Allergic Rhinitis and Asthma - The Link - Pawankar

7/30/2019 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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

% 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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

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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Ruby Pawankar, NMS

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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Allergic Rhinitis and Asthma - The Link - Pawankar

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