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MANAGEMENT OF THE
PATIENT WITH
RHINITIS AND ASTHMA
Giovanni Passalacqua
Allergy & Respiratory Diseases
Dept.Internal MedicineUniversity of Genoa ITALY
ARIA Classification
Intermittent
. < 4 days/week
. or < 4 weeks
•
•
•
•
•
Persistent
. > 4 days/week
. AND > 4 weeks
MILD
Moderate-severe
All the following
One or more:
No sleep disturbance
No daily activity
limitations
normal work/school Activity
No bothersome symptom
. No sleep disturbances
daily activity limitations
• impaired work or school
activity
• bothersome symptoms
ALTERNATIVE: VAS
No
symptoms
X
Untolerable
symptoms
Diagnostic tools. The problem
Differently from asthma, there is no reliable or
Standardized objective measurement.
No objective evaluation of severity
No tool is capable to discriminate allergic and
nonallergic rhinitis.
No tool is capable to discriminate healthy and rhinitics
PERSPECTIVES: Phenotypes of rhinitis?
IgE
PURE
SEASONAL
(hayfever)
OCCUPATIONAL
POLYPS
PERSISTENT
LOCAL
RESPONSE
NARES
NA-NI
NARESMA
VASOMOTOR
HORMONAL
NON
IgE
Rhinitis: comorbidities
ASTHMA
SLEEP
DISORDERS
RHINOSINUSITIS
polyps
RHINITIS
OTITIS
CONJUNCTIVITIS
Allergic rhinobronchitis: the asthma-allergic
rhinitis link.
Simons FER
J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):534-40.
Linking upper and lower respiratory airways.
Aubier M.
J Allergy Clin Immunol 1999; 83: 431-434.
United airways disease: therapeutic aspects.
Passalacqua G, Ciprandi G, Canonica GW
Thorax. 2000 Oct;55 Suppl 2:S26-7.
UNITED AIRWAYS
EPIDEMIOLOGY
Comorbidity rhinitis asthma
Natural history
Rhinitis as risk factor for asthma
STUDY
LOCUS
SUBJECTS
% ASTHMA
Pariente
France
adults
1367
Leynaert
ECRHS
adults
262
Wright
Tucson
children 129
Settipane Providence adolesc 162
Sibbad
England
adults
319
rhin. 13.4
no rhin. 3.8
rhin. 22.5
no rhin. 4
rhin. 32
no rhin. 5
rhin. 10.5
no rhin. 3.6
SAR. 23
PAR 26
both 43
Leynaert et al. JACI 2000
93% of asthmatics have concomitant rhinitis
Kapsali T et al, JACI 1998
Prevalence of asthma (physician diagnosed)
in rhinitis
Bousquet, CEA 2005
35
- 591 patients
- 502 controls
- allergic to pollens, mite,
-epithelia
25
20
% subjects
% pazienti
30
15
10
5
0
contr
mild severe mild severe
persistent
intermittent
Shaaban, Lancet 2008
Allergic rhinitis as a predictor for wheezing onset in schoolaged children.
Rochat et al, JACI 2010
Cohort of 1,314 children followed from birth to 13 yrs
UNITED AIRWAYS
IMMUNOLOGY
Allergic inflammation
Bone marrow response
Neuroinflammation
PATHOPHYSIOLOGY
Naso-broncghial reflex
Physical filter
Nonspecific hyperresponsiveness
Bronchial biopsioes after
Specific provocation in
patients with rhinitis or
asthma
ASTHMA
Same inflammation
Crimi E et al, JAP 2001
RHINITIS ALONE
Nasal allergen challenge
Increases bronchial reactivity
Induces bronchial inflammation
Littell NT, Changes in airways resistance following nasal provocation. Am Rev Respir Dis 1990
Corren J Changes in bronchial responsiveness following nasal provocation with allergens. JACI 1992
Small P ET AL The effects of allergen-induced nasal provocation on pulmonary function in patients with
perennial allergic rhinitis. Am J Rhinol 1989
Induces nasal inflammation
Bronchial endoscopic challenge
With allergen
The nose-lung interaction in
allergic rhinitis and asthma:
united airways disease
G.Passalacqua,
G.Ciprandi & G.W.Canonica
2004
Asthma and rhinitis as different
Aspects of a sinlge disorder
Perennial rhinitis: independent factor
for developing asthma
Leynaert et al, J Allergy Clin Immunol 1999
25
% pazienti asmatici
controls
20
rhnitis
15
10
5
0
atopic
non-atopic
Children with
allergic and
nonallergic
rhinitis have a
similar risk of
asthma.
Chawes et al
JACI 2010
nose
naso-bronchial reflex
physical filter function
allergen
adhesion molecules
INFLAMMATION
viral infection
cytokines
bone marrow
bronchial
hyperreactivity
bronchi
PATIENTS WITH PERSISTENT RHINITIS MUST BE
ASSESSED FOR THE POSSIBILITY OF ASTHMA
HISTORY/EXAMINATION
Do you have recurrent wheezing?
Do you have dry cough?
Do you experience cough after exercise?
Do you have chest tightness?
IF POSITIVE
obstruction
Assess
reversibility
Spirometry
normal
Nonspecific
Bronchial
provocation
UNITED AIRWAYS
THERAPY
Immunotherapy
Nasal steroids
Antihistamines
Combination therapy
TREATMENT OF ALLERGIC RHINITIS
ARIA -Allergic Rhinitis and its Impact on Asthma
mild
intermittent
Moderatesevere
intermittent
Mild
persistent
Antileukotrienes (if asthma)
Nasal steroid
Cromones
2nd Generation antihistamine
Decongestant (<10 days)
Allergen avoidance
Immunotherapy
Moderatesevere
persistent
Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW et
al.
Allergic Rhinitis and its Impact on Asthma (ARIA)
guidelines: 2010 revision.
Journal of Allergy and Clinical Immunology 2010; 126: 466-476
69 CLINICAL QUESTIONS ON THE TREATMENT
RECOMMENDATION: CONDITIONAL/STRONG
LEVEL OF EVIDENCE: HIGH/MODERATE/LOW/VERY LOW
high
Weak: 84%
Strenght of
recommendation
Very low
moderate
low
Grade of
evidence
BASIC QUESTIONS:
Does the treatment of rhinitis affect
comorbid asthma?
Any effect on the natural history?
Cruz, Allergy 2008
asthma
Asthma + rhinitis
Untreated rhinitis increases the risk of asthma attacks.
Bousquet, Clin Exp Allergy 2005
Mean % reduction of AM
instantaneous asthma score
Safety and efficacy of
desloratadine 5 mg in
asthma patients with
seasonal allergic rhinitis
and nasal congestion.
14
8
Berger et al. Ann Allergy
Asthma Immunol 2002
2
Mean % reduction of AM/PM
asthma score
30
15
*
*
5
WKS 1-2
WKS 1-4
Taramarcaz, Cochrane 2008
Effects of mometasone furoate on the Quality of Life: a
randomised placebo controlled trial in persistent allergic
rhinitis and intermittent asthma using the Rhinasthma
questionnaire
Ilaria Baiardini1, Elisa Villa1, Anthi Rogkakou1, Sara Pellegrini1,
Micaela Bacic1, Enrico Compalati1, Fulvio Braido1, Cristina Le Grazie2,
Giorgio Walter Canonica1, Giovanni Passalacqua1
Clin Exp Allergy 2011
MFNS N= 26
52
Placebo N= 26
Run in
1 sett
V1
V2
V3
Primary outcome:
Global Summary (GS) of Rhinasthma,
Changes at 2 and 4 weeks versus
baseline
Secondary outcomes:
Changes vs baseline in the 3 domains of
Rhinasthma
-Upper airways (UA)
-Lower airways (LA)
-Respiratory Allergy Impact (RAI)
-Nasal symptom score
- Nasal + asthma scores
Enrolled
n = 57
Screening failures n = 5
Entry criteria not satisfied, n = 1
Refused to continue for reason
unrelated to study drug, n=2;
Privacy Form not signed, n = 2
Randomized
n = 52
Mometasone
n = 26
Placebo
n = 26
Discontinuations
n=1
Consent withdrawn
Completed
n = 25
Completed
n = 22
Discontinuations
n=4
Adverse event, n = 1
Consent withdrawn, n = 2
Treatment failure, n = 1
Primary endpoint: Rhinasthma Global Score
ITT Population
Mean changes from baseline (V2) to endpoint (V4)
MFNS
Mean change vs baseline
2
p<0.001
0,4
0
-2
-4
-6
-8
-10
-12
Placebo
10,3
-
Rhinasthma global summary
MFNS
Placebo
<.001
<.001
30
Rhinasthma GS mean
25
20
15
10
5
baseline
week 2
week 4
MFNS
40
<.001
<.001
Placebo
35
30
<.001
<.001
25
20
15
10
5
baseline
week 2
UAS
week 4
baseline
week 2
LAS
week 4
baseline
week 2
RAI
week 4
Global Symptom Score (GSS)
Weekly score
12
Mean score
10
8
6
*
*
GSS Placebo
4
GSS MFNS
2
0
basale
1
2
3
4
Conclusions
• Treating persistent rhinitis with mometasone furoate nasal spray resulted
in a significant improvement in QoL for both upper and lower respiratory
tract domains
• There was a significant improvement of the global symptom scores
(rhinitis + asthma)
• No significant change in rhinitis symptoms when analyzed separately (trial
powered on the basis of the primary outcome)
• Good safety profile
SPECIFIC IMMUNOTHERAPY IN ASTHMA AND RHINITIS
Meta-analysis of the efficacy of sublingual immunotherapy in
allergic asthma in pediatric patients, 3 to 18 years of age.
M Penagos, G Passalacqua, E Compalati, C Baena-Cagnani, S Orozco, A Pedroza
GW Canonica
SYMPTOMS
MEDICATIONS
SYMPTOM
DETERIORATION
ASTHMA
SYMPTOMS
MEDICATIONS
Abramson,
Puy, Weiner
Cochrane 2010
Effect of specific
immunotherapy added to
pharmacologic treatment
and allergen avoidance in
asthmatic patients allergic
to house dust mite
Maestrelli et al,
JACI 2004
Effect of SLIT to Parietaria on seasonal BHR in children
Pajno GB & Passalacqua G, Allergy 2004
0.008
NS
0.005
0.001
0.005
10
PLACEBO
5
SLIT
NS
WINTER SPRING
99
99
SPRING
01
WINTER SPRING
99
99
SPRING
01
CONCLUSIONS
Based on the literature, SIT is effective in allergic
asthma associated with rhinitis, and should be
used in association with standard medications
SIT reduces bronchial hyperresponsiveness, that
is an indirect marker of bronchial inflammation.
RISK FACTORS
Based on nonfatal reactions
Uncontrolled asthma
Severe asthma
Use of betablockers
Rush immunotherapy
Use of new vials
Technical errors
Based on fatal reactions
Uncontrolled asthma
Severe asthma
Use of betablockers
Rush immunotherapy
Build-up phase
Use of new vials
Technical errors
Estimated incidence of fatalities < 1/2.000.000 injections
RHINITIS
BHR/
ASTHMA
MONOSENSITIZATION
POLYSENSITIZATION
Allergic rhinitis as a predictor for wheezing onset in schoolaged children.
Rochat et al, JACI 2010
Cohort of 1,314 children followed from birth to 13 yrs
MARTINEZ,PEDERSEN
Long-Term Inhaled Corticosteroids in Preschool Children at High Risk
for Asthma
Guilbert T, NEJM 2006
Specific immunotherapy has
long-term preventive effect of
seasonal and perennial
asthma: 10-year follow-up on
the PAT study
Jacobssen, Allergy 2007
Coseasonal SLIT reduces the
development of asthma in children
with allergic rhinitis. Novembre E. et al, JACI 2004
NO ASTHMA
ASTHMA
37
26
18
Randomized, open,
controlled
79 children
Allergic rhinitis only
Follow-up: 3 yrs
8
SLIT
NO SLIT
PRESENCE OF ASTHMA AFTER 3 YEARS
PREVENTIVE EFFECTS OF SUBLINGUAL
IMMUNOTHERAPY IN CHILDHOOD.
AN OPEN RANDOMIZED CONTROLLED STUDY
MAURIZIO MAROGNA MD1 , D.TOMASSETTI1, A. BERNASCONI1, F.COLOMBO1,
ALESSANDRO MASSOLO BS2, A. DI RIENZO BUSINCO4, GIORGIO W CANONICA
MD3, GIOVANNI PASSALACQUA MD3 AND SALVATORE TRIPODI MD4
1
3
Pneumology Unit, Cuasso al Monte, Macchi Hospital Foundation, Varese
2 Department of Animal Biology, University of Pavia, Pavia
Allergy & Respiratory Diseases,Department of Internal Medicine, Genoa University
4 Pediatric Allergy Unit, S. Pertini Hospital, Rome
AAAI 2008, 101: 261
14 dropout
144 SLIT
PATIENTS
130
SLIT
216
6 dropout
72 CONTROLS
66
CONT
Diary card
Visit
Skin test
MCh challenge
* * * * * * *
*
*
*
*
Year 1
1 year
BASELINE
Year 2
Year 3
RANDOMIZED PHASE
MONOSENSITIZED
PATIENTS
70
70
60
60
***
50
40
% PATIENTS
% PATIENTS
PERSISTENT
ASTHMA
***
30
***
***
50
40
30
20
20
NS
10
10
baseline
CONTROLS
3rd year
baseline
3rd year
SLIT
CONCLUSIONS
Patients with rhinitis should be investigated also
for asthma
Uncontrolled Rhinitis may affect the
severity/control of co-morbid asthma.
In patients with rhinitis and asthma, treating rhinitis
can improve asthma.
Specific immunotherapy, either SCIT or SLIT, is of
benefit also for asthma.
ARIA RECOMMENDATIONS
1- Patients with persistent AR must be
assessed for asthma
2- Patients with asthma should be
assessed for rhinitis
3- The optimal strategy must combine
the treatment of lower and upper
airways, aslo in terms of safety and
costs