Towards restoring the physiological protection against airway narrowing in asthma : take a deep breath!

Abstract

Asthma is characterized by chronic airway inflammation and airway hyperresponsiveness. Deep inspirations affect airway narrowing and may therefore play a role in airway hyperresponsiveness in asthma. The studies described in this thesis were all directed at further elucidating the (patho)physiological mechanism underlying deep inspiration-induced bronchodilation or to restoring this protective mechanism in asthma. We showed that deep inspiration-induced bronchodilation is reduced in asthma and that this reduction is related to increased numbers of CD4+ lymphocytes in the bronchial submucosa and to increased numbers of mast cells in airway smooth muscle bundles in bronchial biopsies. In addition, impaired deep inspiration-induced bronchodilation is related to lower expression of several smooth muscle proteins (calponin, desmin, and MLCK) in bronchial biopsies, whereas lung function and airway hyperresponsiveness wa s related to higher expression of alpha-SM-actin, desmin and elastin. Further, pulmonary congestion had no influence on airway responses to deep inspiration as measured in patients with mitral valve disease. A course of high-dose corticosteroid treatment increased bronchodilation following deep inspiration in patients with asthma, whereas treatment with tiotropium for 21 days had no effect on airway responses to deep inspiration. Positive-pressure inflation of the lungs reduced airway narrowing, even in patients who showed no airway dilation following an active deep inspiration.