Presented by:
Michelle Harkins, MD
University of New Mexico

This session will cover
• Review asthma statistics
• Define asthma
• Outline key pathophysiologic features
• Review signs and symptoms of asthma
• Reference to NAEPP – EPR-3: asthma severity classification system-including impairment and risk domains
• Diagnosing asthma

Prevalence vs Incidence
• Prevalence - the proportion or percentage of a population that has disease at a specific point or period of time
• Incidence – the number of new cases of disease that develop in a population of individuals at risk during a specific point or period of time

• 1980-1996 prevalence of asthma in US increased
• Since 1999, mortality and hospitalization due to asthma have decreased

120
100
80
Asthma – Current Prevalence by Age, 2011
105,5
94,9
86,7
79,9 79,4
68,5
60
40
20
0
Under 5 5-17 <18 18-44
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
45-64 65+

120
100
80
60
40
20
Asthma – Current Prevalence by Sex and Age, 2011
Male Female
71,9
97,3
101,7
87,8
0
Total Under 18
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
61,8
100,1
18 and Over

350
Asthma – Current Prevalence by Race, 2011
Whites Blacks
314,2
287,9
300
250
200
147,3
150
100
80,4
118
50
0
Total Under 18
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
238
18 and Over

New Mexico BRFSS Results for 2010: Current
Prevalence: Percent of New Mexico Children who
Currently Have Asthma by Various Demographic
Characteristics
Race/Ethnicity:
White, Non-Hispanic 8.1%
Hispanic 7.4%
Native American 13.1%
SOURCE: Centers for Disease Control and Prevention (CDC).
Behavioral Risk Factor Surveillance System Survey Data. Atlanta,
Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2009

Asthma – Attack Prevalence by Age and Race, 2011
White Black
100
90
80
70
60
50
40
30
20
10
0
Total <5 5-17 18-44
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
45-64 65+

Asthma – First-Listed Hospital Discharges by Race, 2010
Total White Black All Other
28,5 30
25
20
15
10
14,3
9
5
0
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
11,6

Asthma age-adjusted hospitalization rates per 10,000 standard population by county, New Mexico, 2007-2011 average
Legend
Rate per 10,000 population
State Rate: 8.8
2.5 - 5.9
5.9 - 7.2
7.2- 10.0
10.0 - 12.2
12.2- 21.6

Asthma hospitalization rates per 10,000 standard population among youth (0-14 years) by county, New Mexico, 2007-2011 average
Rate per 10,000 population
State Rate: 16.9
0.0- 6.9
6.9 - 11.4
11.4 - 15.1
15.1- 18.1
18.1 - 57.1

Asthma – Crude Death Rate by Age Group, 2009
12
10
8
6
4
2
0
1-4 5-14 15-24 25-34 35-44 45-54 55-64 65-74 75-84 85+
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.

Asthma – Age-Adjusted Death Rates by Sex and Race, 2009
Male Female
2
1,5
1
0,5
3
2,5
0
Total White
Trends in Asthma Morbidity and Mortality. American Lung Association,
Epidemiology and Statistics Unit, Research and Program Services Division.
September, 2012.
Black Hispanic

Asthma Age-Adjusted Death Rates Based on the
1940 and 2000 Standard populations, 1979-2005
1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
1940 0.9
1.0
1.0
1.0
1.2
1.1
1.2
1.2
1.3
1.4
1.4
1.4
1.5
1.4
1.4
1.5
1.5
1.5
1.4
1.4
1.2
1.1
1.0
1.0
1.0
0.9
0.9
2000 1.3
1.4
1.5
1.5
1.7
1.6
1.8
1.8
1.9
2.0
2.1
2.1
2.2
2.0
2.1
2.2
2.2
2.2
2.1
2.0
1.7
1.6
1.5
1.5
1.4
1.3
1.3

Asthma Impact – Economic Burden
• Childhood asthma accounts for 14.4 million days missed from school annually
– The number-one chronic condition causing children to be absent from school and the third highest ranked cause of pediatric hospitalizations in the
United States
– On average, a child with asthma will miss one full week of school each year due to the disease

Asthma Impact – Economic Burden
• Adult asthma accounts for
14.2 million missed workdays annually
• 4th leading cause of missed work days

National Burden of Asthma
$19.7 billion annually
• $14.7 billion in direct costs
(prescription medications, hospital care, and physician services)
• $5 billion in indirect costs
(lost productivity due to missed work or school and premature mortality)

Develop a collaborative working definition of asthma

1962
American Thoracic Society, 1962.
• Episodic disease characterized by:
– Reversible airway constriction
– Increased airway responsiveness
Evolution of the Definition of Asthma
2007
NAEPP, EPR3, 2007.
• Chronic disease characterized by:
– Chronic airway inflammation
– At least partially reversible airway obstruction
– Increased airway responsiveness

3M Resource Cards
Doctors Designers
11-96

3M Resource Cards
Doctors Designers
11/96

3M Resource Cards
Doctors Designers
11-96

Epithelial Damage in Asthma

Asthma: Pathophysiology
• Inflammatory cell infiltrate consists of mainly of eosinophils and lymphocytes
• “Sudden death” asthma associated with an infiltrate of neutrophils
• Denudation of airway epithelium
• Mucus gland hyperplasia and hypersecretion
• Smooth muscle cell hyperplasia
• Submucosal edema and vascular dilatation
• Fibrin deposition/airway remodeling

• Mast Cells
• Macrophages
• Eosinophils
• T-Lymphocytes
• Epithelial Cells
• Platelets
• Neutrophils
• Myofibroblasts
• Basophils
Mediator
Soup
Histamine
Lipid Mediators*
Peptides †
Cytokines ‡
Growth Factors
*For example, prostaglandins and leukotrienes.
†
For example, bradykinin and tachykinin.
‡
For example, tumor necrosis factor (TNF).
Adapted with permission from Barnes PJ. In: Barnes PJ et al, eds. Asthma: Basic Mechanisms
and Clinical Management. 3rd ed. Academic Press; 1998:487-506.
Bronchoconstriction
Microvascular Leakage
Mucus Hypersecretion
Airway
Hyperresponsiveness

FACTORS LIMITING AIRFLOW IN ACUTE AND PERSISTENT ASTHMA
NAEPP, EPR-3, pg. 15.

Mast cell
Histamine
Eosinophil
Inflammation in Asthma
Allergen/Trigger
Macrophage
Cytokines
T-cell
B-cell
IgE
Airway Inflammation
IgE = immunoglobulin E.
National Asthma Education and Prevention Program Guidelines, 1997.
Busse WW et al. N Engl J Med. 2001;344:350-362.
Bousquet J et al. Am J Resp Crit Care Med. 2000;161:1720-1745.

Aftermath of Inflammation
• Reversibility
– Occurs in most asthma episodes
– Airway returns to normal caliber
– Flow of air through airways returns to normal “speed”
• Remodeling
– Airway lining builds up persistent fibrotic changes
– Airway caliber remains abnormal
– Air flow is decreased
– Permanent changes appear to begin in childhood, but become recognizable in adults

Normal Architecture Disrupted Architecture
Bronchial Mucosa From a
Subject Without Asthma
Hematoxylin and eosin stain.
Photographs courtesy of Nizar N. Jarjour, MD, University of Wisconsin.
Bronchial Mucosa From a
Subject With Mild Asthma

Consequences of Persistent Asthma:
Subepithelial Collagen Deposition
Lumen
Epithelium
Subepithelial Collagen
Deposition
Reprinted with permission from Holloway L et al. In: Busse WW, Holgate ST, eds. Asthma and
Rhinitis. Blackwell Scientific Publications; 1995:109-118.

1
120
100
80
60
40
20
0
10 20 30
Duration of Asthma (years)
40
FEV
1
= forced expiratory volume in 1 second.
Adapted with permission from Brown PJ et al. Thorax. 1984;39:131-136.
n = 89 r = -0.47
P<.001
50

Asthma is. . .
1. Chronic inflammatory disorder of the airways
– Mast cells, eosinophils and lymphocytes infiltrate into airway lining
– Airway hyperresponsiveness develops
2.
Excessive reaction to “minor” irritants results in a host of deleterious airway changes
– Bronchial wall edema
– Smooth muscle contraction
– Excess mucus production
3. Patchy, mostly reversible regions of airway narrowing cause asthma symptoms

Acute Reaction to Triggers
1. Irritated airways become more inflamed after exposure to stimuli
2. Muscle layers around airway constrict
3. Airway lining swells
4. Excess mucus builds up in lumen
5. Result: symptoms of cough, wheeze, shortness of breath, chest tightness

Risk Factors for Developing Asthma
• Genetic predisposition
• Atopy
• Airway hyperresponsiveness
• Gender
• Race/Ethnicity

What Parameters Affect Disease ?
• Intrinsic factors
– Genetics
– Duration of asthma
– Severity of childhood asthma
– Gender
– Response to therapy
• Extrinsic factors
– Viral infections
– Allergen exposure
– Airway irritants
– Exercise
– Compliance
– Season
– Time of day
– Occupational—10-
15% of adult asthma
– Western Lifestyle-obesity

• Indoor allergens
• Outdoor allergens
• Occupational sensitizers
• Tobacco smoke
• Air Pollution
• Respiratory Infections
• Parasitic infections
• Socioeconomic factors
• Family size
• Diet and drugs
• Obesity
• Hygiene hypothesis

Asthma & Airway Inflammation
Genetic
Risk Factors
(for development of asthma)
Environmental
Bronchial
Hyperresponsiveness
Airflow Obstruction
Risk Factors
(for exacerbations)
Symptoms

• Upper Respiratory Infections (URI’s)
– Viral Respiratory infections are the #1 trigger behind asthma hospitalizations
– Influenza vaccines are recommended for people with asthma
• Allergens
• Irritants
• Sudden or extreme changes of weather
• Exercise
• Intense emotions

• Bronchospasm caused by activity
– Some activity more likely than others to trigger it
• Cold environment: skiing, ice hockey
• Heavy exertion: Soccer, long distance running
• Exercising when you have a viral cold

• Symptoms include
– Coughing
– Wheezing
– Chest tightness
• Symptoms may begin during activity and peak in severity 10-20 minutes after stopping
• Can spontaneously resolve 20-30 minutes after its onset

• Prevalence 7-20% of the general population
• 80% of patients with asthma have some degree of EIB
• Exercise is not a risk factor for asthma, rather a trigger
• ?Exercise may help prevent onset of asthma in children
– Decrease in physical activity may play a role in increased in asthma prevalence
• JACI 2005 Lucas SR, Platts-Mills TA

• Use bronchodilator 10-15 minutes before onset of activity
• Do warm-up/cool down exercises
• Check ozone/allergy warnings
• Never encourage anyone to “tough it out”

• Increasing fitness: decreases minute ventilation needs with exercise
• Less severe if inspired air is warmer, more humid
(Evidence
Class C)
– Scarf or mask if cold weather
– Warm-up period before exercise
• Good asthma control: EIB more frequent in patients with poorly controlled disease
(Class A)
– Check for asthma control
– Treating appropriately will reduce frequency and severity of EIB

Impairment and Risk Domains
• Impairment -frequency and intensity of symptoms and functional limitations the patient is experiencing or has experienced
• Riskthe likelihood of either asthma exacerbations, progressive decline in lung function or risk of adverse effects from medication
NIH. NAEPP Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, October 2007.

Risk Factors for Death from Asthma
• History of severe exacerbations
• Prior intubation for asthma
• Prior admission to Intensive Care Unit
• 2 or more hospital admissions in the past year
• 3 or more emergency room visits in the past year
• Hospital or emergency room visit past month
• Use of >2 canisters per month of inhaled shortacting beta2 –agonist

Risk Factors for Death from Asthma
• Chronic use of systemic corticosteroids
• Poor perception of airflow obstruction or its severity
• Co-morbid conditions (other diseases)
• Serious psychiatric disease or psychosocial problems
• Low socioeconomic status and urban residence
• Illicit drug use
• Sensitivity to alternaria-mold
• Lack of written asthma action plan

Diagnosing Asthma
• Recurrent episodes of coughing or wheeze
• Asthma may be present without a wheeze cough may be the sole symptom
• Shortness of breath or difficulty breathing
• Chest Tightness
• Wheezing does not always mean asthma
• Absence of symptoms and physical findings at the time of the examination does not exclude asthma

Asthma
• Diagnosis by history of wheeze, shortness of breath, cough, chest tightness
• Spirometry can help define the severity of the disease, however may be normal if asthma is under control
• Lack of bronchodilator response does not rule out asthma
• Following Peak Flows may be useful

Measures of Assessment & Monitoring
• Spirometry should be performed:
– at initial assessment
– after treatment is initiated and symptoms and PEFs have stabilized
– at least every 1-2 years to assess maintenance of airway function if well controlled
– More often if poor asthma control

Measures of Assessment & Monitoring
• Peak Flows may be performed:
– In all moderate and severe persistent asthmatics
• establish a personal best
• useful in exacerbations and maintenance/ changes of therapy,
• Can be helpful with ‘poor perceivers’

< 2 Years Old: When Is It Asthma?
Risk
Factors for
Developing
Asthma
• Family history of asthma
• Atopy, eczema
• Perinatal exposure to aeroallergens and irritants
(e.g., passive smoke)
• Wheezing triggered by factors other than upper respiratory infections

< 2 Years Old: When Is It Asthma?

Asthma Predictive Index
In an infant or young child with > 3 episodes of wheezing in the past year
or
• MAJOR CRITERIA • MINOR CRITERIA
– Atopic dermatitis
– Parental Asthma
– Wheezing apart from colds
– Allergic rhinitis
– Blood eosinophilia
> ¾ of children with a positive index had some active asthma symptoms between 6 and 13 years of age

Asthma: Children vs. Adults
• Present with symptoms of cough ± noisy or rapid breathing, usually before 5 years of age
• Present with symptoms of cough, shortness of breath, chest pain, wheezing, often intermittent or nocturnal

Commonly
Misdiagnosed in
Children as:
CHRONIC/WHEEZY
BRONCHITIS
RECURRENT CROUP
RECURRENT UPPER
RESPIRATORY INFECTION
RECURRENT PNEUMONIA
Asthma Misdiagnosis
Commonly
Misdiagnosed in
Adults as:
RECURRENT
BRONCHITIS

Asthma Severity Assessments
• < 6 year old often cannot perform reliable Pulmonary Function
Test’s (PFT’s) or peak flow measurements
• Older children with even severe symptoms often have fairly normal PFT’s between episodes
• Severity assessment often focuses on symptoms more than lung function measurements
• PFTs play more important role in assessment
• PFT’s performed at diagnosis and routinely at least every 1-2 years

Long-Term Management of Asthma in Children:
Initiation of Control Therapy
• Symptoms > 2 x week
• Severe exacerbations < 6 weeks apart
• 2 or more burst of prednisone in 6 months for ages 0-4
• 2 or more burst of prednisone in 1 year for ages
5-11
• Positive Asthma Predictive Index