Allergic Rhinitis and Asthma - The Link - Pawankar
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Ruby Pawankar, NMS
Allergic Rhinitis and AsthmaAllergic Rhinitis and AsthmaAllergic Rhinitis and AsthmaAllergic Rhinitis and Asthma----the linkthe linkthe linkthe link
Ruby Pawankar, MD, Ph.D
Nippon Medical School,
Tokyo, Japan
rpawankar @gmail.com
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The Global Burden of AsthmaThe Global Burden of Asthma
Asthma is one of the most commonAsthma is one of the most common
chronic diseases in the world, especiallychronic diseases in the world, especially
in childrenin children
An estimated 300 million people areAn estimated 300 million people are
affected worldwideaffected worldwide
Asthma prevalence increases asAsthma prevalence increases as
communities adopt western lifestyles andcommunities adopt western lifestyles and
become urbanisedbecome urbanised
Asthma mortality is also increasing and isAsthma mortality is also increasing and is
alarmingly highalarmingly high
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Allergic rhinitis is a global health problemaffecting 10 to 50 % of the population
Its prevalence is increasing.
Although it is not usually a severe disease,rhinitis alters social life and affects school
performance and work productivity.
Costs incurred by rhinitis are substantial. Most importantly, Allergic rhinitis is a riskfactor for asthma.
Allergic rhinitis
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Asthma Allergic Rhinoconjunctivitis
International Study of Asthma &
Allergies in Childhood (ISAAC III)
nternat ona tu y o st ma
Allergies in Childhood (ISAAC III)
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Impairment Due to Allergic Rhinitis:work productivity and activity impairment questionnaire
Impairment Due to Allergic Rhinitis:work productivity and activity impairment questionnaire
23
23
93
91
96
0 25 50 75 100
Tanner LA et al.Am J Managed Care1999;5(Suppl):S235
% of patients
Ability to do daily activities
Work productivity
Classroom productivity
Any work time missed
Any classroom time missed
AR markedly impairs the QOL of patients
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22% 41%
48% 33%
44% 38%
51% 35%
0% 20% 40% 60% 80% 100%
ASIAN SURVEY : Impact of AR on
Asthma in Childs Quality of Life
ASIAN SURVEY : Impact of AR on
Asthma in Childs Quality of Life
Participation inleisure & sports . . .
Concentration atwork/ school
Ability to enjoy
social activities
Ability to get a goodnights sleep
A great deal and Quite a lotA great deal and Quite a lot A little bitA little bit
85%85%
82%82%
83%83%
63%63%
Total disrupted:Total disrupted:
Erkka V and Pawankar R, 2007
Most patients (73%) had pre-existing AR when diagnosed with asthma.most troublesome symptom was wheezing (17%) and coughing (17%).
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Asthma and Rhinitis Common Triggers
Epidemiological Link
Common inflammatory processes
Pathophysiological links
Treatment Outcomes
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Allergic Rhinitis Is a Risk Factorfor Asthma
Allergic Rhinitis Is a Risk Factorfor Asthma
80% of asthmatics have rhinitis and 40% ofrhinitis patients have asthma
23-year follow-up of college freshmen undergoing allergy testing; data based on 738 individuals (69% male) with
average age of 40 years.
Adapted from Settipane RJ et al Allergy Proc1994;15:21-25.
12
10
8
6
4
2
0
% ofpatients
whodeveloped
asthma
10.5
Allergic rhinitisat baseline
(n=162)
3.6
No allergic rhinitisat baseline
(n=528)
p
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Perennial rhinitis often preceeds asthma
010
20
30
40
50
60
70%
SAR n = 110 PAR n = 44
Type AR at the beginning of the study
seasonal AR
perennial AR
asthma
symptom-free
Allergic Rhinitis: Risk Factor for Asthma
Development
10 year prognosis for childhood (3-17 years old) allergic rhinitis
Linna, et al. Acta Pediatr 1992
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0
5
10
15
20
25
30
Linneberg et al. Allergy 2002;57:1048
Allergic rhinitis as a risk factor for
the development of asthmaIncidence of asthma over an 8-year period in the
Copenhagen Allergy Study
% of subjects
pollen animal mite
no rhinitis
at baseline
rhinitis
at baseline
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Physician diagnosed allergic rhinitis in children
- By 6 years of age 42%
Began in first year 77%
Began after first year 57%
Prick skin test positive * 20%
Development of asthma by 6 years
When rhinitis began in first year 23% (p
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Outdoor allergensOutdoor allergensOutdoor allergensOutdoor allergens
PollensPollensPollensPollens
MoldsMoldsMoldsMolds
Indoor allergensIndoor allergensIndoor allergensIndoor allergens
HouseHouseHouseHouse----dust mitesdust mitesdust mitesdust mites
Animal danderAnimal danderAnimal danderAnimal dander
Insects (e.g., cockroachInsects (e.g., cockroachInsects (e.g., cockroachInsects (e.g., cockroachallergen)allergen)allergen)allergen)
Nonsteroidal AntiNonsteroidal AntiNonsteroidal AntiNonsteroidal Anti----inflammatory Drugs (NSAIDs)inflammatory Drugs (NSAIDs)inflammatory Drugs (NSAIDs)inflammatory Drugs (NSAIDs)(e.g., aspirin)(e.g., aspirin)(e.g., aspirin)(e.g., aspirin)
Allergic Rhinitis and Asthma
Have Comon Triggers
Allergic Rhinitis and AsthmaAllergic Rhinitis and Asthma
Have Comon TriggersHave Comon Triggers
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Early and Late Phase Responses in Allergic
Rhinitis and Asthma
Early and Late Phase Responses in Allergic
Rhinitis and Asthma
Adapted from Varner AE, et al. Asthma and Rhinitis 2000and Togias A. JACI 2000
(Asthma)
Score for nasal
symptomsSneezing
Nasal pruritusCongestion
Rhinorrhea
Time postchallenge (hours)
1Antigen
challenge
34 812 24
Immediate (early) phase Late phase
FEV1(% change)
Time (hours)
0
50
100
1 10 240 2 3 4 5 6 7 8 9
UpperAirways
LowerAirways
(Allergic
rhinitis)
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Adapted from Casale TB, et al. Clin Rev Allergy Immunol 2001 and
Kay AB N Engl J Med 2001
Early-phaseresponse
Late-phaseresponse
T cellsInflammatory
mediators
Allergen
Cytokines
Preformed MediatorsCysteinyl leukotrienes
Prostaglandins
Platelet-activating factor
Eosinophils
Membrane-boundIgE
Mastcell
Common Inflammatory Cells and
Mediators
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Bronchial biopsies in patients with SAR
0
10
20
30
40
50
60
Ce
lls/mm
2
co
nnectivetissue
out in
pollen season
EG1+
CD45RO+
CD8+
CD4+
Chakir et al, Allergy Clin Immunol 2000
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Ruby Pawankar, NMSnose bronchi
0
20
40
60
80
Asthmatics
untreated
CS-dependen
nose bronchi
0
20
40
60
80
Controls
Eosinophils(/m
m2)
Eosinophilic inflammation in
submucosa
Chanez et al, Am J Respir Crit Care Med 1999
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0
.5
1
1.5
2
Sputum
eosinophils (%)
baseline 24 hrs after nasal
allergen challenge
n = 14
p = 0.03
Nasal provocation results
in bronchial inflammation
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Bronchial Allergen Challenge Produced
Nasal Inflammation
Bronchial Allergen Challenge Produced
Nasal Inflammation
Eosinophils(106Cells/mm2)
600
500
400
300
200
100
0
Blood(N = 16)
BronchialSubepithelium
(N = 16)
T0
18
T0 = before challenge; T24 = 24-hr postchallenge.
* P
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Correlation between nasal and
bronchial inflammationGaga et al. Clin Exp Allergy 2000
40
35
30
25
20
15
10
5
0
EOS in nasalEOS in nasal
mucosamucosa
(asthmatics)(asthmatics)
0
r= 0.851, p
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Nasal Steroids Reduced Asthma Symptoms in
Patients With Seasonal AR and Seasonal Asthma
Nasal Steroids Reduced Asthma Symptoms in
Patients With Seasonal AR and Seasonal Asthma
20
*Chest tightness and wheezing.
Welsh et al. Mayo Clin Proc. 1987;62:125-134
Treatment
Placebo (n = 14)
Flunisolide (n = 19)
Cromolyn (n = 14)
BDP (n = 11)
AsthmaChestSymptom*Score
(MeanWeeklyDifferenceFromBaseline)
15
10
5
0
-5
1400
200
1000
800
600
400
200
0
7/11 7/17 7/24 7/31 8/7 8/14 8/21 8/28 9/4 9/11
9/18
Prepeak PostpeakPeak
Daily
Ragweed
Pollen
Count
(Grain/ m 3 )
1984
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Antihistamine Improved Asthma Symptoms
in Patients With Seasonal AR and Asthma
Antihistamine Improved Asthma Symptoms
in Patients With Seasonal AR and Asthma
21
* P
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Ruby Pawankar, NMS
0
25
50
75
100
montelukast loratadine montelukast
and
loratadine
Inhibition of the bronchial allergic reaction by an
antileukotriene and an antihistamine
early
lateN = 16
% inhibition
of the allergen
induced drop
in FEV1
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Percentage of Children After 3 Years of
SIT vs. Control With or Without Asthma
Percentage of Children After 3 Years of
SIT vs. Control With or Without Asthma
Mller C, et al. J Allergy Clin Immunol. 2002; 109:251-256.
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Asthma and allergic rhinitis Two related
conditions linked by one common airway
Anatomy/Physiology
Upper and lower airways are contiguous
Functional linkage - nose vs. mouth breathing
Similar histology
Same mediators
IgE
Cytokines
Histamine
Leukotrienes
Same drugs
Anti-IgE
Steroids (ICS/INS)
Antihistamines (?)
Antileukotrienes
Asthma
AllergicRhinitis
Asthma
+ AR
Same cells
Mast cells
Eosinophils
Th2 cells
CD34 Stem cells
(the bone marrow
connection)
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% ofpatients
Patients with asthma
+ allergic rhinitis
(n=893)
Patients
with asthma
(n=597)
4.0
3.5
3.02.5
2.0
1.5
1.0
0.5
0
p=0.029
1.7
3.6
Bousquet J, et al. Poster presented at the (EAACI) 2004 (Post hoc analysis of medical resource
use/asthma attacks in asthmatic patients with and without concomitant allergic rhinitis over 52 weeks)
Increased Risk of ER Visits for Asthma in
AR Patients
Patients with AR and asthma had an increased risk of ER visits
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Ruby Pawankar, NMSPrice D, et al. Clin Exp Allergy 2005, in press.(Analysis of health-care resource use in adults 16 to55 years of age with asthma and allergic rhinitis in a general practice in the UK)
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
% ofpatients
hospitalizedannually
0.76
Patients with asthma
+ allergic rhinitis
(n=4611)
0.45
Patients
with asthma
(n=22,692)
p
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Treating Allergic Rhinitis Decreased
Asthma-Related Resource Utilization
Treating Allergic Rhinitis Decreased
Asthma-Related Resource Utilization
Retrospective cohort study of costs over a period of up to one year incurred by patients 12 to 60 years of age with both
allergic rhinitis and asthma.Adapted from Crystal-Peters J et al J Allergy Clin Immunol2002;109(1):57-62.
0.9
2.5
2.0
1.5
1.0
0.5
0
% ofpatients
Patients untreated forallergic rhinitis (n=1357)
Patients treated forallergic rhinitis (n=3587)
2.3
p
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Asthma and Allergic Rhinitis Two Related
Conditions Linked by One Common Airway
Module 1: The underlying mechanisms of the United Airway concept
Asthma and Allergic Rhinitis: WAO Online Lecture Series
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Ruby Pawankar, NMSAdapted from Togias A. JACI 2003
Interactions Nose Lower Airways::
Possible Mechanisms of Relationship
Centralsensitization andnasopharyngo-bronchial reflexes
Drainage ofinflammatorymaterial
Mouth breathing
Air warming &humidification
Particle/irritant
trapping
( Nitric oxide)
Systemicpropagation of(para)nasalinflammation
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Link between Rhinitis and Asthma
Eosinophil
CCR3
CCR4
CCR5
VLA-4VCAM-1
Th2
CCR3
CysLT1 R
CysLT2 R
CysLT1 R
CysLT2 R
IL-5 R, IL-3 R
GM-CSF R
IL-4, IL-5
IL-6, IL-13,
RANTES
Eotaxin
Eo /Ba
progenitor
IL-3IL-5GM-CSF
Asthma
Allergic Rhinitis
Eosinophil
E25 Mc
Histamine
Tryptase
Cys LTs
PGs
IL-4, IL-5
IL-6, IL-13,
GM-CSF
TNF-
IL-4Bone marrow
Blood vessel
Allergen
Upregulated
AdhesionMolecules &
chemoattractactants
Pawankar R 2006-.Clin Exp Allergy 36(1): 1-4, 2006.c
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Ruby Pawankar, NMS
One Airway, One Disease?One Airway, One Disease?
Togias: Asthma and rhinitis aremanifestations of one syndrome, the chronic
allergic respiratory syndrome
JACI 2003
Asthma and Rhinitis
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