Structural and functional changes in the airway smooth muscle of asthmatic subjects.

It has been recognized since the early 1920s that the amount of smooth muscle in asthmatic subjects' airways is markedly increased. More recent studies have confirmed that in fatal asthma there is a significant increase in the thickness of airway smooth muscle. For subjects who have had asthma and who died for other reasons or had a lobectomy, the increase in muscle layer thickness is less striking. An increase in smooth muscle mass could have a dual effect on airway narrowing: one due to the thickening of airway wall, the other due to a concomitant increase in force generation. However, it is not known whether the increased muscle mass, due either to hypertrophy or hyperplasia, is accompanied by an increase in force. Proliferation of smooth muscle cells often produces noncontractile cells in vitro. Comparison of force generation by muscle preparations from asthmatic and control airways shows conflicting results, with some studies demonstrating an increase in force in asthmatic muscle preparations and others showing no increase. The discrepancy could be due to a failure to take into account the length-tension relationship of the muscle preparations in some studies. No force velocity data are available for human airway smooth muscle. However, there is some evidence for an increased amount of shortening in airway smooth muscle preparations from patients with asthma. This could be due to an increase in force generation and/or a decrease in tissue elastance in asthmatic airways. Muscle contractility and tissue elastance are in turn influenced by cytokines, matrix-degrading enzymes, and other inflammatory mediators present in the airways of asthmatic subjects. Data from in vitro studies of a canine "asthma model" indicate an increase in both shortening velocity and amount of shortening compared with littermate control animals. An increase in the compliance of the parallel elastic element of the sensitized airway preparation could account for the mechanical alterations.