Allergic Rhinitis and Asthma ----the linkthe link Rhinitis and Asthma - the link... · Ruby...

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Ruby Pawankar, NMS Allergic Rhinitis and Asthma Allergic Rhinitis and Asthma Allergic Rhinitis and Asthma Allergic Rhinitis and Asthma - - -the link the link the link the link Ruby Pawankar, MD, Ph.D Nippon Medical School, Tokyo, Japan rpawankar @gmail.com

Transcript of Allergic Rhinitis and Asthma ----the linkthe link Rhinitis and Asthma - the link... · Ruby...

Page 1: Allergic Rhinitis and Asthma ----the linkthe link Rhinitis and Asthma - the link... · Ruby Pawankar, NMS Allergic Rhinitis Is a Risk Factor for Asthma 80% of asthmatics have rhinitis

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 common Asthma is one of the most common chronic diseases in the world, especially chronic diseases in the world, especially in childrenin children

�� An estimated 300 million people are An estimated 300 million people are affected worldwideaffected worldwide

�� Asthma prevalence increases as Asthma prevalence increases as communities adopt western lifestyles and communities adopt western lifestyles and become urbanisedbecome urbanised

�� Asthma mortality is also increasing and is Asthma mortality is also increasing and is alarmingly highalarmingly high

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Ruby Pawankar, NMS

● Allergic rhinitis is a global health problem affecting 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 risk

factor for asthma.

Allergic rhinitis

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Asthma Allergic Rhinoconjunctivitis

International Study of Asthma & Allergies in Childhood (ISAAC III)International Study of Asthma & Allergies in Childhood (ISAAC III)

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Impairment Due to Allergic Rhinitis: work productivity and activity impairment questionn aireImpairment Due to Allergic Rhinitis: work productivity and activity impairment questionn aire

23

23

93

91

96

0 25 50 75 100

Tanner LA et al. Am J Managed Care 1999;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 Child’s Quality of LifeASIAN SURVEY : Impact of AR on Asthma in Child’s Quality of Life

Participation in leisure & sports . . .

Concentration at work/ school

Ability to enjoy social activities

Ability to get a good night’s 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 Factor for Asthma

Allergic Rhinitis Is a Risk Factor for Asthma

� 80% of asthmatics have rhinitis and 40% of rhinitis 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 Proc 1994;15:21-25.

12

10

8

6

4

2

0

% of patients

whodeveloped

asthma

10.5

Allergic rhinitisat baseline

(n=162)

3.6

No allergic rhinitisat baseline

(n=528)

p<0.002

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Perennial rhinitis often preceeds asthma

0

10

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 forthe development of asthma

Incidence 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<.005)

– When rhinitis began after first year 13%

* Only 50% of study children skin tested.Wright et al. Pediatrics. 1994; 94:895.

Risk factor in ChildrenRisk factor in Children

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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., cockroach Insects (e.g., cockroach Insects (e.g., cockroach Insects (e.g., cockroach allergen)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 Asthma Allergic 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 symptoms

SneezingNasal pruritus

CongestionRhinorrhea

Time postchallenge (hours)

1Antigen challenge

3–4 8–12 24

Immediate (early) phase Late phase

FEV1

(% change)

Time (hours)

0

50

100

1 10 240 2 3 4 5 6 7 8 9

Upper Airways

Lower Airways

(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 cells Inflammatorymediators

Allergen

Cytokines

Preformed MediatorsCysteinyl leukotrienes

ProstaglandinsPlatelet-activating factor

Eosinophils

Membrane-bound IgE

Mastcell

Common Inflammatory Cells and Mediators

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Bronchial biopsies in patients with SAR

0

10

20

30

40

50

60

Cel

ls/m

m2

con

nec

tive

tis

sue

out inpollen season

EG1+

CD45RO+

CD8+

CD4+

Chakir et al, Allergy Clin Immunol 2000

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Ruby Pawankar, NMSnose bronchi

0

20

40

60

80Asthmatics

untreated

CS-dependent

nose bronchi

0

20

40

60

80Controls

Eos

inop

hils

(/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

Page 18: Allergic Rhinitis and Asthma ----the linkthe link Rhinitis and Asthma - the link... · Ruby Pawankar, NMS Allergic Rhinitis Is a Risk Factor for Asthma 80% of asthmatics have rhinitis

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Bronchial Allergen Challenge ProducedNasal Inflammation

Bronchial Allergen Challenge ProducedNasal Inflammation

Eos

inop

hils

(10

6C

ells

/mm

2 ) 600

500

400

300

200

100

0

Blood(N = 16)

Bronchial Subepithelium

(N = 16)

T0

18

T0 = before challenge; T24 = 24-hr postchallenge.* P <.05 vs control (T0);

†P <.01 vs allergic patients (T0).Braunstahl et al. Am J Respir Crit Care Med. 2000;161:2051-2057.

Nasal Lamina Propria(N = 16)

Eos

inop

hils

(N

o. C

ells

/mm

2 )

Eos

inop

hils

(N

o. C

ells

/mm

2 )

T24

Allergic Patients Control Patients

1600

1200

800

400

0

100

80

60

40

20

0

T0 UnchallengedLeft Lung

T0 T24Allergen-ChallengedRight Middle

Lobe

T24

†* *

*

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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 nasal EOS in nasal mucosa mucosa

(asthmatics)(asthmatics)

0

r= 0.851, p<0.001r= 0.851, p<0.001

EOS in bronchial mucosa (asthmatics)EOS in bronchial mucosa (asthmatics)

5 10 15 20 25 30

(n= 17)

There exists nasal inflammation in asthma despite the presThere exists nasal inflammation in asthma despite the preseence nce of allergic rinitis in atof allergic rinitis in atoopic individuals (20 to 66 yr old)pic individuals (20 to 66 yr old)

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Nasal Steroids Reduced Asthma Symptoms inPatients With Seasonal AR and Seasonal Asthma

Nasal Steroids Reduced Asthma Symptoms inPatients 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)

Ast

hma

Che

st S

ympt

om*

Sco

re

(Mea

n W

eekl

y D

iffer

ence

Fro

m B

asel

ine)

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

DailyRagweed

PollenCount

(Grain/ m 3 )

1984

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Antihistamine Improved Asthma Symptomsin Patients With Seasonal AR and Asthma

Antihistamine Improved Asthma Symptomsin Patients With Seasonal AR and Asthma

21

* P <.05 vs placebo.Grant et al. J Allergy Clin Immunol. 1995;95:923-932.

0

1

2

3

4

5

6

7

8

0 1 2 3 4 5 6

Placebo (n = 93) Cetirizine (10 mg/d) (n = 93)

Week

Tot

al A

sthm

a S

core

*****

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Ruby Pawankar, NMS

0

25

50

75

100

montelukast loratadine montelukast

and

loratadine

Inhibition of the bronchial allergic reaction by anantileukotriene and an antihistamine

early

lateN = 16

% inhibition

of the allergen

induced drop

in FEV1

Page 23: Allergic Rhinitis and Asthma ----the linkthe link Rhinitis and Asthma - the link... · Ruby Pawankar, NMS Allergic Rhinitis Is a Risk Factor for Asthma 80% of asthmatics have rhinitis

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Percentage of Children After 3 Years ofSIT vs. Control With or Without AsthmaPercentage of Children After 3 Years ofSIT vs. Control With or Without Asthma

Möller 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

Allergic Rhinitis

Asthma+ AR

Same cells• Mast cells

• Eosinophils

• Th2 cells

• CD34 Stem cells (the bone marrow connection)

Page 25: Allergic Rhinitis and Asthma ----the linkthe link Rhinitis and Asthma - the link... · Ruby Pawankar, NMS Allergic Rhinitis Is a Risk Factor for Asthma 80% of asthmatics have rhinitis

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% of patients

Patients with asthma + allergic rhinitis

(n=893)

Patientswith asthma

(n=597)

4.0

3.5

3.0

2.5

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 o f ER visits

Page 26: Allergic Rhinitis and Asthma ----the linkthe link Rhinitis and Asthma - the link... · Ruby Pawankar, NMS Allergic Rhinitis Is a Risk Factor for Asthma 80% of asthmatics have rhinitis

Ruby Pawankar, NMSPrice D, et al. Clin Exp Allergy 2005, in press.(Analysis of health-care resource use in adults 16 to 55 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

% of patients

hospitalizedannually

0.76

Patients with asthma + allergic rhinitis

(n=4611)

0.45

Patientswith asthma(n=22,692)

p<0.006

Increased Risk of Hospitalization for Asthma in AR Patients

Patients with AR and asthma had an increased risk o f hospitalization

Page 27: Allergic Rhinitis and Asthma ----the linkthe link Rhinitis and Asthma - the link... · Ruby Pawankar, NMS Allergic Rhinitis Is a Risk Factor for Asthma 80% of asthmatics have rhinitis

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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 Immunol 2002;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<0.01

61% fewer hospitalizations in patients treated for AR

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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

Central sensitization and nasopharyngo-bronchial reflexes

Drainage of inflammatory material

� Mouth breathing

� ↓↓↓↓ Air warming & humidification

� ↓↓↓↓ Particle/irritant trapping

� (↓↓↓↓ Nitric oxide)

Systemic propagation of (para)nasal inflammation

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Link between Rhinitis and Asthma

Eosinophil

CCR3CCR4CCR5

VLA-4VCAM-1

Th2

CCR3CysLT1 RCysLT2 R

CysLT1 RCysLT2 RIL-5 R, IL-3 RGM-CSF R

IL-4, IL-5IL-6, IL-13,RANTESEotaxin

Eo /Ba progenitor

IL-3IL-5GM-CSF

Asthma

Allergic Rhinitis

Eosinophil

E25 Mc

HistamineTryptaseCys LTsPGsIL-4, IL-5IL-6, IL-13,GM-CSFTNF-α

IL-4Bone marrow

Blood vessel

Allergen

UpregulatedAdhesion Molecules & chemoattractactants

Pawankar R 2006-.Clin Exp Allergy 36(1): 1-4, 2006.c

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One Airway, One Disease?One Airway, One Disease?

Togias: ‘Asthma and rhinitis are manifestations of one syndrome, the chronic

allergic respiratory syndrome’JACI 2003

Asthma and Rhinitis

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