In contrast to methacholine, a stimulus that induces airway constriction mainly by" direct" stimulation of airway smooth muscle cells, AMP airway responsiveness reflects" indirectly" induced airway narrowing via inflammatory or neural reflex mechanisms. In order to determine inflammatory contribution to airway narrowing in COPD, we performed AMP and methacholine inhalation provocation tests in nonatopic subjects with COPD and compared the results with those obtained from atopic nonsmoking asthmatics and from healthy smoking volunteers. AMP caused airway narrowing in all but two subjects with COPD and in only three of the 12 healthy smoking subjects. Patients with COPD were significantly more responsive to AMP and methacholine than were healthy smoking volunteers. Geometric mean PC20 AMP was significantly lower in the smokers with COPD (7.2 mg/ml) than in the nonsmokers with COPD (58.5 mg/ml), whereas PC20 methacholine values and baseline FE~ were comparable. In the nonatopic nonsmoking subjects with COPD, PC20 AMP was significantly higher than in the atopic nonsmoking asthmatics (3.8 mg/ml), whereas they responded similar to methacholine provocation. These results indicate that most subjects with COPD respond to AMP provocation and that smoking determines the degree of airway responsiveness to AMP in COPD. We suggest that increased susceptibility to mediator release by mast cells or neural reflex mechanisms are involved in AMP-induced airway constriction in asthma and in COPD.

Airway hyperresponsiveness (AH) is defined as an exaggerated airway constrictive reaction on exposure to a provoking stimulus and is a characteristic feature in subjects with chronic obstructive pulmonary disease (COPD) and asthma (1, 2). However, it is recognized that the kind of stimulus used matters and that differences in responsiveness between COPD and asthma exist when" direct" and" indirect" stimuli are used for provocation (3). Methacholine is regarded as a direct stimulus that acts mainly via muscarinic receptors on smooth muscle cells. Upon methacholine challenge airway constriction is induced in both COPD and asthma, though generally in asthma the sensitivity is higher and the slope of the dose-response curve is steeper than in COPD (4, 5).