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Published ahead of print on October 1, 2009
Am. J. Respir. Crit. Care Med. 2009, doi:10.1164/rccm.200906-0828OC
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Submitted on June 3, 2009
Accepted on September 30, 2009

Airway Epithelial Changes in Smoking but not in Ex-Smoking Asthmatics

Martine Broekema1*, Nick H.T. ten Hacken2, Franke Volbeda3, Monique E. Lodewijk1, Machteld N. Hylkema4, Dirkje S. Postma2, and Wim Timens4

1 Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, 2 Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, 3 Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Pulmonary Rehabilitation Center Beatrixoord, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, 4 Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

* To whom correspondence should be addressed. E-mail: m.broekema{at}path.umcg.nl.

Rationale: Smoking has detrimental effects on asthma outcome defined by increased cough, wheezing, sputum production and frequency of asthma attacks. This ultimately results in accelerated lung function decline. At present, the underlying pathological process of smoke-induced deterioration of asthma is unknown. Objective: To compare bronchial inflammation and remodeling in never-, ex- and current smoking asthma patients. Methods:147 asthma patients, 66 never-smokers, 46 ex-smokers and 35 current smokers were investigated. Measurements: 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. Main results: Smoking asthmatics had lower FEV1 and alveolar and bronchial nitric oxide levels than never-smokers. In addition, smokers had more goblet cells and mucus-positive epithelium, increased epithelial thickness and a higher proliferation rate of intact and basal epithelium than ex- and never-smokers. Additionally, 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, and similar epithelial thickness, epithelial proliferation rate and mast cell numbers as never-smokers. Conclusions: Smoking asthma patients have epithelial changes that associate 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







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