Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo

Inflammatory changes and airway wall thickening are suggested to cause increased airway responsiveness in patients with asthma. In five sheep, 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 bronchial artery. At 4 cmH₂O transpulmonary pressure (Ptp), 5 μg/ml MCh constricted the airways to a maximum of 18 ± 3%. At 30 cmH₂O Ptp, MCh resulted in less constriction (to 31 ± 5%). Bradykinin increased airway wall area at 4 and 30 cmH₂O Ptp (159 ± 6 and 152 ± 4%, respectively; P < 0.0001). At 4 cmH₂O Ptp, bradykinin decreased airway luminal area (13 ± 2%; P < 0.01), and the dose-response curve was significantly lower (P = 0.02). At 30 cmH₂O, postbradykinin, the maximal airway narrowing was not significantly different (26 ± 5%; P = 0.76). Bradykinin produced substantial airway wall thickening and slight potentiation of the MCh-induced airway constriction at low lung volume. At high lung volume, bradykinin increased wall thickness but had 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.