Potential mechanism of hyperresponsive airways

It has been known for many years that the response of asthmatic subjects to a deep inspiration differs from that observed in normal healthy subjects. A deep inspiration causes a decrease in airway resistance in normal subject s, whereas asthmatics demonstrate either no change or a slight increase in airway resistance. It has been suggested by several investigators that the inability to dilate airways during lung inflation may be a primary defect i n asthma. One study (Skloot and colleagues, J. Clin. Invest. 1995;96:2393-2 403) showed that in the absence of a deep inspiration during methacholine ( MCh) challenge, normal subjects had a greatly exaggerated and sustained res ponse to this agonist. It was suggested that asthmatic airways could be mod eled by this condition in normal, subjects. Other investigators, however, s uggest that there are more intrinsic differences between the responses to l ung inflation in airways from asthmatic and normal subjects (Brusasco and c olleagues, J. Appl. Physiol. 1999;87:567-573). Resolution of this controver sy requires the ability to assess the responses of airways directly, but un fortunately conventional pulmonary function tests in human subjects are not specific enough to allow this evaluation. In the present study, we have pe rformed experiments using a direct imaging approach that allows us to obtai n measurements of airway and parenchymal dimensions that can be used to tes t the responses of individual airways to deep inspiration in vivo. Our resu lts show that the presence of normal tidal stresses allows airway smooth mu scle to respond normally to deep inspirations. Removing tidal stresses at F RC after MCh challenge is sufficient to change the normal dilatory response to deep inspiration into an abnormal one of contraction. Altered sensitivi ty of airway smooth muscle to normal tidal stresses thus may be operative i n the development of the asthmatic pathology.