The Bronchial Response, but not the Pulmonary Response to Inhaled Methacholine Is Dependent on the Aerosol Deposition Pattern
Asthma is characterized by increased bronchial responsiveness to a variety of pharmacologic and immunologic stimuli of the bronchial mucosa. Bronchial responsiveness to inhaled parasympathomimetic agents, eg, methacholine, is used in clinical settings to estimate the intensity of the asthmatic process. Stimulation of muscarinic receptors on airway smooth muscle cells and submucosal glands induces airway muscle contraction and mucus secretion. Several animal studies have shown different types of pharmacologic responsiveness in different airway generations, and in humans, less histamine was required to produce bronchoconstriction when deposited in the large, central airways, than when it was distributed in the small, peripheral airways. Heterogeneity of muscarinic receptor localization has also been suggested in humans, and the intra-pulmonary aerosol pattern determined the bronchial responsiveness to methacholine in clinical studies. there
Studies on animals revealed that cholinergic smooth muscle receptors tend to influence bronchomotor tone both in large and small airways down to the level of the respiratory bronchiole and alveolar duct. Involvement of gas-exchanging elements after a bronchial challenge with methacholine has also been suggested in humans. To the best of our knowledge, there has been no report on heterogeneity of responses of the gas-exchanging elements after deposition of bronchoconstrictors in central and peripheral airways.
In the present study, we evaluated whether identical doses of nebulized methacholine elicit different responses in airway constriction and gas exchange, dependent on the site of deposition of the aerosol. Eight asthmatics inhaled matched and identical doses of radio-labeled methacholine. To avoid changing pattern of aerosol deposition during the provocation procedure, the aerosols were given as “single” doses during 3 min in two separate experiments, with the bulk of the aerosol deposited either in the central or the peripheral airways.