Increased in vitro histamine responses in human small airways smooth muscle from patients with chronic obstructive pulmonary disease

Abstract

We tested the hypothesis that abnormal responses of airway smooth muscle contribute to the pathogenesis of airway obstruction in chronic obstructive pulmonary disease (COPD). For this purpose, lung tissue from 10 patients with and 10 patients without COPD was obtained during thoracotomies. Lung function was measured preoperatively. The in vitro responses of isolated bronchioles were measured using histamine, leukotriene (LT)C4, and methacholine as contracting agents, and the results of the in vitro measurements were compared between patients with and without COPD. Histamine efficacy (maximal isometric force, Tmax) in vitro of bronchioles from patients with COPD was significantly greater than the histamine Tmax of the bronchioles from patients without COPD (p less than 0.01). This difference was probably not due to histamine tachyphylaxis or the production of relaxing prostaglandins by airways without COPD, as neither mechanism could be detected in separate experiments on airways without COPD. No differences were found between in vitro bronchiolar responses to LTC4 and methacholine in patients with and patients without COPD. Increased histamine responses of small airways may be one of the determinants of airway obstruction in COPD.