Commentaries on Viewpoint: Airway smooth muscle and airway hyperresponsiveness in human asthma: have we chased the wrong horse?

TO THE EDITOR: The Viewpoint by Professor Lutchen is timely and appropriate (3). There is now uncertainty as to the importance of airway smooth muscle (ASM) dynamics to normal airway function and whether disruption in the airway-lung dynamic environment contributes to airway hyperresponsiveness (AHR). Seemingly negative findings in airways in vitro, in which simulated tidal breathing failed to provide dominant control of airway responsiveness (1, 2, 4, 5), have led to the trepidation so clearly expressed by Lutchen in assigning too much importance to this dynamic mechanism. Although Lutchen proposes that the “chasm between a tiny piece of excised ASM tissue and a breathing lung inside a human is enormous” we are not sure bronchial tubes do not leave a large gap unbridged. Although bronchial tubes are our own preferred model, can we be sure the “real breathing” matches what happens during a bronchial challenge? How large are the transmural pressures and how much does the ASM stretch if respiratory effort is increased to overcome the added impedance? We also do not share the fear that the literature concentrates too much on ASM dynamics. There is enough information on airway inflammation and innervation in airway disease to fill textbooks many times over, yet no compelling mechanism surfaced to explain AHR. Much could be gained by revisiting early work under more physiologically relevant dynamic conditions. The field has not simply backed one horse. Present and past strategies are to make several wagers, at a greater outlay, but increasing the probability of a win.