Asthma and lower airway diseaseAn ex vivo model of severe asthma using reconstituted human bronchial epithelium
Section snippets
Methods
Additional details are provided in the Methods section in this article’s Online Repository at www.jacionline.org.
Patients with mild (n = 7) and severe (n = 12) asthma were recruited at the Arnaud de Villeneuve Hospital, Montpellier, France. Asthma was diagnosed based on the presence of clinical features consistent with asthma and objective measures of variable airflow obstruction investigated 15 minutes before bronchoscopy (improvement in FEV1 of ≥15% after inhalation of 200 μg of salbutamol).
Demographic data
Bronchial biopsy specimens were obtained from 19 subjects (7 with mild and 12 with severe asthma). Demographic characteristics are reported in Table I. Patients with severe asthma had greater airflow impairment (FEV1 percentage) than those with mild asthma, and their symptoms were uncontrolled (daily symptoms and exacerbation rate) despite treatment. Biopsy specimens were analyzed from 5 control subjects (ie, no asthma, no allergies, nonsmokers, with normal results from chest radiographs and
Discussion
We developed air-liquid interface cultures of bronchial epithelial cells and demonstrated that they maintained characteristics specifically associated with mild and severe asthma. Functional and morphologic analyses of these cultures revealed epithelial differences associated with disease severity. Samples from patients with severe asthma differed in mucus production, cytokine production (sustained IL-8 release), and resolution mechanisms (a defect in LXA4 production associated with
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Disclosure of potential conflict of interest: P. Chanez is a consultant for Amgen, AstraZeneca, Centocor, Chiesi, GlaxoSmithKline, MSD, Novartis, and Nycomed and has received research support from Centocor. The rest of the authors declare that they have no relevant conflicts of interest.