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Airway Epithelial Changes in Smokers but Not in Ex-Smokers with Asthma

¹ Department of Pathology, ² Department of Pulmonology, and ³ Pulmonary Rehabilitation Center Beatrixoord, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Correspondence and requests for reprints should be addressed to M. Broekema, Ph.D., Dept. of Pathology, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. E-mail: m.broekema{at}path.umcg.nl

Rationale: Smoking has detrimental effects on asthma outcome, such as increased cough, wheezing, sputum production, and frequency of asthma attacks. This results in accelerated lung function decline. The underlying pathological process of smoke-induced deterioration of asthma is unknown.

Objectives: To compare bronchial inflammation and remodeling in never-smokers, ex-smokers, and current smokers with asthma.

Methods: A total of 147 patients with asthma (66 never-smokers, 46 ex-smokers, and 35 current smokers) were investigated.

Measurements and Main Results: Lung function, exhaled nitric oxide levels, and symptom questionnaires were assessed, and induced sputum and bronchial biopsies were obtained for determination of airway inflammation and remodeling. Smokers with asthma had lower FEV₁ and alveolar and bronchial nitric oxide levels than never-smokers. Smokers also had more goblet cells and mucus-positive epithelium, increased epithelial thickness, and a higher proliferation rate of intact and basal epithelium than ex-smokers and never-smokers. Smokers had higher numbers of mast cells and lower numbers of eosinophils than never-smokers. Ex-smokers had similar goblet cell numbers and mucus-positive epithelium, epithelial thickness, epithelial proliferation rate, and mast cell numbers as never-smokers.

Conclusions: Smokers with asthma have epithelial changes that are associated with increased asthma symptoms, such as shortness of breath and phlegm production. The fact that epithelial characteristics in ex-smokers are similar to those in never-smokers suggests that the smoke-induced changes can be reversed by smoking cessation.

Key Words: cigarette smoking • airway inflammation • airway remodeling • smoking cessation • asthma symptoms

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Smoking has detrimental effects on asthma outcome, such as increased cough, wheezing, sputum production, and frequency of asthma attacks. This ultimately results in accelerated lung function decline. The underlying pathological process of smoke-induced deterioration of asthma is unknown. What This Study Adds to the Field This study shows that smoking in asthma induces epithelial changes, thereby possibly increasing asthma symptoms such as shortness of breath and phlegm production. The fact that epithelial characteristics were similar in ex-smokers and never-smokers with asthma suggests that the smoke-induced changes can be reversed by smoking cessation.