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 rec ent studies have confirmed that in fatal asthma there is a significant increase in the thickness of airway smooth muscle. For subjects who h ave had asthma and who died for other reasons or had a lobectomy, the increase in muscle layer thickness is less striking. An increase in sm ooth muscle mass could have a dual effect on airway narrowing: one due to the thickening of airway wall, the other due to a concomitant incr ease in force generation.. However, it. is not known whether the incre ased muscle mass, due either to hypertrophy or hyperplasia, is accompa nied by an increase in force. Proliferation of smooth muscle cells oft en produces noncontractile cells in vitro. Comparison of force generat ion by muscle preparations from asthmatic and control airways shows co nflicting results, with some studies demonstrating an increase in forc e 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 f orce velocity data are available for human airway smooth muscle. Howev er, there is some evidence for an increased amount of shortening in ai rway 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 elasta nce are in turn influenced by cytokines, matrix-degrading enzymes, and other inflammatory mediators present in the airways of asthmatic subj ects. Data from in vitro studies of a canine ''asthma model'' indicate an increase in both shortening velocity and amount of shortening comp ared with littermate control animals. An increase in the compliance of the parallel elastic element of the sensitized airway preparation cou ld account for the mechanical alterations.