Asthmatic cough cough variant asthma nonasthmatic eosinophilic bronchitis
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Asthmatic Cough (Cough variant asthma) & Nonasthmatic Eosinophilic Bronchitis. Necla Songür, MD Süleyman Demirel University School of Medicine Department of Chest Diseases. Spontaneous or induced sputum eosinophils ratio > 2.5 %. Eosinophilic Bronchitis.

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Asthmatic cough cough variant asthma nonasthmatic eosinophilic bronchitis

Asthmatic Cough (Cough variant asthma) & Nonasthmatic Eosinophilic Bronchitis

Necla Songür, MD

Süleyman Demirel University School of Medicine

Department of Chest Diseases


Spontaneous or induced sputum eosinophils ratio > 2.5 %

Eosinophilic Bronchitis

Gibson PG et al, Thorax 2002


Eosinophilic bronchitis clinical presentation

Asthma > 2.5 %

Cough variant asthma

Nonasthmatic eosinophilic bronchitis

Atopic cough

Allergic rhinitis

Gastro-esophageal reflux disease (GERD)

Chronic obstructive pulmonary disease (COPD)

Eosinophilic BronchitisClinical Presentation


Eosinophilic bronchitis prevalance
Eosinophilic Bronchitis > 2.5 %Prevalance

100

80

60

%

40

20

Healthy

Rhinitis

Cough

ERS

CVA

Asthma

Gibson PG et al, Thorax 2002


Eosinophilic bronchitis pathogenesis
Eosinophilic Bronchitis > 2.5 %Pathogenesis

  • Asthma

  • Chronic cough IL5

  • COPD

  • Allergic rhinitis?

  • GERD?

Gibson PG et al, J Allergy Clin Immunol 1998

Brightling CE et al, Am J Respir Crit Care Med 2000

Saette et al, Clin Exp Allergy 1996


Eosinophilic bronchitis chronic cough
Eosinophilic Bronchitis > 2.5 %Chronic Cough

  • Cough variant asthma

  • Nonasthmatic eosinophilic bronchitis

  • Atopic cough



Cough variant asthma diagnosis
Cough Variant Asthma > 2.5 %Diagnosis

  • Chronic cough lasting more than 8 weeks

  • Absence of a history of wheezing or dyspnea

  • Absence of post-nasal drip

  • Physical examination of lungs is normal

  • Chest roentgenography is normal

Corrao et al, N EJM 1979


Cough variant asthma diagnosis1
Cough Variant Asthma > 2.5 %Diagnosis

  • FEV1> 80% (pred), FVC>80%(pred)

    FEV1 / FVC ≥ 70 %(pred)

  • PC20-FEV1< 10 mg/ml

  • Relief of cough after bronchodilator

    theraphy

Corrao et al, NEJM 1979


Cough variant asthma
Cough Variant Asthma > 2.5 %

Is a subgroup of asthma ?


Detection of Eosinophils in Hypertonic Saline-Induced Sputum in Patients with Chronic Nonproductive Cough

Songür N et al, J Asthma 1997


Presence of Eosinophils in Induced sputum in Each Patients Group

Eosinophils 1-25 % 26-75 % 76-100%

Songür N et al, J Asthma 1997


Percentage of eosinophils in bal and number of eosinophils in bronchial tissue
Percentage of Eosinophils in BAL and Number of Eosinophils in Bronchial Tissue

Niimi A et al, Eur Res J 1998


Subepithelial layer thickness ( in Bronchial Tissueµm)

Eosinophilic inflammation in patients with CVA may cause remodelling of the airway.

Control

Asthma

CVA

NiimiA et al, Lancet 2001


Cough variant asthma and asthma share a similar airway inflammatory marker profile

IL5 IL8TNFά

De Diego et al, Allergy 2005


Cough variant asthma comprises a subgroup of asthma
Cough variant asthma comprises a subgroup of asthma inflammatory marker profile

  • Eosinophilic airway inflammation in asthma and cough variant asthma is similar.

  • The ratio of eosinophilic inflammation is not related to differences between symptoms of cough variant asthma and classic asthma


Cough
Cough inflammatory marker profile

  • Heightened airway cough receptor sensitivity( C5≤ 3.9uM)

  • Bronchoconstruction

    Songür N et al, Respirology, 2000

    Fujimura M et al, Thorax 1992

    Fujimura M et al, Eur Res J 1992


Cough receptor sensitivity is within normal limits in patients with cough variant asthma and inhale corticosteroids does not affect the sensitivity

Patients without ICS

Patients with ICS

Fujimura M et al, Cough 2005

Songür N et al, J Asthma 1997


Cough variant asthma cough reflex sensitivity
Cough Variant Asthma patients with cough variant asthma and inhale corticosteroids does not affect the sensitivity“Cough Reflex Sensitivity”

  • within normal limits (C5>3.9µM)

  • not a feature of disease

Fujimura M et al, Eur Res J 1992

Fujimura M et al, J Asthma 1994

Songür N et al, J Asthma 1997

Fujimura M et al, Cough 2005


Cough variant asthma1
Cough Variant Asthma patients with cough variant asthma and inhale corticosteroids does not affect the sensitivity

  • Cough in the middle of the night and early in the morning

  • PEFR monitoring → morning dip

  • Increase in FEV1 after therapy

  • Relief of cough with bronchodilator

    therapy

Shirata et al, Respirology 2005

Sano T et al, Lung 2004

Fujimura M et al, Clin Exp Allergy 2003

Kim CK etal, Clin Exp Allergy 2003


Cough variant asthma2
Cough patients with cough variant asthma and inhale corticosteroids does not affect the sensitivityVariant asthma

Small degree contractions of airway smooth muscle trigger cough.


Cough variant asthma3
Cough Variant Asthma patients with cough variant asthma and inhale corticosteroids does not affect the sensitivity

  • Pre-asthmatic state

  • Early stage of mild persistant asthma


Nearly 30% of cough variant asthma develop typical asthma within several years

Study/Year CVA (n) Median fallow up (year) Asthma (%)

Corrao et al 1979 6 1 2 (33)

Braman et al 1985 16 3-5 6 (37)

Kim et al 2003 51 4 24 (47)

Fujimura et al 2003 55 4 8 (14)

Fujimura et al 2005 20 3 3 (15)

Fujimura et al 2005 27 4 7 (29)


Cough Variant Asthma within several years

Predictor of Subsequent Development of Classic Asthma

An increased ratio of eosinophil in induced sputum can predict the subsequent development of classic asthma

Development of Classic Asthma %

2.5-4.7

4.8-8.2

0-2.4

8.3-17.3

Sputum eosinophil (%)

Kim CK et al, Clin Exp Allergy 2003


Cough variant asthma predictors of subsequent development of classic asthma

Univariate analysis within several years

Bronchial hyperresponsiveness

Blood eosinophils (%)

No use of inhaled corticosteroids

Multivariate analysis

Bronchial hyperresponsiveness

CoughVariant AsthmaPredictors of Subsequent Development of Classic Asthma

Fujimura M et al, J Asthma 2005


Cough variant asthma treatment
Cough Variant Asthma within several years Treatment

?

Inhaled bronchodilators (β agonist)

Inhaled corticosteroids (mean: 400mcg, 200-800 mcg)

Leukotriene receptor antogonists

Oral corticosteroids (30 or 40mg prednizone/daily / for one week)

Suplatast tosilate

Dicpinigaitis PV, Thorax 2004

Dicpinigaitis PV, Chest 2006


Nonasthmatic eosinophilic bronchitis diagnosis
Nonasthmatic Eosinophilic Bronchitis within several years Diagnosis

  • Isolated chronic cough lasting more than 8 weeks

  • Absence of a history of wheezing and dyspnea

  • Absence of post-nasal drip

  • Physical examination of lungs is normal

  • Chest roentgenography is normal

Gibson PG et al, Lancet 1989


Nonasthmatic eosinophilic bronchitis diagnosis1
Nonasthmatic Eosinophilic Bronchitis within several years Diagnosis

FEV1> 80% (pred), FVC> 80% (pred)

FEV1/FVC ≥70% (pred)

PC20-FEV1> 16 mg/ml

Sputum eosinophil > 3% (11% - 85%)

Relief of cough treatment with inhaled corticosteroids or oral corticosteroids

Gibson PG et al, Lancet 1989


Nonasthmatic Eosinophilic Bronchitis within several years

Clinical Features

Brightling CE et al, Thorax 2003


Eosinophil counts in induced sputum, bronşial wash and BAL fluid in patients with nonasthmatic eosinophilic bronchitis

*p<0.05,**p<0.01,

Brightling CE et al, Thorax 2003


Nonasthmatic Eosinophilic Bronchitis fluid in patients

Pathogenesis

**p<0.01

Brightling CE et al, Thorax 2003


Conclusion
Conclusion fluid in patients

Airway inflammation is similar in both conditions and the site of inflammation is mainly in the lower airway.


Why is NAEB not asthma ? fluid in patients


The difference in symptoms of NAEB is not due to the differences in mediator production

Brightling CE et al, AJCCM 2000


Mast cell infiltration of airway smooth muscle in asthma differences in mediator production

Brightling CE et al , NEJM 2002


There is no mast cell infiltration of airway smooth muscle in nonasthmatic eosinophilic bronchitis

Brightling CE et al, NEJM 2002 p<0.001


Why is Eosinophilic Bronchitis not Asthma in nonasthmatic eosinophilic bronchitis


Why is eosinophilic bronchitis not asthma
Why is Eosinophilic Bronchitis not Asthma in nonasthmatic eosinophilic bronchitis


Nonasthmatic eosinophilic bronchitis cough reflex sensitivity
Nonasthmatic Eosinophilic Bronchitis in nonasthmatic eosinophilic bronchitis“Cough Reflex Sensitivity”

  • The cause of cough is the hightened cough reflex sensitivity (C5< 3.9uM ).

  • The therapy of inhaled or oral corticosteroid suppresse of coughing, sputum eosinophilia, and cough reflex sensitivity to inhaled capsaicin.

Gibson PG et al, Clin Exp Allergy 1998

Brightling CE et al, Eur Respir J 2000


The specific role of mast cells in the bronchial epithelium of patients with nonasthmatic eosinophilic bronchitis and its interactions with cough sensory afferents needs further study.


NAEB is generally benign and of patients with nonasthmatic eosinophilic bronchitis and its interactions with cough sensory afferents needs further study.

self-limiting disease (?)

Hancox RJ et al, Lancet 2001


Naeb may be forerunner the subsequent development of classic asthma and copd
NAEB of patients with nonasthmatic eosinophilic bronchitis and its interactions with cough sensory afferents needs further study.may be forerunner the subsequent development of classic asthma and COPD

52 patients with NAEB (1996-2003)

32 patients (follow up >1year)

  • 3 (9%) patients developedclassic asthma

  • 5 (16%) patients developedfixed airflow obstruction

Berry MA et al, Clin Exp Allegy 2005


Nonasthmatic eosinophilic bronchitis treatment
Nonasthmatic Eosinophilic Bronchitis of patients with nonasthmatic eosinophilic bronchitis and its interactions with cough sensory afferents needs further study.Treatment

  • Inhale corticosteroids (200-400 mcg)

  • Oral corticosteroids

  • Avoidance strategies

Brightling CE, Chest 2006


Nonasthmatic eosinophilic bronchitis
Nonasthmatic Eosinophilic Bronchitis of patients with nonasthmatic eosinophilic bronchitis and its interactions with cough sensory afferents needs further study.

Persistent eosinophilic inflammation

Airway remodelling

Progressive irreversible airflow obstruction



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