Airway responsiveness to methacholine: effects of deep inhalations and airway inflammation

We determined the dose-response curves to inhaled methacholine (MCh) in 16 asthmatic and 8 healthy subjects with prohibition of deep inhalations (DIs) and with 5 DIs taken after each MCh dose. Flow was measured on partial exp iratory flow-volume curves at an absolute lung volume (plethysmographically determined) equal to 25% of control forced vital capacity (FVC). Airway in flammation was assessed in asthmatic subjects by analysis of induced sputum . Even when DIs were prohibited, the dose of MCh causing a 50% decrease in forced partial flow at 25% of control FVC (PD(50)MCh) was lower in asthmati c than in healthy subjects (P < 0.0001). In healthy but not in asthmatic su bjects, repeated DIs significantly decreased the maximum response to MCh [f rom 90 +/- 4 to 62 +/- 8 (SD) % of control, P < 0.001], increased PD(50)MCh (P < 0.005), without affecting the dose causing 50% of maximal response. I n asthmatic subjects, neither PD(50)MCh when DIs were prohibited nor change s in PD(50)MCh induced by DIs were significantly correlated with inflammato ry cell numbers or percentages in sputum. We conclude that 1) even when DIs are prohibited, the responsiveness to MCh is greater in asthmatic than in healthy subjects; 2) repeated DIs reduce airway responsiveness in healthy b ut not in asthmatic subjects; and 3) neither airway hyperresponsiveness nor the inability of DIs to relax constricted airways in asthmatic subjects is related to the presence of inflammatory cells in the airways.