INTERACTION BETWEEN AIRWAY EDEMA AND LUNG-INFLATION ON RESPONSIVENESSOF INDIVIDUAL AIRWAYS IN-VIVO

Inflammatory changes and airway wall thickening are suggested to cause increased airway responsiveness in patients with asthma. In five shee p, the dose-response relationships of individual airways were measured at different lung volumes to methacholine (MCh) before and after wall thickening caused by the inflammatory mediator bradykinin via the bro nchial artery. At 4 cmH(2)O transpulmonary pressure (Ptp), 5 mu g/ml M Ch constricted the airways to a maximum of 18 +/- 3%. At 30 cmH(2)O Pt p, MCh resulted in less constriction (to 31 +/- 5%). Bradykinin increa sed airway wall area at 4 and 30 cmH(2)O Ptp (159 +/- 6 and 152 +/- 4% , respectively; P < 0.0001). At 4 cmH(2)O Ptp, bradykinin decreased ai rway luminal area (13 +/- 2%; P < 0.01), and the dose-response curve w as significantly lower (P = 0.02). At 30 cmH(2)O, postbradykinin, the maximal airway narrowing was not significantly different (26 +/- 5%; P = 0.76). Bradykinin produced substantial airway wall thickening and s light potentiation of the MCh-induced airway constriction at low lung volume. At high lung volume, bradykinin increased wall thickness but h ad no effect on the MCh-induced airway constriction. We conclude that inflammatory fluid leakage in the airways cannot be a primary cause of airway hyperresponsiveness.