% (SE 0.5%), with males at 14.8% (SE 0.7%) compared
to 13.8% (SE 0.6%) in females. Prevalence of adult asthma in the rural area
is slightly higher than in the urban area (15.3% vs 13.3%), but not statistically
significant.5 Table 1.1 summarizes the asthma prevalence studies done in the
Philippines.
2001-2005
2011-2015
R
U
IB
L
IA
R
TE
TR
IS
D
Non-communicable diseases (NCDs) are now overtaking communicable
diseases as leading causes of death globally, affecting 60% among people
of all ages, 80% of these deaths occurring in non-affluent countries.1
O
A
M
R
O
B
Italy
Netherlands
Austria
Canada
Japan
Slovenia
Switzerland
Sweden
Portugal
Belgium
Slovakia
Denmark
Croatia
Czech Republic
France
Germany
Hungary
Finland
Hong Kong SAR
Poland
Lithuania
Norway
Spain
Argentina
United States of America
Israel
Latvia
United Kingdom
New Zealand
Australia
Estonia
Chile
Puerto Rico
Venezuela
Uruguay
Republic of Korea
PY
D
PY
DALYs per (100,000)
TE
40-44 yrs.
17.2
H
45-49 yrs.
ECHRS Questionnaire
IG
5-9 yrs.
O
35-39 yrs.
22.4
R
10-14 yrs.
C
25-29 yrs.
Combined
PY
25-29 yrs.
T
30-34 yrs.
18.1
According to the latest WHO data published in 2017, asthma deaths in the
Philippines reached 13,186 or 2.13% of total deaths; age-adjusted death rate
is 19.47 per 100,000 population, which ranks the Philippines number 15 in
the world.6 In the WHO Mortality Database, the Philippines ranked number 2
in the low- and middle-income countries.7
females
males
30-34 yrs.
O
A
Probable Asthma
O
35-39 yrs.
4.3
C
40-44 yrs.
YLD
Definite asthma
Malolos, Bulacan
N
15-19 yrs.
Mindanao
14.3 (0.5)
P
20-24 yrs.
et al
O
5-9 yrs.
Luzon, Visayas,
8.7 (0.4)
NNHeS* - National Nutrition and Health Survey; ISAAC** - International Study of Asthma and Allergies in Childhood;
NAES*** - National Asthma Epidemiology Study; ECHRS**** - European Community Health Respiratory Survey
TE
10-14 yrs.
Wang
D
YLL
O
1-4 yrs.
Questionnaire
Pagcatipunan,
Figure 1.1. Disability adjusted life years (DALYs) attributed to asthma per
100,000 population, 2010: (A) years lived with disability (YLD)
and years of life lost (YLL) per 100,000 by age group.
(B) DALYs by age group and sex.
4
ECHRS****
3 major cities in
65-69 yrs.
15-19 yrs.
C
A
1,964 adults;
2003, Roa,
Questionnaire
H
0
NAES*** Data
PREVALENCE
OF ASTHMA %
(SE)
Wheezing at anytime
ECHRS
20-24 yrs.
T
100
rural, nationwide
(18-44 y/o),
IG
O
200
et al
1,005 adults
49-45 yrs.
R
N
300
months
Roa,
55-59 yrs.
PY
O
400
Wheezing in past 12
Questionnaire
1998 Cua-Lim,
50-54 yrs.
O
D
500
ISAAC**
>20 y/o; urban,
60-64 yrs.
C
600
7,202 adults
2008, Varone
C
P
700
CASE DEFINITION
OF ASTHMA
NNHeS* Data
70-74 yrs.
75-79 yrs.
C
800
DAYS (per 100,000)
80+ yrs.
SURVEY
INSTRUMENT
POPULATION
PC
PC
900
STUDY
Bulgaria
Ecuador
Colombia
Malaysia
Republic of Maldova
Romania
Peru
Costa Rica
Georgia
Brazil
Mexico
Panama
Kyrgyzstan
Morocco
El Salvador
Nicaragua
Cuba
Paraguay
Dominican Republic
Serbia
Thailand
Guatemala
Egypt
Uzbekistan
Mauritius
South Africa
Philippines
Fiji
Low- and middleincome countries
0
50
100
150
200
250
300
350
400
450
Age-standardised deaths per million population
Figure 1.2. Age-standardized asthma mortality rates (all ages) 2001-2005
and 2011-2015 by country, ranked by 2011-2015 age-standardized mortality
within World Bank 2014 income group.
5
CHAPTER 1
How is asthma defined?
A diagnostic flowchart for clinicians is recommended in making the initial
diagnosis of asthma based on clinical history and objective assessments to
confirm presence of variable and reversible expiratory airflow limitation
(Figure 1.3).8
M
D
L-
IA
-
U
IB
TR
L
Objective assessment to confirm variability and reversibility of
expiratory airflow limitation.
TE
TE
•
R
IS
IA
U
IB
TR
R
TE
R
TE
IS
D
A
O
Consider other diagnosis in the following clinical conditions:
1) when cough is isolated without other respiratory symptoms;
2) when sputum production is chronic; 3) when shortness of breath
is associated with lightheadedness, paresthesia, dizziness or chest
pain; 4) when inspiration becomes noisy during exercise, and;
5) when there is presence of crackles or inspiratory wheezes. These
are not features of asthma and the probability of asthma is less likely.
A
R
O
M
D
PY
O
D
TE
H
IG
R
TE
PY
O
C
H
T
O
IG
N
PY
O
R
C
Making the diagnosis of asthma is based on identifying both a characteristic
pattern of respiratory symptoms such as wheezing, shortness of breath
(dyspnea), chest tightness or cough, and variable expiratory airflow
limitation.1 Practical tools for the diagnosis of asthma are recommended to
reduce over or underdiagnosis of asthma.
O
C
D
PY
T
O
N
How is asthma diagnosed?
Clinical history. The clinical probability of asthma increases when
symptoms are more than one, especially in adults, worse at night or
early morning, vary in intensity over time, and triggered by certain
factors like viral infections, exercise, changes in weather, laughter or
exposure to allergens or irritants like car exhaust fumes, smoke or
strong smells. Presence of respiratory symptoms in childhood,
history of allergic rhinitis or eczema, or family history of asthma or
allergy, although non-specific, likewise increases the probability for
asthma. Expiratory wheezing, when appreciated on quiet or forced
breathing, is the most frequent abnormal finding for asthma.
P
•
O
C
O
D
In attempts to clinically characterize asthma (and in the process,
individualize patient management), there are various underlying
recognizable clusters of demographic, clinical and/or pathophysiological
features known as asthma phenotypes that may be based on onset, atopic
status, severity (mild/moderate/severe), triggers (nocturnal, exerciseinduced, cough variant, aspirin sensitive, occupational), associated
conditions (smoking, COPD, obesity, Churg-Strauss Syndrome) or treatment response (steroid-sensitive/insensitive, responders to specific
therapies).
6
The overall increase in asthma awareness by physicians has resulted in the
overdiagnosis of asthma, which can be as high as 25-35% in developed
countries.9 Overdiagnosis of asthma10, 11, 12, 13 is a potential problem, resulting
in unnecessary or inappropriate medication use, increased healthcare costs
and mislabeling of patients. Linden Smith et al recommend greater use of
objective diagnostic tests such as spirometry, peak flow diaries and
bronchial provocation to establish a clinical diagnosis of asthma.14
C
P
Since asthma is affected by significant genetic and environmental factors,
its pathogenesis and underlying mechanisms are still not clear. The main
pathophysiological feature of asthma is episodic airway obstruction
characterized by expiratory airflow limitation. The dominant pathological
feature is airway inflammation, sometimes associated with airway structural
changes. The predominant feature of the clinical history is episodic
shortness of breath, particularly at night, often accompanied by cough.
Wheezing appreciated on auscultation of the chest is the most common
physical finding.8 The interaction of these features determines the clinical
manifestations and severity of asthma. While most of asthma subsets
possess the well-known inflammatory markers of the disease, not all do,
and
the
relationship
between
airway
inflammation,
airway
hyperresponsiveness, symptoms and exacerbations is not straightforward.
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PC
C
PC
Based on a consensus statement considering typical asthma
characteristics, asthma is a heterogeneous disease, usually characterized
by chronic airway inflammation, defined by history of respiratory
symptoms such as wheeze, shortness of breath, chest tightness and cough
that vary in intensity over time, together with variable expiratory airflow
limitation.8 Symptoms and airway obstruction are often reversible either
spontaneously or with treatment, usually triggered by factors such as
exercise, allergen or irritant exposure, weather changes or viral respiratory
infections.
CHAPTER 1
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Airflow limitation: confirmed at least once by a reduced
FEV1 /FVC ratio (normally >0.75-0.80 in adults)8
Variability: improvement and/or deterioration in lung function
within the day (diurnal variability), from day to day, from visit to
visit, or seasonally, or from reversibility tests. This is defined as
diurnal variability in PEF by >10% over 2 weeks; increase in FEV1
by at least 12% AND 200 mL or PEF by >20% from baseline after
4 weeks of anti-inflammatory treatment; fall in FEV1 by >10%
AND >200 mL from baseline after exercise; fall in FEV1 from
7
CHAPTER 1
baseline of at least 20% with standard methacholine or histamine
dose or at least 15% with standard hyperventilation, hypertonic
saline or mannitol challenge; or variations in FEV1 of at least 12%
AND >200 mL between visits outside of respiratory infections.
Reversibility: increase in FEV1 by at least 12% AND 200 mL from
baseline after 10-15 minutes of albuterol 200-400 mcg or
equivalent (following proper medication wash-out of ≥4 hours for
SABA and ≥15 hours for LABA)
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
What diseases may mimic asthma?
Alternative diagnoses may mimic asthma, or may co-exist with asthma.
When patients fail to respond to asthma therapy, the following alternative
diagnoses should be entertained:15
Vocal Cord Dysfunction (VCD). This is an upper aerodigestive tract
respiratory disorder characterized by abnormal and inappropriate
movement of the vocal cords. Many patients with this condition,
with or without asthma, receive inappropriate treatment because
they are misdiagnosed as just having difficult-to-control asthma.
Diagnosis is often missed and can be a barrier to adequately
treating patients with uncontrolled respiratory symptoms. A finding
of wheezing or stridor on auscultation of the cervical region is
suggestive of vocal cord dysfunction, especially in elderly patients,
and such dysfunction can be confirmed through laryngoscopy, the
gold standard for its identification (i.e., inspiratory adduction of the
anterior two-thirds of the vocal cords).
•
Chronic Obstructive Pulmonary Disease (COPD). This is a differential
diagnosis when patients initially present with asthma symptoms after
the age of 40 years with significant history of smoking or other inhaled
irritant exposure. Spirometry may distinguish asthma from COPD if
lung function shows complete reversibility of the obstruction;16 or
Asthma-COPD Overlap (ACO) may be a possibility among asthmatics
who develop COPD later in life.
PC
PC
•
C
Patient with respiratory symptoms
D
TE
H
PY
D
L-
For young adults 12 to 39-years old:
IA
•
U
IB
TE
ICS: inhaled corticosteroids; PEF: peak expiratory flow (highest of three readings). When measuring PEF, use the same
meter each time as the value may vary by up to 20% between different meters. SABA: short-acting beta2-agonist.
Other differential diagnoses in a patient with suspected asthma varies with
age and are listed below.8
TR
-
TE
Treat for alternative diagnosis
R
IS
L
IA
YES
TE
R
A
M
O
R
U
IB
NO
IG
TE
NO
Consider trial of treatment
for most likely diagnosis, or
for further investigations
Treat for asthma
O
A
YES
TR
IS
Empiric treatment with
ICS and prn SABA
Review response
Diagnostic testing within
1-3 months
R
M
D
YES
Repeat on another
occasion or arrange
other tests
Confirms asthma diagnosis?
C
Alternative diagnosis
confirmed?
D
R
NO
T
O
Further history and tests for
alternative diagnoses
TE
Results support asthma diagnosis?
O
Perform spirometry/PEF with
reversibility test
N
H
PY
O
C
NO
PY
O
IG
T
O
YES
O
D
R
N
PY
O
O
D
NO
Detailed history/examination
for asthma
History/examination supports
asthma diagnosis?
Clinical urgency,
and other diagnoses
unlikely
C
C
P
P
C
Are the symptoms typical of asthma?
YES
CHAPTER 1
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Chronic upper airway cough syndrome – sneezing, itching, blocked
nose, throat clearing
Hyperventilation dysfunctional breathing – dizziness, paresthesia,
sighing
Bronchiectasis – productive cough, recurrent infections
Cystic fibrosis – excessive cough and mucous production
Congenital heart diseases – cardiac murmurs
Alpha1-antitrypsin deficiency – shortness of breath, family
history of early emphysema
Inhaled foreign body – sudden onset of symptoms
Figure 1.3. Diagnostic flowchart for diagnosing asthma
at initial presentation in clinical practice.
8
9
CHAPTER 1
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
•
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
For adults 40 years and above:
References:
1.
2.
3.
P
D
TE
PY
L-
IA
R
U
IB
-
TE
TE
16.
TR
L
U
IB
15.
TE
A
M
14.
IS
IA
R
13.
D
TE
TR
IS
D
R
A
O
M
R
O
12.
H
IG
D
11.
O
TE
PY
O
10.
C
H
T
O
9.
R
PY
O
C
IG
N
R
C
10
O
PY
T
O
N
8.
D
O
C
O
D
7.
C
P
6.
Global Asthma Report 2014. Auckland, New Zealand: Global Asthma Network, 2014.
Global Asthma Report 2018. Auckland, New Zealand: Global Asthma Network, 2018.
Asher MI, Montefort S, Bjorksten B, Lai CK, Strachan DP, Weiland SK, Williams H; ISAAC
Phase Three Study Group. Worldwide time trends in the prevalence of symptoms of
asthma, allergic rhinoconjunctivitis, and eczema in childhood: The International Study
of Asthma and Allergies in Childhood (ISAAC) Phase One and Three repeat multicountry cross-sectional surveys. Lancet. 2006;368(9537):733-43.
World Health Survey (WHS), 2003 – 2004.
Varona LL, Alava HA, Abong JA, Castor MA, de Leon JC, Kwong SL. Prevalence of
asthma among Filipino adults based on the National Nutrition and Health Survey
(NNHeS). Phil J Int Med 2014;52(4):1-7.
World Health Statistics. 2017. https://www.worldlifeexpectancy.com/philippinesasthma
WHO Mortality Database updated from http://www.who.int/healthinfo/statistics/
mortality_rawdata/en/(version dated 1 October 2017).
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention,
2018. Available from www.ginasthma.org [Accessed: 26 April 2018].
Wise J. Use clinical tests to diagnose asthma and to avoid overdiagnosis, says NICE.
BMJ 2015:350:h522.
Heffler E, Pizzimenti S, Guida G, Bucca C, Rolla G. Prevalence of over-/misdiagnosis of
asthma in patients referred to an allergy clinic. J Asthma. 2015 Nov;52(9):931-4.
José BP, Camargos PA, Cruz Filho ÁA, Corrêa Rde A. Diagnostic accuracy of
respiratory diseases in primary health units. Rev Assoc Med Bras. 2014;60(6):599-612
Perry TT, Rettiganti M, Brown RH, Nick TG, Jones SM. Uncontrolled asthma and factors
related to morbidity in an impoverished, rural environment. Ann Allergy Asthma
Immunol. 2012 Apr;108(4):254-9
Luks VP, Vandemheen KL, Aaron SD. Confirmation of asthma in an era of
overdiagnosis. Eur Respir J. 2010 Aug;36(T2):255-60
Linden Smith J, Morrison D, Deveau C, Hernandez P. Overdiagnosis of asthma in the
community. Can Resp J. 2004 Mar; 11(2): 111-6.
Amundson, DA. Seda G. Daheshia M. Recognizing asthma mimics and asthma
complications. Military Medicine, 2011;176:1162-8.
Perez de Llano L, Cosio BG, Miravitles M, Plaza V, CHACOS study group. Accuracy of a
new algorithm to identify Asthma-COPD Overlap (ACO) patients in a cohort of patients
with chronic obstructive airway disease. Arch Broncopneumol. 2017 Dec 9: pii:
S0300-2896(17)30396-4. doi: 10.1016/j.arbres.2017.10.007. [E-pub ahead of print]
PC
4.
5.
C
PC
Hyperventilation dysfunctional breathing – dizziness, paresthesia,
sighing
Bronchiectasis – productive cough, recurrent infections
Cardiac failure – dyspnea with exertion, nocturnal symptoms
Medication-related cough – treatment with angiotensin converting
enzyme (ACE) inhibitors
Parenchymal lung disease – dyspnea with exertion, non-productive
cough, finger clubbing
Pulmonary embolism – sudden onset of dyspnea, chest pain
Central airway obstruction – dyspnea, unresponsive to
bronchodilators
11
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
CHAPTER
D
L-
IA
R
TE
TE
U
IB
TR
-
U
IB
L
IA
IS
R
TE
R
TE
TR
IS
D
A
M
O
A
R
O
M
D
PY
O
D
TE
H
IG
R
C
TE
PY
O
C
H
T
O
IG
N
PY
O
O
R
T
O
N
PY
D
O
O
D
12
2
C
C
P
P
C
C
PC
PC
Assessment and Classification of Asthma
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
CHAPTER 2
O
D
O
N
R
TE
R
IA
IS
TE
D
Table 2.1. Assessment of asthma in adults, adolescents and children 6-11 years.
R
L-
IA
-
• Assess symptom control over the last 4 weeks
• Identify other risk factors for exacerbations, fixed airway limitation or side effects
• Measure lung function at diagnosis/start of treatment, 3-6 months after
starting controller treatment, then periodically
TE
TE
U
IB
TR
1. Assess asthma control = symptom control and future risk of adverse outcomes
L
U
IB
TR
IS
D
A
M
O
A
R
O
M
D
PY
O
D
TE
H
IG
C
TE
PY
O
C
H
T
O
IG
R
Asthma should be assessed according to asthma control. (Evidence D)
Asthma control assessment is comprised of two parts: symptom control
(previously “current clinical control”) and future risks for adverse outcome
(Table 2.1).5 Both are important because of the close link between
current level of control which is the immediate concern of the patient and
the future risk especially of exacerbation or flare-ups. Lung function test is
now included as an important part in the assessment of future risk.
R
T
O
N
PY
How should we assess asthma?
PY
O
D
O
C
C
P
P
C
C
PC
PC
The most important paradigm shift for asthma care is the shift to evaluating
control rather than severity, which reflects the progress that has been
made in the understanding of the disease and in the pharmacologic care of
patients.1, 2, 15 Since 2006, the Global Initiative for Asthma (GINA) committee
recommends that asthma assessment be based on asthma control
(manifestations of the disease) rather than on severity (intermittent, mild
persistent, moderate persistent and severe persistent).1 This key point of
assessment was emphasized in the 2009 Philippine Consensus Report on
Asthma Diagnosis and Management (PCRADM),3 the GINA 20144 and more
recently, in the updated 2018 GINA guidelines.5 Assessment based on
asthma control more directly reflects the effectiveness of therapeutic
interventions and be more useful clinically as asthma is a variable disease.6, 7
On the other hand, classification of asthma according to severity suggests
a static measure and is less helpful in guiding subsequent treatment.4, 8
2. Assess treatment issues
• Document the patient’s current treatment steps
• Watch inhaler technique, assess adherence and side effects
• Check that the patient has a written asthma action plan
• Ask about patient’s attitudes and goals for their asthma and medications
3. Assess comorbidities
• Rhinitis, rhinosinusitis, gastroesophageal reflux, obesity, obstructive sleep apnea,
depression and anxiety can contribute to symptoms and poor quality of life, and
sometimes to poor asthma control.
15
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
What are the tools for assessing asthma symptom control?
CHAPTER 2
Whichever numerical tool is used, it is important to note that respiratory
symptoms may not be specific and, therefore, one needs to ascertain that
the symptoms are due to asthma and are not from other comorbid
conditions.
How do we assess future risk of adverse outcomes?
PC
The second part of asthma control is to assess future risk of adverse asthma
outcomes, particularly exacerbations, fixed airflow limitation and sideeffects of medication (Table 2.3).5, 15
P
C
P
C
PC
A. Categorical symptom control tools
Questions answerable by yes or no are asked. The consensus-based
GINA symptom control tool is an example (Table 2.2). Together with
risk assessment of adverse outcomes, these may be used to guide
treatment decisions. This classification correlates with assessment
using numerical asthma control scores.9, 10
O
R
PY
IG
T
O
H
C
D
TE
L-
IA
TE
Risk factors for developing fixed airway obstruction
R
• Ever intubated or in intensive care unit for asthma32
• Having one or more exacerbations in the last 12 months33
Having any of
these risk
factors
increases the
patient’s risk of
exacerbations
even if they
have few
asthma
symptoms
U
IB
TR
IS
D
Other major independent risk factors for flare-ups (exacerbations)
•
•
•
•
TE
A
M
R
Some examples of numerical tools are:
• Asthma Control Questionnaire (ACQ).11, 12 There are three ACQ
versions and may contain 5, 6 or 7 items that give the version its name.
All include 5 symptom questions, ACQ 6 adds reliever use and ACQ
7 includes a pre-bronchodilator score. The lower the number, the
better the level of control.
High SABA use16 (with increased mortality if >1 x 200-dose canister/month17)
Inadequate ICS: not prescribed ICS; poor adherence18, incorrect inhaler technique19
Low FEV1, especially if <60% predicted20, 21
Higher bronchodilator reversibility22, 23
Major psychological or socioeconomic problems24
Exposures: smoking21, allergen exposure if sensitized21
Comorbidities: obesity25, chronic rhinosinusitis26, confirmed food allergy27
Sputum or blood eosinophilia28, 29
Pregnancy31
Elevated FENO (in adults with allergic asthma)30
O
-
TE
B. Numerical ‘asthma control’ tools
These tools, validated against healthcare provided assessment,
provide scores and cut-off points to differentiate between levels of
symptom control.10 These are more sensitive to change and therefore
may be used to document patient progress than categorical tools.
•
•
•
•
•
•
•
•
•
•
PY
O
L
U
IB
Well controlled asthma has none of these features, partly controlled has 1-2 of these and poorly controlled asthma has
3-4 of these features.
16
N
IS
D
IA
NO
R
YES
TE
Any activity limitation due to asthma?
3-4
of these
A
NO
1-2
of these
TR
YES
None
of these
M
Reliever needed for symptoms*
more than once a week?
D
NO
R
YES
O
Any night waking due to asthma?
Assess risk factors at diagnosis and periodically, particularly for patients experiencing exacerbations.
Measure FEV1 at start of treatment, after 3-6 months of controller treatment to record the patient’s
personal best lung function, then periodically for ongoing risk assessment.
Having uncontrolled asthma symptoms is an important factor for exacerbations.8
Additional, potentially modifiable risk factors for flare-ups (exacerbations),
even in patients with few symptoms†, include:
TE
PY
NO
O
H
O
C
YES
D
IG
T
O
Partly
Well
Uncontrolled
controlled controlled
In the past 4 weeks, has the patient had:
Daytime asthma symptoms more than
twice/week?
Table 2.3. Risk factors for poor asthma outcomes.
Level of asthma symptom control
R
N
PY
O
D
O
C
C
Table 2.2. GINA assessment of asthma control in adults, adolescents
and children 6-11 years.
A. Asthma symptom control
CHAPTER 2
More refined assessment tools resulted in better understanding of the
behavior of an asthmatic over time and in this regard have been designed
and validated to better reflect levels of control that have been used in treatment intervention studies.
• Asthma Control Test (ACT).10, 13, 14 The ACT includes four symptom/
reliever questions plus a patient self-assessed level of control. In ACT,
the range of score is 5-25. The higher score indicates better control.
Preterm birth, low birth weight and greater infant weight gain34
Lack of ICS treatment35
Exposure: tobacco smoke;36 noxious chemicals; occupational exposures37
Low initial FEV1 ;38 chronic mucous hypersecretion;36, 38 sputum or blood eosinophilia38
Risk factors for medication side effects
•
•
Systemic: frequent OCS; long-term, high-dose and/or potent ICS; also taking P450 inhibitors39
Local: high-dose or potent ICS;39, 40 poor inhaler technique41
FEV1: forced expiratory volume in 1 second; FENO: fraction of exhaled nitric oxide; ICS: inhaled corticosteroids;
OCS: oral corticosteroids; P450 inhibitors: cytochrome P450 inhibitors such as ritonavir, ketoconazole, itraconazole;
SABA: short-acting beta2-agonist.
† Independent risk factors are those that are significant after adjustment for the level of symptom control. Poor symptom
control and exacerbation risk should not be simply combined numerically, as they have different causes and may need
different treatment strategies.
17
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Lung function does not correlate strongly with asthma symptoms in
adults.42 When combined in numerical asthma control tools, symptoms
frequency can outweigh important lung function results.43 However, a low
initial FEV1 is a strong independent predictor of risk of exacerbations, even
after adjustment for symptom frequency.
In situations where the line between poorly controlled asthma or actual
exacerbation is hard to distinguish, previous recommendation states to err
on the side of treatment as if it is an exacerbation.
• Watch the patient use their inhaler(s), check against inhaler checklist.
Show correct method, and recheck, up to 3 times. Re-check each visit.
Watch patient using
their inhaler
PC
Discuss adherence and
barriers to use
C
• If no evidence variable airflow limitation or spirometry or other testing, consider
having ICS dose and repeating lung function after 2–3 weeks; check patient has
action plan. Consider referring for challenge test.
IG
TE
H
O
IS
L-
IA
U
IB
-
• If asthma is still uncontrolled after 3-6 months on high-dose ICS-LABA, or with
ongoing risk factors, refer to a specialist or severe asthma clinic
TE
Refer to a specialist or
severe asthma clinic
R
• Use shared decision-making and balance potential benefits and risks.
TR
L
TE
Asthma exacerbation, also termed acute asthma deterioration, is defined as
a change in the stable condition that warrants a change in therapy and for
both patient and the physician has an element of urgency. The patient
experiences mild to severe deterioration in symptoms and is recognized by
the patient’s ability to talk, presence or absence of distress by physical
examination and if available the use of an objective measure of airway
caliber like PEFR. Each level of severity, whether mild-to-moderate, are
used to recommend the necessary steps to control/reverse the condition
and prevent morbidity and/or mortality.
• Consider step-up to next treatment level or alternative option on present level.
D
IA
U
IB
TR
Poorly controlled asthma is another label that closely applies to the stable
asthma condition that is characterized by more symptoms, increased use of
medications and resulting in interference with activities of daily living very
much akin to uncontrolled asthma. Some patients may not achieve the
goals of good asthma control even with maximal therapy.44 There are initial
steps recommended to investigate a patient with poor symptom control
and/or exacerbation despite treatment (Figure 2.1).5
Consider treatment
step-up
TE
R
R
TE
IS
D
A
M
O
A
R
O
M
D
• Check for and manage comorbidities (e.g., rhinitis, obesity, GERD, obstructive sleep
apnea, depression/anxiety) that may contribute to symptoms.
PY
Assess and manage
comorbidities
• Check for risk factors or inducers such as smoking, beta-blockers or NSAIDs, or
occupational or domestic allergen exposure, and address as possible
(Treating modifiable risk factors).
C
If possible, remove
potential risk factors
T
O
R
N
D
TE
PY
O
C
H
IG
T
O
R
PY
O
O
D
N
PY
O
C
P
P
O
D
How do you differentiate poorly controlled asthma and asthma
exacerbations?
18
Confirm the diagnosis
of asthma
The use of PEFR in asthma, either as part of an initial objective measure of
airways caliber to be followed by a formal spirometry, or part of periodic
assessment of control has long been advocated to be incorporated in an
asthma management plan. Its use has been evaluated in multiple studies
that supports better outcome when used as part of a more comprehensive
asthma program and is discussed in the pharmacological management of
stable asthma and in acute asthma exacerbations or flare-ups.
• Have emphatic discussion to identify poor adherence, e.g., “Many patients don’t use
their inhaler as prescribed. In the last 4 weeks, how many days a week have you taken
it?” (0 days, 1, 2, 3, etc.) and/or: “Do you find it easier to remember your inhaler in the
morning or the evening?” Ask about beliefs, cost of medications, and refill frequency.
C
C
PC
Lung function should be assessed at diagnosis or start of treatment; after 3
to 6 months of controller treatment to assess the patient’s personal FEV1 ;
and periodically thereafter depending on the risk of adverse outcomes.
In most adult patients, lung function can be recorded at least every 1 to 2
years.5 Interval lung function determinations (spirometry monitoring) are
usually indicated in hard-to-control asthma and are preferably referred for
specialist care.
CHAPTER 2
CHAPTER 2
What is the role of lung function determination in the assessment of
future risk of adverse outcomes?
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
• Refer earlier than 6 months if asthma is very severe or difficult to manage, or if
doubts about diagnosis.
GERD: gastroesophageal reflux disease; ICS: inhaled corticosteroid; LABA: long-acting beta2-agonist;
NSAID: non-steroidal anti-inflammatory drugs.
For clinical efficiency, this flowchart starts with the most common reasons for uncontrolled asthma (i.e., incorrect inhaler
technique and poor adherence), as these can be indentified in clinical practice – and often remedied – without any
special resources. If symptoms and/or lung function improve when inhaler technique or adherence are addressed, this
can provide confirmation of the diagnosis of asthma. However, the various steps may be carried out in a different order
depending on the clinical context and available resources.
Figure 2.1. Investigating a patient with poor symptom control
and/or exacerbations despite treatment.
19
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
17.
References:
18.
19.
20.
C
P
D
TE
L-
33.
TE
32.
IA
31.
R
30.
U
IB
TE
29.
TR
-
28.
IS
D
27.
TE
A
M
R
O
L
IA
R
U
IB
TR
IS
D
TE
A
M
R
O
26.
PY
25.
O
C
H
IG
R
24.
T
O
N
PY
O
O
23.
C
22.
D
D
TE
PY
O
C
H
IG
R
T
O
N
PY
O
C
O
D
20
PC
21.
P
C
PC
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2. Koshak EA. Classification of asthma according to the revised 2006 GINA: Evolution
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3. Philippine College of Chest Physicians. Philippine Consensus Report on Asthma
Diagnosis and Management 2009.
4. Reddel HK, Bateman ED, Becker A, Boulet, LP, Cruz AA, Drazen JM, Haahtela T, et. al. A
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Eur. Respir J 2008: 31 (1): 143-78.
7. Thomas M, Kay S, Pile J, Williams A, Carrranza Rosenzweig JR, Hillyer EV, et al. The
Asthma Control Test (ACT) as predictor of GINA guideline- defined asthma control:
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2009: 18 (1): 41-9.
8. Humbert M, Holgate S, Bousquet J. Asthma control or severity: that is the question.
Allergy 2007; 62(2): 95-101.
9. Haselkorn T, Fish JE, Zeiger RS, Szefler SJ, Miller DP, Chipps BE, Simons FE, et al.
Consistently very poorly controlled asthma, as defined by the impairment domain of
the Expert Panel Report 3 guidelines, increases risk for future severe asthma
exacerbations in The Epidemiology and Natural History of Asthma: Outcomes and
Treatment Regimens (TENOR) study. J Allergy Clin Immunol 2009; 124:895-902.e1-4.
10. Patel M, Pilcher J, Reddel HK, Pritchard A, Corin A, Helm C, Tofield C, et al. Metrics of
salbutamol use as predictors of future adverse outcomes in asthma. Clin Exp Allergy
2013; 43:1144-51.
11. Suissa S, Ernst P, Boivin JF, Horwitz RI, Habbick B, Cockroft D, Blais L, et al. A cohort
analysis of excess mortality in asthma and the use of inhaled beta agonists. Am J Respir
Crit Care Med 1994; 149:604-10.
12. Ernst P, Spitzer WO, Suissa S, Cockroft D, Habbick B, Horwitz RI, Bolvin JF, et al. Risk of
fatal and near-fatal asthma in relation to inhaled corticosteroid use. JAMA 1992;
268:3462-4.
13. Melani AS, Bonavia M, Cilenti V, Cinti C, Lodi M, Martucci P, Serra M, et al. Inhaler
mishandling remains common in real life and is associated with reduced disease control.
Respir Med 2011; 105:930-8.
14. Fuhlbrigge AL, Kitch BT, Paltiel AD, Kuntz KM, Neumann PJ, Dockery DW, Weiss ST.
FEV1 is associated with risk of asthma attacks in a pediatric population. J Allergy Clin
Immunol 2001; 107:61-7.
15. Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, Casale TB, Chanez P, et al.
A new perspective on concepts of asthma severity and control. Eur Respir J 2008; 32
(3):545-54.
16. Patel M, Pilcher J, Reddel HK, Pritchard A, Corin A, Helm C, Tofield C, et al. Metrics of
salbutamol use as predictors of future adverse outcomes in asthma. Clin Exp Allergy
2013;43:1144-51.
Suissa S, Ernst P, Boivin JF, Horwitz RI, Habbick B, Cockroft D, Blais L, et al. A cohort
analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J
Respir Crit Care Med 1994;149:604-10.
Ernst P, Spitzer WO, Suissa S, Cockcroft D, Habbick B, Horwitz RI, Boivin JF, et al. Risk
of fatal and near-fatal asthma in relation to inhaled corticosteroid use. JAMA
1992;268:3462-4.
Melani AS, Bonavia M, Cilenti V, Cinti C, Lodi M, Martucci P, Serra M, et al. Inhaler
mishandling remains common i
Fuhlbrigge AL, Kitch BT, Paltiel AD, Kuntz KM, Neumann PJ, Dockery DW, Weiss ST.
FEV1 is associated with risk of asthma attacks in a pediatric population. J Allergy Clin
Immunol 2001;107:61-7.
Osborne ML, Pedula KL, O'Hollaren M, Ettinger KM, Stibolt T, Buist AS, Vollmer WM.
Assessing future need for acute care in adult asthmatics: the Profile of Asthma Risk
Study: a prospective health maintenance organization-based study. Chest 2007;132:
1151-61.
Ulrik CS, Frederiksen J. Mortality and markers of risk of asthma death among 1,075
outpatients with asthma. Chest 1995;108:10-5.
Pongracic JA, Krouse RZ, Babineau DC, Zoratti EM, Cohen RT, Wood RA, Khurana
Hershey GK, et al. Distinguishing characteristics of difficult-to-control asthma in
inner-city children and adolescents. J Allergy Clin Immunol 2016;138:1030-41.
Sturdy PM, Victor CR, Anderson HR, Bland JM, Butland BK, Harrison BD, Peckitt C,
et al. Psychological, social and health behaviour risk factors for deaths certified as
asthma: a national case-control study. Thorax 2002;57:1034-9.
Fitzpatrick S, Joks R, Silverberg JI. Obesity is associated with increased asthma
severity and exacerbations, and increased serum immunoglobulin E in inner-city
adults. Clin Exp Allergy 2012;42:747-59.
Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, Zuberbier T,
et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration
with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008;63 Suppl
86:8-160.
Burks AW, Tang M, Sicherer S, Muraro A, Eigenmann PA, Ebisawa M, Fiocchi A, et al.
ICON: food allergy. J Allergy Clin Immunol 2012;129:906-20.
Belda J, Giner J, Casan P, Sanchis J. Mild exacerbations and eosinophilic inflammation
in patients with stable, well-controlled asthma after 1 year of follow-up. Chest
2001;119:1011-7.
Ulrik CS. Peripheral eosinophil counts as a marker of disease activity in intrinsic and
extrinsic asthma. Clin Exp Allergy 1995;25:820-7.
Zeiger RS, Schatz M, Zhang F, Crawford WW, Kaplan MS, Roth RM, Chen W. Elevated
exhaled nitric oxide is a clinical indicator of future uncontrolled asthma in asthmatic
patients on inhaled corticosteroids. J Allergy Clin Immunol 2011;128:412-4.
Murphy VE, Clifton VL, Gibson PG. Asthma exacerbations during pregnancy:
incidence and association with adverse pregnancy outcomes. Thorax 2006;61:169-76.
Turner MO, Noertjojo K, Vedal S, Bai T, Crump S, FitzGerald JM. Risk factors for nearfatal asthma. A case- control study in hospitalized patients with asthma. Am J Respir
Crit Care Med 1998;157:1804-9.
Miller MK, Lee JH, Miller DP, Wenzel SE. Recent asthma exacerbations: a key predictor
of future exacerbations. Respir Med 2007;101:481-9.
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Risk Factors for Asthma Exacerbations
3
CHAPTER
D
TE
PY
O
C
H
IG
R
T
O
N
PY
O
C
O
L-
IA
R
-
TE
TE
U
IB
TR
IS
D
TE
A
M
R
O
L
IA
R
U
IB
TR
IS
D
TE
A
M
R
O
22
D
D
TE
PY
O
C
H
IG
R
T
O
N
PY
O
D
O
C
P
C
PC
P
C
PC
34. den Dekker HT, Sonnenschein-van der Voort AMM, de Jongste JC, Anessi-Maesano I,
Arshad SH, Barros H, Beardsmore CS, et al. Early growth characteristics and the risk
of reduced lung function and asthma: A meta-analysis of 25,000 children. J Allergy
Immunol 2016;137:1026-35.
35. O'Byrne PM, Pedersen S, Lamm CJ, Tan WC, Busse WW. Severe exacerbations and
decline in lung function in asthma. Am J Respir Crit Care Med 2009;179:19-24.
36. Lange P, Parner J, Vestbo J, Schnohr P, Jensen G. A 15-year follow-up study of
ventilatory function in adults with asthma. N Engl J Med 1998;339:1194-200.
37. Baur X, Sigsgaard T, Aasen TB, Burge PS, Heederik D, Henneberger P, Maestrelli P,
et al. Guidelines for the management of work-related asthma.[Erratum appears in Eur
Respir J. 2012 Jun;39(6):1553]. Eur Respir J 2012;39:529- 45.
38. Ulrik CS. Outcome of asthma: longitudinal changes in lung function. Eur Respir J
1999;13:904-18.
39. Raissy HH, Kelly HW, Harkins M, Szefler SJ. Inhaled corticosteroids in lung diseases.
Am J Respir Crit Care Med 2013;187:798-803.
40. Foster JM, Aucott L, van der Werf RH, van der Meijden MJ, Schraa G, Postma DS, van
der Molen T. Higher patient perceived side effects related to higher daily doses of
inhaled corticosteroids in the community: a cross-sectional analysis. Respir Med
2006;100:1318-36.
41. Roland NJ, Bhalla RK, Earis J. The local side effects of inhaled corticosteroids: current
understanding and review of the literature. Chest 2004;126:213-9.
42. Moore V, Jakkola M, Burge S. A systematic review of serial peak flow measurements
in the diagnosis of occupational asthma. Eur Respir J 2011; 38: Suppl 55, P4941
43. Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, et al.
International ERS/ATS Guidelines on definition, evaluation and treatment of severe
asthma. Eur Respir J 2014; 43:343-73
44. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, Pedersen SE;
GOAL Investigators Group. Can guideline-defined asthma control be achieved?
The Gaining Optimal Asthma ControL Study. Am J Respir Crit Care Med 2004;
170:836-44.
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
A variety of risk factors, referred to as “triggers,” cause asthma exacerbations. As a result, there is worsening of asthma symptoms and deterioration
of asthma control, often despite existing maintenance treatment. Respiratory infections, allergens, irritants, environmental and occupational
exposures are among the more common asthma triggers. Each of these
factors are postulated to act through different mechanisms but has a final
common pathway that includes cellular inflammation, heightened bronchial
hyperresponsiveness and increased airflow obstruction.1
CHAPTER 3
O
O
TE
H
IG
R
C
TE
D
IA
R
TR
What is the burden imposed by allergen exposure in asthma?
L-
Allergenic triggers include indoor allergens, such as house dust mites
(HDMs), molds, animal dander, cockroaches, and outdoor allergens, such as
pollens and molds. HDMs are by far the most common aeroallergen implicated
in allergic individuals in Asian countries. Data from most of the Asian
countries have reported rates of greater than 60% and even up to 80% in
sensitized atopic individuals. The highest rates of HDM sensitization were
reported in Singapore, Taiwan and South India, reaching almost 90%. The
Philippines has one of the lowest sensitization rates at 33-47%. The most
common species strongly associated with wheezing and asthma in atopic
Asians is the Dermatophagoides HDM species, with a slightly lower
percentage sensitized to Blomia Tropicalis.3 Southeast Asian countries,
such as the Philippines, with stable year-round tropical climates typically do
not experience wide fluctuations in environmental or indoor allergens such
as dust mites and, thus, allergic disease phenotypes tend to be perennial
rather than seasonal in these regions.3
TE
TE
U
IB
-
U
IB
L
IA
IS
R
TE
R
TE
TR
IS
D
AEROALLERGENS
A
M
O
A
R
O
M
D
PY
This chapter discusses updates and important issues of a few of these
asthma triggers.
D
PY
O
C
H
T
O
IG
N
PY
O
D
R
T
O
N
PY
O
D
O
C
C
P
P
C
C
PC
PC
For many of these risk factors, such as tobacco smoke, occupational
agents, certain foods, additives and drugs, reducing or eliminating an
affected patient’s exposure improves asthma control and reduces
medication needs. For other known asthma triggers, such as allergens,
respiratory infections and pollutants, avoidance measures where possible
should be taken. However, because many asthma patients react to multiple
factors that are ubiquitous in the environment, complete avoidance of
these factors is usually impractical and very limiting to the patient. Thus,
controller medications have an important role because patients are often
less sensitive to these risk factors when their asthma is under good
control.2
25
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Dust mite population and sensitization patterns are heavily influenced not
only by urbanization but by climatic conditions. However, the overall
burden of dust mite sensitization in Asia is much higher than that seen in the
United States and Europe, even in areas of similar climate and/or
urbanization, and the question has been posed as to whether other factors
such as genetics may play a role.3
There are measures that may show some benefit. A recent review indicated
the level of evidence for these measures as follows:8
CHAPTER 3
•
Efforts could be made to restrict the presence of carpets,
upholstered furniture and drapes in the environment of the dust
mite allergic patients, in particular in the rooms where the patient
spends the greatest amount of time, first of all in the bedroom.
Although there is a lack of evidence to support this recommendation
alone, these may be useful as a part of a comprehensive intervention
plan.
•
Humidifier use should be avoided while dehumidifiers can be used,
although these do not generally filter the air as air conditioners do.
(Evidence B)
•
Washing sheets, pillowcases, mattress pads and blankets weekly
effectively reduces mite counts. (Evidence B) Using a heated drier, in
fact hot water (>130°F) is able to kill mites while cold water may
reduce HDM concentrations by 90%.
•
Chemical products, so called acaricides such as benzyl benzoate and
tannic acid, showed only modest effects on reducing mite allergen,
(Evidence B) therefore their use is not recommended.
D
TE
TE
TE
The GINA guidelines acknowledge that measures should be implemented
wherever possible to prevent the development of asthma and asthma
symptoms and exacerbations. However, considering that mite allergens
may trigger asthma symptoms, the GINA guidelines conclude that no single
avoidance measure is likely to reduce exposure to mite allergens, but also
that an integrated approach to avoidance cannot be widely recommended.9, 10
U
IB
-
L-
IA
R
TR
IS
D
TE
A
M
R
O
L
IA
R
U
IB
TR
IS
D
TE
A
R
Are avoidance measures directed to house dust mite (HDM) beneficial to
asthma patients?
H
PY
M
O
Studies have found that exposure to dust mite allergens is associated with
dust mite sensitization and with asthma. House dust mite allergen exposure
is involved in triggers of asthma attacks and asthma outcomes such as
asthmatic symptoms and a frequent requirement for medication in allergic
asthmatic patients. However, the relationship of HDM exposure with visits
to the emergency department has provided conflicting results.5 An updated
review of findings from 11 studies from the scientific literature on indoor
exposures and exacerbations of asthma concluded that in children
sensitized to dust mites, there seems to be a causal relationship between
exposure to dust mite allergen and asthma exacerbation. However, this
causal relationship is not very evident in children not sensitized to dust
mites and in adults, whether sensitized or non-sensitized.6
O
D
PY
O
Is the association of house dust mite (HDM) allergen exposure and
asthma established?
C
TE
C
H
T
T
HOUSE DUST MITE (HDM) ALLERGENS
IG
R
O
N
PY
O
O
D
IG
R
O
N
PY
O
D
O
Because many asthmatic individuals especially children tend to be
sensitized to more than one allergen, the more current approach to
environmental remediation is multifaceted and targets multiple allergens.4
C
C
P
P
C
C
PC
PC
Frequent vacuum cleaning has not been proven to be sufficiently
effective in reducing HDM exposure, while specific physical barriers, in
particular pillow and mattress encasing, have been demonstrated to
be more useful at this purpose. (Evidence B)
CHAPTER 3
Sensitization to other aeroallergens was generally lower compared to mites
across the Asian population. Cockroach, followed by mold and animal
dander, and subsequently grass and tree pollen, in descending order of
positivity, formed the remainder of aeroallergens commonly seen in Asia.
Pollen sensitization in Asia, apart from Japan, generally has less medical
significance in Asia than in the West.3
•
MOLDS AND FUNGI
What is the effect of indoor dampness and mold on asthma?
Many studies which have examined the efficacy of HDM interventions in
HDM sensitized asthmatics revealed inconsistent results. A systematic
review of 54 studies show that HDM interventions did not significantly
decrease asthma symptoms compared to control groups.7
26
Published epidemiologic studies and meta-analyses show consistently that
indoor dampness or mold or measured dampness was positively associated
with exacerbation or severity of asthma. This causal relationship is
27
Washing cats or dogs at least weekly can reduce airborne cat allergen
Fel d 1 or dog allergen Can f 1; however, the clinical benefit is yet to be
proven. Moreover, the effect of washing is not sustained. (Evidence B)
Chemical treatments used to denature, oxidize or modify these allergens
represent only temporary measures. Because the source is not removed,
the allergen will re-accumulate after the treatment is applied. In addition,
chemicals in the home need to be used with caution because some agents
are volatile and can trigger symptoms in sensitized individuals. Long-term
regular use of high-efficiency or central vacuum cleaners is associated with
reduced exposure to Fel d 1 and Can f 1 in homes with cats or dogs living in
them, although the health effects are uncertain.9, 21 (Evidence B)
O
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Does cockroach allergen exposure cause exacerbation of asthma?
O
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What are the effects of furry animal exposure on asthma?
TE
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There is sufficient evidence of a causal relationship between cockroach
allergen exposure and asthma exacerbation in individuals specifically
sensitized to cockroaches, especially adults, but there is limited or suggestive evidence of such an association in children not sensitized to
cockroaches.6, 23, 24
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COCKROACH ALLERGENS
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FURRY ANIMALS
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Exposure to cockroach allergen in homes should be minimized to reduce
the risk of cockroach sensitization (Evidence B) and reduce the risk of
asthma morbidity in sensitized subjects.25 (Evidence C)
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Avoidance is the most effective way to manage cat and dog allergy and
patients should be advised to consider removing the cat or dog from the
environment, if present, to improve respiratory health.21 (Evidence A)
TE
In general, individual interventions are not successful at eliminating exposure to cockroach contaminants, and therefore, it is necessary to use a
combination of interventions depending on the specifics of the infestation.
These interventions include initial removal of facilitating factors, elimination
of the cockroaches and removal of reservoirs of cockroach-derived
contaminants. Facilitating factors are conditions in the environment that
facilitate or promote the production of contaminants by a source. For
cockroaches, such factors include a means of ingress, as well as sources of
water, food and shelter.25 (Evidence D)
D
In an updated review, it was stated that there is sufficient evidence of a
causal relationship between cat allergen exposure and exacerbation of
asthma in individuals sensitized to cats. It also stated that an association of
dog allergen exposure to exacerbation of asthma in sensitized children, and
also suggests associations in non-sensitized adults.6, 22
R
What intervention strategies can be adopted to minimize the effects of
cockroach allergens?
IS
The health effects of furry animal exposure include development of allergen
specific IgE (defined as sensitization) in susceptible individuals, often
leading to manifestations of allergic diseases, such as asthma and rhinitis, if
the exposure persists. Once a sensitized individual develops an allergic
disease, continued exposure to the allergens is likely to exacerbate
symptoms and lead to poorer outcomes.21
What intervention strategies can be adopted?
CHAPTER 3
There are inexpensive measures to help discourage mold expansion, for
example, reducing humidity by increasing ventilation, covering cold
surfaces such as water pipes with insulation and increasing the air temperature to reduce surface humidity.17 It is often assumed that the specific causal
agents for exacerbations of asthma that are associated with dampness are
fungal, but this has not been confirmed. Other causal agents in dampness
may include other biologic exposures such as bacteria, amoebas, dust
mites that thrive in dampness or non-biologic exposures such as chemicals
emitted from damp materials.13 It can therefore be challenging to isolate the
health effects of fungal exposure in damp environments.
PC
Additional strategies include interventions aimed at reducing exposure to
reservoirs and blocking pathways from reservoirs to home occupants.
Credible research has shown that adverse health effects are associated with
damp indoor environments, and governmental or professional bodies
recommended that persistent dampness and mold damage in the
nonindustrial workplace, including schools and residential housing, requires
prevention, management and effective remediation.18, 19, 20
28
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
established with sufficient evidence in children, but less so in adults. The
evidence, however, does not suggest that this relationship is restricted to
those with specific sensitization to fungi or dust mites.5, 6, 11, 12, 13, 14, 15, 16
PC
CHAPTER 3
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
29
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
IRRITANTS AND POLLUTANTS
Can air pollution trigger asthma exacerbations?
Air pollution that involve changes in gaseous and particulate outdoor air
pollutants are associated with daily asthmatic symptoms, a decrease in lung
function, emergency room (ER) visits and hospitalizations for asthma
attacks.5
OUTDOOR AIR POLLUTION
What are the effects of air pollution on asthma?
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CHAPTER 3
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What avoidance measures reduce the impact of air pollution exposure on
asthma?
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Four main mechanisms have been identified by which air pollution could
contribute to asthma development: oxidative stress and damage, airway
remodeling, inflammatory pathways and immunological responses and
enhancement of respiratory sensitization to aeroallergens.29, 30, 31 However,
air pollutants are likely to make only a small contribution, compared with
other factors, in the development of asthma, and in only a small proportion
of the population.29
TE
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For patients with clear association of exposure to air pollutants and
increase in asthma symptoms, it is often advised to stay indoors and to limit
physical exertion when air pollutant levels exceed health-based thresholds.
However, there is limited evidence that these individual actions can reduce
health risks. Relative contribution of indoor- and outdoor-generated
pollutants to personal exposures depends on multiple factors, including the
type of pollutants, building structure, indoor sources and personal activities
and these should be considered so that healthcare providers and their
patients may tailor interventions to individual circumstances in order to
maximize the net exposure reduction based on individual circumstances.35
O
M
O
Increasing amounts of evidence suggest that long-term exposures to air
pollution, especially traffic-related air pollution (TRAP) and its surrogate,
NO2, can contribute to new-onset asthma in both children and adults.26 The
UK’s Committee on the Medical Effects of Air Pollutants found that the
evidence is consistent with the possibility that outdoor air pollution might
play a role in causing asthma in susceptible individuals living very close to
busy roads carrying a lot of truck traffic.28
CHAPTER 3
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Can air pollution cause the development of asthma?
C
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Air pollutants exert their detrimental effects on airways and lungs by:
attenuating ciliary activity of airway epithelial cells, increasing permeability
of airway epithelium leading to inflammatory changes in cells of airways
and lung parenchyma, and modulating cell cycle and death of cells of
respiratory system. Air pollutants show these effects by causing direct
cellular injury or by inducing intracellular signaling pathways and
transcription factors that are known to be sensitive to the oxidative stress.27
Specific pollutants such as ozone (O3), nitrogen dioxide (NO2) and particulate matter <2.5 μm in diameter (PM2.5) can induce airway inflammation and
airway hyperresponsiveness. In addition, such pollutant exposures have
been associated with oxidative stress, thought to be a feature of severe
asthma.26
A recent meta-analysis provided evidence of the association between
selected pollutants, namely, NO2, PM2.5, O3, carbon monoxide (CO) but not
sulfur dioxide (SO2) and particulate matter <10 µm in diameter (PM10).28 In
children, the association was significant for NO2, SO2 and PM2.5.28
Short-term exposures to O3, NO2, SO2, PM2.5 and TRAP may increase the risk
of exacerbations of asthma symptoms.26, 32, 33 A meta-analysis using various
database has shown that acute elevation of PM concentration in the air may
increase hospital admission for asthma. It was specifically noted when the
concentration of PM2.5 is increased to 10 µg/m3, the increment of asthmarelated hospital admissions is nearly twice than that when the
concentration of PM10 is increased to 10 µg/m.3, 26, 34
PC
Within the past decade, a substantial body of research on the adverse
effects of air pollution on asthma has been published. Air pollutants, at high
concentrations, such as those noted in megacities of India and China, might
have direct irritant and inflammatory effects on airway neuroreceptors and
epithelium. However, other mechanisms are probably in operation in high
income countries whose concentrations of air pollutants are lower.26
30
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
INDOOR FUEL EXPOSURE
Indoor fuels include solid, liquid and gas fuels. Solid fuels include biomass
and coal. Biomass fuel refers to any living or recently living plant and/or
animal-based material that is deliberately burned by humans as fuel, such
as wood, twigs, dried animal dung, charcoal, grass or agricultural crop
residues.36 Stoves fueled by coal or biomass, which are major sources of
indoor combustion, release respiratory irritants such as particulate matter
(PM), CO, SO2, NO2 and organic toxins. Burning biomass fuels, mainly wood,
crop residues and livestock dung, remain as the important source of exposure to a variety of toxins.37
31
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
What is the effect of indoor fuel exposure on asthma?
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Of all forms of SHS, maternal exposure seems to have the largest impact on
asthma by increasing the frequency and severity of the disease and
decreasing lung function during pregnancy. Asthmatic children exposed to
multiple household smokers face an increased risk for respiratory illnessrelated absences from school, and these effects persist during adolescence
but weaken during adulthood.52
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Furthermore, several investigators have found that asthmatic patients who
smoke are more likely to have poorer disease control compared with
asthmatic non-smokers.44, 45, 46, 47 Asthmatic smokers are at risk of developing
more severe symptoms, higher frequency of exacerbations and worse
asthma-specific quality of life. Cigarette smoking in asthma is also associated
with increased numbers of life-threatening asthma attacks and greater
asthma mortality.42
TR
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It has been established in several studies that the risk of developing asthma
was significantly higher among current smokers and among ex-smokers
compared with those who have never smoked.41, 42, 43 Their results support
the hypothesis that smoking causes asthma in adulthood. In addition, they
found that women may be more susceptible to the adverse effects of
smoking. It is debatable whether smoking induces the development of
asthma in adolescents.
TE
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Smoking cessation improves several asthma outcomes. In a prospective
study by Tonnesen et al, asthmatic smokers who stopped smoking
experienced a significant improvement in quality of life, decreased
hyperreactivity and a reduction in their usage of rescue medications.53
It has also been shown that asthmatic ex-smokers exhibited significant
improvement in FEV1 , asthma control, recovery to corticosteroid response
and decrease in neutrophil counts in sputum compared with individuals
who continued to smoke. In another study, it was demonstrated that the
improvement in airway hyperresponsiveness was maintained one year after
smoking cessation which was not seen in the control group.54, 55, 56
O
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What is the effect of tobacco smoke on asthma?
What are the benefits of smoking cessation and the interventions that are
needed?
C
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TOBACCO SMOKE
CHAPTER 3
Secondhand smoke (SHS), also referred to as passive smoking, environmental
tobacco smoke and involuntary smoking, contain irritant gases, such as
ammonia, nitrogen dioxide, sulfur dioxide, hydrogen cyanide and acrolein
which can contribute to the development of airway disease.52, 53
D
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It is currently unclear if prevention of chronic disease can be achieved by
reducing solid fuel exposure and how much reduction in exposure is
required to achieve a useful benefit. The importance of increased
awareness about the health effects of solid fuel smoke inhalation still needs
to be emphasized. The promotion of preventive initiatives through
education, research and policy change is recommended.36
32
What is the effect of secondhand smoke (SHS) on asthma?
C
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C
PC
A more recent review by Desai and colleagues have estimated that exposure to solid fuel smoke exacerbates asthma with a relative risk of 1.6 (95%
CI, 1.0–2.5%) in children between 5 and 14 years and 1.2 (95% CI, 1.0–1.5) in
persons older than 15 years.40 In adults with asthma, however, there is no
evidence that indoor biomass use contributes to worse morbidity and
exacerbations. Existing evidence from five studies is mixed for use of other
fuels and exacerbations in adults. Although there is no direct evidence to
implicate indoor biomass fuel burning for exacerbation of asthma in
children, there is supportive evidence by gas stove use.38
Airway mucosal permeability is increased in smokers, which could lead to
increased clearance of inhaled corticosteroids (ICS) from the airways.
Smokers also have decreased histone deacetylase activity, which is
necessary for corticosteroids to fully suppress cytokine production, and
can lead to corticosteroid resistance.48, 49, 50, 51
PC
CHAPTER 3
Studies examining biomass and adult asthma are not uniformly positive and
the associations with specific fuel type are inconsistent.38 A population
survey study from India indicates that adult women living in households
using biomass and solid fuels have a significantly higher risk of asthma than
those living in households using cleaner fuels (OR: 1.26; 95% CI: 1.06–1.49;
p = .010), even after controlling for the effects of a number of potentially
confounding factors.39
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
The evidence reviewed in published articles regarding the multiple negative
effects of smoking and SHS on patients with asthma pose the urgent need
to emphasize the obligation of all physicians and other healthcare
professionals to assist patients and those they live with to quit smoking.
Specific instructions for family members, caregivers and friends of patients
with asthma should include never smoking in the home, car or workplace.
Simply smoking in another room of the house is not sufficient, nor are any
forms of air cleaners effective in reducing SHS exposure.57 It has been
estimated that with successful smoking cessation, a parent can add an
average of 7 years to his or her life, eliminate SHS exposure to other family
members and reduce tobacco-related pregnancy outcomes.58, 59, 60
33
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
The management of asthmatic smokers should begin with emphatic
recommendations to stop smoking, including having no contact with
environmental smoke.61
bioaerosol from the natural environment or from indoor environments in
enclosed spaces, workplaces and homes.66
CHAPTER 3
CHAPTER 3
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What is the effect of exercise on asthma?
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How is exercise-induced bronchoconstriction (EIB) diagnosed?
U
IB
Symptoms alone are insufficient to identify patients with EIB.74 In order to
establish a secure diagnosis, it is important to perform objective testing to
confirm dynamic changes in airway function by measuring the change in
the FEV1 before and after a standardized exercise challenge test (ECT), in
the laboratory or in the field.
TE
Climate change will increase the frequency and intensity of floods and
cyclones72 and thus fungal spore production, a powerful asthma and rhinitis
trigger. Both diseases are caused or aggravated by components of
TE
-
TE
Climate changes affect allergenic plants and pollen distribution worldwide.
There is evidence that, during pollen season, thunderstorms can be
associated with allergic asthma outbreaks in patients suffering from pollen
allergy.68, 69 There is a close temporal association between the arrival of a
thunderstorm, a major rise in concentration of pollen grains and the onset
of asthma epidemics. Thunderstorms occurring during the pollen season
have been observed to induce severe asthma attacks in pollinosis
patients.68 Associations between thunderstorms and asthma morbidity
have been identified in multiple locations around the world.68, 69, 70, 71
O
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Climate change poses a massive threat to respiratory health by directly
promoting or aggravating respiratory diseases or by increasing exposure to
risk factors for respiratory diseases.66 The key climatic change factors that
could potentially influence respiratory disease are extreme temperature
events (both hot and cold), changes in air pollution, flooding, damp
housing, thunderstorms, changes in allergen disposition and consequent
allergies, forest fires and dust storms. The effects of climate change may
either be short or long term.67
PY
D
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Recent clinical practice guidelines recommended to abandon the term of
exercise-induced asthma (EIA) because exercise is not the cause, but only
a trigger of asthma. It was suggested to use the terms EIB with asthma
(EIBA), the occurrence of bronchial obstruction after exercise in asthmatic
patients, and EIB without asthma (EIBwA), the occurrence of bronchial
obstruction in subjects without other symptoms and signs of clinical
asthma.74, 75 The latter may be seen particularly in children, athletes and
patients with atopy or rhinitis, or following respiratory infections.76
O
What is the effect of climate change on asthma?
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EXERCISE-INDUCED BRONCHOCONSTRICTION (EIB)
It has long been recognized that physical exercise may trigger symptoms of
asthma. Exercise-induced bronchoconstriction (EIB) is acute airway
narrowing that occurs as a result of exercise.
CLIMATE CHANGE AND GLOBAL WARMING
34
Climate change, coupled with air pollutant exposures, may have potentially
serious adverse consequences for human health. Rising temperatures will
contribute to the elevation of the concentrations of ozone (due to more
sunlight and higher temperature) and particulate matter (due to wildfire,
droughts, desertification, sandstorms and an increased use of coal-fired
power to produce energy for cooling) at ground level.66, 73
PC
It is recommended that asthmatic smokers may need specific medications
for smoking cessation in a concurrent schema of behavioral techniques.
A new perspective is electronic cigarettes, but many uncertainties currently
exist about their utility in smoking cessation. Cross-sectional studies on
adolescents on e-cigarette use is associated with increase prevalence of
asthma and chronic bronchitis.62, 63 Several new drugs are being
introduced in the arsenal of asthma treatment, but most of them have not
been tested for the asthmatic smokers. Although no single pharmacotherapy can serve as a universally successful treatment given the complexities of tobacco dependence and individuality of smokers, the clinician
should emphasize clearly that people with asthma should not smoke.61, 64, 65
An ECT should be performed in subjects with EIBA only when their baseline
FEV1 is ≥70% of normal. A diagnosis of EIB is established when there is
≥10% fall in FEV1 at any two consecutive time point recordings (1, 3, 5, 10, 15,
20, 25, 30 minutes) after 6 to 8 minutes of treadmill or cyclo-ergometer
exercise in ambient conditions (20-25°C; relative humidity <50%). The
intensity of exercise should be enough to reach in the first 2 to 3 minutes
40-60% of the predicted maximum voluntary ventilation (estimated as
baseline FEV1 X 35) or 80-90% of the predicted maximal heart rate.76
35
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Other bronchoprovocative tests (BPTs) may be optional diagnostic tools
for EIB, such as methacholine or histamine bronchoprovocation that
directly documents bronchial hyperreactivity, or indirect tests, such as
eucapnic voluntary hyperpnea (EVH), hypertonic saline challenge and
mannitol inhaled powder challenge reproduce the effects of exercise on the
airways and may be more accurate to diagnose EIBwA.76
BETA-BLOCKERS
CHAPTER 3
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In a recent population-based nested case control study, a cohort consisted
of 35,502 people identified with active asthma and cardiovascular disease,
of which 14.1% and 1.2% were prescribed cardioselective and non-selective
beta-blockers, respectively, during follow-up. It was shown that cardioselective beta-blocker use was not associated with a significantly increased
risk of moderate or severe asthma exacerbations and, thus, potentially
could be used more widely when strongly indicated.80
T
What is the impact of viral respiratory infections on asthma?
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RESPIRATORY INFECTIONS
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Nonpharmacological therapy for all patients with EIB, interval or
combination warm-up exercise before planned exercise is recommended.74
(Strong recommendation, Moderate-quality evidence) For patients with
EIB who exercise in cold weather, use of a device (e.g., face mask or scarf)
that warms and humidifies the air during exercise is suggested.74 (Weak
recommendation, Low-quality evidence) The potential occurrence of EIBA
should not prevent asthmatic patients from an adequate practice of
physical exercise, which is not associated to an increased risk of asthma
developing or worsening and should instead represent part of their
treatment.74
O
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O
In cases where the baseline lung function is below normal, an ICS is
appropriate. Additional therapies are appropriate for patients who continue
to have symptoms despite using an inhaled SABA before exercise or who
require an inhaled SABA daily or more frequently.74
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Because EIBA is a sign of poor asthma control, prevention essentially
consists of following international guidelines to achieve asthma control.77
For all patients with EIB, use of an inhaled SABA before exercise is
recommended.78 (Strong recommendation, High-quality evidence) The
SABA is typically administered 15 minutes before exercise. For patients who
continue to have symptoms despite using an inhaled SABA before exercise,
or who require an inhaled SABA daily or more frequently, daily administration of an ICS (Strong recommendation, Moderate-quality evidence) or
a leukotriene receptor antagonist (LTRA) (Strong recommendation,
Moderate-quality evidence) is recommended.74
A systematic review of literature published in 2013 concluded that the
available, although limited, evidence suggests that a dose-escalating model
of beta-blocker therapy to patients with asthma is well tolerated, does not
induce acute bronchoconstriction, and, not least, may have beneficial
effects on airway inflammation and airway hyperresponsiveness in some
patients with asthma. Further studies addressing the potential role of betablocker therapy for asthma are clearly needed, but careful selection of the
target population is warranted.79
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Treatment of both EIBA and EIBwA is essentially based on reversing
bronchial obstruction by using short-acting beta2-agonists (SABA).76
When indicated, cardioselective beta-blockers are preferred over noncardioselective beta-blockers. (Strong recommendation, High-quality
evidence)
PC
PC
CHAPTER 3
What is the treatment and prevention of exercise-induced
bronchoconstriction (EIB)?
Can beta-blockers be given to asthmatics?
In both children and adults, viral infections of the airways may be
associated with the development of chronic asthma, as well as with acute
exacerbations for those with existing asthma.81, 82, 83, 84, 85, 86, 87, 88, 89, 90
The most commonly involved viruses associated with asthma
exacerbations include human rhinovirus (HRV), respiratory syncytial virus
(RSV), influenza and parainfluenza viruses, coronavirus, enterovirus and
adenovirus. Human rhinovirus represents the most frequent cause of
infectious respiratory illnesses affecting adults while influenza and
parainfluenza viruses affect all age groups.84, 85
37
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Several recent studies have also shown that respiratory allergy may partner
with certain viral infections to synergistically produce airway inflammation
and increase cold and asthma symptoms.91, 92 Environmental factors may
act synergistically with viral infections and other known triggers leading to
acute exacerbations.92, 93
It was also hypothesized that bacteria interact with respiratory cold viruses
to alter outcomes of respiratory infections in asthmatic individuals, but little
is known about the role of secondary bacterial infections in increasing the
severity and persistence of symptoms.102
Are there effective treatment and preventive strategies for virus-induced
exacerbations?
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CHAPTER 3
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In a recent Cochrane review of six published studies that included 681
adults and children with asthma, the authors concluded that there was very
limited evidence that antibiotics may help people having asthma attacks.
However, they did not find much information about important outcomes
such as hospital admissions or side-effects.103
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Antibiotics should not be routinely used in the treatment of asthma
exacerbations. However, despite guideline recommendations, antibiotics
are often included in the treatment regimen for exacerbations.
Current guidelines state that antibiotics should be reserved for cases in
which clear signs, symptoms or laboratory test results are suggestive of
bacterial infection. Bacterial infections are thought to be responsible for
asthma exacerbation, however, evidence show that this is true for
only a minority.101, 102, 103
CHAPTER 3
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Should antibiotics be routinely used in the treatment of asthma
exacerbations?
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Optimization of current therapies may be beneficial. Treatment with antiinflammatory drugs such as ICS can reduce the risk of exacerbations by
40% to 50%, and this suggests that moderating inflammation may reduce
the chances that a cold will precipitate bronchospasm.93, 94 Exacerbations
have also been prevented by combined treatment with ICS and
long-acting beta2-agonists (LABAs).95, 96, 97, 98, 99, 100, 101
PC
Eradication of respiratory viruses would be the ideal approach but it is not
realistic nor feasible. Virus-induced asthma exacerbations are likely to
involve multiple mechanisms and, as such, a single treatment modality is
unlikely to be effective in all people with asthma. For specific antiviral
therapies to be implemented into clinical practice, it also may be necessary
to develop accurate, affordable and rapid viral diagnostics.93
The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA)
randomized, double-blind, placebo-controlled, multicenter clinical trial
conducted in the United Kingdom from September 2011 to April 2014
studied the effect of azithromycin in patients presenting in the emergency
room for asthma exacerbation requiring a course of systemic steroids.
This study conclusively showed that azithromycin treatment resulted in no
statistically or clinically significant benefit. For each patient randomized,
more than 10 were excluded because they had already received
antibiotics.104
Atypical organisms, such as M. pneumoniae and Chlamydophila
pneumoniae, may have possible association with asthma exacerbations.
However, studies have shown inconsistent results and their role in acute
exacerbations has not been definitively established. These organisms seem
to be involved more with asthma persistence rather than with disease
exacerbations.101
38
39
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
References:
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19. ASHRAE Position document on limiting indoor mold and dampness in buildings, 2012.
Available from: www.ashrae.org/about-ashrae/position-documents
20. American Industrial Hygiene Association (AIHA). Position statement on mold and
dampness in the built environment, 2013. Available from: www.aiha.org/governmentaffairs/Position-Statements/P-Mold-03-26-13.pdf
21. Joint Task Force on Practice Parameters, chief eds. Portnoy J, Kennedy K, Sublett J.
Environmental assessment and exposure control: a practice parameter – furry animals.
Ann Allergy Asthma Immunol 2012;108:223.e1-223.e15.
22. Langley SJ, Goldthorpe S, Craven M, Woodcock A, Custovic A. Relationship between
exposure to domestic allergens and bronchial hyperresponsiveness in non-sensitised,
atopic asthmatic subjects. Thorax 2005;60:17-21.
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71. D’Amato G. Airborne paucimicronic allergen-carrying particles and seasonal
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Robison L, Sattar Z, Jackson D, et al. Azithromycin for acute exacerbations of asthma:
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75. Weiler JM, Anderson SD, Randolph C, Bonini S, Craig TJ, Pearlman DS, Rundell KW,
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bronchoconstriction: a practice parameter. Ann Allergy Asthma Immunol
2010;105:S1-S47.
76. Bonini M, Palange P. Exercise-induced bronchoconstriction: new evidence in
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78. Bonini M, Di Mambro C, Calderon MA, Compalati E, Schunemann H, Durham S,
Canonica GW. Beta2-agonists for exercise-induced asthma. Cochrane Database
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79. Arboe B, Ulrik CS. Beta-blockers: friend or foe in asthma? Int J Gen Med 2013;6:549-55.
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Asthma Medications
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
The goals of asthma management are to achieve good symptom control,
to control exacerbations and to minimize future risk of exacerbations,
fixed airflow limitation and side-effects of treatment. In this chapter,
pharmacologic options for treatment of asthma will be discussed.
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The pharmacologic options for treatment of asthma fall into three main
categories, namely: controller medications, reliever medications and
add-on therapies. Controller medications reduce airway inflammation,
control symptoms and reduce future risks for exacerbations and decline in
lung function and are therefore advised to be used regularly for
maintenance treatment. On the other hand, reliever medications, which
relieve acute bronchospasm, are “rescue” medications provided to all
patients for relief in case of breakthrough symptoms including worsening
asthma or exacerbations. These are also recommended for short-term
exercise-induced bronchoconstriction. Reducing and, ideally, eliminating
the need for reliever treatment is both an important goal in asthma
management and a measure of success of asthma treatment. Add-on
therapies are given for patients already on optimized controller
medications with treatment of modifiable risk factor, who remained
uncontrolled, with severe symptoms or persistent exacerbations.1
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Inhaled corticosteroids (ICS) are the cornerstone of therapy and are
currently the most effective anti-inflammatory medications for the
treatment of persistent asthma. Several studies consistently demonstrate
that ICS are effective in reducing symptoms, improving quality of life,
decreasing frequency of flare-ups, decreasing the need for bronchodilator
rescue therapy, improving lung function and reducing asthma mortality.
Studies showed that ICS are relatively safe. At low to moderate doses, ICS
do not frequently exhibit clinically important side-effects and provide
asthmatics a good risk-benefit profile.
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Are all inhaled corticosteroids (ICS) the same?
Not all ICS are the same. The available ICS differ in their: relative
glucocorticoid receptor binding affinity, lipophilicity or aqueous solubility,
plasma protein binding, plasma clearance and half-life. The most potent
ICS is fluticasone furoate while flunisolide has the least potent
attributes. Comparatively, oral prednisolone ranks even lower based on
49
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
these attributes with considerably higher incidence of side-effects.
The potential advantage of a more potent ICS is that a lower dose is
required to occupy the same numbers of glucocorticoid receptors in the
airways, resulting in a lower daily dose with equivalent efficacy. Figure 4.1
depicts mid-range nominal therapeutic daily doses of ICS used in adult
asthma plotted against potency and expressed as relative glucocorticoid
receptor binding affinity. This clearly shows the exponential decline in
therapeutic daily dose with increasing potency.2 Despite differences in
potency of ICS, at recommended doses, clinical efficacy has been noted to
be equipotent.
The different ICS are listed below (Table 4.1) with the corresponding
pharmacological characteristics of binding affinity, lipophilicity, aqueous
solubility, plasma protein binding percentage, plasma clearance and
half-life.2
4.73
<0.1
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Budesonide DPI
935
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16
91.4
Triamcinolone
acetonide MDI
233
1.85
21
73.2
Flunisolide MDI
190
1.36
140
<0.1 (7)
98.7
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TE
2000
IA
1500
R
1000
U
IB
500
Ciclosonide
(des-CIC)
MDI
TE
TR
IS
0
O
A
M
D
50
O
Beclometasone
dipropionate
(BDP) MDI
D
R
FF
Aqueous Plasma
solubility protein
(mcg/mL-1) binding
(%)
C
TE
O
MF
2100
N
H
PY
FP
P
Fluticasone
propionate (FP)
DPI
IG
O
BUD
500
2989
O
R
C
CIC BDP
Lipophilicity
C
Mometasone
fluroate DPI
PY
T
O
FLU
Relative
glucocorticoid
receptor
binding
affinity
D
O
C
N
TAA
INHALED
CORTICOSTEROIDS
Fluticasone
fluroate (FF)
DPI
P
O
D
5000
Table 4.1. Inhaled corticosteroid pharmacological characteristics.
PC
C
PC
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
What are the recommended doses of inhaled corticosteroids (ICS)?
Fluticasone furoate (FF), mometasone furoate (MF), fluticasone propionate (FP), budesonide
(BUD), beclometasone dipropionate (BDP), ciclesonide (CIC), flunisolide (FLU).
Figure 4.1. Relationship between glucocorticoid receptor binding affinity
and mid-range nominal therapeutic daily doses of
inhaled corticosteroids (ICS) (r2 = 0.980).
50
Doses of ICS may be classified as low, medium and high, based on clinical
comparability. Table 4.2 shows low, medium and high daily doses of ICS
for adults and adolescents (12 years and older).1 Once good symptom
control has been maintained for 3 months, the ICS dose should be
carefully titrated to the minimum dose, taken regularly to maintain good
symptom control and minimize exacerbation risk, while reducing
the potential side-effects. Those patients that need high dose of ICS
must be referred to a specialist for expert assessment and advice.1
Additional benefits of ICS include modification of airway remodeling
and prevention of an accelerated decline in lung function.
51
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Their long term use in adequate doses has been shown to decrease
exacerbations and mortality.
Table 4.2. Low, medium and high daily doses of inhaled corticosteroids (ICS).
C
D
IA
R
TR
IS
TE
A
M
R
L-
-
TE
TE
For patients discharged from the ER setting after effective control of
symptoms, prescribing a short course of OCS was found to reduce the rate
of relapse.9 However, courses longer than 5 days were not found to provide
any additional benefit.10, 11, 13
U
IB
L
IA
U
IB
Clinically important adverse events are rare with doses of 800 mcg/day or
less. Inhaled corticosteroids given long-term use with doses greater than
800 mcg/day is likely to cause osteoporosis. Side-effects may occur at
doses above 1 mg/day such as HPA suppression, cataracts, skin thinning
and easy bruisability,3 but these may be acceptable risks in a patient who
would otherwise take oral corticosteroids (OCS). There are no reports of
any life-threatening events.
CHAPTER 4
D
TE
O
>2000
R
TR
How safe is long term use of inhaled corticosteroids (ICS)?
H
PY
>440
TE
>1000-2000
IG
O
>500
>220-440
R
C
>500
>250-500
PY
T
O
>250-500
IS
400-1000
200
A
110-220
n.a.
M
Mometasone furoate
>320
D
100-250
>160-320
D
Fluticasone propionate (HFA)
>800
R
100-250
O
Fluticasone propionate (DPI)
>400-800
TE
H
PY
O
100
>400
N
IG
80-160
>200-400
O
The usual dose of systemic corticosteroids is computed at 1-2 mg/kg/day of
prednisone. Table 4.3 shows the relative potencies of commonly used
corticosteroids.8 There was no significant added benefit from giving
high-dose systemic corticosteroids (above 60-80 mg/day or 2 mg/kg/day),
in terms of improving the pulmonary function, rate of admission or length of
hospital stay. A systematic review of randomized controlled studies
of patients with acute severe asthma compared different doses of
corticosteroids with a minimum follow-up of 24 hours. Corticosteroids used
in the included trials were divided into three groups as an equivalent dose of
methylprednisolone over 24 h: low dose (≤80 mg), medium dose (>80 mg
and ≤360 mg) and high dose (>360 mg). Nine trials were included with a
total patients' number of 344 adults. No differences were found among the
different doses.9
O
R
200-400
C
CHAPTER 4
>1000
D
PY
100-200
T
O
N
Fluticasone furoate (DPI)
Triamcinolone acetonide
>500-1000
O
C
O
Ciclesonide (HFA)
200-500
P
P
D
Budesonide (DPI)
HIGH
C
C
Beclometasone dipropionate
(CFC)
Beclometasone dipropionate
(HFA)
MEDIUM
What is the role of systemic corticosteroids?
PC
PC
Daily dose (mcg)
LOW
Inhaled corticosteroid use has been shown to increase the risk of tuberculosis
(TB) in an intermediate TB burden country. Clinicians should be aware of the
possibility of TB development among long-term high-dose users.5
Systemic corticosteroids, if given early in the treatment of asthma
exacerbations in the emergency room (ER) setting, were shown to be
effective in reducing symptoms and decreasing rate of hospitalization.6 In a
Cochrane database review by Rowe et al, the greatest benefit of systemic
corticosteroids in reducing rate of hospital admission was observed in
patients with more severe symptoms and not on any corticosteroid therapy.7
Adults and adolescents (12 years and older)
DRUG
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Effects of local deposition of ICS can cause the following: dysphonia, topical
candidiasis and contact hypersensitivity. Symptomatic candidiasis affects
less than 5% and can be usually controlled by measures that limit
oropharyngeal deposition (i.e., gargle with water, topical antifungal
treatment).4
52
53
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Table 4.4. Pharmacologic characteristics of long-acting bronchodilators.
Table 4.3. Common types of systemic corticosteroids
and their relative properties.
Preparation
Relative
Biological
Potency relative
sodium
half-life
to hydrocortisone
retention
(h)
potency
1
12-15 days
Formoterol
1-3
12
10
Olodaterol
5
24
7.5
Vilanterol
5.08+0.5
24
2.5
4.0+0.2
24
>30
Indacaterol
IA
R
TR
IS
D
TE
A
M
R
L-
-
There are no studies yet for the role of monotherapy with olodaterol,
vilanterol and indacaterol in the treatment of persistent asthma.
What is the benefit of inhaled corticosteroid – long-acting beta2-agonists
(ICS-LABA) combination in achieving asthma control?
TE
TE
U
IB
L
IA
R
U
IB
TR
IS
D
TE
A
R
O
M
D
PY
D
O
Long-acting bronchodilators differ in their onset of action, duration of
action and half-life.14 (Table 4.4) Sustained action bronchodilators such as
salmeterol and formoterol are administered twice daily dosing due to its
12-hours’ duration of action. They are useful in controlling nocturnal
symptoms and exercise-induced asthma. Formoterol has a rapid onset of
action of about 1-3 minutes after administration and has a wide dose range,
hence its usefulness as reliever. On the other hand, salmeterol is not suitable
for acute relief of asthma since it has a long onset of action and is limited by
the ceiling dose of 50 mcg twice a day. However, it cannot be overemphasized that LABAs should never be used alone as it has been reported
in several studies that monotherapy with LABA increases asthma related
deaths.
TE
O
TE
C
H
IG
R
T
H
PY
O
C
Are all long-acting beta2-agonists (LABAs) the same?
CHAPTER 4
PY
O
IG
R
T
O
N
PY
O
D
Monotherapy with a LABA given on a long-term basis leads to down
regulation of beta2-receptors, a process associated with beta2-agonist
tolerance which may result in increasing doses of beta2-agonist and higher
prevalence of adverse events and even death. Therapy with inhaled LABA
may cause cardiovascular stimulation, skeletal muscle tremor and
hypokalemia. Data indicating a possible increased risk of asthma-related
death associated with the use of salmeterol in a small group of individuals
led to advisories from the US Food and Drug Administration (FDA) and
Health Canada that LABAs are not a substitute for inhaled or oral
glucocorticosteroids, and should only be used in combination with an
appropriate dose of ICS.
O
36-72
12
C
0
25
10-30
N
12-36
Salmeterol
P
0.5
Half-life (h)
O
5
Duration of
action (h)
D
12-36
O
C
0.8
Onset of action
(mins)
C
P
4
Methylprednisolone
CHAPTER 4
8-12
C
Prednisone/
prednisolone
Dexamethasone
1
LABA
PC
PC
Hydrocortisone
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Analysis of several studies clearly show that adding a LABA to ICS is more
effective than increasing the dose of ICS in terms of improving asthma
control and reducing exacerbations.15
Inhaled corticosteroid – long-acting beta2-agonists combination in clinical
studies and systematic reviews consistently show improvement in
symptom scores, decrease in nocturnal asthma symptoms, improvement in
lung function, decrease in the use of rapid-acting inhaled beta2-agonists,
reduction in the number of exacerbations and achievement of clinical
control of asthma in more patients, more rapidly, and at a lower dose of ICS
than ICS given alone.
54
55
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Long-acting beta2-agonists, when given concomitantly with corticosteroids,
can activate glucocorticoid receptors and enhance the transcription of
anti-inflammatory mediators and, at the same time, provide a protective
mechanism against the down-regulation of beta2-receptors. Glucocorticoids
and beta2-agonists both inhibit proliferation of airway smooth muscle cells in
vitro.14 The exact signal transduction process involved in this synergistic
mechanism is not yet fully understood.
Short-acting anti-muscarinic agents are anticholinergic bronchodilators that
are also quick acting medications but generally less potent than
beta2-agonists. For patients with moderate-severe exacerbation seen at the
ER, the addition of ipratropium to a SABA was associated with fewer
hospitalizations and greater improvement in PEF and FEV1 compared with
SABA alone.17, 18, 20
T
D
D
U
IB
L-
What is the mechanism of action of leukotriene modifiers?
IA
R
TR
IS
ADD-ON THERAPIES
TE
A
M
R
Leukotrienes are released from mast cells, basophils and eosinophils which
causes airway constriction, increased mucus production, swelling and
inflammation in the lungs. Leukotriene modifiers prevent the action of
leukotrienes in the body. Montelukast, the only available leukotriene modifier
in the Philippines, is a cysteinyl leukotriene receptor antagonist (LTRA) used
for the maintenance treatment of asthma and to relieve symptoms of
seasonal allergies. Montelukast acts by blocking the action of leukotriene D4
(and secondary ligands, leukotrienes C4 and E4) on the cysteinyl leukotriene
receptor CysLT1 in the lungs and bronchial tubes by binding to it. This
reduces the bronchoconstriction otherwise caused by the leukotriene and
results in less inflammation.21
TE
TE
Patients who regularly use SABAs alone without concomitant antiinflammatory therapy are at an increased risk for asthma-related death15
and urgent asthma-related healthcare.17 (Evidence A) As such, in the chronic
management of asthma, SABA-only treatment for as-needed relief of
symptoms is no longer a preferred option.
TE
-
U
IB
L
IA
R
TE
A
TR
IS
D
Short-acting beta2-agonists have more rapid onset of action and provide
three to four times more bronchodilatation than the SAMAs and were
recommended for use on an as-needed basis at the lowest dose and
frequency required. Increased use, especially daily use, is a warning of
deterioration of asthma control and indicates the need to reassess
treatment. Failure to achieve a quick and sustained response to
beta2-agonist treatment during an exacerbation mandates medical
attention and may indicate the need for short-term treatment with oral
glucocorticosteroids.
Under certain circumstances, high-dose intravenous (IV) corticosteroids and
OCS may also relieve acute asthma symptoms.
O
M
R
O
Reliever medications are usually bronchodilators that quickly relieve
bronchospasm. These medications generally do not treat the underlying
inflammatory process of asthma. Reliever medications for asthma are mainly
short-acting sympathomimetic beta2-agonists (SABAs), such as salbutamol
and terbutaline and short-acting muscarinic antagonists (SAMAs), such as
ipratropium.
PY
D
PY
O
TE
C
H
IG
O
R
N
H
O
C
What are the reliever medications for asthma?
CHAPTER 4
PY
O
C
O
CHAPTER 4
P
C
D
IG
T
RELIEVERS
56
The rapid-onset LABA, formoterol, is as effective as SABA as a reliever
medication in adults and children, but use of regular or frequent LABA
without ICS is strongly discouraged because of the risk of exacerbations.1
(Evidence A)
The use of low-dose ICS-formoterol for as-needed symptom relief in mild
asthma is based on a large double blind study comparing this regimen
with SABA-only treatment.21 (Evidence B) At present, as-needed
ICS-formoterol is considered off label in most countries, including the
Philippines.
R
O
N
PY
O
D
O
C
The use of ICS-formoterol has an added advantage of serving both as
controller and reliever when used as a single inhaler therapy in the
maintenance and reliever strategy.
PC
P
C
PC
In the local setting, initial therapy with ICS-LABA in patients with mild
persistent asthma may provide greater improvements in lung function and
asthma control, improve compliance and has comparable safety to ICS
alone.
Oral SABA or short-acting theophylline are potential alternatives to SABA
for relief of asthma symptoms; however, these agents have a slower onset of
action than inhaled SABA, (Evidence A) and oral SABA and theophylline
have a higher risk of side-effects.1
A recent meta-analysis of randomized, controlled trials (RCTs) on
montelukast confirms its usefulness as on montelukast confirms its
usefulness as monotherapy and add-on therapy to ICS in mild-to-moderate
57
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
childhood asthma across all age groups. Inhaled corticosteroids are generally
superior to montelukast for asthma management.21 In adults, it is mainly
used as a complementary therapy in addition to ICS if ICS alone do not bring
the desired effect. It is also used to prevent allergic reactions and asthma
flare-ups during the administration of intravenous immunoglobulin.
What is the mechanism of action of omalizumab?
IG
R
O
N
D
TE
PY
O
C
H
Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal
antibody against human immunoglobulin E (IgE). It binds to free IgE with a
greater affinity than high affinity IgE receptor (FcεRI) present on basophils.
Thus, it reduces availability of free IgE for binding.27
T
M
L-
IA
U
IB
TR
R
TE
A
IS
TE
Doxofylline, a newer generation methylxanthine, an alternative to
theophylline that differs with the presence of a dioxolane group in position
7. It is thought to have a wider therapeutic window than theophylline.24
D
-
TE
Theophylline is a relatively poor bronchodilator and adverse effects limit the
dose and make it less effective than inhaled bronchodilators.23 Thus, it is no
longer recommended for routine use in asthma.
R
L
IA
R
U
IB
TR
IS
Omalizumab is a medication originally designed to reduce sensitivity to
allergens. It has been used to try to control severe allergic asthma which
does not respond to high doses of corticosteroids. Its primary use is for
patients mostly with severe, persistent allergic asthma, uncontrollable with
oral or injectable corticosteroids. Omalizumab is currently recommended for
the treatment of patients >12 years in the U.S., administered subcutaneously
once every 2 or 4 weeks. For each patient, the dosing schedule (2 vs 4 weeks
between injections; and the amount of omalizumab, in milligrams for each
injection) is determined according to the serum IgE level and the body
weight of the patient.
O
D
TE
A
R
Theophylline is the most well known and most commonly used methylxanthine.
At low dosages, it has an immunomodulatory, anti-inflammatory and
bronchoprotective effect. Theophylline is also a nonselective inhibitor of
phosphodiesterase (PDE) isoenzymes, which may account for the effects of
theophylline at higher doses.
CHAPTER 4
PY
O
C
O
CHAPTER 4
P
C
M
O
What is the role of methylxanthines in asthma treatment?
Tiotropium has been recommended as add-on therapy for severe asthma.
In the study of Rodrigo et al, tiotropium as an add-on to ICS showed
statistically significant increases in PEF (22-24 L/min) and FEV1
(140-150 mL). Tiotropium was observed to have decreased the rate of
exacerbations (number needed to treat for benefit [NNTB], 36) and
improved asthma control. The use of tiotropium in poorly controlled asthma
patients despite the use of medium-to-high doses of ICS was not inferior to
salmeterol. Finally, the use of tiotropium as an add-on to ICS-salmeterol
combination increased pulmonary function to a clinically significant magnitude,
reduced asthma exacerbations (relative risk, 0.70; 95% CI, 0.53-0.94;
p value <.02; i2 = 0%; NNTB, 17), and improved asthma control compared
with ICS-salmeterol. Tiotropium was well tolerated, and no potential safety
signals were observed.26
D
D
TE
PY
O
C
H
IG
R
T
O
N
PY
O
D
O
C
These medications are usually well-tolerated. Side-effects are uncommon
but include: headache, nausea, stomach upset, pain, fever, muscle ache,
fatigue, sore throat, laryngitis and liver enzyme elevation. Churg-Strauss
Syndrome, a form of vascular inflammation, rarely is noted with these
medications and can include vague symptoms of fever, fatigue, weight loss,
vasculitis leading to kidney disease, hypotension, abdominal pain, bowel
damage, heart disease, muscle aches and wasting, nervous system damage
and arthritis. Liver function abnormalities have been reported with all of
these agents and should be periodically monitored.
Does tiotropium have a role in asthma management?
PC
P
C
PC
Montelukast is administered orally once daily and is approved for treatment
of asthma in patients two years or older. The bioavailability is similar
regardless of patient age and absorption is not affected by food. No drug
interactions have been documented. Side-effects in adults are similar to
those found with placebo; they occurred in less than 2 percent of patients
6 to 14 years of age.
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
In addition to omalizumab, there are other US-FDA approved biological
agents in asthma, namely: mepolizumab, reslizumab and benralizumab,
which are not currently available locally.
In a recent pooled analysis of two double-blind, randomized, placebocontrolled trials, both doxofylline and theophylline demonstrated
significantly better results on functional and clinical outcomes in asthma
versus placebo. Doxofylline demonstrated a favorable safety profile superior
to theophylline.25
58
59
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
INHALER THERAPY
asthma is currently limited as a delivery device for tiotropium as add-on
therapy to the usual ICS-LABAs.1, 34
Inhaler or aerosolized therapy delivers medicines directly to the lumen of the
airways and onto their therapeutic sites.28 This enables the delivery of low
doses of the medicine to its site of action for a localized effect, leading to a
rapid clinical response and reducing the risk for systemic side-effects.29
Is there a difference between pressurized metered-dose inhalers (pMDIs)
and dry powder inhalers (DPIs)?
Advantages
Disadvantages
Convenient
Generally inexpensive
Portable
Widely available for most
inhaled medicines
No drug preparation required
Difficut to contaminate
Patient coordination essential
Patient actuation required
Large pharyngeal deposition
Difficult to deliver high dose
IA
R
L-
Requires moderate
to high inspiratory flow
U
IB
Some units are single dose
TE
TE
Breath actuated
Less portable than
MDI alone
TR
-
Inhaler (DPI)
Less patient coordination
required
Convenient
Portable
TE
A
IS
L
IA
Soft mist inhalers are a new type of inhaler which utilizes the mechanical
energy from a compressed spring to force the drug solution through an
extremely fine nozzle system, producing a fine, slow moving mist.28
Although this provides advantages over pMDIs and DPIs on ease of
coordination and improved lung deposition, its use in the management of
More expensive than
MDI alone
D
R
U
IB
TR
IS
Nebulizers convert solutions and suspensions into small droplets using
compressed air (in the case of pneumatic or jet nebulizers) or sound waves
(in the case of ultrasonic nebulizers). They are able to aerosolize high doses
of drugs that are not available with DPIs or pMDIs. In addition, nebulizers
may be fitted into facemasks, allowing use by patients <2-years old, the
elderly and those with severe respiratory distress.28
More complex for some
patients
M
R
TE
D
Less patient pharyngeal
deposition
Dry Powder
CHAPTER 4
D
Less patient coordination
required
O
A
M
R
O
chamber
PY
O
D
MDI with holding
TE
C
H
IG
R
T
O
N
PY
O
C
O
Inhaler (MDI)
TE
CHAPTER 4
P
C
D
Metered-Dose
H
PY
O
C
Dry powder inhalers (DPIs) are inhalers which contain the medicine in a
powder form, which deaggregates into respirable particles when the patient
inhales thru the device.27 Dry powder inhalers help overcome the
coordination issues associated with pMDIs. However, they also suffer from
inherent limitations, particularly, that the inhaler’s success depends on the
generation of sufficient inspiratory flow.33, 35
60
Types
IG
R
T
O
N
PY
O
D
O
C
Pressurized metered-dose inhalers (pMDIs) are pressurized metal canisters
containing a mixture of propellants, surfactants, preservatives and drug.
They vary in the used propellants, in the combined drug formulations, in the
sizes of the metering valves and in the diameters of the actuator nozzle.
These differences influence the medicine’s stability, particle size, plume
velocity and temperature.30, 32 Pressurized metered-dose inhalers may be
used with spacers, which are add-on devices that help reduce
oropharyngeal deposition and increase lung deposition by increasing the
distance between the pMDI mouthpiece and the back of the pharynx.
Further, spacers make pMDIs easier to use by reducing or eliminating the
need for coordination between actuation and inhalation and by reducing the
cold Freon effect.30, 33
Table 4.5. Advantages and disadvantages between pressurized metered-dose inhalers
(pMDIs) and dry powder inhalers (DPIs).
PC
P
C
PC
In clinical practice, several types of inhalers are used for aerosol delivery in
asthma. Each class of device is associated with a different approach to
inhalation and, in turn, specific requirements in handling and inhalation to
optimize drug delivery.27, 30
Since pMDIs and DPIs are the recommended outpatient inhalers to be used,
further discussion will focus on these two inhaler types. Table 4.5 lists the
general advantages and disadvantages between these two inhalers.35
Large pharyngeal deposition
Difficult to deliver high dose
The effectiveness of inhaled treatments is influenced by their efficacy,
i.e., their positive effects when used under optimal conditions, directly
resulting from their pharmacological properties; and the way they are used,
i.e., the appropriateness of prescription and patients’ adherence and ability
to use inhalation devices.36
Reviews of RCTs comparing inhaler devices report no difference in efficacy
between devices.37 In 2005, the American College of Chest Physicians
(ACCP) issued an evidence-based guideline on inhaler device
selection for inhaler therapy. Multiple meta-analyses revealed that
61
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
there was no significant difference between pMDIs and DPIs in an
efficacy outcome in any patient group that was investigated. The guideline
concluded that either device may be used provided that patients are able to
use the correct technique for inhalation.38
Not all inhalation devices are appropriate for all patients. Patients with
severe airway obstruction, as well as young children and the elderly, may be
unable to inhale with sufficiently fast acceleration to use DPIs; conversely,
patients with cognitive or motor problems suffer from poor coordination to
be able to use pMDIs correctly. When choosing the appropriate device, it
could be useful for clinicians to have a means of mapping the patient’s
natural inhalation profile and of assessing whether the patient is more likely
to master the inhalation required of the chosen device.44
CHAPTER 4
CHAPTER 4
TE
H
IG
O
D
PY
M
• If different options are available, encourage the patient to participate in the choice.
O
A
• For pMDIs, use of a spacer improves delivery and (with ICS) reduces the potential for side-effects.
R
U
IB
L-
IA
R
TE
TR
• Check inhaler technique at every opportunity
IS
D
-
• Ask the patient to show you how they use their inhaler (don’t just ask if they know how to use it)
• Identify any errors using a device-specific checklist
CORRECT
TE
•pMDI + spacer
R
L
•pMDI + spacer
•Respimat
• Choose the most appropriate inhaler device for the patient before prescribing. Consider the
medication options, the available devices, patient skills and cost.
CHECK
TE
•pMDI + spacer
• DPI
C
IA
R
U
IB
•pMDI
•DPI
•Respimat
PY
TE
A
TR
IS
D
Hand-breath
dyscoordination
CHOOSE
T
M
R
Hand-breath
coordination
O
D
O
Hand-breath
dyscoordination
O
PY
TE
H
IG
O
C
Hand-breath
coordination
Table 4.6. Strategies to ensure effective use of inhaler devices.
• Ensure that there are no physical barriers, e.g., arthritis, that limit use of the inhaler.
• Avoid use of multiple different inhaler types where possible, to avoid confusion.
Conscious inhalation NOT possible
Inspiratory flow
<30L/min
N
R
T
O
Figure 4.229, 34 outlines a general algorithm in the proper selection of inhalers
for particular patients. A pMDI requires good actuation-inhalation coordination
for optimal lung deposition, whereas a DPI requires sufficient inspiratory
flow.
Inspiratory flow
30L/min
C
O
PY
N
Treatment guidelines do not provide adequate recommendations on inhaler
selection. Unfortunately, determining the appropriateness of the inhaler for
a particular patient is paramount to the success of inhaler therapy.37
Conscious inhalation possible
P
D
O
C
O
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What patient factors should be considered in the choice of inhaler device?
Patient
Overcoming problems with the use of inhalers starts with the prescriber
choosing the most appropriate device for the individual patient, followed by
educating and training the patient in the use of the chosen device
(Table 4.6).1 Patient education and inhaler training are discussed in the
chapter on Patient Education.
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These considerations place great importance in the selection of the
appropriate inhaler and in the provision of adequate education and training
on correct inhaler technique to the patient.
What strategies can ensure effective use of inhaler devices?
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Unfortunately, errors in inhaler technique are common. The frequency of
misuse for each particular type of device varies between studies, depending
on the studied population and on the criteria used to define proper
technique.36, 39, 40, 41 What is certain is that poor inhaler technique is associated
with poor asthma control.42, 43
• Show the patient how to use the device correctly with a physical demonstration, e.g., using a
placebo inhaler
• pMDI + spacer
• Nebulizer
• Check technique again, paying attention to problematic steps. You may need to repeat this process
2-3 times.45
• Only consider an alterantive device if the patient cannot use the inhaler correctly after several repeats
of training
• Re-check inhaler technique frequently. After initial training, errors often recur within 4-6 weeks.46
CONFIRM
• Clinicians should be able to demonstrate correct technique for each of the inhalers they prescribe
Figure 4.2. How to choose the right inhaler.
(Adapted from Laube, BL, 2011 and Lavorini F, 2015)
62
• Pharmacists and nurses can provide highly effective inhaler skills training47, 48
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Although not always feasible, use of a single type of device to deliver all
medications is preferable since using a variety of devices increases the
likelihood of error. Using multiple types of inhalers requires the patient to
master (and maintain mastery of) more than 1 inhaler technique. Such
possibility of errors will need to be considered during training, retraining and
education to avoid loss of disease control and stability.29
What is the role of nebulizers in asthma management?
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There is question that pMDIs and DPIs may not be appropriate to use among
the elderly due to age-related changes, and that nebulizers may be more
appropriate for these patients. Unfortunately, no studies have been made
among asthmatic elderly patients to address this concern. Experts agree,
though, that considerations on device factors (device type, complexity of
use), patient factors (inspiratory capabilities, manual dexterity and hand
strength, cognitive ability, comorbidities) and healthcare system factors
(patient and physician education, cost reimbursement) should be made in
selecting the appropriate inhaler for an elderly patient, similar to any other
patient.51, 52
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention,
2018. Available from http://ginasthma.org [Accessed: 26 April 2018]
2. Daley-Yates PT. Inhaled corticosteroids: potency, dose equivalence and therapeutic
index. Clinical Pharmacology, GlaxoSmithKline, Research and Development. British J
of Clin Pharmacol 2015;80(3):372-80. DOI:10.1111/bcp.12637.
3. Philippine College of Chest Physicians. Philippine Consensus Report on Asthma
Diagnosis and Management 2004.
4. Geddes DM. Inhaled corticosteroids: benefits and risks. Thorax 1992;47(6):404-7.
5. Lee CH, Kim K, Hyun MK, Jang EJ, Lee NR, Yim JJ. Use of inhaled corticosteroids and
the risk of tuberculosis. Thorax 2013;68(12):1105-13.
6. Littenberg B, Gluck EH. A controlled trial of methylprednisolone in the emergency
treatment of acute asthma. N Engl J Med 1986;314:150-2.
7. Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency
department treatment of acute asthma with systemic corticosteroids. Cochrane
Database Syst Rev 2001:CD002178.
8. Alangari AA. Corticosteroids in the treatment of acute asthma. Ann Thora Med
2014;9:187-92.
9. Marquette CH, Stach B, Cardot E, Bervar JF, Saulnier F, Lafitte JJ, Goldstein P, et al.
High-dose and low-dose systemic corticosteroids are equally efficient in acute severe
asthma. Eur Respir J 1995;8:22-7.
10. Manser R, Reid D, Abramson M. Corticosteroids for acute severe asthma in
hospitalized patients. Cochrane Database Syst Rev 2001:CD001740.
11. Rowe BH, Spooner CH, Ducharme FM, Bretzlaff JA, Bota GW. Corticosteroids for
preventing relapse following acute exacerbations of asthma. Cochrane Database Syst
Rev 2001:CD000195.
12. Hasegawa T, Ishihara K, Takakura S, Fujii H, Nishimura T, Okazaki M, Katamami N,
et al. Duration of systemic corticosteroids in the treatment of asthma exacerbation; a
randomized study. Intern Med 2000;39:794–7.
13. Jones AM, Munavvar M, Vail A, Aldridge RE, Hopkinson L, Rayner C, O’Driscoll BR.
Prospective, placebo-controlled trial of 5 vs 10 days of oral prednisolone in acute adult
asthma. Respir Med 2002;96:950-4.
14. Tamm M, Richards DH, Beghe B, Fabbri L. Inhaled corticosteroid and long-acting
β2-agonist pharmacological profiles: effective asthma therapy in practice. Respir Med
2012;106(S1):S9-S19.
15. Gibson PG, Powell H, Ducharme FM. Differential effects of maintenance long-acting
beta-agonist and inhaled corticosteroid on asthma control and asthma exacerbations.
J Allergy Clin Immunol 2007;119:344-50.
16. Suissa S, Ernst P, Kezouh A. Regular use of inhaled corticosteroids and the long term
prevention of hospitalisation for asthma. Thorax 2002;57:880-4.
17. Reddel HK, Busse WW, Pedersen S, Tan WC, Chen YZ, Jorup C, Lythgoe D, et al.
Should recommendations about starting inhaled corticosteroid treatment for mild
asthma be based on symptom frequency: a post-hoc efficacy analysis of the START
study. Lancet 2017:389:157-66.
18. Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and
adults with acute asthma: a systematic review with meta-analysis. Thorax
2005;60:740-6.
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An in vitro study on mechanically ventilated subjects indicate that pMDIs
were associated with greater aerosol delivery than nebulizers.49 However, a
retrospective observational study among mechanically ventilated patients
did not indicate any significant difference between the two types of inhalers
on number of days receiving ventilation, in-hospital mortality or
ventilator-associated pneumonia.50
1.
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Nebulizers offer no distinct advantage over pMDIs with spacers or holding
chambers in acute asthma management. The use of nebulizers may actually
be associated with problems such as a greater dose of drugs, leading to
systemic side-effects, and contamination with bacteria, increasing the risk
for nosocomial pneumonia.38 Further discussion on acute asthma
management is provided in the chapter on Asthma Exacerbations.
References:
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The role of nebulizers in asthma management should be limited in patients
in severe respiratory distress or in patients in mechanical ventilation.
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
65
19. Griffith B, Ducharme FM. Combined inhaled anticholinergics and short-acting
beta2-agonists for initial treatment of acute asthma in children. Cochrance Database
Syst Rev 2013;8:CD000060.
20. Kirkland SW, Vandenberghe C, Voaklander B, Nikel T, Campbell S, Rowe BH.
Combined inhaled beta-agonist and anticholinergic agents for emergency
management in adults with asthma. Cochrane Database Sys Rev 2017;1:CD001284.
21. O'Byrne PM, FitzGerald JM, Bateman ED, Barnes PJ, Zhong N, Keen C, Jorup C, et al.
Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J
Med2018;378:1865-76.
22. Hon KLE, Leung TF, Leung AKC. Clinical effectiveness and safety of montelukast in
asthma. What are the conclusions from clinical trials and meta-analyses? Drug Des
Devel Ther 2014;8:839-59.
23. Barnes PJ. Theophylline. Am J Respir Crit Care Med. 2013 Oct 15;188(8):901-6.
24. Riffo-Vasquez Y, Venkatasamy R, Page CP. Steroid sparing effects of doxofylline. Pulm
Pharmacol Ther 2018; (48): 1-4.
25. Calzetta L, Hanania NA, Dini FL, Goldstein MF, Fairweather WR, Howard WW, Cazzola
M. Impact of doxofylline compared to theophylline in asthma: A pooled analysis of
functional and clinical outcomes from two multicentre, double blind, randomized
studies (DOROTHEO 1 and DOROTHEO 2). Pul Pharmacol Ther 2018; 53 : 20–6.
26. Rodrigo GJ, Castro-Rodriguez JA. What is the role of tiotropium in asthma? a systematic review with meta-analysis. Chest 2015;147(2):388-96.
27. Belliveau PP. Omalizumab: a monoclonal anti-IgE antibody. MedGenMed 2005;7(1):27.
28. Dolovich MB, Dhand R. Aerosol drug delivery: developments in device design and
clinical use. Lancet 2011;377:1032-45.
29. Laube BL, Janssens HM, de Jongh FHC, Devadason SG, Dhand R, Diot P, Everard ML,
et al. What the pulmonary specialist should know about the new inhalation therapies.
Eur Respir J 2011;37:1308-31.
30. Braido F, Chrystyn H, Baiardini I, Bosnic-Anticevich S, van der Molen T, Dandurand RJ,
Chisholm A, et al. “Trying but failing” – the role of inhaler technique and mode of
delivery in respiratory medication adherence. J Allergy Clin Immunol Pract 2016;4:
823-32.
31. Newman SP. Principles of metered-dose inhaler design. Respir Care 2005;50:1177-90.
32. Rubin BK, Fink JB. Optimizing aerosol delivery by pressurized metered-dose inhalers.
Respir Care 2005;50:1191-200.
33. Newman SP. Spacer devices for metered-dose inhalers. Clin Pharmacokinet
2004;43:349-60.
34. Lavorini F, Mannini C, Chellini E. Challenges of inhaler use in the treatment of asthma
and chronic obstructive pulmonary disease. Eur Respir J 2015;3:98-105.
35. Lavorini F, Mannini C, Chellini E, Fontana GA. Optimising Inhaled Pharmacotherapy for
elderly patients with chronic obstructive pulmonary disease: The importance of
delivery devices. Drugs Aging. 2016;33:461-73.
36. Philippine College of Chest Physicians. Philippine Consensus Report on Asthma
Diagnosis and Management 2009.
37. Roche N, Chrystyn H, Lavorini F, Agusti A, Virchow JC, Dekhuijzen R, Price D. Effective
ness of inhaler devices in adult asthma and COPD. EMJ Respir 2013;1:64-71.
38. Haughney J, Price D, Barnes NC, Virchow JC, Roche N, Chrystyn H. Choosing inhaler
devices for people with asthma: current knowledge and outstanding research needs.
Respir Med 2010;104:1237-45.
39. Dolovich MB, Ahrens RC, Hess DR, Anderson P, Dhand R, Rau JL, Smaldone GC, et al:
American College of Chest Physicians; American College of Asthma, Allergy and
Immunology. Device selection and outcomes of aerosol therapy: evidence-based
guidelines Chest 2005;127:335-71
40. Lavorini F, Magnan A, Dubus JC, Voshaar T, Corbetta L, Broeders M, Dekhuijzen R, et
al. Effect of incorrect use of dry powder inhalers on management of patients with
asthma and COPD. Respir Med 2008;102:593-604.
41. Levy ML, Hardwell A, McKnight E, Holmes J. Asthma patients’ inability to use a
pressurized metered-dose inhaler correctly correlates with poor asthma control as
defined by the Global Initiative for Asthma strategy: a retrospective analysis. Prim
Care Respir J 2013;22:406-11.
42. Dudvarski Ilic A, Zugic V, Zvezdin B, Kopitovic I, Cekerevac I, Cupurdija V, Perhoc N,
et al. Influence of inhaler technique on asthma and COPD control: a multicenter
experience. Int J Chron Obstruct Pulmon Dis 2016;11:2509-17.
43. Melani AS, Bonavia M, Cilenti V, Cinti C, Lodi M, Martucci P, Serra M, et al. Inhaler
mishandling remains common in real life and is associated with reduced disease
control. Respir Med 2011;105:930-8.
44. Price DB, Roman-Rodriguez M, McQueen RB, Bosnic-Anticevich S, Carter V,
Gruffydd-Jones K, Haughney J, et al. Inhaler errors in the CRITIKAL study: type,
frequency, and association with asthma outcomes. J Allergy Clin Immunol Pract
2017;5:1071-81.
45. Papi A, Haughney J, Virchow JC, Roche N, Palkonen S, Price D. Inhaler devices for
asthma: a call for action in a neglected field. Eur Respir J 2011;37:982-5.
46. Basheti IA, Reddel HK, Armour CL, Bosnic-Anticevich SZ. Improved asthma outcomes
with a simple inhaler technique intervention by community pharmacists. J Allergy Clin
Immunol 2007;119-1537-8.
47. Crompton GK, Barnes PJ, Broeders M, Corrigan C, Corbetta L, Dekhuijzen R, Dubus JC,
et al. The need to improve inhalation technique in Europe: a report from the Aerosol
Drug Management Improvement Team. Respir Med 2006;100:1479-94.
48. Armour CL, Reddel HK, LeMay KS, Saini B, Smith LD, Bosnic-Anticevich SZ, Song YJ,
et al. Feasibility and effectiveness of an evidence-based asthma service in Australian
community pharmacies: a pragmatic cluster randomized trial. J Asthma 2013;50:302-9.
49. Kuethe MC, Vaessen-Verberne AA, Elbers RG, van Aalderen WM. Nurse versus
physician-led care for the management of asthma. Cochrane Database Syst Rev
2013;2:CD009296.
50. Ari A, Harwood RJ, Sheard MM, Fink JB. Pressurized metered-dose inhalers versus
nebulizers in the treatment of mechanically ventilated subjects with artificial airways:
an in vitro study. Respir Care 2015;60:1570-4.
51. Dubosky MN, Chen YF, Henriksen ME, Vines DL. Vibrating mesh nebulizer compared with
metered-dose inhaler in mechanically ventilated subjects. Respir Care 2017;62:391-5.
52. Barrons R, Pegram A, Borries A. Inhaler device selection: special considerations in elderly
patients with Chronic Obstructive Pulmonary Disease. Am J Health Syst Pharm
2011;68:1221-32.
53. Lavorini F, Mannini C, Chellini E, Fontana GA. Optimising inhaled pharmacotherapy for
elderly patients with Chronic Obstructive Pulmonary Disease: the importance of
delivery devices. Drugs Aging 2016;33:461-73.
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CHAPTER
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Management of Asthma Exacerbations
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Exacerbations of asthma are defined as episodes characterized by a
progressive increase in symptoms of shortness of breath, cough, wheezing
or chest tightness and progressive decrease in lung function, i.e., they
represent a change from the patient’s usual status that is sufficient to require
a change in treatment.1 These exacerbations may occur in patients as an
initial presentation or in those previously diagnosed to have asthma.
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An exacerbation is usually triggered by exposure to an external agent or
stimuli but a few patients may develop an exacerbation without a known
trigger. Although exacerbations are more common in patients with poor
adherence to controller medications, i.e., poorly controlled asthma, it can also
occur in patients with mild or well-controlled asthma.1
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How is an asthma exacerbation diagnosed?
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Lung function measurements are more reliable indicators of severity of
exacerbation, but the frequency of symptoms may be a more sensitive
measure of the onset of exacerbation than PEF.4
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In a patient previously diagnosed to have asthma, asthma exacerbation is
diagnosed by getting a history of increase in frequency of symptoms and
documenting the change in lung function measurements, either a decrease in
peak expiratory flow rates (PEF) or forced expiratory volume in the first
second (FEV1 ), compared with the patient’s previous lung function or
predicted values.3
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The goals of treatment of acute exacerbations are to rapidly relieve airflow
obstruction, relieve the hypoxemia, address the underlying inflammatory
pathophysiology and prevent relapse.1
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The 2018 GINA guidelines recommend the use of the term “flare-up” since it
is “simpler and conveys the sense that asthma is present even when
symptoms are absent.”2 For the rest of this document however, exacerbation
and flare-up are used interchangeably to mean the same thing.
How is the severity of an asthma exacerbation evaluated?
A brief focused history, relevant physical examination and objective
measurements should be conducted concurrently with the prompt initiation
of therapy.
The history should include:
• Timing of onset and cause (if known) of the present exacerbation
• Severity of asthma symptoms, including any limiting exercise or
disturbing sleep
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•
•
•
Any symptoms of anaphylaxis
Any risk factors for asthma-related death (Table 5.2)
All current reliever and controller medications, including doses and
devices prescribed, adherence pattern, any recent dose changes and
response to current therapy.
Why is it important to identify patients who are at risk for asthma-related
deaths?
The physical examination should assess:
•
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Preferred body position
Prefers sitting to lying
Sits hunched forward
Mental state
Not agitated
Agitated
Confused
Respiratory rate
Increased
>30/min
Silent chest
Accessory muscle use
Not used
In use
Pulse rate
100-120 bpm
>120 bpm
O2 sat (room air)
90-95%
<90%
PEF
>50% pred. or best
≤50% pred. or best
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Conversation
• Food allergy in a patient with asthma
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• Poor adherence with asthma medications and/or poor adherence
(or lack of) a written asthma action plan
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• A history of psychiatric disease or psychosocial problems
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• Over-use of SABAs, especially use of more than one canister of salbutamol
(or equivalent) monthly
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Table 5.1. Classification of severity of exacerbation.
Mild to Moderate
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• Currently using or having recently stopped using oral corticosteroids
(a marker of event severity)
Depending on the patient’s signs and symptoms, the asthma exacerbation
can usually be classified as shown in Table 5.1.2 After classification of
severity of exacerbation, appropriate treatment may be instituted.
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• A history of near-fatal asthma requiring intubation and mechanical ventilation
• Hospitalization or emergency care visit for asthma in the past year
Pulse oximetry. Saturation levels <90% in children or adults signal the
need for aggressive therapy
PEF in patients older than 5 years.
Symptom or Sign
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Table 5.2. Risk factors for asthma-related deaths.
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Objective measurements should include:
It is important to identify patients with risk factors for asthma-related deaths
because these patients should be encouraged to seek urgent medical care
regardless of severity of symptoms or early in the course of exacerbation.
The presence of one or more of these risk factors listed in Table 5.22 should
be quickly identifiable in the clinical notes, and these patients should be
encouraged to seek urgent medical care early in the course of an
exacerbation.1
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Signs of exacerbation severity and vital signs (e.g., temperature, pulse
rate, respiratory rate, blood pressure) and other signs such as level of
consciousness, ability to complete sentences, use of accessory
muscles, presence or absence of wheeze
Complicating factors (e.g., anaphylaxis, pneumonia, pneumothorax)
Signs of alternative conditions that could explain acute breathlessness
(e.g., cardiac failure, upper airway dysfunction, inhaled foreign body or
pulmonary embolism).
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What is the ideal first-line therapy for symptom relief in asthma
exacerbations?
The ideal first-line therapy for an acute exacerbation of asthma is inhaled
SABA. It should be administered frequently for patients presenting with
acute asthma. Usually, SABA is administered through nebulization, however,
studies show that delivery of SABA via a pMDI with spacer leads to a similar
improvement in lung function as delivery via nebulizer. (Evidence A) Please
note that patients with acute severe asthma were not included in these
studies.5, 6
Modified from GINA 2018
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
To administer pMDI doses with spacer, it is recommended to give 4 to 10
puffs every 20 minutes for the first hour. Subsequently, 4 to 10 puffs every 3
to 4 hours OR 6 to 10 puffs every 1 to 2 hours can be given. If there is a good
response to the initial treatment (i.e., PEF >60-80% of predicted or personal
best for 3 to 4 hours), there is no need to administer additional treatment.
the exacerbation developed while the patient was already taking OCS, and;
the patient has a history of previous exacerbations requiring OCS.
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Is there a role for inhaled corticosteroids (ICS) in the management of
asthma exacerbations?
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In the acute care setting, high-dose ICS given within the first hour after
presentation reduces the need for hospitalization in patients not receiving
systemic corticosteroids.16 (Evidence A) However, when given in addition to
systemic corticosteroids, evidence is conflicting.16 (Evidence B)
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Overall, ICS are well tolerated and may be given in the acute care setting,
especially at home or at the out-patient department. However, cost is a
significant factor, and the agent, dose and duration of treatment with ICS in
the management of asthma in the acute care setting remain unclear.
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Systemic corticosteroids should be utilized in all but the mildest
exacerbations in adults, adolescents and children 6 to 11-years, because it has
been shown to speed the resolution of exacerbations and prevent relapse.14, 15, 16
(Evidence A)
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What is the first-line therapy for control of inflammation in asthma
exacerbations?
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In the treatment of moderate-severe exacerbations in the ER, the addition of
ipratropium, a short-acting anticholinergic, to SABA was associated with
fewer hospitalizations and greater improvement in PEF and FEV1 compared
with SABA alone.11, 12 It is, therefore, reasonable to administer the combination
as initial treatment for moderate to severe exacerbations. For mild exacerbations, it may be enough to give SABA alone.
The duration of treatment may vary but 5- and 7-day courses in adults have
been found to be as effective as 10- and 14-day courses respectively, and a
3–5-day course in children is usually considered sufficient.17, 18 (Evidence B)
Evidence from studies in which all patients were taking maintenance ICS
after discharge suggests that there is no benefit in tapering the dose of OCS,
either in the short term19 or over several weeks.20 (Evidence B)
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An earlier study in hospitalized patients found that intermittent on-demand
therapy led to a significantly shorter hospital stay, fewer nebulizations and
fewer palpitations when compared with 4-hourly intermittent therapy.9
Therefore, a reasonable approach to inhaled SABA in exacerbations would
be to initially use continuous therapy, followed by intermittent on-demand
therapy for hospitalized patients. There is no evidence to support the
routine use of intravenous beta2-agonist in patients with severe asthma
exacerbations.10 (Evidence A)
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There have been conflicting results as to the more effective way of
administering nebulized SABA, whether intermittently or continuously. One
study found no significant differences in lung function or hospital admissions
between the two strategies but a later review with additional studies found
reduced hospitalizations and better lung function with continuous compared
with intermittent nebulization, particularly in patients with worse lung
function.7, 8
Oral corticosteroids are as effective as intravenous systemic corticosteroids.
The oral route is preferred because it is quicker, less invasive and less
expensive.15, 16 Oral corticosteroids require at least 4 hours to produce a
clinical improvement. Intravenous corticosteroids can be administered when
patients are too dyspneic to swallow; if the patient is vomiting; or when
patients require non-invasive ventilation or intubation. A treatment regimen
consisting of daily doses of OCS equivalent to 50 mg prednisolone as a
single morning dose, or 200 mg hydrocortisone in divided doses, are
adequate for most patients. (Evidence B)
There are few randomized and blinded studies examining the effect of
nebulized corticosteroids as add-on therapy to systemic corticosteroids.
Although most of these studies were conducted in children and the patient
number is usually very small not allowing for subgroup analyses, these earlier
studies found no differences in the pulmonary index scores.21, 22, 23, 24, 25
It is recommended that systemic corticosteroids should be administered
within one hour of presentation. In the ER, the use of systemic
corticosteroids is particularly important in situations where the initial SABA
treatment fails to achieve lasting improvement in symptoms;
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Is there a role of inhaled long-acting beta2-agonist – inhaled corticosteroid
(LABA-ICS) in the management of acute asthma?
A written asthma action plan helps patients to recognize and respond
appropriately to worsening asthma. It should include specific instructions for
changes in reliever and controller medications, how to use OCS if needed
and when and how to access medical care. Figure 5.1 outlines how to
increase reliever medications, how to increase controller medications and
how to add corticosteroids.2
P
C
C
O
D
L-
IA
R
-
TE
TE
U
IB
TR
IS
D
L
IA
R
U
IB
TR
IS
TE
A
M
R
TE
D
There is no role for methylxanthines, whether parenteral or oral, in the
management of an asthma exacerbation because of poor efficacy and safety
profile.13 The use of intravenous aminophylline is, in fact, associated with
severe and potentially fatal side-effects, particularly in patients already
treated with sustained-release theophylline. Evidence has shown that, in
patients with severe asthma exacerbations, add-on treatment with
aminophylline does not improve outcomes compared with SABA alone.13
CHAPTER 5
D
O
A
R
O
M
What is the role of methylxanthines in the management of asthma
exacerbations?
TE
D
PY
O
C
H
IG
R
PY
T
O
N
TE
PY
O
C
H
IG
T
O
R
Intravenous magnesium sulfate can be given to adults and children who
fail to respond to initial treatment and have persistent hypoxemia. When
administered as a single 2 g infusion over 20 minutes, intravenous magnesium
sulfate reduces hospital admissions in adults with FEV1 <25–30% predicted at
presentation.31, 32, 33 (Evidence A)
The patient should be instructed to follow up with their physician within
1 to 2 weeks following a self-managed exacerbation for assessment of
symptom control and additional risk for exacerbation and to identify the
potential cause of the exacerbation. The written action plan should be reviewed
if it met the patient’s needs. The usual maintenance doses can usually be
resumed after 2 to 4 weeks after the exacerbation, unless history suggests
that patient has long-term poorly controlled asthma, in which case a step-up
in treatment is indicated provided the inhaler technique and adherence is
adequate.
O
N
PY
O
D
O
C
What is the role of magnesium sulfate in the management of asthma
exacerbations?
CHAPTER 5
The criteria for initiating an increase in controller medication will vary from
patient to patient. For patients taking conventional maintenance
ICS-containing treatment, this should generally be increased when there is a
clinically important change from the patient’s usual level of asthma control,
for example, if asthma symptoms are interfering with normal activities, or
PEF has fallen by >20% for more than 2 consecutive days.34
PC
P
C
PC
The role of these medications in the ER or hospital is unclear. One study
showed that high-dose budesonide-formoterol in patients in the ER, all of
whom received prednisolone, had similar efficacy and safety profile to SABA.26
For exacerbations of asthma treated at home, patients already on combination formoterol and low-dose ICS (budesonide or beclomethasone) in a
single inhaler, increasing doses of up to 72 mcg of formoterol in a day is
effective in achieving control of symptoms.27 (Evidence A) Studies have shown
that this strategy is effective in improving asthma control and in at-risk
patients, reduces exacerbations requiring OCS and hospitalizations.28, 29, 30
How should asthma exacerbations be managed at home?
All patients with asthma should be provided with guided self-management
education, including monitoring of symptoms and/or lung function, a written
asthma action plan and regular review by a healthcare professional.12
76
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Effective asthma self-management education requires:
How should asthma exacerbations be managed in the out-patient setting?
• Self-monitoring of symptoms and/or lung function
After an evaluation of the severity of exacerbation, initial therapy may be
started consisting of repetitive administration of short-acting bronchodilators, i.e., SABA, early introduction of corticosteroids and controlled-flow
oxygen supplementation.
If PEF or FEV1
<60% best, or not
improving
after 48 hours
• Written asthma action plan
• Regular medical review
All patients
PC
Review response
TE
H
Tapering is not needed if OCS are prescribed for
<2 weeks
B
L-
D
The patient may be discharged from the out-patient service department
(OPD) if symptoms have improved and SABA is not needed any more, PEF
60-80%, and O2 sat >94% at room air. Home instructions or a written action
plan should include instructions on reliever medications, controller medications,
OCS to be given for 5-7 days in adults and 3-5 days in children.
TE
Adults: prednisone 1 mg/kg/day (maximum 50 mg)
usually for 5-7 days. Children: 1-2 mg/kg/day
(maximum 40 mg) usually for 3-5 days
IA
A
R
Add OCS for severe exacerbations (e.g., PEF or FEV1
<60% personal best or predicted), or patient not
responding to treatment over 48 hours
U
IB
Add oral corticosteroids (OCS) and contact doctor
TR
-
TE
D
TE
A
M
L
IA
B
IS
D
R
U
IB
TR
IS
B
CHAPTER 5
D
R
O
A
TE
Step up to higher dose formulation of ICS/other
LABA, or consider adding separate ICS inhaler
(to maximum total 2000 mcg/day BDP equivalent)
D
Maintenance ICS/other
LABA, with SABA as
reliever
The clinical response to the initial treatment should be evaluated after one
hour. If the patient’s condition is worsening, with deteriorating vital signs,
transfer immediately to an acute care facility. While waiting to be
transported, give a combination of inhaled SABA and ipratropium bromide,
oxygen inhalation and systemic corticosteroids. If the patient partially
improved after initial treatment, continue SABA 4 to 10 puffs via pMDI with
spacer every four hours or 6 to 10 puffs every 1-2 hours. If, however, the
patient has good response, no need for further SABA, and the patient is
evaluated for discharge.
PY
A
R
Quadruple maintenance ICS-formoterol
(maximum formoterol 72 mcg/day)
O
M
O
Maintenance ICS-formoterol
with SABA as reliever
C
D
TE
PY
O
Maintenance ICS with
SABA as reliever
Continue maintenance ICS-formoterol and
increase reliever ICS-formoterol as needed*
(maximum formoterol total 72 mcg/day)
At least double ICS; consider increasing ICS to
high dose (maximum 2000 mcg/day BDP equivalent)
IG
R
PY
A
T
Increase frequency of reliever use
(maximum formoterol total 72 mcg/day)
OCS (prednisone or
prednisolone)
O
O
Low dose ICS-formoterol*
H
A
A
C
CHAPTER 5
C
IG
T
Increase frequency of SABA use
For pMDI, add spacer
Maintenance and reliever
ICS-formoterol*
N
R
O
Short-acting beta2-agonist
(SABA)
Increase usual controller:
O
PY
level
For mild-to-moderate exacerbations (Figure 5.2), an initial treatment at the
out-patient setting should consist of SABA 4 to 10 puffs via pMDI + spacer
administered every 20 minutes for one hour, prednisolone or equivalent at
1 mg/kg/day for adults, maximum of 50 mg and 1-2 mg/kg/day for children,
maximum of 40 mg. Controlled oxygen, if available, should be given to
achieve an oxygen saturation of 93-95% in adults and 94-95% in children.2
D
O
Evidence
Short-term change (1-2 weeks) for worsening asthma
N
Increase usual reliever:
P
C
O
D
Medication
LATE OR SEVERE
C
P
C
EARLY OR MILD
Severe and life-threatening exacerbations should not be managed in the
out-patient setting. These patients should immediately be transferred to an
acute care facility. While waiting for transfer, a combination of inhaled SABA
and ipratropium bromide either through pMDI + spacer or by nebulization,
O2 inhalation and systemic corticosteroids should promptly be administered.
PC
Continue reliever
Continue controller
Add prednisolone
40-50 mg/day
Contact doctor
Increase reliever
Early increase in
controller as below
Figure 5.1. Self-management of worsening asthma in adults
and adolescents with action plan.
78
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
OUT-PATIENT CARE
Patient presents with acute or sub-acute asthma exacerbation
Is it asthma?
ASSESS the PATIENT
Severity of exacerbation?
Talks in phrases, prefers
sitting to lying, not agitated
Talks in words, sits in hunched
forwards, agitated
C
P
IG
R
L-
IA
R
U
IB
TR
The patient’s clinical status and oxygen saturation should be assessed
frequently, with further treatment titrated according to the patient’s
response. Lung function (PEF) should be measured after one hour, and
patients who deteriorate despite intensive bronchodilator and corticosteroid
treatment should be re-evaluated for transfer to the intensive care unit
(Figure 5.3).2
TE
Reliever: continue as needed
Controller: start, or step up.
Check inhaler technique, adherence
Prednisolone: continue, usually for 5-7 days
(3-5 days for children)
Follow up: within 2-7 days
-
Symptoms improved, not needing SABA
PEF improving, and >60-80% of personal
best or predicted
Oxygen saturation >94% room air
Resources at home adequate
TE
ARRANGE at DISCHARGE
For adults with mild-to-moderate exacerbation, systemic corticosteroids
should be given either through intravenous route, if the patient is too
dyspneic to swallow, or by oral administration.
IS
L
IA
ASSESS FOR DISCHARGE
CHAPTER 5
D
R
U
IB
TR
IS
WORSENING
TE
A
M
R
D
TE
R
A
O
M
D
PY
O
D
TE
TE
C
H
For patients in severe exacerbation seen at the ER, SABA and ipratropium
may be administered via nebulization intermittently at 2.5 mcg ipratropium
bromide and 2.5 mcg salbutamol every 20 minutes for three doses, or
continuously every 10-15 minutes back to back for one hour. Short-acting
beta2-agonist (SABA) and ipratropium can also be given via pMDI with
spacer at 4 to 10 puffs every 20 minutes for one hour.
While waiting: give inhaled
SABA and ipratropium
bromide, O2 , systemic
corticosteroids
O
IMPROVING
T
TRANSFER TO ACUTE
CARE FACILITY
H
PY
O
CONTINUE TREATMENT with SABA as needed
ASSESS RESPONSE AT 1 HOUR (or earlier)
O
IG
N
R
C
WORSENING
PY
O
URGENT
PY
T
O
N
SABA 4-10 puffs by pMDI + spacer
repeat every 20 minutes for 1 hour
PREDNISOLONE: adults 1 mg/kg, max
50 mg, children 1-2 mg/kg, max. 40 mg
Controlled oxygen (if available): target
saturation 93-95% (children: 94-96%)
O
O2 saturation (on air) <90%
PEF ≤50% predicted or best
D
O
C
C
O
START TREATMENT
PC
Accessory muscles in use
Pulse rate >120 bpm
D
Pulse rate 100-120 bpm
O2 saturation (on-air) 90-95%
PEF >50% predicted or best
P
Accessory muscles not used
Once the patient has arrived in the ER with a life-threatening exacerbation,
initial treatments should be given concurrently to achieve rapid
improvement. Combined SABA and ipratropium bromide via nebulization
continuously should be started while awaiting transfer to the intensive care
unit (ICU). Low flow oxygen therapy should be administered by nasal
cannulae or mask to achieve oxygen saturation of 93-95% in adults (94-98%
for children) and IV corticosteroids at 200 mg hydrocortisone in divided
doses should be given while preparing for intubation.2
Drowsy, confused
or silent chest
Respiratory rate >30/min
Respiratory rate increased
CHAPTER 5
LIFE-THREATENING
C
PC
SEVERE
How should asthma exacerbations be managed in the emergency room
(ER)?
Severe exacerbations of asthma are life-threatening medical emergencies
and should be managed in an acute care setting such as an ER. An evaluation
based on history, physical examination and objective measures should
indicate whether the patient is in mild to moderate, severe or life-threatening
exacerbation. (Figure 5.3)
Risk factors for asthma-related deaths?
MILD OR MODERATE
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
FOLLOW UP
Reliever: reduce to as needed
Controller: continue higher dose for short term (1-2 weeks) or long term (3 months),
depending on background to exacerbation
Risk factors: check and correct modifiable risk factors that may have contributed to
exacerbation, including inhaler technique and adherence
Action plan: Is it understood? Was it used appropriately? Does it need modification?
O2: oxygen; PEF: peak expiratory flow; SABA: short-acting beta2-agonist (doses are for salbutamol)
80
Figure 5.2. Management of asthma exacerbations in the out-patient setting.
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
INITIAL ASSESSMENT
Are any of the following present?
A: airway B: breathing C: circulation
Drowsiness, confusion, silent chest
What are the indications for hospitalization?
Clinical status and lung function after one hour of bronchodilator and
corticosteroid treatment are more reliable predictors of the need for
hospitalization than the patient’s status on arrival.35, 36
NO
YES
Further TRIAGE BY CLINICAL STATUS
According to worst feature
Based on lung function measurements, hospitalization is recommended if
pre-treatment FEV1 or PEF is <25% predicted or personal best, or posttreatment FEV1 or PEF is <40% predicted or personal best.36
Consult ICU, start SABA and O2 , and
prepare patient for intubation
P
C
C
Talks in words
Sits hunched forwards
Agitated
Respiratory rate >30/min
Accessory muscles being used
Pulse rate >120 bpm
O2 , saturation (on air) <90%
PEF ≤50% predicted or best
D
L-
IA
R
-
TE
TE
U
IB
TR
L
IA
U
IB
If post-treatment lung function is 40–60% predicted, discharge may be
possible after considering the patient’s risk factors (Table 5.2) and
availability of follow-up care. If post-treatment lung function is >60%
predicted or personal best, discharge37 is recommended after considering
risk factors and availability of follow-up care. Prior to discharge, instructions
should be given on correct medications and inhaler skills, a written action
plan should be provided, and a follow up appointment within one week from
discharge should be arranged.2 (Table 5.3)
IS
R
TE
R
TE
TR
IS
D
A
O
A
R
M
When do we discharge patients after being treated in the emergency room
(ER)?
M
O
CHAPTER 5
D
PY
D
TE
O
TE
C
H
IG
T
O
R
N
H
PY
O
C
ASSESS CLINICAL PROGRESS FREQUENTLY
MEASURE LUNG FUNCTION
PY
O
D
IG
T
O
Short-acting beta2-agonists
Ipratropium bromide
Controlled O2 to maintain
saturation 93-95% (children 94-98%)
Oral or IV corticosteroids
Consider IV magnesium
Consider high-dose ICS
If continuing deterioration, treat as
severe and re-assess for ICU
O
• Female sex, older age and non-white race
• Use of more than 8 beta2-agonist puffs in the previous 24 hours
• Severity of the exacerbation (e.g., need for resuscitation or rapid
medical intervention on arrival, respiratory rate >22 breaths/minute,
O2 saturation <95%, final PEF <50% predicted)
• Past history of severe exacerbations (e.g., intubations, asthma admissions)
• Previous unscheduled office and emergency department visits requiring
use of OCS.
R
PY
O
C
N
Short-acting beta2-agonists
Ipratropium bromide
Controlled O2 to maintain
saturation 93-95% (children 94-95%)
Oral corticosteroids
CHAPTER 5
Other factors associated with increased likelihood of need for admission
include:38, 39, 40
SEVERE
P
O
D
Talks in phrases
Prefers sitting to lying
Not agitated
Respiratory rate increased
Accessory muscles not used
Pulse rate 100-120 bpm
O2 , saturation (on air) 90-95%
PEF >50% predicted or best
PC
C
PC
MILD or MODERATE
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
in all patients one hour after initial treatment
FEV1 or PEF 60-80% of predicted or
personal best and symptoms improved
FEV1 or PEF <60% of predicted or
personal best, or lack of clinical response
MODERATE
Consider for discharge planning
SEVERE
Continue treatment as above
and re-assess frequently
ICS: inhaled corticosteroids; ICU: intensive care unit; IV: intravenous; O2: oxygen; PEF: peak expiratory flow;
FEV1: forced expiratory volume in 1 second; SABA: short-acting beta2-agonist (doses are for salbutamol)
Figure 5.3. Management of asthma exacerbations at the emergency room (ER).
82
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Table 5.3. Discharge management after hospital or emergency room care for asthma.
References:
Medications
1.
Oral Corticosteroids (OCS)
Prescribe at least a 5-7 days’ course of OCS for adults (prednisolone or equivalent 1 mg/kg/day to a
maximum of 50 mg/day) and 3-5 days for children (1-2 mg/kg/day to a maximum of 40 mg). For
patients considered at risk of poor adherence, intramuscular corticosteroids may be considered.
(Evidence B)
3.
P
L-
IA
U
IB
TR
CHAPTER 5
R
TE
A
M
IS
TE
A follow-up appointment within 2-7 days of discharge should be made with the patient’s usual
healthcare provider to ensure that treatment is continued, that asthma symptoms are well controlled
and that the patient’s lung function reaches their personal best (if known).
D
17.
D
Follow-up appointment
R
TE
16.
TE
15.
O
• Review the patient’s use of controller treatment before and during exacerbation. Was it increased
promptly and by how much? Were OCS added and if not, why not? Consider providing short-course
of OCS to be on hand for subsequent exacerbations.
H
14.
-
• Evaluate patient’s response to exacerbation. If it was inadequate, review the action plan and
provide written guidance to assist if asthma worsens again.
13.
PY
L
IA
R
U
IB
12.
IG
TE
• Provide a written asthma action plan or review patient’s existing plan, either at discharge or as soon
as possible afterwards. Patient discharged from the emergency room with an action plan and PEF
meter have better outcomes than patients discharged without these resources.
O
A
TR
IS
D
11.
C
M
R
O
10.
Self-management skills and written asthma action plan
T
9.
O
D
PY
O
8.
R
PY
O
C
N
TE
C
H
7.
Identify factors that may have contributed to the exacerbation and implement strategies to reduce
modifiable risk factors. An exacerbation severe enough to require hospitalization may follow irritant or
allergen exposure, inadequate long-term treatment, problems with adherence, and/or lack of written
asthma action plan, as well as unavoidable factors such as viral respiratory infections.
• Review technique with PEF if used.
O
T
IG
Risk factors that contributed to the exacerbation
• Review inhaler technique.
C
6.
D
5.
R
O
N
PY
O
D
O
C
Inhaled Corticosteroids (ICS)
Initiate ICS prior to discharge, if not previously prescribed. Patients currently prescribed ICS-containing
medication should generally have their treatment stepped up for 2-4 weeks and should be reminded
about the importance of adherence with daily use.
PC
4.
P
C
PC
Reliever Medication
Transfer patients back to as-needed rather than regular reliever medication use, based on symptomatic
and objective improvement. If ipratropium bromide was used in the emergency department or
hospital, it may be quickly discontinued as it is unlikely to provide ongoing benefit.
2.
Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, Casale TB, et al.
American Thoracic Society/European Respiratory Society Task Force on Asthma Control
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Rodrigo GJ, Rodrigo C. Continuous vs intermittent beta-agonists in the treatment of
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Griffiths B, Ducharme FM. Combined inhaled anticholinergics and short-acting
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Gibson PG, Powell H, Coughlan J, et al. Self-management education and regular
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Manser R, Reid D, Abramson MJ. Corticosteroids for acute severe asthma in hospitalised
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Rowe BH, Spooner CH, Ducharme FM, Bretzlaff JA, Bota GW. Corticosteroids for
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Edmonds ML, Milan SJ, Camargo CA, Jr., Pollack CV, Rowe BH. Early use of inhaled
corticosteroids in the emergency department treatment of acute asthma. Cochrane
Database Syst Rev 2012;12:CD002308.
Hasegawa T, Ishihara K, Takakura S, Fujili H, Nishimura T, Okazaki M, Katakami N, Umeda B.
Duration of systemic corticosteroids in the treatment of asthma exacerbation; a randomized
study. Intern Med 2000 Oct;39(10):794-7.
ICS: inhaled corticosteroids; OCS: oral corticosteroids; PEF: peak expiratory flow
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18.
19.
20.
21.
P
D
TE
PY
O
C
H
IG
40.
T
O
R
PY
O
C
N
L-
IA
R
U
IB
TR
IS
D
TE
A
M
R
O
TE
86
39.
O
32.
38.
C
31.
-
TE
30.
37.
D
L
IA
R
U
IB
TR
IS
D
29.
TE
A
M
R
O
28.
36.
Gallegos-Solorzano MC, Perez-Padilla R, Hernandez-Zenteno RJ. Usefulness of inhaled
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emergency department. Pulm Pharmacol Ther 2010 Oct;23(5):432-7.
Gibson PG, Powell H. Written action plans for asthma: an evidence-based review of the
key components. Thorax 2004 Feb;59(2):94-9.
Kelly A-M, Kerr D, Powell C. Is severity assessment after one hour of treatment better for
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Wilson MM, Irwin RS, Connolly AE, Linden C, Manno MM. A prospective evaluation of the
1-hour decision point for admission versus discharge in acute asthma. J Intensive Care
Med 2003 Sep;18(5):275-85.
Grunfeld A, FitzGerald JM. Discharge considerations for adult asthmatic patients treated
in emergency departments. Can Respir J 1996 Jan;3(5):322 -7.
Pollack CV, Jr., Pollack ES, Baren JM, Smith SR, Woodruff PG, Clark S, Camargo CA, for
the Multicenter Airway Research Collaboration Investigators. A prospective multicenter
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Rowe BH, Villa-Roel C, Abu-Laban RB,Stenstrom R, Mackey D, Stiell IG, Campbell S,
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Weber EJ, Silverman RA, Callaham ML, Pollack C V, Woodruff PG, Clark S, Camargo CA.
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PC
D
PY
27.
TE
H
IG
O
C
26.
35.
R
PY
T
O
N
25.
34.
O
O
D
24.
33.
C
23.
P
22.
C
PC
Jones AM, Munavvar M, Vail A, Alridge RE, Hopkinson L, Rayner C, O’Driscoll BR.
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O'Driscoll BR, Kalra S, Pickering CA, Carroll KB, Woodcock AA, Wilson M. Double-blind
trial of steroid tapering in acute asthma. Lancet 1993 Feb; 341(8841):324-7.
Lederle FA, Pluhar RE, Joseph AM, Niewoehner DE. Tapering of corticosteroid therapy
following exacerbation of asthma. A randomized, double-blind, placebo-controlled
trial. Arch Intern Med 1987;147(12):2201-3.
Guttman A, Afilalo M, Colacone A, Kreisman H, Dankoff J and Asthma ED Study Group.
The effects of combined intravenous and inhaled steroids (beclomethasone
dipropionate) for the emergency treatment of acute asthma. The Asthma ED Study
Group. Acad Emerg Med. 1997 Feb;4(2):100–6.
Nuhoglu Y, Atas E, Nuhoglu C, Iscan M, Ozcay S. Acute effect of nebulized budesonide
in asthmatic children. J Invest Allergol Clin Immunol. 2005;15(3):197–200.
Sung L, Osmond MH, Klassen TP. Randomized, controlled trial of inhaled budesonide
as an adjunct to oral prednisone in acute asthma. Acad Emerg Med. 1998;5(3):209–13.
Upham BD, Mollen CJ, Scarfone RJ, Seiden J, Chew A, Zorc JJ. Nebulized budesonide
added to standard pediatric emergency department treatment of acute asthma: A
randomized, double-blind trial. Acad Emerg Med. 2011 Jul;18(7):665–73.
Alangari AA, Malhis N, Mubasher M, Al-Ghamedi N, Al-Tannir M, Riaz M, Umetsu DT,
Al-Tamimi S. Budesonide nebulization added to systemic prednisolone in the
treatment of acute asthma in children: Double-Blind, randomized, controlled trial.
Chest. 2014 Apr;145(4):772–8.
Balanag VM, Yunus F, Yang PC, Jorup C. Efficacy and safety of budesonide/formoterol
compared with salbutamol in the treatment of acute asthma. Pulm Pharmacol Ther
2006 Apr;19(2):139-47.
Bateman ED, Reddel HK, Eriksson G, Peterson S, Ostlund O, Sears MR, Jenkins C, et al.
Overall asthma control: the relationship between current control and future risk. J
Allergy Clin Immunol 2010 Feb;125(3):600-8.
Cates CJ, Karner C. Combination formoterol and budesonide as maintenance and
reliever therapy versus current best practice (including inhaled steroid maintenance),
for chronic asthma in adults and children. Cochrane Database Syst Rev
2013;4:CD007313.
Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as
maintenance and reliever therapy versus combination inhaler maintenance for chronic
asthma in adults and children. Cochrane Database Syst Rev 2013;12:CD009019.
Papi A, Corradi M, Pigeon-Francisco C, Baronio R, Sierkgiejko Z, Petruzzelli S, Fabbri
LM, et al. Beclometasone–formoterol as maintenance and reliever treatment in patients
with asthma: a double-blind, randomised controlled trial. Lancet Respir Med 2013
Mar;1(1):23-31.
Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Blitz S, Camargo CA, Jr. Magnesium
sulfate for treating exacerbations of acute asthma in the emergency department.
Cochrane Database Syst Rev 2000;1:CD0014990.
FitzGerald JM. Magnesium sulfate is effective for severe acute asthma treated in the
emergency department. West J Med 2000 Mar;172(2):96.
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CHAPTER
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6
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Chronic Asthma Management
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Asthma cannot be cured, but appropriate management can result in control
of the disease and enable those affected to enjoy a good quality of life.1
What are the goals of chronic asthma management?
The aim of asthma management is control of the disease.2 The long-term
goals are:3
•
•
C
PC
PC
To achieve good control of symptoms and maintain normal activity levels
To minimize future risk of exacerbations, fixed airflow limitation and
side-effects.
D
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O
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IG
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O
N
PY
O
O
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O
C
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N
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O
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•
no daytime symptoms
no night-time awakening due to asthma
no need for rescue medication
no asthma attacks
no limitations on activity including exercise
normal lung function (in practical terms FEV1 and/or PEF >80% predicted
or best)
minimal side-effects from medication.
C
C
•
•
•
•
•
•
P
P
C
Complete control of asthma is defined2 as:
M
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Discrepancies between patient and physician understanding of asthma
control have been observed in Asia.7 Patients’ asthma control targets need to
evolve from quick symptomatic relief to long-term prevention. In clinical
practice, patients may have different goals and may wish to balance the aims
of asthma management against the potential side-effects or inconvenience
of taking medication necessary to achieve perfect control.3 Healthcare
providers are best positioned to address these differences in perception and
goals, as well as influence patient attitudes towards treatment.
TR
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Current degree of asthma control has been found to predict future risk of
instability and exacerbations.4 On the other hand, an exacerbation in the past
year is a strong independent predictor of future exacerbations, particularly in
patients with severe or difficult-to-treat asthma.5, 6
What is control-based asthma management?
Control-based asthma management is a continual process of adjustment of
pharmacological and non-pharmacological strategies and involves a cycle of
assessment, treatment modifications based on current status and review of
clinical response (Figure 6.1).3
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Successful asthma management requires a system of regular objective
monitoring, stepwise adjustment of medications based on clinical
response and patient preference, addressing non-pharmacologic
interventions and comorbidities, nurturing an excellent patient-healthcare
provider partnership and self-management education planning.
Once good asthma control has been maintained for 2-3 months, taking a
lower treatment step is done in order to find the minimum effective drug and
dosing that can maintain control. On the other hand, if a patient has persisting
symptoms and/or exacerbations despite 2-3 months of controller
treatment, the following common problems need to be assessed and
corrected before considering any step-up in treatment:3
A
PY
O
a
Esc
CONTROLLER
STEP 4
RELIEVER
TE
CONTROLLER
Consider
early
low-dose
ICS
RELIEVER
OTHER OPTIONS
L-
As-needed low-dose ICS-formoterol
or as-needed ICS-SABA+
U
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After a diagnosis of asthma is made, pharmacotherapy is initiated. The
choice of medications is based on the patient’s current level of asthma
control, the presence of future risks of adverse outcomes and the response
to current asthma treatment, if any.3 On subsequent clinic visits, controller
therapy is adjusted up or down in a stepwise fashion depending on whether
the goals of asthma management are met or not.
Step 4 regimen
+ specialist
referral for
add-on
treatment,
e.g., tiotropium
(if not yet
started),
anti-IgE,
anti-IL5+
Daily
high-dose
ICS-LABA
or
high-dose
ICS-formoterol
as MART**
What is the stepwise approach for adjusting asthma treatment in adults?
The approach to asthma treatment in Filipino adults is a 5-step continuum of
care that involves a stepwise escalation or de-escalation of the number and
dosing of asthma controller medications that are required to achieve and
maintain control. (Figure 6.2)
STEP 5
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As-needed low-dose
ICS-formoterol*
or as-needed ICS-SABA+
e
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Daily
medium-dose
ICS-LABA
or
medium-dose
ICS-formoterol
as MART**
PY
R
TE
IS
As-needed
low-dose
ICS-formoterol
as MART**
or
daily low-dose
ICS-LABA
alat
STEP 3
H
O
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A
M
D
As-needed
low-dose
ICSformoterol
or
esc
de-
IG
T
O
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R
O
In low- and middle-income countries such as the Philippines, affordability
and availability8 are additional important considerations in the choice of
medications, aside from efficacy and safety. Physicians should check the
accessibility of free generic inhaled asthma medications in local health units.9
STEP 2
STEP 1
late
R
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H
PY
Figure 6.1. The control-based asthma management cycle.
CHAPTER 6
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Asthma medication
Non-pharmacological strategies
Treat modifiable risk factors
PREFERRED OPTION
R
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ES
SS
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O
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O
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REVIEW
C
NSE
PO
S
E
Incorrect inhaler technique
Poor adherence
Persistent exposure to agents which trigger asthma
Presence of uncontrolled comorbidities
Incorrect diagnosis
PC
Diagnosis
Symptom control & risk factors
(including lung function)
Inhaler technique & adherence
Patient preference
P
C
PC
Symptoms
Exacerbations
Side-effects
Patient satisfaction
Lung function
•
•
•
•
•
Consider
as-needed
SABA&
Daily
low-dose ICS
or
LTRA
Daily
medium-dose
ICS
or
low-dose ICS
+ LTRA
Daily high-dose
ICS + tiotropium
or
high-dose
ICS + LTRA
± theophylline
Add to Step 4
treatment
a course of
low-dose OCS
and seek
specialist
referral
As-needed SABA&
*Off-label; **Maintenance and reliever therapy
+
Not available locally; &Should not be used alone
ICS: inhaled corticosteroid; LABA: long-acting beta2-agonist; LTRA: leukotriene receptor antagonist;
OCS: oral corticosteroid; SABA: short-acting beta2-agonist
Figure 6.2. Stepwise approach to treatment in Filipino adults.
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
STEP 1
STEP 2
Preferred option: As-needed combination low-dose ICS-formoterol
Preferred option: Low-dose ICS-formoterol as maintenance and
reliever therapy (MART) OR regular low-dose
ICS-LABA combination plus as-needed SABA
P
N
PY
O
C
O
D
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PY
O
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Recent data has shown benefit of as-needed budesonide-formoterol in a
52-week study for mild asthma in reducing severe exacerbations by 64%
compared with SABA only treatment.22 This is also in congruence with older
studies by Zetterstrom and O’Byrne showing that budesonide-formoterol
single inhaler therapy provided better asthma control than budesonide
alone in patients not previously fully controlled by glucocorticoids.17, 23
In patients who are not currently taking ICS, a low dose of inhaled
budesonide in addition to formoterol reduced the rate of severe exacerbations
and poorly controlled asthma days by more than half and the addition of
formoterol resulted in improved lung function.17 On the other hand, Bateman
et al24 showed that budesonide–formoterol used as needed was noninferior
to twice-daily budesonide with respect to the rate of severe asthma
exacerbations during 52 weeks of treatment but was inferior in controlling
symptoms.
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Regular early low-dose ICS should be considered, in addition to as-needed
SABA, to reduce the risk of exacerbation.3 (Evidence B) The use of ICS-SABA as
reliever is off-label and currently not available in the Philippines. However, it
would be a better option than SABA alone.
C
D
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PY
O
C
H
IG
T
O
Other options:
D
R
N
PY
O
C
O
D
Eosinophilic airway inflammation and remodeling have been demonstrated
even in the mildest forms of asthma.14-16 The results of a recent post-hoc
analysis of the 3-year Inhaled Steroid Treatment As Regular Therapy
(START) study on mild recent-onset asthma do not support restriction of ICS
to patients with symptoms on more than 2 days per week and suggest
that treatment recommendations for such patients should consider
both risk reduction and symptoms. (Evidence B) Indeed, anti-inflammatory
treatment with ICS has been found to reduce asthma symptoms, increase
lung function, improve quality of life and reduce the risk of exacerbation and
asthma-related hospitalization or death.17-21 (Evidence A) Note that the use of
ICS-formoterol as symptom-driven treatment for mild asthma, as of this
writing, is still off-label.
In the local setting, patients often carry the financial burden of out-of-pocket
cost of treatment, and the medical care of a significant number of Filipinos is
neither covered by Health Maintenance Organizations nor subsidized by
their employers. Furthermore, Filipino asthmatics prioritize medications that
can provide rapid relief of symptoms.7 To assure the delivery of antiinflammatory therapy while providing bronchodilator efficacy for the
majority of symptomatic asthmatics, the consensus is to start at Step 2, with
either low doses of ICS-formoterol as maintenance and reliever therapy or
low doses of a fixed dose ICS-LABA combination inhaler. (Evidence D)
PC
P
C
PC
For step 1, which mostly consist of patients with mild intermittent asthma,
previous local consensus report10 recommended the use of as-needed SABA
with no maintenance controller but recent studies have raised concerns
regarding such a strategy. The REALISE Asia study that included Filipino
subjects has shown that 50% of patients who use a reliever inhaler as sole
medication have uncontrolled asthma.7 Among Chinese asthmatics, only
4.9% of patients in GINA Step 1 have well-controlled asthma and 12.2% are
uncontrolled.11 A Spanish survey reports an even higher proportion of
uncontrolled asthmatics in GINA Step 1 (52.4%).12 In the REALISE Europe
survey, 26.1% of patients in GINA Step 1 experienced exacerbations in the
previous 12 months that required short course oral steroids.13
CHAPTER 6
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
In both studies by O’Byrne and Bateman,22, 24 patients in the budesonide–
formoterol group had substantially lower glucocorticoid exposure than
the patients on budesonide maintenance therapy. No safety signals were
identified. Quite notably, the adherence level to the study medications was
high in both studies (>60%).
Alternatively, the regular use of combination ICS-LABA in adolescents and
adults with suboptimal asthma control on low-dose ICS monotherapy is
more effective than ICS alone in reducing the risk of exacerbations requiring
OCS, provides greater improvement in lung function, symptoms, use of
rescue SABA and leads to fewer withdrawals due to poor asthma control
than a higher dose of ICS.25 (Evidence A)
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Access to corticosteroid inhalers has become a problem in many parts of
the Philippines. Fixed dose ICS-LABA combination inhalers are more easily
available, including the cheaper generic brands that are freely provided in
selected local health units. Where ICS as monotherapy cannot be obtained,
maintenance treatment with low-dose ICS-LABA is an alternative option.
(Evidence D)
Other options:
P
PY
O
C
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Other options:
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Other options in Step 3 include increasing ICS from low- to
medium-dose 25, 35 or combining a low-dose ICS with LTRA.36 These two
approaches have been shown to be less effective than the addition of an
inhaled LABA to ICS. (Evidence A)
D
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Other options:
R
IS
D
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A
R
Low-dose ICS-formoterol combination inhalers can be prescribed as both
maintenance and reliever therapy (MART). This approach has been shown
to result in a reduction in exacerbations and improvement in lung function
and asthma symptoms in adults and adolescents at relatively low doses of
ICS, compared with a fixed dose of ICS-LABA as maintenance treatment, or
a higher dose of ICS combined with as-needed SABA.30-34 (Evidence A)
Pre-defined total asthma control through stepped-up treatment with
ICS-LABA (maximum of 500 μg ICS twice a day) can be achieved by
about a third of patients.38 Combination high-dose ICS-LABA may thus be
considered in adult patients with more severe asthma, but the increase in ICS
dose generally provides little additional benefit,35, 39, 40 (Evidence A) and
there is an increased risk of side-effects, including adrenal suppression.41 A
high dose is recommended only on a trial basis for 3–6 months when good
asthma control cannot be achieved with medium-dose ICS plus LABA
and/or a third controller (e.g., LTRA).3
O
M
O
If control is suboptimal despite combination low-dose ICS-LABA, maintenance
treatment may be increased to medium-dose ICS-LABA.29 (Evidence B)
TE
D
PY
O
TE
C
H
IG
R
T
O
H
PY
O
For patients already on combination low-dose ICS-formoterol as MART, the
maintenance dose may be increased if necessary. In patients with moderate
to severe asthma, MART strategy was found to be more effective and less
expensive than a strategy of clinician-directed titration of ICS-LABA with
salbutamol as reliever therapy.37 (Evidence A)
N
IG
C
Preferred option: Combination medium-dose ICS-LABA plus
as-needed SABA OR combination ICS-formoterol
as maintenance and reliever therapy (MART)
CHAPTER 6
Step 4 treatment options depend on prior selections at Step 3. As previously
stated, before stepping up, the presence of common problems
such as incorrect asthma diagnosis, suboptimal inhaler technique, poor
adherence, continuing environmental exposure to triggers and uncontrolled
comorbidities must be reviewed and addressed accordingly. Where
possible, patients who are not controlled on Step 3 treatment should be
referred early to an asthma specialist for investigation of alternative
diagnoses and/or causes of difficult-to-treat asthma and further management.
C
R
T
O
N
PY
O
STEP 3
Preferred option: Combination high-dose ICS-LABA plus as-needed
SABA OR combination ICS-formoterol as
maintenance and reliever therapy (MART)
D
O
C
D
Daily LTRA is another option although less effective for prevention of
exacerbations than ICS containing therapy.3 (Evidence A)
STEP 4
PC
P
C
PC
Alternatively, daily low-dose ICS may be used regularly for mild asthma.
This is based on evidence for the benefits of low-dose ICS in this population
in significantly reducing the risk for asthma-related deaths,26 asthma-related
hospitalizations,27 and risk of severe exacerbations.28
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
The long-acting muscarinic antagonist tiotropium delivered via soft-mist
inhaler may be used as add-on therapy for adult or adolescent patients with
a history of frequent exacerbations; it modestly improves lung function and
delays the time to severe exacerbation.42-44 (Evidence A) Tiotropium is not
indicated in children <12 years.
Leukotriene modifiers45-46 as add-on therapy in asthma have been shown to
exhibit steroid sparing effects. (Evidence B)
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
therapy for prevention of osteoporosis, if appropriate.3 Screening for
tuberculosis (TB) is likewise important as the risk of TB reactivation increases
2.8- to 7.7-fold.52
STEP 5
Preferred option: Referral for asthma specialist investigation and
consideration of add-on treatment
P
O
TE
H
IG
R
C
D
PY
M
R
TE
A
IS
D
•
Short-term step-up (for 1–2 weeks): an occasional short-term increase
in maintenance ICS dose for 1–2 weeks may be necessary; for example,
during viral infections or seasonal allergen exposure. This may be
initiated by the patient according to their written asthma action plan or
by the healthcare provider.
L-
Sustained step-up (for at least 2–3 months): some patients may fail to
respond adequately to initial treatment. A step-up in treatment may be
recommended if the symptoms are confirmed to be due to asthma;
inhaler technique and adherence are satisfactory, and; modifiable risk
factors such as smoking have been addressed (Table 6.2). Any step-up
should be regarded as a therapeutic trial, and the response reviewed
after 2–3 months. If there is no response, treatment should be reduced
to the previous level, and alternative treatment options or referral
considered.
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The Philippine consensus has adopted these GINA 2018 recommendations:3
TR
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Asthma is a variable condition and patients may have more symptoms
during allergen season. Periodic treatment adjustments by the clinician
and/or the patient may be needed.56
Other options:
98
PY
T
O
N
What are the guidelines for the escalation of asthma treatment?
Published guideline recommendations in the evaluation and management of
severe asthma can be accessed.48-50
Add-on low-dose OCS (≤7.5 mg/day prednisone or equivalent) may be
considered in adults with poor symptom control and/or frequent
exacerbations despite good inhaler technique and adherence with Step 4
treatment, and after exclusion of other contributory factors.3 However, this
option is often associated with significant systemic side-effects.51 (Evidence B)
Patients who are expected to be treated with systemic steroids for
≥3 months should be provided lifestyle counselling and prescription
O
C
The frequency of healthcare visits and assessments depends upon the
patient’s initial clinical severity and the patient’s training and confidence in
playing a role in the ongoing control of his or her asthma, including
adherence and proficiency to use the assigned inhaler. Typically, patients are
seen one to three months after the initial visit, and every 3-12 months
thereafter.3 After an exacerbation, follow-up should be scheduled within one
week.55 (Evidence D)
O
D
TE
PY
O
C
Other add-on options in Step 5 which are not yet available in the Philippines
include anti-interleukin 5 (subcutaneous mepolizumab and intravenous
reslizumab) for patients ≥12 years with severe eosinophilic asthma
uncontrolled by Step 4 treatment and bronchial thermoplasty. Their efficacy
and safety are well covered by international guidelines.2, 3
C
H
IG
R
T
O
1. Add-on tiotropium by soft-mist inhaler, if not yet started in Step 4
2. Add-on Anti-Immunoglobulin E (anti-IgE) treatment with omalizumab
for patients ≥6 years with moderate to severe allergic asthma that
is uncontrolled in Step 4 treatment.48 (Evidence A)
To achieve asthma control, review of symptoms, risk factors and occurrence
of exacerbations as well as response to treatment adjustments, patients
should be monitored on a regular basis.3 For most controller medications,
improvement begins within days of initiating treatment, but the full benefit
may only be evident after 3-4 months.53 In severe and chronically under
treated disease, this may take even longer.54
D
N
PY
O
C
O
D
Treatment options which are currently available in the local setting that may
be considered in Step 5:
How often should response to treatment be assessed and monitored?
PC
P
C
PC
Patients with persistent symptoms or exacerbations despite correct inhaler
technique and good adherence to Step 4 treatment, and in whom other
controller options have been considered, should be referred to a tertiarylevel medical center with a severe asthma clinic or to a specialist with
expertise in the management and treatment of severe asthma.3 (Evidence D)
Sputum-guided treatment based on eosinophilia (>3%) in induced sputum
may be considered for patients with difficult-to-treat asthma, specifically
those with persisting symptoms and/or exacerbations despite higher doses
of ICS-LABA. This strategy can lead to reduced exacerbation and/or lower
doses of ICS.47 (Evidence A)
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
•
Day-to-day adjustment: for patients prescribed combination ICSformoterol as MART, the patient adjusts the number of as-needed
doses of ICS-formoterol from day to day according to their symptoms,
while continuing the maintenance dosage.
What are the guidelines for the de-escalation of asthma treatment?
When ICS monotherapy in medium to high doses is being used, a 50%
reduction in dose should be attempted at 3-month intervals. (Evidence B)
•
Where control is achieved at a low dose of ICS alone, in most patients,
treatment may be switched to once-daily dosing. (Evidence A)
•
If control is maintained, further reductions in the inhaled steroid should
be attempted until a low dose is reached, at which time, the LABA may
be stopped. (Evidence D)
•
When asthma is controlled with ICS in combination with controllers
other than LABA, the dose of inhaled steroid should be reduced by
50% until a low dose is reached, then the combination treatment can
be stopped, as described above. (Evidence D)
•
Controller treatment may be stopped if the patient’s asthma remains
controlled on the lowest dose of controller and no recurrence of
symptoms occurs for at least one year. (Evidence D)
C
O
TE
H
What are the strategies to reduce the risk of asthma exacerbations?
C
D
For all asthma patients, risk factors for exacerbation need to be identified
and addressed. Table 6.1 lists the modifiable conditions with their
corresponding level of evidence.3
PY
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• To establish the lowest step and dose of treatment necessary
(i.e., minimum effective treatment), which minimizes the cost and
maximizes the safety of treatment
• To encourage the patient to continue regular controller treatment.3
O
D
TE
PY
O
The goals of stepping down are as follows:
D
C
H
IG
R
T
O
N
PY
O
C
C
P
P
O
D
Independent risk factors associated with asthma worsening or exacerbation
during treatment de-escalation include reduced baseline lung function, an
exacerbation that necessitated an ER visit in the past year, and early onset
disease, even if otherwise well controlled.57 Patients with these risks may
require more meticulous monitoring to prevent treatment failures and
asthma exacerbation during step down of therapy.
PC
•
C
PC
When asthma control has been achieved and maintained for at least 3
months and lung function has reached a plateau, treatment can often be
successfully reduced without loss of asthma control. The appropriate time to
step down therapy is when the patient currently has no respiratory infection,
not travelling, not pregnant or will have minimal exposure to triggers such as
weather/season change. Approach to stepping down of treatment should
also be regarded as a therapeutic trial. Patients must be provided with
enough information and a written action plan and instructions on how and
when to resume their previous treatment if their symptoms worsen. If the
patient has risk factors for exacerbations or fixed airflow limitation, close
supervision by a clinician is necessary.3
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
The following are some of the strategies that can be adopted in the local
setting:3
• When asthma is controlled with a combination of ICS and LABA, the
preferred approach is to begin by reducing the dose of inhaled steroid
by approximately 50% at 3-month intervals while continuing the
inhaled LABA. (Evidence B)
100
101
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Table 6.1. Treating modifiable risk factors to reduce exacerbations.
Risk factor
Any patient with ≥1
risk factor for
exacerbations
(including poor
symptom control)
• Ensure patient is prescribed regular ICS-containing controller
• Ensure patient has a written action plan appropriate for their
health literacy
• Review patient more frequently than low-risk patients
• Check inhaler technique and adherence frequently
• Identify any modifiable risk factors
A
A
A
A
D
A
L-
CHAPTER 6
Compared to the general population, asthmatics are at higher risk of the
development of pneumococcal pneumonia and invasive pneumococcal
disease.63, 64 Well-designed and robust randomized clinical trials to determine
the efficacy of pneumococcal vaccine in reducing mortality or morbidity
from pneumococcal disease in asthmatic individuals are lacking.65 Nevertheless,
both the 2017 Philippine Society for Microbiology and Infectious Diseases
and the 2019 U.S. CDC adult immunization recommendations include
pneumococcal polysaccharide and conjugate vaccination schedules for all
adults age 65 years and over and for younger adults with chronic lung
diseases, e.g., asthma.66, 67
U
IB
-
TE
CHAPTER 6
IA
R
TR
L
TE
A
TE
A
M
IS
D
IA
U
IB
102
D
R
TE
TR
IS
D
ICS: inhaled corticosteroids; OCS: oral corticosteroids; FEV1 : forced expiratory volume in 1 second; COPD: chronic obstructive pulmonary disease; SLIT: sublingual immunotherapy; HDM: house dust mite; AR: allergic rhinitis
*Based on evidence from relatively small studies in selected populations.
R
A
TE
• Increase ICS dose independent of level of symptom control
Although there were concerns that influenza vaccination might aggravate
respiratory symptoms, any such effect would be outweighed by the benefits
of the vaccination.2, 61 A Cochrane review did not find an increased rate of
exacerbation for two weeks following vaccination.62 (Evidence B)
O
Sputum eosinophilia
(limited centers)
H
C
D
B
PY
• Consider trial of simple avoidance strategies; consider cost
• Consider step up of controller treatment
• Consider adding SLIT in adult HDM-sensitive patients with
AR and exacerbations despite ICS, provided FEV1 is
≥70% predicted
IG
Allergen exposure if
sensitized
O
• Appropriate food avoidance; injectable epinephrine
R
Confirmed food
allergy
C
• Identify most cost-effective ICS-based regimen
D
D
PY
A
M
Major socioeconomic
problems
D
• Arrange mental health assessment
• Help patient to distinguish between symptoms of anxiety and
asthma; provide advice about management of panic attacks
T
D
R
O
Major psychological
problems
O
TE
H
O
C
• Strategies for weight reduction
• Distinguish asthma symptoms from symptoms due to
deconditioning, mechanical restriction and/or sleep apnea
The U.S. Centers for Disease Control and Prevention (CDC) recommend
annual seasonal influenza vaccination for all persons aged 6 months and
older in general, and in particular for individuals with chronic pulmonary
diseases including asthma. For the latter population, this vaccine aims to limit
influenza-related mortality and decrease transmission of the virus.60
O
T
D
D
N
PY
B
D
IG
B
What is the role of vaccination among asthmatics?
O
R
• Consider trial of 3-months’ treatment of high-dose ICS and/or
2 weeks’ OCS
• Exclude other lung disease, e.g., COPD
• Refer for expert advice if no improvement
D
PY
O
O
N
Obesity
B
C
C
O
Low FEV1 especially if
≤60% predicted
A
P
P
• Encourage smoking cessation by patient/family;
provide advice and resources
• Consider higher dose of ICS if asthma is poorly controlled
Sublingual immunotherapy (SLIT) as an add-on option may be considered
for adult HDM-sensitive patients with allergic rhinitis who have exacerbations
despite ICS, provided FEV1 is >70% predicted. In these patients, SLIT for HDM
has been shown to decrease mild to moderate asthma exacerbations.59
C
C
A
C
Allergen-specific immunotherapy has a role in patients with allergic asthma and
allergic rhinoconjunctivitis. In patients with asthma and allergic sensitization,
subcutaneous immunotherapy (SCIT) is associated with a reduction in
symptom scores and medication requirements and improved allergenspecific and nonspecific airway hyperresponsiveness.58 Anaphylactic
reactions are uncommon but may be life-threatening.
PC
• Consider alternative controller regimens to reduce exacerbation
risk, e.g., ICS-formoterol maintenance and reliever regimen
• Consider stepping up treatment if no modifiable risk factors
• Identify any avoidable triggers for exacerbations
D
Exposure to tobacco
smoke
What is the role of immunotherapy in asthma?
Evidence
PC
≥1 severe exacerbation
last year
Treatment strategy
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
What are the non-pharmacological interventions for asthma?
There are other interventions, activities and strategies aside from pharmacotherapy that can help in managing asthma. These are listed and summarized
in Table 6.2.3
103
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Table 6.2. Non-pharmacological interventions for asthma.
Intervention
Advice/recommendation
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Table 6.2. Non-pharmacological interventions for asthma. (continued)
Evidence
Intervention
Cessation of smoking
and ETS exposure
• Advise parents/carers of children with asthma not to smoke and
not to allow smoking in rooms or cars that their children use
A
• Strongly encourage people with asthma to avoid environmental
smoke exposure
B
• Assess smokers/ex-smokers for COPD or overlapping features of
asthma and COPD (asthma-COPD overlap or ACO) as additional
treatment strategies may be required
D
Advice/recommendation
Avoidance of
indoor allergens
A
• For patients sensitized to HDM and/or pets, there is limited
evidence of clinical benefit for asthma with avoidance
strategies (only in children)
B
• Allergen avoidance strategies are often complicated and
expensive, and there are no validated methods of identifying
those who are likely to benefit
D
PY
O
C
N
IG
R
T
O
TE
Allergen
immunotherapy
• As for any treatment, potential benefits of allergen immunotherapy (SCIT or SLIT) for individual patients should be weighed
against the risk of adverse effects and the cost to the patient and
health system, including for SCIT the minimum half-hour wait
required after each injection
D
Breathing exercises
• Breathing exercises may be a useful supplement to asthma
pharmacotherapy
Avoidance of indoor
air pollution
• Encourage people with asthma to use non-polluting heating and
cooking sources, and for sources of pollutants to be vented
outdoors where possible
B
• People with asthma, particularly the children and the elderly,
are at higher risk of pneumococcal disease, but there is
insufficient evidence to recommend routine pneumococcal
vaccination in people with asthma
B
• Advise patients with moderate-severe asthma to have an
influenza vaccination every year, or at least when vaccination
of the general population is advised
D
• Encourage patients with asthma to consume a diet high in fruit and
vegetables for its general health benefits
A
Vaccinations
CHAPTER 6
D
L-
• If cardioselective beta-blockers are indicated for acute coronary
events, asthma is not an absolute contraindication, but the relative
risks/benefits should be considered
TE
D
IA
• Decide about prescription of oral or intra-ocular beta-blockers on a
case-by-case basis. Initiate treatment under close medical
supervision by a specialist
R
A
U
IB
• Aspirin and NSAIDs are not generally contraindicated unless there
is a history of previous reactions to these patients
TE
D
TR
• Always ask people with asthma about concomitant medications
A
-
TE
A
IS
L
IA
R
U
IB
TR
IS
D
TE
R
• Always ask about asthma before prescribing NSAIDs, and advise
patients to stop using them if asthma worsens
D
A
R
• Patients with suspected or confirmed occupational asthma should
be referred for expert assessment and advice, if available
M
B
O
A
A
• In management of occupational asthma, identify and eliminate
occupational sensitizers as soon as possible, and remove
sensitized patients from any further exposure to these agents
B
• For adult patients with allergic rhinitis and sensitized to HDM,
with exacerbations despite low- to high-dose ICS, consider adding
SLIT, provided FEV1 >70% predicted
M
A
D
PY
D
O
• Ask all patients with adult-onset asthma about their work history
and other exposures
B
TE
H
• For obese adults with asthma, a weight reduction program plus
twice weekly aerobic and strength exercises is more effective for
symptom control than weight reduction alone
C
H
PY
O
C
Weight reduction
O
T
CHAPTER 6
• Remediation of dampness or mold in homes reduces asthma
symptoms and medication use in adults
• Include weight reduction in the treatment plan for obese patients
with asthma
D
COPD: chronic obstructive pulmonary disease; NSAID: non-steroidal anti-inflammatory drugs; HDM: house dust mite; ICS: inhaled
corticosteroids; SLIT: sublingual immunotherapy; SCIT: subcutaneous immunotherapy; FEV1 : forced expiratory volume in 1 second
104
A
O
R
O
N
PY
O
Healthy diet
• For sensitized patients, there is limited evidence of clinical benefit
for asthma with single-strategy indoor allergen avoidance
D
B
O
A
IG
C
• Provide advice about prevention and management of exerciseinduced bronchoconstriction
• There is little evidence to recommend one form of physical
activity over another
Avoidance of
medications
that may make
asthma worse
A
P
P
A
• Regular physical activity improves cardiopulmonary fitness, but
confers no other specific benefit on lung function or asthma
symptoms, with the exception of swimming in young people
with asthma
Avoidance of
occupational
exposures
• Allergen avoidance is not recommended as a general strategy in
asthma
C
C
• Encourage people with asthma to engage in regular physical
activity for its general health benefits
D
Physical activity
Evidence
PC
A
PC
• At every visit, strongly encourage people with asthma who
smoke to quit. Provide access to counselling and smoking cessation
programs (if available)
B
COPD: chronic obstructive pulmonary disease; NSAID: non-steroidal anti-inflammatory drugs; HDM: house dust mite; ICS: inhaled
corticosteroids; SLIT: sublingual immunotherapy; SCIT: subcutaneous immunotherapy; FEV1 : forced expiratory volume in 1 second
105
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Table 6.2. Non-pharmacological interventions for asthma. (continued)
References:
Intervention
Bronchial
thermoplasty
Advice/recommendation
Evidence
B
• Caution should be used in selecting patients for this procedure
as the number of studies is small and people with chronic sinus
disease, frequent chest infections or FEV1 <60% predicted were
excluded
D
2.
3.
4.
PC
5.
• If food chemical sensitivity is confirmed, complete avoidance is
not usually necessary, and sensitivity often decreases when
asthma control improves
D
15.
16.
17.
L-
D
TE
• For confirmed food allergy, food allergen avoidance may reduce
asthma exacerbations
14.
IA
D
R
TE
• Food avoidance should not be recommended unless an allergy
or food chemical sensitivity has been clearly demonstrated,
usually by carefully supervised oral challenges
U
IB
L
TR
IA
IS
D
13.
TE
A
M
R
O
12.
R
U
IB
TR
D
-
IS
D
CHAPTER 6
D
PY
O
10.
TE
H
IG
R
C
9.
11.
TE
R
A
D
COPD: chronic obstructive pulmonary disease; NSAID: non-steroidal anti-inflammatory drugs; HDM: house dust mite; ICS: inhaled
corticosteroids; SLIT: sublingual immunotherapy; SCIT: subcutaneous immunotherapy; FEV1 : forced expiratory volume in 1 second
106
PY
M
O
Avoidance of foods
and food chemicals
T
D
TE
PY
O
C
• In general, when asthma is well-controlled, there is no need for
patients to modify their lifestyle to avoid unfavorable outdoor
conditions (air pollutants, weather)
• It may be helpful during unfavorable environmental conditions
(very cold weather, low humidity or high air pollution) to avoid
strenuous outdoor physical activity and stay indoors in a
climate-controlled environment; and during viral infections to
avoid polluted environments
O
D
O
C
• Arrange a mental health assessment for patients with symptoms
of anxiety or depression
8.
H
B
N
IG
R
• There is insufficient evidence to support one stress reduction
strategy over another, but relaxation strategies and breathing
exercises may be helpful
O
PY
T
O
N
Avoidance of
outdoor air
pollutants/
weather
conditions
D
D
O
O
7.
• Encourage patients to identify goals and strategies to deal with
emotional stress if it makes their asthma worse
Dealing with
emotional
stress
6.
P
C
D
C
P
C
• For sensitized patients, when pollen and mold counts are highest,
closing windows and doors, remaining indoors and using
air conditioning may reduce exposure to outdoor allergens
D
Avoidance of
outdoor allergens
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TE
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58. Abramson MJ, Puy RM, Weiner JM. Injection allergen immunotherapy for asthma.
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59. Virchow JC, Backer V, Kuna P, Prieto L, Nolte H, Villesen HH, Ljorring C, et al. Efficacy
of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic
asthma: a randomized clinical trial. JAMA 2016;315(16):1715-25.
60. Centers for Disease Control. Asthma and Influenza. Retrieved from from: https://
www.cdc.gov/flu/about/disease/high_risk.htm/[Last accessed March 18, 2019].
61. Nicholson KG, Nguyen-Van-Tam JS, Ahmed AH, Wiselka MJ, Leese J, Ayres J,
Campbell JH, et al. Randomised placebo-controlled crossover trial on effect of
inactivated influenza vaccine on pulmonary function in asthma. Lancet 1998;
351(9099):326-31.
62. Cates CJ, Jefferson TO, Bara AI, Rowe BH. Vaccines for preventing influenza in people
with asthma. Cochrane Database Syst Rev 2004: CD000364.
63. Talbot TR, Hartert TV, Mitchel E, Halasa NB, Arbogast PG, Poehling KA, Schaffner W,
et al. Asthma as a risk factor for invasive pneumococcal disease. N Engl J Med
2005;352:2082-90.
64. Shea KM, Edelsberg J, Weycker D, Farkouh RA, Strutton DR, Pelton SI. Rates of
pneumococcal disease in adults with chronic medical conditions. Open Forum Infect
Dis 2014;1(1):ofu024.
65. Sheikh A, Alves B, Dhami S. Pneumococcal vaccine for asthma. Cochrane Database
Syst Rev 2002:CD002165.
66. Solante R. PSMID and PFV. 2017 Adult immunization guidelines. Retrieved from:
https://ohnap.ph/ohnap/archive/07611b28-f329-4ba8-9da6-979fe6c10d05.pdf [Last
accessed March 18, 2019].
67. Centers for Disease Control and Prevention. Recommended adult immunization
schedule by medical condition and other indications, United States, 2019. Retrieved
from: https://www.cdc.gov/vaccines/vpd/pneumo/hcp/who-when-to-vaccinate.html
[Last accessed March 18, 2019]
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
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Guided or Supported Self-Management Education is an individualized,
dynamic, continuous, progressive, sequential and regular educational
process that emphasizes on patient’s involvement to take responsibility in his
or her own care. It enhances self-efficacy in symptom monitoring, treatment
and prevention. It is achieved through physician-caregiver-patient
collaboration at all points-of-care. The family and other caregivers are
oriented on the treatment plan designed by the patients with the guidance
of the physician. It is tailored to the literacy level,6 cultural beliefs7 and
practices of the patient.1
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What is Guided Self-Management Education and its impact on asthma
outcomes?
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Patient education is an equally crucial factor as the other pillars of asthma
control which are: (1) accurate diagnosis, level of severity assessment and
asthma control monitoring; (2) control of environmental triggers and
comorbid conditions affecting asthma, and; (3) highly effective
pharmacologic therapy.1 For the past three decades, guidelines advocated
for the provision of Guided or Supported Asthma Self-Management
Education to patients and their caregivers because of its evidence-based
effectiveness in asthma outcomes. Despite global recommendations, its
impact on asthma care has not been fully realized because of its suboptimal
use in clinical practice. Only one-third (1/3) of asthmatic patients have
ownership of asthma action plans. Factors identified as barriers for its use or
implementation include: time constraints, lack of training of the asthma
education providers, lack of belief of patient’s ability to self-manage and lack
of confidence completing self-management plans.2 A whole system
approach is needed to break the barriers which would include: intensified
patient education, intensified professional training and strong organizational
commitment.3, 4, 5 This chapter will focus on (1) patient’s Guided Asthma
Self-Management Education with their families and caregivers and (2)
Asthma Education Provider training. Empowering asthma patients,
caregivers and asthma education providers would encourage its
implementation in clinical practice.
CHAPTER 7
If asthma symptoms are controlled, the patient should have fewer
exacerbations, a higher quality of life, lower costs, slower progression of
airway remodeling from inflammation, less morbidity and lower risk of death
from asthma.2
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
What are the core components of Guided Self-Management Education
program?
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Assess asthma control
a. Review patient’s level of symptom control and risk factors
b. Elicit episodes of flare-up and identified contributory factors.
Evaluate if the patient’s response or actions taken were
appropriate. Elicit if a written asthma action plan was used to
guide the actions taken.
c. Review symptom and/or peak expiratory flow diary, if the patient
keeps one
d. Assess comorbidities
3.
Assess treatment issues
a. Watch the patient use their inhaler. Re-checking and
correcting inhaler techniques using a standardized checklist
leads to improved asthma control.1 (Evidence A)
b. Assess medication adherence and identify barriers
c. Assess adherence with other interventions, e.g., smoking cessation
d. Review the asthma action plan and update it if the level of asthma
control or treatment has changed.
An asthma self-management education program integrates the four components of Guided Asthma Self-Management Education. The following core
asthma information and technical skills will be taught, reviewed, refined and
reinforced on every patient’s clinic visit.1
1.
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Elicit questions and concerns. Discuss and provide additional educational
messages. Patient may be referred to a trained asthma education
provider, if available.
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In designing asthma action plans, studies are not clear if the traffic light
configuration format is better than the standard instructions.8 Studies in
adults revealed that outcomes are comparable whether the written action
plan is based on symptoms or peak flow measurements. Benefits are greater
when asthma action plans are based on percentage personal best peak flow
than percentage predicted peak flow.1 (Evidence A) The 2-3 action points
action plan (peak flow <80% best: increase inhaled steroids; peak flow <60%
best: commence oral steroids and seek medical advice and peak flow <40%
best: seek urgent medical advice) is consistently effective in reducing
admissions and ER visits than the use of 1-action point or 4-action points
plan.1
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Regular review by a healthcare provider is a vital management skill in asthma
education. Asthmatic patients should collaborate with his/her healthcare
provider. The healthcare provider review includes the following
components:1
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2. Recognizing and handling worsening asthma
a. Signs, symptoms and peak flow values that indicate worsening
asthma
b. Medications and dosages to take in response to worsening symptoms
c. Signs, symptoms and peak flow values that indicate the need for
urgent medical attention
d. Emergency telephone numbers of the physician, emergency
department and service to rapidly transport the patient to medical
care
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Daily management, which includes:
a. Medicines to take daily (medication names and doses)
b. Actions to take to control and avoid asthma triggers
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By modifying patient’s therapy based on home monitoring of disease
severity, patients can improve control of their asthma and avoid visits to
acute care facilities. PEF monitoring has been advocated as useful in
detecting asthma exacerbations especially in those who have difficulty in
recognizing changes in their symptoms.
What are the components of a written asthma action plan?
The following are included in the action plan:
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2.
Basic facts about asthma (natural history of disease, signs and
symptoms, triggers)
What defines well-controlled asthma and patient’s current level of
control
Role of medications
Skills (e.g., inhaler technique, use of valve holding chamber or
spacer and; self monitoring [peak flow meter use or based on
symptom diaries])
When and how to handle signs and symptoms of worsening asthma;
when and where to seek care
Environmental exposure control measures
Develop an active partnership with the patient
Provide a written action plan
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2.
Whether in written instructions or paper template or electronic plans, the
action points in the asthma action plan should be agreed upon by the
patient, caregiver and primary care physician. The asthma action plan should
be regularly reviewed by the physician and updated accordingly. The family
and caregiver should be oriented to the treatment plan for home education
reinforcement.
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Who should deliver Asthma Education?
What are the effective strategies for asthma adherence management?
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Effective information delivery also hinges on the asthmatics’ ability to sort
out questions and arrive at answers themselves rather than being told. The
Socratic method has proven effective in helping learners learn. Through
questions, asthmatics are able to surface and articulate their own insights, in
the process often discovering the answers within themselves. The skill of
using questions involves four subskills: asking questions, rephrasing questions,
answering questions and deferring questions. Questions must be phrased
clearly and simply, with a single focus on what is being explored. Questions
must be rephrased if the original questions did not elicit response or
appeared muddled and unclear. A desired default should be to ask a
question in response to a question rather give an answer.
The World Health Organization (WHO) defined three types of
non-adherence: intelligent/intentional, erratic (forgetfulness) and unwitting
non-adherence. Erratic and unwitting types are both unintentional forms of
non-adherence.19 GINA 20181 listed factors contributing to poor adherence
( Table 7.1).
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High-impact learning is always targeted in any information delivery
situation.14, 15 Asthmatics are envisioned to be competent to control and
manage their asthma, and confident in their ability to do Guided Asthma
Self-Management with their health professional.
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Objective adherence monitoring (e.g., self-reports, caregiver reports,
canister weight, electronic monitoring devices) and asthma control
monitoring (e.g., Asthma Control Questionnaire and Asthma Control
Test)
2. Identification of the reasons for non-adherence
3. Delivery of an individually-tailored strategy to address each specific
cause of non-adherence
4. Use of motivational interviewing (MI)17, 18 communication skills to
enhance the delivery of each strategy.
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Andrew Weinstein16 proposed an approach composed of four sequential
adherence management principles to enhance asthma guidelines, which
could be adapted in the local clinical practice:
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What are the effective methods of asthma information delivery?
CHAPTER 7
Asthmatics learn best when they are able to connect what they know (head)
with how they feel (heart) and the skills they need to do what is needed
(hands). Learning should be experienced, not taught.
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Healthcare providers teaching patients with asthma should have the basic
skills and knowledge necessary to transmit current principles of asthma
self-management and to assess individual needs and the efficacy of the
teaching.11, 13, 14 Educational programs for asthma educators was developed in
2015, as a result of a collaboration between the Philippine College of Chest
Physicians (PCCP) through the Asthma Council and the American College of
Chest Physicians (ACCP) currently known as CHEST Philippine Delegation,
produced the Handshake Project on Asthma Education, which will
standardize the information provided and improve the quality of asthma
education in the Philippines.
116
Example: “I love my cat very much but I know she gives me asthma. Should I
give my cat away?” This can be answered with another question which will
help the person arrive at an answer on his/her own. The following question
can be asked: “What do you think is more important to you – your cat or the
discomforts you feel with the asthma that she brings?”
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Provision of asthma education is usually practiced by the primary care
physicians or subspecialists in a clinic setting during clinic visits or hospital
setting during hospitalization due to exacerbation. Current evidence
supports that trained and certified asthma educators, who are neither
subspecialists nor primary care physicians, are as effective in providing
asthma education and improving asthma outcomes. Respiratory therapists,9
nurse practitioners,1, 10, 11 (Evidence A) clinical pharmacists1, 9, 11 (Evidence A) or
community health workers12 deployed to primary care clinics, community
health centers, school and office clinics and pharmacies can bridge the gap
in patient care.9-12
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Table 7.1. Poor medication adherence in asthma.
Factors contributing to poor asthma
medication adherence
How to identify poor adherence
in clinical practive
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• Burdensome regimen (e.g., multiple times per day)
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• Cost
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electronically by clinicians and/or pharmacists
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• Check the date and dose counter on the
inhaler
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• Check the date of the last controller
prescription
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• Cultural or religious issues
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• Stigmatization
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Intentional poor adherence
• Dissatisfaction with healthcare providers
“Do you find it easier to remember your
inhaler in the morning or evening?”
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Misunderstanding about instructions
Forgetfulness
Absence of a daily routine
Cost
Technological advances17, 21, 24, 25, 26, 27 pave the way for innovations in improving
and promoting healthcare system delivery. The guided asthma
self-management education has expanded from simple asthma education
delivery to a whole system approach program implementation.25, 27 Mobile
technology interventions have moderate-to-large effect size on medication
adherence and clinical outcomes to standard treatment and appears
as efficacious as paper-based monitoring.24 Currently, the following
technologies are available: (1) electronic monitoring devices;17 (2) internet or
web-based27 interactive media, including social media, and; (3) mobile
applications26 or short message service (SMS). Current evidence involving
internet or phone-based monitoring system noted main benefits to patients
with severe asthma.1 (Evidence B) A more comprehensive, guideline-based,
user-centered designed program should be developed for these applications
to be embraced by patients and healthcare providers in clinical practice.25
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Unintentional poor adherence
•
•
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•
“Many patients don’t use their inhaler as
prescribed in the last 4 weeks, how many
days a week have you been taking
it – not at all, 1,2,3, or more days a week?”
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• Multiple different inhalers
What is the impact of information and communication technology in the
Guided Self-Management Education?
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• Acknowledge the likelihood of incomplete
adherence and encourage an open
non-judgemental discussion.
Examples are:
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• Difficulties using inhaler devices (e.g., arthritis)
Only about 30% of patients have asthma action plan ownership and the
barriers include: (1) patients do not see its value and (2) lack of time, training
and confidence of healthcare provider in creating appropriate asthma action
plans.8 The above strategies maybe used in addressing asthma action plan
and regular review non-adherent patients. Healthcare providers must
undergo intensified training to improve adherence to guidelines in clinical
practice.13
PC
Ask an emphatic question
PC
Medication/regimen factors
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
•
•
•
•
CHAPTER 7
CHAPTER 7
Examples of successful adherence intervention
Shared decision making for medication/dose choice
Inhaler reminders for missed doses
Prescribing ICS once daily versus twice daily
Home visits for a comprehensive asthma program by an asthma nurse
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
References:
1.
2.
3.
4.
19.
20.
21.
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PY
26.
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25.
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Van Boven J, Trappenburg JCA, can der Molen T, Chavennes N. Towards tailored and
targeted adherence assessment to optimize asthma management. NPJ Prim Care
Respir Med 2015;25:1-6
Marcum Z, Hanlon J, Murray M. Improving medication adherence and health outcomes
in older adults: an evidence-based review of randomized controlled trials. Drugs Aging
2017;34(3):191-201.
Wilson EA, Park DC, Curtis LM, Cameron KA, Mlayman ML, Makoul G, von Eigen K, et al.
Media and memory: the efficacy of video and print materials for promoting patient
education about asthma. Patient Educ Couns 2010;80(3):393-8.
Bousquet J, Chavannes N, Guldemond N, Haahtela T, Hellings P, Sheikh A. Realizing the
potential of mHealth to improve asthma and allergy care: how to shape the future. Eur
Respir J 2017;49:1-5
McLean G, Murray E, Band R, Moffatt K, Hanlon P, Bruton A, Thomas M, et al. Interactive
digital interventions to promote self-management in adults with asthma: a systematic
review and meta-analysis. BMC Pulm Med 2016;16(83):1-14.
Miller L, Shuz B, Walters J, Walters EH. Mobile technology interventions for asthma
self-management: systematic review and meta-analysis. JMIR Mhealth Uhealth
2017;5(5):e57.
Simpson AJ, Honkoop PJ, Kennington E, Snoeck-Stroband JB, Smith I, East J, Coleman
C, et al. Perspectives of patients and healthcare professionals on mHealth for asthma
self-management. Eur Respir J 2017;49(5). pii;1601966.
Tinschert P, Jakob R, Barata F, Kramer JN, Kowatsch T. The potential of mobile apps for
improving asthma self-management: a review of publicly available and well-adopted
asthma apps. JMIR Mhealth Uhealth. 2017;5(8):e113
Ahmed S, Ernst P, Bartlett SJ, Valois MF, Zaihra T, Pare G, Grad R et al. The effectiveness
of web-based self-management system, My Asthma Portal (MAP): a pilot randomized
controlled trial. J Med Internet Res 2016;18(12):e313.
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Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention,
2018. Available from www.ginasthma.org [Accessed: 30 April 2018]
Roberts NJ, Younis I, Kidd L, Partridge MR. Barriers to the implementation of selfmanagement support in long term lung conditions. London J Prim Care 2012;5(1):35-47.
Pinnock H. Supported self-management for asthma. Breathe 2015;11(2):98-109.
Pinnock H, Epiphaniou E, Pearce G, Parke H, Greenhaigh T, Sheikh, Griffiths CJ, et al.
Implementing supported self-management for asthma: a systematic review and
suggested hierarchy of evidence of implementation studies. BMC Medicine 2015;13:127.
Pinnock H, Parke HL, Panagioti M, Daines L, Pearce G, Epiphaniou E, Bower P, et al.
Systematic meta-review of supported self-management for asthma: a healthcare
perspective. BMC Medicine 2017;15:64.
Sobel RM, Paasche-Orlow MK, Waite KR, Rittner SS, Wilson EA, Wolf MS. Asthma 1-2-3:
a low literacy multimedia tool to educate African American adults about asthma. J
Community Health 2009;34(4):321-7.
Bailey EJ, Cates CJ, Kruske SG, Morris PS, Brown N, Chang AB. Culture-specific programs
for children and adults from minority groups who have asthma. The Cochrane Library
2009; 2:1-35.
Kouri A, Boulet LP, Kaplan A, Gupta S. An evidence-based, point of care tool to guide
completion of asthma action plans in practice. Eur Respir J 2017;49:1-10.
Mishra R, Kashif M, Venkatram S, George T, Luo K, Diaz-Fuentes G. Role of adult asthma
education in improving asthma control and reducing emergency room utilization and
hospital admissions in an inner city hospital. Can Respir J 2017;8:1-6.
Williams D, Portnoy J, Meyerson K. Strategies for improving asthma outcomes:
a case-based review of successes and pitfalls. J Manag Care Pharm 2010;16(1c):S3-S17.
Klijn SL, Hiligsmann M, Evers SMAA, Roman-Rodriguez M, van der Molen T, van Boven
JFM. Effectiveness and success factors of educational inhaler technique interventions in
asthma and COPD patients: a systematic review. NPJ Prim Care Respir Med
2017;27(24):1-10.
Krieger J, Song L, Philby M. Community health worker home visits for adults with
uncontrolled asthma: the HomeBASE trial randomized clinical trial. JAMA Intern Med
2015;175(1):109-17
Cabana MD, Le TT. Challenges in asthma patient education. J Allergy Clin Immunol
2005;115:1225-7.
McDonald VM, Gibson PG. Asthma self-management education. Chronic Respir Dis
2006;3:29-37.
Alatawi A. The effectiveness of asthma education approaches for children: group versus
individual education. Biomed J Sci & Tech Res 2017; 1(3):794-9.
Weinstein AG. The potential of asthma adherence management to enhance asthma
guidelines. Ann Allergy Asthma Immunol 2011;106(4):283-91.
Lavoie KL, Moullec G, Lemiere C, Blais L, Labrecque M, Beauchesne MF, Pepin V, et al.
Efficacy of brief motivational interviewing to improve adherence to inhaled corticosteroids among adult asthmatics: results from a randomized controlled pilot feasibility trial.
Patient Prefer Adherence 2014;8:1555-69.
Roman-Rodriguez M, Ibarrola-Ruiz L, Mora F, Plaza V, Sastre J, Torrego A, Vega JM, et al.
Motivational interviewing for adherence: post-training attitudes and perceptions of
physicians who treat asthma patients. Patient Prefer Adherence 2017:11:811-20.
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
There are certain types of patients with asthma who may be more difficult to
manage, and/or may require closer attention because of coexisting
comorbid conditions, or during special circumstances such as pregnancy,
menstruation, surgery and others.
PREGNANCY AND ASTHMA
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How common is asthma in pregnancy?
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Two factors seem to correlate significantly with the course of asthma during
pregnancy: the severity of a patient’s asthma before she became pregnant,
and the use of asthma medications.7 It should be noted that even patients
with “mild” pre-pregnancy asthma may deteriorate significantly during
pregnancy.8
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The “rule of thirds” has always been cited when the course of asthma in
pregnancy is discussed, that is, one-third of patients will remain stable,
one-third will have symptomatic improvement, and in one-third of pregnant
patients, their asthma will deteriorate.6 Unfortunately, it may not always be
easy to predict which patients will go into which group.
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What is the course of asthma during pregnancy?
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Asthma is one of the most common chronic conditions that is found in
women in the reproductive age group. It is considered as the most common
respiratory condition of pregnancy complicating 4%–8% of pregnancies with
increasing healthcare utilization and cost.1, 2, 3, 4 Different regions of the world
have varying data on the incidence of asthma in pregnancy. Values range
from 2 to 13%, which mimics the incidence of asthma in the community.3, 4, 5
In the Philippines, there is a lack of local data on the incidence of asthma in
pregnant patients.
Asthma exacerbations usually occur towards the second half of pregnancy.
In a recent prospective cohort study, 50% of all exacerbations and losses of
control were noted to occur before 20 weeks of gestation.8 The risk appears
to be increased in smokers (or ex-smokers), in those who are obese, and in
those who are infected with respiratory viruses, and whose asthma is
uncontrolled before their pregnancy.9
CHAPTER
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
associated with a progressively enlarging abdomen may be difficult to
differentiate from dyspnea caused by obstructive airway disease.
Asthma is strongly associated with preeclampsia, placental abruption and
placenta previa, and obstetric hemorrhage.3, 10 Pregnant women with asthma
are at a significantly increased risk of a range of adverse perinatal
outcomes, including low birthweight, small for gestational age (SGA),
preterm labor and delivery.3, 10, 11 Evidence pointed to a direct correlation
between the severity of the asthma, the higher occurrence of
exacerbations, and the increase in the incidences of these adverse events on
the baby. Evidence also revealed that optimal treatment of the asthma
reduced these risks, including exacerbations, significantly.3, 10, 12 A recent
prospective cohort study highlighted recurrent uncontrolled asthma as a
greater contributor to poor perinatal outcomes than exacerbations.8
Spirometry is still the gold standard for the diagnosis. Peak flow variability
may also be helpful. Other tests have been proposed, particularly the use of
fraction of exhaled nitric oxide (FENO), not so much in the diagnosis of
asthma, but in the management.18
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The pregnant asthmatic should be prescribed an ICS, the mainstay of
controller therapy. Majority of the studies have declared that ICS are safe in
pregnancy, and their regular use does not result in complications in the
mother or the fetus. It has been shown that regular use of ICS as maintenance
in achieving asthma control has led to a lower incidence of complications
and adverse outcomes.14, 21, 22, 23 If asthma is well controlled throughout
pregnancy, there is little or no increased risk of adverse maternal or fetal
complications.19, 20 Inhaled corticosteroids reduce the risk of exacerbations of
asthma during pregnancy, (Evidence A) and cessation of ICS during
pregnancy is a significant risk factor for exacerbations.19, 20, 21 (Evidence A)
Some studies have suggested using the FENO to monitor for the need to
adjust the ICS dosage to reduce the risk for exacerbations.18
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Budesonide is the ICS with the most published human gestational safety data
and is considered the preferred ICS for use in pregnant patients.22 There are
no published studies for other ICS preparations and there are no data to
show that they are not safe.22 Therefore, if a patient is well
controlled on an ICS other than budesonide prior to getting pregnant, it may
be more beneficial to just continue the current ICS rather than shift to
budesonide especially if changing formulations may jeopardize asthma
control.22
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Inhaled SABAs are the rescue medications of choice for the pregnant
asthmatic. Inhaled albuterol (salbutamol) has been the most extensively
studied SABA, and almost all the researches point to its very good
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The usual parameters for the diagnosis of asthma in the general asthma
population are, for the most part, applicable to the pregnant asthmatic
patient. A problem may arise in a pregnant patient who was never
previously diagnosed with asthma, and who, during her pregnancy, starts
manifesting with symptoms of shortness of breath. The breathlessness
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How is asthma diagnosed in pregnancy?
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Asthma in pregnancy has also been associated with multiple comorbid
maternal conditions, such as a higher risk of developing gestational
diabetes but that aggressive and optimal treatment of asthma reduced this
risk significantly.12 There were also reports of an increased risk of pulmonary
embolism16 and a greater frequency and severity of respiratory viral
infections.17
The ultimate goal of asthma therapy in pregnant patients is to protect both
the mother and the fetus by achieving good asthma control. This can be
accomplished by prescribing the same medications as one would to a
non-pregnant patient. Although there is a general concern about any
medication use in pregnancy, the advantages of actively treating asthma in
pregnancy markedly outweigh any potential risks of usual controller and
reliever medications.19, 20 (Evidence A)
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There have been some published studies that showed that congenital
malformations are more common in asthma patients who took OCS in the
first trimester of pregnancy. Other studies, however, have found no direct
correlation.13, 14, 15 Exacerbations, use of bronchodilators, or use of ICS were
not associated with congenital malformation.3
What medications can be prescribed for pregnant asthmatics?
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What are the possible adverse maternal and fetal outcomes in
pregnant asthmatics?
There were studies that implied an increased need for caesarian section
delivery, however, a recent meta-analysis revealed that the increase in
caesarian sections was secondary to elective caesarian sections and not
emergencies.11, 12 The risk of cesarean delivery was higher for patients with
severe asthma as compared to those with mild asthma.12
126
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
safety profile.21, 22 In a meta-analysis of cohort studies from 1975 to 2012, there
appeared to be no increased risk of congenital malformations, caesarean
section or postpartum hemorrhage in pregnant women with asthma who
used inhaled bronchodilators during pregnancy.15
Although the treatment of asthma exacerbations is exactly the same in the
pregnant and non-pregnant patients, a pregnant asthmatic in acute
exacerbation will require more intensive monitoring and management.
Pregnant women with acute asthma should be considered to be high-risk
patients, and their management requires a close multidisciplinary
collaboration and coordination of all the healthcare professionals managing
the patient such as primary care physicians, pulmonologists, obstetricians
and pediatricians.
Patients not fully controlled on ICS alone may be given LABA in
combination.23 The safety profile of salmeterol and formoterol are expected
to be the same as albuterol or salbutamol. LABAs should always be given in
combination with ICS and never as monotherapy.20, 22, 24
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What is the approach to the management of the pregnant asthmatic during
labor and delivery?
TR
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Acute exacerbations are uncommon during labor and delivery, perhaps due
to endogenous steroid production. The usual controller medications should
be taken, with reliever if needed. Bronchoconstriction may be induced by
hyperventilation during labor, and should be managed with SABA. Pregnant
asthmatics on oral steroids at a dose exceeding prednisolone 7.5 mg per day
for more than two weeks prior to delivery should receive parenteral
hydrocortisone 100 mg 6–8 hourly during labor.24, 28, 29
TE
TE
Although some data suggest that the risk of postpartum asthma attacks is
increased in women having caesarean sections, this may be related more to
the asthma severity rather than to the caesarean section, or to factors such
as postoperative pain with diaphragmatic splinting, hypoventilation and
atelectasis. In the absence of an acute severe asthma attack, caesarean
section should be reserved for the usual obstetric indications. If anesthesia is
required, regional blockade is preferable to general anesthesia.24, 29
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Asthma exacerbations are one of the most common medical problems in
pregnant women, and can have the most significant impact on fetal
morbidity and mortality. From 33 to 45% of pregnant women will have
exacerbations requiring immediate medical attention. Prevention of
exacerbations is important since there is an increased incidence of
congenital anomalies, i.e., cleft lip and palate in infants whose mothers had
an exacerbation, particularly in the first trimester.
Acute severe asthma in pregnancy is an emergency and should be treated
vigorously in hospital. Patients in the third trimester and who are very
symptomatic may have to be admitted to the hospital for close monitoring.
The avoidance of maternal and fetal hypoxia is of primary importance and
this requires aggressive treatment of acute exacerbations during pregnancy
with SABA, oxygen and early administration of systemic corticosteroids.20
It is recommended that high flow oxygen be delivered immediately to
maintain saturation above 95%.29 Continuous fetal monitoring should be
performed when asthma is uncontrolled or severe, or when fetal assessment
on admission is not reassuring.29 The cause of the exacerbation also has to
be addressed.
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O
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What is the approach to the management of asthma exacerbations in
pregnancy?
When should pregnant asthmatics be hospitalized?
D
PY
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Some patients with severe asthma may require regular OCS use to achieve
adequate asthma control. Oral corticosteroids are also typically given as part
of the discharge regimen after an acute asthma episode. Its use in pregnancy
has been associated with an increased risk of preterm birth and low birth
weight infants.27 Since these risks would be less than the potential risks of a
severe asthma exacerbation, which include maternal or fetal mortality, OCS
is recommended when indicated for the management of severe asthma
during pregnancy.24
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As for other medications, only montelukast and zafirlukast have been found
in most studies to be safe although data on their use in pregnancy are more
limited.25 In contrast, zileuton was associated with teratogenicity in animal
studies and should be avoided.22, 24 More studies are needed for omalizumab
although animal studies have been reassuring and an ongoing registry
showed that rates of prematurity and SGA were not unlike those seen in
other studies of pregnant women with severe asthma.26
PC
PC
Theophylline is also an alternative, but not preferred, add-on treatment for
moderate to severe persistent asthma but its use is limited by its many
adverse side-effects and potential drug interactions, resulting in possible
toxicity.22
All asthma patients will benefit tremendously from patient education.
Pregnancy is a good time to review the patient’s basic understanding of
asthma and its management, including trigger avoidance, asthma control
and adequate use of devices, medication and personal action plans.28
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
MENSTRUATION AND ASTHMA
The peri-menstrual phase is characterized by a decline in progesterone and
estradiol levels which triggers mast cell degranulation at the basal layer of
the endometrium which induces a local inflammatory reaction with
endometrial tissue breakdown and menstruation. There is also a systemic
inflammation that occurs with mast cell and eosinophil degranulation and
consequent increase in inflammatory markers in tissues where hyperactive
mast cells are already present, such as the lung/bronchial tissues of an
asthmatic woman.36-38
What is the association of menstruation with asthma?
TE
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Despite the studies carried out so far and the reviews published on the
subject, the research results are inconclusive and the causal factors of this
entity remain unknown.34, 40
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How is pre-menstrual asthma (PMA) diagnosed?
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The cyclical deterioration in PMA is defined as a worsening of asthma
symptoms and/or deterioration of lung function tests, such as a decrease of
≥20–40% in the PEF. Most authors diagnose PMA on the basis of either
asthma questionnaires, PEF measurements or questionnaires combined with
PEF measurements.40
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The etiology of PMA remains unknown. The available data link the endocrine
system with the influence of female sex hormones on inflammatory
mediators and asthma symptoms.35 The significant fluctuation in the levels of
many hormones, such luteinizing hormone, follicle stimulating hormone,
estradiol, progesterone and testosterone, during the menstrual cycle is
thought to contribute significantly to the pathogenesis of PMA.
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Another study showed that an increase in bronchial hyperresponsiveness
documented as a decrease in PC20FEV1 in the follicular phase of the
menstrual cycle in about 30% of women.39 This was associated with lower
cAMP levels in sputum samples, which may contribute to
bronchoconstriction.39 A link between PMA and lower testosterone levels
were also noted.39, 40
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The reports on the incidence of PMA vary, ranging from 17% to 44% likely due
to the fact that some studies rely on purely subjective data from the patients
while others require objective parameters such as lung function studies.30-34
The precise prevalence is difficult to determine due to a lack of explicit
diagnostic criteria and appropriate epidemiological surveys.35 Nevertheless,
there seems to be a significant percentage of asthmatic females who
experience deterioration in their symptoms during the peri-menstrual phase.
These patients with PMA represent a certain asthma phenotype that should
be recognized, as there is an increased incidence of asthma-related
ER visits, hospitalizations and intubation in this group.36
Women with pre-menstrual asthma are older, have more severe asthma, a
higher body mass index, a longer duration of asthma and a greater likelihood
of aspirin sensitive asthma.42 They more often have dysmenorrhea, premenstrual syndrome, shorter menstrual cycles and longer menstrual bleeding.42
The patients with PMA had significantly higher depressive symptoms and
water retention than other asthmatic patients.43
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How common is pre-menstrual asthma (PMA)?
What causes pre-menstrual asthma (PMA)?
P
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There is no clear definition of PMA,30 although it is considered to be a
cyclical deterioration of asthma during the pre-menstrual (luteal) phase,
sometimes including the first few days of the menstrual cycle.31 This is
thought to be due to fluctuations in the various hormones associated with
ovulation and the menstrual cycle.
130
Studies have also demonstrated the changes in the female immune response
throughout the respiratory cycle such as increased wheal-flare response to
skin prick testing and hyperactivity to histamine of the nasal mucosa during
the peak ovulatory estrogen levels of days 12-16 of the menstrual cycle.36
PC
C
PC
Some females with asthma experience an increase in their symptoms, or
worse, an increased incidence of exacerbations, during the peri-menstrual
period, a condition that is known as peri-menstrual asthma. Asthma
deterioration has been described in the periovulatory phase, in the middle of
the preovulatory or luteal phase, and more frequently in the pre-menstrual
phase, an entity defined as pre-menstrual asthma (PMA).
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
How is pre-menstrual asthma (PMA) treated?
As in any patient with asthma, the mainstay of treatment is still regular
ICS-LABA, with SABA as rescue medication. However, the hormonal imbalances that have been shown to precipitate the worsening of the symptoms
have been evaluated.
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(3) For patients receiving OCS during the 6 months prior to surgery
and for selected patients on long-term high-dose ICS, give 100 mg
hydrocortisone every 8 hours intravenously during the surgical
period, and reduce the dose rapidly within 24 hours after surgery.
TE
TE
For patients requiring emergency surgery, the risks of proceeding without
first achieving good asthma control should be weighed against the need for
immediate surgery. As stated above, patients taking long-term high-dose
ICS, or those who have received OCS for more than 2 weeks during the
previous 6 months, should receive hydrocortisone perioperatively as they
are at risk of adrenal crisis in the context of surgery.52 For all patients,
maintaining regular controller therapy throughout the perioperative period is
important.
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At present, there is no hard evidence of increased perioperative risk for the
general asthma population.49 There are asthmatic patients, however, who are
at risk for complications during and after surgery and these
(2) Provide medications before surgery to improve lung function if
lung function is not well controlled. A short course of OCS may
be necessary.
TR
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Are there increased perioperative risks of surgery among asthmatic
patients?
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SURGERY AND ASTHMA
CHAPTER 8
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For elective surgery, patients with asthma should be evaluated at least one
week prior surgery to allow time for modification of treatment, if necessary,
especially for those patients who are scheduled for procedures with a high
risk of postoperative pulmonary complications. Postoperative pulmonary
complications are most common following thoracic surgery, upper
abdominal surgery, open aortic aneurysm repair, neurosurgery and surgery
on the head and neck. Meticulous attention should be paid preoperatively to
achieving good asthma control, especially for patients with more severe
asthma, uncontrolled symptoms, significant exacerbation history (more than
one exacerbation per year) or fixed airflow limitation.51 The following actions
are recommended to reduce the risk of complications during surgery:50
(1) Before surgery, review the level of asthma control, medication use
(especially OCS within the past 6 months) and pulmonary function.
Since PMA is significantly associated with fluctuations in hormones during
the menstrual cycle, stabilizing estradiol and progesterone/progestin levels
and reducing the hormone-free intervals with OC may be considered.36
Although more studies are needed, reducing the hormone free intervals may
result in less menstrual symptoms through the reduction of genital and
systemic inflammation that is seen with hormone withdrawal.36
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Can pre-menstrual asthma (PMA) be prevented?
What is the approach to the management of asthmatic patients
undergoing surgery?
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The other associated comorbid conditions also have to be addressed.
complications include bronchoconstriction, hypoxemia, possible hypercapnia,
impaired cough reflex, possible atelectasis and respiratory infection.50 While
an increased risk for surgery exists for patients with COPD,49 this may also
apply to asthma patients with reduced FEV1 or an incomplete reversibility of
airway obstruction (IRAO) despite optimal treatment and the absence of a
significant smoking history. Therefore, the incidence of severe perioperative
bronchospasm in people with asthma, although admittedly low, may be
significant, even life threatening.51
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A role for both exogenous estrogen and progesterone using oral
contraceptives (OC) in the management of PMA was demonstrated in
studies.36, 44, 45, 46 In a prospective study on post-pubertal women with asthma,
the 106 women using OC had reduced asthma symptoms, improved lung
function and improved asthma control compared with those not using OC.45
Findings in another study showed that asthmatic patients receiving the OC
had attenuated cyclical change in airway reactivity as well as reduced diurnal
peak expiratory flow rate variability, which was associated with suppression
of the normal luteal phase rise in sex-hormones.46 This stabilization of the
airways may be due to regulation of the immune system, in particular, regulation
of Th2-driven response by induced regulatory T cells (iTregs) reduces the
severity of the inflammatory response in asthma.47 Both estrogen and
progesterone may also stimulate the function of the smooth airway muscles
and inhibit the activities of Th2 responses.48
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Vigilant monitoring of the asthmatic patient is of primary importance in
preventing perioperative pulmonary complications. Proper preoperative
evaluation of disease level and medical compliance with prescribed
medication regimens, along with perioperative strategies for prevention of
bronchospasm decrease postoperative pulmonary complications in
asthmatics.53
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Epidemiological evidence suggests a strong relationship between AR and
asthma. Allergic rhinitis can occur in more than 75% of patients with asthma,
whereas asthma can affect up to 40% of patients with AR.60 Both diseases,
which are IgE mediated, can be triggered by similar allergens, including
mold, animal dander and HDMs.61, 62 Temporally, AR often occurs before the
onset of asthma.
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The ‘united allergic airway’ is a theory that connects sinonasal disease,
specifically allergic rhinitis (AR), chronic rhinosinusitis (CRS) and nasal
polyps, with asthma in which seemingly disparate diseases, instead of being
thought of separately, are instead viewed as arising from a common atopic
entity.57, 58 Literature supports the relationship but there is no direct evidence
of causality.59
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There is also a common pathophysiological relationship between AR and
asthma with four mechanisms postulated to account for this relationship.68
First, the nose functions to warm, filter, humidify inhaled and via the
numerous submucous glands located in the nasal passages, sterilize air
through the release of antibacterial enzymes. With AR, nasal function may be
partially or completely lost as the congestion forces the patient to become a
mouth breather. This may predispose to bronchospasm caused by cooling
and drying in the airways, as what occurs with obligate mouth breathing
during vigorous activity. Second, during an exacerbation of AR, the
inflammatory products from the upper airways may be aspirated directly
into the lower airways. Third, nasal inflammation may result in local cytokine
release into the bloodstream, which eventually causes bronchoconstriction
in the lower airways. Fourth, a nasal-bronchial reflex may exist, where
histamine and bradykinin stimulate the afferent nasal sensory nerve which
sends a neural signal that travels to the central nervous system and activates
the efferent vagus nerve, resulting in bronchial smooth muscle
hyperreactivity.68
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Is there a relationship between asthma and allergic rhinitis (AR), sinusitis,
nasal polyps?
A frequent association between bronchial hyperresponsiveness (BHR) and
rhinitis has also been noted and patients suffering from AR frequently, in up
to 80% of cases, manifest with BHR.69 A prospective study of a large group
of patients with moderate-to-severe persistent AR alone, tree and HDM
sensitization, rhinitis duration longer than 5 years and FEV1 of 86% or less of
predicted value demonstrated a significant association with severe BHR:
6.4% of patients had severe BHR, 21.6% had mild BHR, 56.2% had borderline
BHR and only 15.8% of patients had a negative methacholine test.70
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SINUS DISEASE (RHINITIS, SINUSITIS, NASAL POLYPS)
AND ASTHMA
134
Allergic rhinitis is a risk factor for asthma, and its presence is related to
asthma severity.57 Patients with nasal symptoms appear to experience worse
asthma control.63 This was supported by a recent cross-sectional studies
looking at the relationship between nasal symptom scores and asthma
symptoms.64 Many of the studies that have looked at the relationship
between asthma control and rhinitis have been cross-sectional or
retrospective. However, a prospective cohort study of patients with severe
asthma showed that those with rhinitis had increased ER visits, and that the
severity of rhinitis correlated with the severity of asthma as assessed by
standardized questionnaires.65 Overall, studies suggest both children and
adults with comorbid rhinitis and asthma have more frequent physician’s
visits, ER visits and hospital admissions for asthma, and higher asthmarelated drug expenses.66, 67
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Several guidelines on the management of asthma are available. One can
easily refer to such publications as the Expert Panel Report 3 (EPR-3) on the
diagnosis and management of asthma and the American College of
Physicians report on risk assessment for and strategies to reduce
perioperative pulmonary complications for patients undergoing
non-cardiothoracic surgery.54, 55 Also, such scoring systems as ARISCAT can
serve as a guide to assess more effectively and systematically an asthmatic
patient undergoing surgery.56
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
The etiology for the connection between asthma and AR is likely
multifactorial. Although nasal blockage and aspiration of nasal contents
have long been accepted as contributing factors, there is a growing body of
evidence that suggests that a systemic response plays an important role in
the AR–asthma relationship.57
WORK-RELATED ASTHMA (WRA)
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Occupational asthma refers to asthma caused by occupational exposures
which can be sensitizers or irritants.82 Occupational asthma caused by workplace sensitizers are immunological and characterized by WRA appearing
after a latency period. It encompasses OA caused by most high and certain
low-molecular weight agents for which an allergic IgE-mediated mechanism
has been proven.82 Occupational asthma caused by irritants or irritantinduced asthma occur with or without a latency period. This category
includes reactive airways dysfunction syndrome which may occur after
single or multiple exposures to non-specific irritants at high concentrations.83
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Sensitizer-induced OA should be suspected in every adult with new-onset
asthma.84 A latency period ranging from weeks to years after the first
exposure to the sensitizer is observed before the initial onset of work-related
symptoms. Sensitizer-induced symptoms begin variably— at the beginning
of the work shift, toward its end, or even in the evening after working hours.
Improvement or even remission typically occurs during weekends and
holidays. Rhinitis often accompanies or precedes lower respiratory
symptoms, especially when high-molecular-weight agents are the inciting
factors.
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A thorough clinical and occupational history must be obtained but a
compatible history alone is insufficient for diagnosis and has a low positive
predictive value.84, 85
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Occupational asthma has been defined as a disease characterized by
variable airflow limitation and/or hyperresponsiveness and/or inflammation
due to causes and conditions attributable to a particular occupational
environment and not to stimuli encountered outside the workplace.82
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Results of a meta-analysis demonstrated that intranasal corticosteroid
medications used to treat AR significantly improve some asthma-specific
outcome measures in patients suffering from both AR and asthma but only
in patients not also receiving ICS.76 There is weak evidence that treatment of
CRS may improve asthma outcomes, demonstrating only a small decrease in
asthma symptoms after using mometasone but no difference in
asthma-related quality of life, lung function or episodes of poorly controlled
asthma.77 A randomized, prospective trial on patients with CRS with or
without nasal polyps and asthma found that medical as well as surgical treatments for CRS showed improvements in asthma status with a good
correlation to the improvement achieved in upper airway symptoms.78, 79
Patients with nasal polyps showed better results on exhaled nitric oxide
levels and FEV1 in the medical treatment group.78, 79 Although the promise of
targeted biologic therapies seem encouraging, more research needs to be
done to further characterize the complex relationship between upper and
lower airway disease.59
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What is the impact of treatment of sinonasal disease on asthma outcomes?
What is occupational asthma (OA) and how is it diagnosed?
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It has been reported that 20%–60% of patients with CRS with nasal polyps
have asthma.72, 73 Chronic rhinosinusitis has been associated with both more
severe and more difficult to control asthma.73 Asthmatic patients have a
higher rhinosinusitis severity score than non-asthmatic patients, and more
presence of nasal polyps regardless of atopic status, indicative of a strong
relationship between CRS with nasal severity and chronic airway
inflammatory diseases.59, 74, 75
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With respect to CRS, it has been reported that around 90% of patients with
mild to moderate asthma and almost 100% of those with severe asthma have
radiological abnormalities of the sinuses.71 There is evidence supporting an
association between rhinosinusitis and asthma, although it appears less clear
whether CRS is a direct trigger for asthma or the two conditions are simply
manifestations of a common underlying process.69 Possible mechanisms for this
relationship include naso-pharyngo–bronchial reflexes, postnasal drip,
abnormal breathing and the local production of inflammatory
mediators that trigger pulmonary inflammation.70
Work-related asthma (WRA) is a term that includes occupational asthma
(OA), i.e., asthma that is caused by work, and work-exacerbated asthma
(WEA) or work-aggravated asthma (WAA), i.e., asthma that is worsened by
work but not initially caused by work.80, 81 It has been estimated that at least
15% of adult asthma is work-related. Some studies have reported that more
than 25% of working adults with asthma have exacerbations of asthma
at work.80, 81
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
Diagnostic tests can be divided into: tests that confirm asthma, tests that
identify that the asthma is work-related or that the workplace as the cause of
the respiratory symptoms, and tests that identify the agent causing the OA.82
Primary prevention aims to prevent sensitization to workplace agents, thus
preventing disease. One way to achieve this aim would be to replace known
sensitizing agents with non-sensitizers, however, this may not be readily
achieved. Reduction of exposure to respiratory sensitizers may be achieved
by instituting occupational hygiene measures such as containment,
improved ventilation, and (as a last option) the use of personal protective
equipment, as well as worker education to enhance adherence to
recommended measures.85
The best method of confirming that the asthma is work-related is measuring
lung function in relation to work exposure. This can only be done when the
patient is still exposed to the suspected cause of their symptoms, so it needs
to be the first confirmatory test.
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Appropriate management after diagnosis, in addition to prevention of
further exposure when possible, involves tertiary prevention with
pharmacologic management that follows clinical-practice guidelines.85
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PY
TE
There is less information on the prevention of irritant-induced asthma since
the most straightforward cases of irritant-induced asthma are due to
accidental exposure. Prevention should include occupational-hygiene
measures that ensure the safety of workers in environments where there is
the potential for accidental exposure to irritants. General measures include
containment, good ventilation, worker education regarding safety practices,
and, when other measures are not sufficient, use of fit-tested respiratory
protective devices.85
O
L-
IA
R
U
IB
TR
IS
D
WORK-EXACERBATED ASTHMA (WEA)
TE
A
M
R
O
-
What is work-exacerbated asthma (WEA) and how is it recognized?
TE
TE
Work-exacerbated asthma (WEA), also termed work-aggravated asthma,
describes a subset of work-related asthma that is worsened but not caused
by work (unlike OA that is caused by work). It is defined as pre-existing or
concurrent (adult new-onset) asthma that is worsened by workplace
conditions or exposures.88 This can manifest as an increase in frequency
and/or severity of asthma symptoms and/or increase in asthma medication
required to control symptoms on work days.
For any individual, OA and WEA are not mutually exclusive, meaning that
someone with OA can subsequently experience WEA, and vice versa.
138
139
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CHAPTER 8
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A
R
In contrast to non-WRA, optimal management of OA consists of primary,
secondary and tertiary prevention. Primary, secondary and tertiary
preventive measures may reduce the incidence and severity of
sensitizer-induced asthma.
O
M
O
How is work-related asthma (WRA) managed?
C
D
TE
PY
O
C
H
IG
T
O
A specific inhalation challenge (SIC) (i.e., the subject inhales the agent of
concern) is the best method of confirming the specific cause of OA when
workplace
measurements
are
not
possible
or
specific
IgE
measurements are not available, as is the case for many low molecular
weight agents. But it is not readily available and false-positive or
false-negative responses can occur.82, 84, 86, 87 A supervised return to work with
either a workplace challenge (for those with severe symptoms) or
unsupervised PEF measurement on days at and away from work is helpful
when occupational asthma is likely and SIC is negative.82
D
R
N
PY
O
C
O
D
Both skin-prick and specific IgE measurements are highly sensitive for
detecting type 1 sensitization to most high molecular weight agents, but are
not specific for diagnosing OA.84 This is because sensitization is more
common than disease. However, the presence of specific IgE in a worker
with confirmed OA from workplace measurements is sufficient to identify
the specific cause.
Secondary prevention includes early identification of workers with
occupational exposure to asthma-causing agents by means of medical
surveillance (periodic respiratory questionnaires with or without spirometry
and immunologic tests) and further investigations to confirm diagnosis and
after diagnosis, removal of the affected worker from further exposure.85
PC
P
C
PC
Guidelines recommend serial measurement of PEF on days at and away from
work which is considered the best validated method with good sensitivity
and specificity in the diagnosis of WRA.84 Minimum criteria are ≥3 weeks of
usual work exposure with measurements at least four times a day, or 8 work
days and 3 rest days with 2-hourly measurements, with treatment being kept
constant.
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
The prevalence of WEA from the 12 published studies conducted in the
general population or general healthcare settings ranged from 13% to 58%,
with a median of 21.5%. Three of the studies had more objective criteria for
WEA had prevalence estimates of 13%, 14% and 22%, with a median of 14%.88, 90
OBESITY AND ASTHMA
C
C
T
D
TE
PY
O
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IG
R
PY
O
O
IA
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TR
IS
D
TE
A
M
R
L-
-
TE
TE
Obese asthmatics as compared to non-obese patients generally report more
symptoms and limitation of activities due to their symptoms, even if they are
already on the same therapeutic regimens as the non-obese asthmatics.100
This may partly be due to the respiratory effects of the obesity itself, or,
these patients may truly represent a different asthma phenotype that is less
responsive to medications such as inhaled steroids and LABA.101 The
mechanism behind this is not clear, but there may be a certain phenotype of
obese asthmatics who have a different type of inflammation that is less
responsive to glucocorticoids. This was mostly found in asthma patients who
were morbidly obese.
U
IB
L
IA
R
U
IB
TR
IS
Most studies have shown that females who are obese have a higher risk for
developing asthma, which suggests that hormones may play a role.97 Other
studies observed that the risk is the same for both males and females.98 There
are fewer studies in obese children citing that boys have higher risks than
girls.99
O
D
TE
A
R
The goal of treatment is to minimize asthma exacerbations by reducing work
exposures (e.g., by limiting sources of exposure, improving ventilation) and
optimizing standard medical management with non-work environmental
control measures and pharmacologic treatment. Avoidance or reduction of
exposure can often lead to an improvement in asthma symptoms.
N
M
O
How is work-exacerbated asthma (WEA) managed?
O
D
TE
PY
O
C
H
IG
T
O
Identification of exacerbation triggers is important both for confirming WEA
and for reducing or eliminating harmful conditions to prevent future
problems in the index case and co-workers. However, identification of a
specific causative agent for WEA is often not possible, and mixed exposures
are common. Non-work factors that can exacerbate asthma, such as viral
infections and environmental allergies, should also be evaluated.90, 91
Numerous studies in the last two decades have revealed that obesity is truly
an independent risk factor for the development of asthma.92-96 There is a
2.3-fold increased odds of developing asthma in the future in both allergic
and non-allergic obese individuals with a dose-response effect: 1.7-fold
increased risk for BMI 25–29; 2.3-fold increased risk for BMI >30.92 Some
authors claim that the risk for asthma is increased by up to 50% in patients
who are overweight/obese.92
D
R
N
PY
O
C
O
D
The diagnosis of WEA depends on demonstrating a relationship between
work exposures and asthma exacerbations, most commonly documented
by changes in symptoms (e.g., frequency, severity) or medication use
temporally related to work.89, 90 In the common context of preceding asthma
prior to the work exposures and/or an absence of a specific
sensitizer at work, the findings of work-related worsening of asthma
documented by serial PEF recordings, symptoms and medications are
supportive of WEA.88
Is there a relationship between obesity and asthma?
P
P
WEA should be considered in any patient with asthma that is worsening
and/or who has work-related symptoms. The initial diagnostic step is to
clarify whether the patient has asthma.
How are obese asthmatics managed?
Weight loss as part of the management is important and has been
documented to lessen asthma symptoms, improve quality of life, decrease
BHR, reduce markers of systemic inflammation, reduce the need for
medications and improve lung function parameters.101-104
140
141
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CHAPTER 8
The patient may be able to stay at the same job with reduced exposures,
depending on the severity of asthma and extent of exacerbating factors at
work, but a job change to a workplace with fewer triggers may be necessary
if this approach fails to adequately prevent work-related exacerbation of
symptoms. Preventive strategies resemble those of disease management
which are reduction of work exposures and optimization of medical
management.89
PC
C
PC
Patients with WEA who experience persistent work-related symptoms
resemble OA cases with respect to severity of asthma and medication
requirements, as well as socioeconomic factors like unemployment and loss
of labor-derived income. However, compared with asthma unrelated to
work, WEA is associated with more symptomatic days, a greater utilization
of healthcare resources, higher direct costs and a lower quality of life.90, 91
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
The mainstay of pharmacologic treatment is still the inhaled corticosteroid
combined with a long-acting beta2-agonist (ICS-LABA), with a SABA as a
rescue medication. A higher dosage of ICS may be necessary as some obese
patients may show a degree of resistance to corticosteroid treatment.102
GASTROESOPHAGEAL REFLUX DISEASE (GERD)RELATED ASTHMA
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L-
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U
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How is gastroesophageal reflux disease (GERD)-related asthma managed?
Proton pump inhibitors are the main therapeutic regimen for GERD and this
is commonly recommended for suspected GERD-related asthma. Nonpharmacologic treatment include: weight loss patients who are overweight
or have had recent weight gain; head of bed elevation and avoidance of
meals 2–3 hours before bedtime for patients with nocturnal GERD;
avoidance of food that can trigger reflux such as alcohol and caffeine.
Some patients may respond well to PPI therapy. However, studies to date
have shown only limited benefits for the treatment of symptomatic GERD on
asthma outcomes and results from well-designed studies are inconsistent.
143
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Asthma can also result in physiological changes that might predispose to
GERD which may be related to the hyperinflation within an increased
pressure gradient between thorax and abdominal cavity and flattening of the
diaphragm which could impair the anti-reflux barrier and result in GERD.107
O
IA
R
TR
IS
TE
A
M
D
A study by Sharifi and Ansarin utilizing impulse oscillometry (IOS) to
measure airway resistance among patients who had asthma and GERD
demonstrated that the distal airways were more affected than the proximal
airways, and these findings suggested that the main mechanism was the
reflex bronchospasm secondary to acid exposure of the distal esophagus
rather than direct effect of micro-aspiration of the proximal airways.111
TE
H
D
R
Although further research is needed in order to elucidate the mechanisms
that link GERD with asthma, postulated mechanisms on acid reflux-induced
asthma include: vagal mediated reflex;105, 107 increased bronchial reactivity;107
bronchoconstriction due to aspiration of gastric acid.105-107
PY
O
TE
Because GERD and asthma are often encountered together, complex
interactions occur during which GERD may increase asthmatic symptoms or
asthma may trigger or worsen GERD.107 Gastroesophageal reflux diseaserelated asthma has been defined as asthmatic symptoms being induced or
exacerbated by gastroesophageal reflux.111
O
For patients with asthma and symptoms suggestive of reflux, an empirical
trial of anti-reflux medication, such as a proton pump inhibitor (PPI) or
motility agent, may be considered.20 A good response of asthmatic
symptoms to PPI treatment may permit a more confident diagnosis of
GERD-related asthma.112 Failure to respond to a course of PPI should prompt
a careful re-assessment of the patient, with consideration for specific
investigations such as 24-hour pH monitoring or endoscopy as well as other
work-up for other causative factors for the persistent asthmatic
symptoms.112 There is no value in routine screening of patients with
uncontrolled asthma for GERD.20 (Evidence A) Nevertheless, it is important
that GERD should be assessed in asthmatic patients who also have typical
symptoms of GERD, as well as in patients with non-atopic, refractory or
difficult asthma.112
C
H
PY
O
C
IG
R
T
O
N
PY
O
C
O
D
T
IG
R
PY
O
O
N
The diagnosis of GERD as the cause of GERD-related asthma may pose a
challenge.112 In patients with confirmed asthma, GERD should be
considered as a possible cause of a dry cough.20 However, the most common
classic symptoms of GERD such as heartburn or regurgitation may not
always be manifested in patients with asthma.20, 105-113 In addition, while there
are many tests that can be done to work up patients who are suspected as
having GERD, there are no diagnostic gold standards.105 Current available
diagnostic tests performed for GERD such as esophagogastroduodenoscopy
and esophageal pH monitoring or ambulatory esophageal reflux
monitoring have uncertain sensitivity and specificity for the diagnosis of
GERD-related asthma.112
P
C
O
D
What is gastroesophageal reflux disease (GERD)-related asthma and
what mechanisms are involved?
CHAPTER 8
How is gastroesophageal reflux disease (GERD)-related asthma
diagnosed?
C
P
C
There is evidence that GERD is more common in patients with asthma
compared to the general population.105-107, 108-109, 110 Various studies have shown
that this increased incidence of GERD in asthmatic range from as low as 25%
to as high as 90%.105-106, 108, 111-112
142
Medications taken for asthma, such as beta2-agonists, theophylline and
high doses of OCS which may reduce lower esophageal sphincter pressure,
may also increase acid reflux.105, 107
PC
PC
Is gastroesophageal reflux disease (GERD) more common in patients with
asthma?
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
The association with asthma of food additives such as benzoates, tartrazine
and monosodium glutamate is probably minimal but sulfites which is a
common preservative in processed foods, dried fruits, medicines, beer and
wine may trigger acute asthma (uncommon).131
In general, the benefits of PPIs in asthma appear to be limited to patients
with both symptomatic reflux and night-time respiratory symptoms.20, 114, 115
But patients with poorly controlled asthma should not be treated with
anti-reflux therapy unless they also have symptomatic reflux.20 (Evidence A)
Anti-reflux surgery is an option for asthmatics with well-defined reflux
disease, if indicated and available, preferably done by a skilled, experienced
surgeon.112
How is food allergy, anaphylaxis in asthma managed?
P
C
D
D
M
IS
D
TE
A
ASPIRIN-EXACERBATED RESPIRATORY DISEASE
(AERD)
R
IA
R
What is aspirin-exacerbated respiratory disease (AERD)?
TR
IA
R
TR
IS
D
TE
A
R
O
M
O
PY
O
TE
H
IG
R
C
D
PY
TE
H
T
O
IG
O
C
Although it is known that food allergic reactions can trigger lower respiratory
symptoms, food allergy generally does not present with chronic or isolated
asthmatic symptoms.118, 119 But asthmatic reactions can be part of the allergic
response.120 During food allergic reactions, non-specific BHR may increase.121
N
R
T
It has been reported that food allergy and asthma are characterized by an
increasing prevalence and that food allergy and asthma often coexist.116 Food
allergy in early childhood often precedes asthma at a later time point in
child- or adulthood as described in the atopic march hypothesis.116, 117
PY
O
PY
O
N
In addition to education in appropriate food avoidance strategies, patients
who have a confirmed food allergy that puts them at risk for anaphylaxis
must be trained and have an epinephrine auto-injector available at all
times.20, 132-134 It is especially important to ensure that their asthma is well
controlled, that they have a written action plan, and that they understand the
difference between asthma and anaphylaxis, and are assessed and seen on a
regular basis.20 A multi-faceted approach to managing this subset of patients
leads to optimal care.
O
O
O
What is the relationship of food allergy and anaphylaxis among asthmatics?
In a meta-analysis of prevalence studies, AERD occurs in approximately 7%
of adult asthmatic patients and higher prevalence among severe
asthmatics.136 It is a distinct subtype of asthma and polypoid sinus disease
characterized by greater morbidity and healthcare costs for those
affected.137 Aspirin-exacerbated respiratory disease generally occurs
due to abnormalities in mediators and expression of arachidonic acid
biosynthesis.138
-
L-
Although any substance has the potential to cause anaphylaxis, the most
common causes of IgE-mediated anaphylaxis are foods, particularly peanuts,
tree nuts, shellfish and fish, cow’s milk, eggs and wheat; medications
(most commonly penicillin), and natural rubber latex.125, 126 Exercise, aspirin,
non-steroidal anti-inflammatory drugs (NSAIDs), opiates and radiocontrast
agents can also cause anaphylaxis from non-IgE-mediated mechanisms, and,
in other cases, the cause of anaphylactic reactions is unknown (idiopathic
anaphylaxis).125, 127-130
TE
TE
U
IB
Aspirin-exacerbated respiratory disease (AERD), also called non-steroidal
anti-inflammatory drug exacerbated respiratory disease (NERD) and
previously referred to as aspirin-induced asthma, is the combination of
asthma, chronic rhinosinusitis (CRS) with nasal polyposis (the “Samter’s
triad”), and acute upper and lower respiratory tract reactions to ingestion of
aspirin (acetylsalicylic acid or ASA) and other cyclooxygenase-1 (COX-1)inhibiting non-steroidal anti-inflammatory drugs (NSAIDs).135
L
Although foods are rarely important triggers of asthma exacerbation,
occurring in <2% of people with asthma, coexisting asthma is a strong risk
factor for more severe food-induced allergic reactions (anaphylaxis), as well
as for a fatal outcome from food-induced anaphylaxis.20, 120, 121, 122 In addition,
findings in some studies on both children and adults with asthma and
concurrent food allergy showed an association with worse asthma
morbidity with increased hospitalizations, ER visits and use of oral steroid
than those with asthma alone.123, 124
U
IB
145
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CHAPTER 8
C
C
D
FOOD ALLERGY, ANAPHYLAXIS AND ASTHMA
144
For patients with suspected food allergy, a referral to a specialist for
accurate allergy assessment diagnosis is usually necessary.20 Treatment of
food allergy involves strict avoidance of the trigger food. Currently, there is
no cure for food allergy and medications only manage the symptoms of
disease.120
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P
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Most studies report a small increase in lung function and better
asthma-related quality of life with less exacerbations, but there are studies
that show no improvement in both symptoms as well as peak flow, and no
change in rescue SABA days as well as frequency of exacerbations.105-106, 109, 112
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
How is aspirin-exacerbated respiratory diease (AERD) diagnosed?
Inhaled corticosteroids are the mainstay of asthma therapy in AERD, but
OCS are sometimes required; LTRA may also be useful.143, 148 An additional
option is desensitization, which may be conducted under specialist care in a
clinic or hospital.138, 149 Desensitization to aspirin followed by daily aspirin
treatment can significantly improve overall symptoms and quality of life,
decrease formation of nasal polyps and sinus infections, reduce the need for
OCS and sinus surgery, and improve nasal and asthma scores.143
STRESS AND ASTHMA
P
Is there a relationship between stress and asthma?
C
H
IG
Psychosocial status of patients: severe psychological stressors
where found to significantly increase the risk of asthma if there was
also chronic stress
•
Environmental stressors: including noise and violence
•
Family or caregiver stressors: presence of even minor psychiatric
disorders in mothers was significantly associated with increased
incidence of asthma in their children
D
PY
O
TE
•
C
D
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IA
R
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IS
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A
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IA
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Several factors have been cited as contributing to the worsening of asthma
due to stress.150, 152 A dysfunctional hypothalamic pituary adrenal (HPA) axis
resulting in less cortisol production in asthmatic patients and/or cortisol
insensitivity, along with promotion of the number of eosinophils in blood and
sputum and activation of mast cells by corticotropin releasing hormone
(CRH), is a proposed mechanism.
Another proposed mechanism is the occurrence of changes in the
methylation and expression of genes that regulate behavioral, autonomic,
neuroendocrine and immunologic responses to stress. There are
“susceptibility genes” that predispose chronically stressed patients to
worsening of asthma symptoms.153
147
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CHAPTER 88
The management of AERD involves guideline-based treatment of the
patient's asthma and CRS, in addition to suppression of the consequences of
abnormal leukotriene metabolism.138 Patients with AERD should avoid aspirin
or NSAID-containing products and other medications that inhibit
cyclooxygenase-1 (COX-1).138, 145 However, this does not prevent progression
of the disease. If an NSAID is indicated for other medical conditions, a COX-2
inhibitor (e.g., celocoxib or etoricoxib), or paracetamol (acetaminophen),
may be considered with appropriate healthcare provider supervision and
observation for at least 2 hours after administration.146, 147
R
T
O
N
Quality of life: studies showed an inverse relationship between the
socioeconomic status and pulmonary function in children. Immigrant
status and poverty also showed some correlation with increased
frequency of ER visits among wheezing infants
R
TR
IS
D
TE
A
R
How is aspirin-exacerbated respiratory disease (AERD) managed?
PY
O
D
•
M
O
It should be noted that oral aspirin challenge tests must only be conducted
in a specialized center with cardiopulmonary resuscitation capabilities
because of the high risk of severe reactions.142, 143, 144
O
There is some evidence that different stressors can worsen asthma. But
many factors have to be taken into consideration: the timing, chronicity and
even the quality of the stress.150 Acute stress may not be a significant
precipitant of asthma attacks,151 however, chronic stress seems to play a
more important role.150 Included as significant stressors are the following:
D
TE
PY
O
C
H
IG
R
T
O
N
PY
O
O
D
Aspirin challenge (oral, bronchial or nasal) is the gold standard for diagnosis
as there are no reliable in vitro tests.135 History of an asthma attack following
ingestion of aspirin or other NSAIDs is suggestive and sometimes
diagnostic.135
CHAPTER 8
C
C
The diagnosis of AERD can often be made clinically when all three of the
conditions that characterize AERD are present: asthma, visible nasal polyposis (or even just a history of nasal polypectomy), and a history of a typical
reaction to NSAID. Nocturnal nasal obstruction with sleep deprivation
fatigue occurs routinely in these patients. Asthma may precede the upper
airway disease or develop later. Computerized tomography (CT) or plain
radiographs of the sinuses reveal complete opacification in nearly all AERD
patients and normal imaging of the sinuses essentially rules out the diagnosis
of AERD.135
146
PC
P
C
PC
The clinical presentation begins with nasal congestion and anosmia,
progresses to chronic rhinosinusitis with nasal polyps that tend to re-grow
rapidly after surgery and asthma and hypersensitivity to aspirin inevitably
develop.138, 139 Following ingestion of aspirin or NSAID, an acute asthma
attack develops within minutes to 1–2 hours. It is usually accompanied by
rhinorrhea, nasal obstruction, conjunctival irritation, and scarlet flush of the
head and neck, and may sometimes progress to severe bronchospasm,
shock, loss of consciousness and respiratory arrest.140, 141 Aspirin-exacerbated
respiratory disease is more likely to be associated with low lung function and
severe asthma.137
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
It has also been theorized that chronic stress may result in a new
“homeostasis” with a short term parasympathetic rebound or shifts in the
balance between the sympathetic and parasympathetic systems.151
Uncontrolled asthma in this context is defined as at least one of the following:
•
The most important mainstays in the treatment of any asthma patient are
maintenance ICS and SABA used as rescue medication. Stress, however, may
contribute to persistence of symptoms by reducing response to these
medications. It has been theorized that chronic stress may result in
down regulation of glucocorticoid receptor expression and function.153
•
C
P
Patients who do not meet the criteria for uncontrolled asthma, but whose
asthma worsens on tapering of corticosteroids, will also meet the definition
of severe asthma.20, 157
PY
O
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O
D
O
M
L-
IA
R
What is the approach to the diagnosis of difficult-to-treat asthma?
An initial step in the evaluation is to determine whether the diagnosis of
asthma has been confirmed. A careful history and physical examination
should be done to identify whether the pattern of signs and symptoms are
typical of asthma or more likely due to an alternative diagnosis.
Confirmation of the asthma diagnosis can be made through objective
measures such as spirometry to assess baseline lung function and evidence
of variable expiratory airflow limitation. There may be persistent airflow
limitation in those with long-standing asthma and a specialist advice should
be obtained if the history is suggestive of asthma but the diagnosis cannot
be confirmed by spirometry.20
TE
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IS
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A
R
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L
IA
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TR
IS
The next step is to assess whether modifiable risk factors that contribute to
poor asthma outcomes are present. A review of treatment adherence and
149
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Difficult-to-treat or simply termed ‘difficult’ asthma is asthma that
remains uncontrolled despite treatment with medium- or high-dose ICS plus
a second controller or those requiring maintenance OCS.20, 157
Severe asthma, on the other hand, is considered a subset of
difficult-to-treat asthma and includes individuals with uncontrolled asthma
despite adherence with maximal optimized therapy and treatment of
contributory factors, or that worsens when high-dose treatment is
decreased.20, 157
O
A
M
D
How is difficult-to-treat asthma differentiated from severe asthma?
D
PY
D
R
O
Despite the efficacy of the standard treatments for asthma, many patients
remain uncontrolled and a small minority of about 5% to 10% can be
classified as having severe asthma. In the approach to the management of
difficult-to-treat and severe asthma, referral of patients to a specialist with
expertise in asthma management may be helpful for investigation and
treatment. When potential reasons for a lack of treatment response have
been considered and addressed, a compromise level of asthma control may
need to be accepted and discussed with the patient to avoid futile
over-treatment (with its attendant cost and potential side-effects).20
(Evidence D) The objective is then to minimize exacerbations and the need
for emergency medical interventions while achieving as high a level of
symptom control as is feasible. This should be achieved with as little
disruption of activities and as few daily symptoms and side-effects as
possible.20
TE
C
H
IG
T
O
R
Individuals with difficult-to-treat asthma often have ongoing modifiable
factors such as poor inhaler technique, poor adherence, ongoing allergen
exposure or comorbidities that interfere with achieving good asthma
control.20, 157 As such, difficult asthma patients are those in whom
appropriate diagnosis and/or treatment of contributory factors and
comorbidities result in improvement of their current condition.20, 157
N
TE
PY
O
C
H
IG
R
T
O
N
PY
O
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O
D
DIFFICULT-TO-TREAT ASTHMA
CHAPTER 8
•
Poor symptom control: ACQ >1.5, ACT <20 or not well controlled
by GINA guidelines
Frequent exacerbations: two or more bursts of systemic
corticosteroids (>3 days each) in the previous year
Serious exacerbations: at least one hospitalization, ICU stay
or mechanical ventilation in the past year
Airflow limitation: FEV1 <80% predicted (in the face of reduced
FEV1 /FVC) following a withhold of both short- and long-acting
bronchodilators.20, 157-158
PC
P
C
PC
How is asthma worsened by stress managed?
Aside from the pharmacologic treatment, other interventions may be
attempted to address the stress which may be contributing to the
persistence/worsening of symptoms. Several of these interventions have
been studied: written emotional disclosures,154 muscle and mental
relaxation158 and relaxation breathing techniques.156 However, all these
interventions should be done in conjunction with the regular medications
for asthma, and not as stand-alone treatments.
148
•
PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
inhaler technique is required because incorrect inhaler use and poor
adherence are the most common reasons for failure to achieve good asthma
control. An investigation for persistent environmental exposure to
tobacco smoke, allergens or toxic substances should also be done. Ongoing
triggers, if present at home or at the workplace, should be addressed and
removed whenever possible. The presence of comorbidities that can
contribute to poor asthma control should be investigated according to
clinical suspicion. Medication side-effects, local or systemic, should be
evaluated as these may contribute to poor quality of life and increase the
likelihood of poor adherence.20
Comorbidities, when present, such as obesity, GERD, CRS and OSA, should
be managed appropriately. Non-pharmacologic management strategies
deemed relevant, such as smoking cessation, physical exercise, healthy diet,
weight loss, counseling, breathing exercises, mucus clearance techniques
and allergen avoidance, may be implemented.20
P
C
H
IG
R
T
O
N
PY
Other add-on controller medications such as theophylline and LTRAs,
although suggested for severe asthma, appear in the small number of
available studies to be of limited benefit. LTRAs may be helpful for patients
found to be aspirin sensitive.20, 157-158 (Evidence A)
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How is treatment response of difficult-to-treat asthma assessed and
addressed?
IS
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The response to treatment includes a review of the following: symptom
control (symptom frequency, reliever use, night waking due to asthma,
activity limitation), exacerbation frequency, medication side-effects, inhaler
technique, adherence, lung function, patient satisfaction and concerns.20
U
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If asthma is well controlled, consider stepping down treatment. If the
symptoms and exacerbations remain well controlled despite stepping down
treatment, the patient does not have severe asthma and optimal
management should be continued.20
If asthma symptoms become uncontrolled or an exacerbation occurs when
high-dose treatment is stepped down, the diagnosis of severe asthma is
confirmed. The patient’s previous dose should be restored to regain good
asthma control and a referral to a specialist and/or to a severe asthma clinic
should be done.20
151
CHAPTER
CHAPTER 88
Addressing problems of incorrect inhaler technique and poor treatment
adherence should be prioritized in patients with difficult-to-treat asthma.
These factors are also found in severe asthma but in most difficult-to-treat
asthma patients, adherence and health outcomes may be improved with a
comprehensive adherence-promoting intervention that includes patient
education and behavioral modification. It is important to ensure that the
inhaler is suitable for the patient and that the inhaler technique is checked,
corrected and re-checked at each clinic visit. Patient education is important
and clinicians should empower patients to make informed choices about
their medicines and individualized interventions to manage non-adherence
should be developed.
PY
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A trial of high-dose ICS may be instituted since some patients may respond
to higher doses of ICS than are routinely recommended for general use.
(Evidence B) However, this carries the risk of systemic side-effects so
stepping down slowly at 3–6 month intervals after some months dose
optimization is recommended.158 (Evidence D)
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There is difficulty in confirming the diagnosis of asthma
The patient has frequent urgent healthcare utilization
The patient needs frequent or maintenance OCS
Occupational asthma is suspected
Presence of food allergy or anaphylaxis
Clinical features that suggest coexisting or complication bronchiectasis
Symptoms suggestive of an infective or cardiac cause
Presence of multiple comorbidities
What is the approach to the management of difficult-to-treat asthma?
CHAPTER 8
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Indications for early referral to a specialist or severe asthma clinic are:20
150
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A referral may be done at any stage of the evaluation but it is
recommended that patients presenting with “difficult asthma” have their
asthma diagnosis confirmed and be evaluated and managed by an asthma
specialist for more than 3 months. Referral to a specialized center where
patients can undergo a systematic evaluation resulted in 30–50% of patients
previously called severe asthma being initially classed as difficult-to-control.157
•
•
•
•
•
•
•
•
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P
When should referral to a specialist or severe asthma clinic be considered?
The pharmacologic treatment of difficult-to-treat asthma both in adults and
children still relies heavily on the maximal optimal use of corticosteroids
and bronchodilators, and other controllers recommended for
moderate-to-severe asthma. A switch to ICS-formoterol maintenance and
reliever therapy or non-biologic add-on therapy to ICS such as LABA
(if not already using ICS-LABA combination) or anti-muscarinic agents
(i.e., tiotropium)159, 160 or other controllers may be options.20
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PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019
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