1 Asthmatic Cough Asthmatic Cough (Cough variant asthma) & (Cough variant asthma) & Nonasthmatic Eosinophilic Nonasthmatic Eosinophilic Bronchitis Bronchitis Necla Songür, MD Necla Songür, MD Süleyman Demirel University School of Süleyman Demirel University School of Medicine Medicine Department of Chest Diseases Department of Chest Diseases
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. - PowerPoint PPT Presentation
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Chronic cough lasting more than 8 weeks Chronic cough lasting more than 8 weeks Absence of a history of wheezing or Absence of a history of wheezing or dyspneadyspneaAbsence of post-nasal drip Absence of post-nasal drip Physical examination of lungs is normalPhysical examination of lungs is normalChest roentgenography is normalChest roentgenography is normal
Detection of Eosinophils in Hypertonic Saline-Induced Sputum in Patients with Chronic Nonproductive Cough
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GroupGroup nn varvar %%
yokyok %%
no.no.%%
no.no.%%
no.no.%%
BronchialBronchialasthmaasthma
2525 25 25 (100 %)(100 %)
0 0 ( 0 %)( 0 %)
15 15 (60.9%)(60.9%)
10 10 (40%)(40%)
00
CoughCoughvariant variant asthmaasthma
1212 8 8 (66%)(66%)
4 4 (33.3%)(33.3%)
3 3 (37.5%)(37.5%)
5 5 (62.5%)(62.5%)
00
Atopic Atopic coughcough
1717 1515( 88 %)( 88 %)
22(11.8%)(11.8%)
1212( 80 %)( 80 %)
33(20%)(20%)
00
ControlControl 2323 22( 8.6 %)( 8.6 %)
2121( 91.3%)( 91.3%)
00( 0 %)( 0 %)
22(100%)(100%)
00
Presence of Eosinophils in Induced sputum in Each Patients Group
Eosinophils 1-25 % 26-75 % 76-100 %
Songür N et al, J Asthma 1997
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Percentage of Eosinophils in BAL and Percentage of Eosinophils in BAL and Number of Eosinophils in Bronchial TissueNumber of Eosinophils in Bronchial Tissue
Niimi A et al, Eur Res J 1998
1515Niimi A et al, Lancet 2001
Eosinophilic inflammation in patients with CVA may cause remodelling of the airway.
Control CVA Asthma
Sub
epith
elia
l lay
er th
ickn
ess
(µm
)
1616
De Diego et al, Allergy 2005
IL5 IL8 TNFά
Cough variant asthma and asthma share a similar airway inflammatory marker profile
1717
Cough variant asthma comprises a Cough variant asthma comprises a subgroup of asthmasubgroup of asthma
Eosinophilic airway inflammation in asthma Eosinophilic airway inflammation in asthma and cough variant asthma is similar.and cough variant asthma is similar.
The ratio of eosinophilic inflammation is not The ratio of eosinophilic inflammation is not related to differences between symptoms of related to differences between symptoms of cough variant asthma and classic asthmacough variant asthma and classic asthma
within normal limits (Cwithin normal limits (C55>3.9>3.9µµMM) )
not a feature of diseasenot 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
2121
Cough Variant AsthmaCough Variant Asthma
Cough in the middle of the night and early Cough in the middle of the night and early in the morningin the morningPEFR monitoring PEFR monitoring →→ morning dip morning dipIncrease in FEV1 after therapyIncrease in FEV1 after therapyRelief of cough with bronchodilator Relief of cough with bronchodilator
therapytherapyShirata et al, Respirology 2005Sano T et al, Lung 2004Fujimura M et al, Clin Exp Allergy 2003Kim CK et al, Clin Exp Allergy 2003
2222
Cough Cough VariantVariant asthma asthma
Small degree contractions of airway Small degree contractions of airway smooth muscle trigger cough.smooth muscle trigger cough.
2323
Cough Variant AsthmaCough Variant Asthma
Pre-asthmatic statePre-asthmatic state
Early stage of mild persistant asthmaEarly stage of mild persistant asthma
2424
Study/Year CVA (n) Median fallow up (year) AsthmaStudy/Year CVA (n) Median fallow up (year) Asthma (%) (%)
Corrao et al 1979Corrao et al 1979 6 1 2 (33) 6 1 2 (33) Braman et al 1985Braman et al 1985 16 3-5 6 (37)16 3-5 6 (37) Kim et al 2003Kim et al 2003 51 4 24 (47)51 4 24 (47)
Fujimura et al 2003Fujimura et al 2003 55 4 8 (14) 55 4 8 (14)
Fujimura et al 2005Fujimura et al 2005 20 3 3 (15) 20 3 3 (15)
Fujimura et al 2005Fujimura et al 2005 27 4 7 (29) 27 4 7 (29)
Nearly 30% of cough variant asthma develop typical asthma within several years
25250
10
20
30
40
50
60
70
80
D
evel
opm
ent o
f Cla
ssic
Ast
hma
% Cough Variant Asthma
Predictor of Subsequent Development of Classic Asthma
An increased ratio of
eosinophil in induced
sputum can predict the subsequent
development of classic asthma
Kim CK et al, Clin Exp Allergy 2003
0-2.4 2.5-4.7 4.8-8.2 8.3-17.3
Sputum eosinophil (%)
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CoughCough Variant AsthmaVariant Asthma Predictors of Subsequent Development of Predictors of Subsequent Development of
Classic AsthmaClassic Asthma
Univariate analysisUnivariate analysis
Bronchial Bronchial hyperresponsivenesshyperresponsivenessBlood eosinophils (%) Blood eosinophils (%) No use of inhaled No use of inhaled corticosteroidscorticosteroids
Isolated chronic cough lasting more than 8 Isolated chronic cough lasting more than 8 weeks weeks Absence of a history of wheezing and Absence of a history of wheezing and dyspneadyspneaAbsence of post-nasal drip Absence of post-nasal drip Physical examination of lungs is normalPhysical examination of lungs is normalChest roentgenography is normalChest roentgenography is normal
The cause of cough is the hightened The cause of cough is the hightened cough reflex sensitivity cough reflex sensitivity (C5< 3.9(C5< 3.9uuM ). M ). The therapy of inhaled or oral The therapy of inhaled or oral corticosteroid suppresse of coughing, corticosteroid suppresse of coughing, sputum eosinophilia, and cough reflex sputum eosinophilia, and cough reflex sensitivity to inhaled capsaicinsensitivity to inhaled capsaicin..
Gibson PG et al, Clin Exp Allergy 1998Brightling CE et al, Eur Respir J 2000
4141
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.
4242
NAEB is generally benign andNAEB is generally benign and self-limiting disease (?)self-limiting disease (?)
Hancox RJ et al, Lancet 2001
4343
NAEBNAEB may be forerunner the subsequent may be forerunner the subsequent development of classic asthma and COPDdevelopment of classic asthma and COPD
52 patients with NAEB (1996-2003)52 patients with NAEB (1996-2003) 32 patients (follow up >1year)32 patients (follow up >1year)
The early diagnosis and The early diagnosis and suscessful treatment is very suscessful treatment is very important in patients with NAEB. important in patients with NAEB.