Chronic cough resembles asthma with IL-5 and granulocyte-macrophage colony-stimulating factor gene expression in bronchoalveolar cells

doi:10.1016/S0091-6749(98)70242-8

Journal of Allergy and Clinical Immunology

Volume 101, Issue 3, March 1998, Pages 320-326

https://doi.org/10.1016/S0091-6749(98)70242-8 Get rights and content

Abstract

Background: Chronic cough is a multifactorial condition, which, like asthma, can be associated with eosinophilic airway inflammation. In asthma, airway eosinophilia is believed to be mediated by cytokines such as interleukin-5 and granulocyte-macrophage colony stimulating factor (GM-CSF). The role of these cytokines in chronic cough is unclear. Objective: The aim of this study was to examine gene expression for IL-5 and GM-CSF in chronic cough and compare the results with those found in asthma. Methods: We studied adults with asthma (n = 12), chronic cough responsive to inhaled corticosteroid (ICS-responsive cough) (n = 9), and chronic cough not responsive to inhaled corticosteroid (non-ICS–responsive cough) (n = 4). Bronchoalveolar lavage (BAL) was performed, and cytokine gene expression was assessed by using a semiquantitative reverse transcriptase polymerase chain reaction. Results: IL-5 mRNA was expressed by BAL cells from nine of 12 asthmatic subjects and six of nine subjects with ICS-responsive chronic cough. IL-5 mRNA was not detected in subjects with non-ICS–responsive chronic cough (zero of four subjects, p < 0.05). GM-CSF mRNA was expressed in BAL cells from seven of 12 asthmatic subjects and six of nine subjects with ICS-responsive cough. GM-CSF mRNA was not detected in non-ICS responsive cough subjects (zero of four subjects, p < 0.05). GM-CSF gene expression was related to the degree of methacholine airway responsiveness in asthmatic subjects (r = –0.59). Conclusion: We conclude that chronic cough, like asthma, is associated with airway inflammation and gene expression for IL-5 and GM-CSF. Ongoing expression of these cytokines is likely to be related to the persistence of airway inflammation and chronic cough. (J Allergy Clin Immunol 1998;101:320-6.)

Section snippets

Subjects

Adult nonsmokers (n = 25) were recruited from patients attending the Respiratory Medicine Unit at John Hunter Hospital, and their clinical characteristics are shown in Table I. Asthmatic subjects (n = 12) gave a history of episodic cough, wheeze, or breathlessness and had objective evidence of methacholine airway hyperresponsiveness (PD₂₀ < 4 μmol) or FEV₁ bronchodilator responsiveness of greater than 20%. The asthmatic subjects had controlled asthma on the basis of stable symptoms and

Bronchoscopy and cell counts

Bronchoscopy was performed safely in each subject. BAL recovered 66% of the instilled fluid, which contained an average cell number 16 to 30 × 10⁴ cells/ml in the three groups (Table III).

. Cell counts in BAL and brushings (mean [SEM])

	Asthma	Chronic Cough(ICS-responsive)	Chronic cough(non-ICS–responsive)
BAL
Percent return	69 (3)	68 (3)	63 (2)
Total cell count× 10⁴/ml	16 (2)	25 (3)	26 (7)
Macrophages (%)	84 (4)	87 (4)	88 (2)
Lymphoctytes (%)	3.6 (1.2)	1.7 (0.7)	1.1 (0.8)
Neutrophils (%)	4.8 (2.8)	3.6 (2.1)	3.2 (1.9)

DISCUSSION

This study confirms the presence of eosinophilic bronchitis in chronic cough that is responsive to ICS therapy, and has identified the novel finding of IL-5 and GM-CSF gene expression in this condition. Chronic cough and asthma appear to share a common pattern of inflammation in terms of both cellular infiltration and inflammatory cytokine gene expression. This profile can also persist in subjects with controlled asthma treated with ICS. In asthma, GM-CSF mRNA was related to the severity of

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Citation Excerpt :
EB is defined by an increase of eosinophils in sputum, but it lacks AHR, in contrast to CVA [5,12,23,24]. Metachromatic cells (mast cells or basophils) are increased in sputum and mucosal brushings as well [23,25]. Patients with EB and those with asthma similarly showed an increase of epithelial, subepithelial and BAL eosinophils and SBM thickness compared with healthy controls [5].
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^☆: From ^aRespiratory Medicine Unit, John Hunter Hospital, Newcastle; ^bCancer Research Unit, Faculty of Medicine and Health Sciences, University of Newcastle, Newcastle; and ^cCenter for Immunology, St. Vincent's Hospital, Sydney.

^☆☆: Supported by the National Health and Medical Research Council of Australia, the Asthma Foundation of New South Wales, and the Rebecca L. Cooper Medical Research Foundation.

^★: Reprint requests: Peter G. Gibson, MBBS, FRACP, Respiratory Medicine Unit, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, NSW 2310.

^★★: 1/1/87712

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Chronic cough resembles asthma with IL-5 and granulocyte-macrophage colony-stimulating factor gene expression in bronchoalveolar cells☆,☆☆,★,★★

Abstract

Section snippets

Subjects

Bronchoscopy and cell counts

DISCUSSION

Pediatr Clin North Am

Lancet

J Allergy Clin Immunol

Anal Biochem

J Allergy Clin Immunol

Chronic cough: the spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy

Am Rev Respir Dis

A systematic evaluation of mechanisms in chronic cough

Am J Respir Crit Care Med

Inhaled glucocorticosteroids in chronic cough

Bronchial epithelial inflammation in children with chronic cough after early lower respiratory tract illness

Am Rev Respir Dis

Chronic cough with eosinophilic bronchitis examination for variable airflow obstruction and response to corticosteroid

Clin Exp Allergy

Airway inflammation in non asthmatic subjects with chronic cough

Am J Respir Crit Care Med

IL-5 is the predominant eosinophil-active cytokine in the antigen-induced pulmonary late-phase reaction

Am Rev Respir Dis