ABSTRACT
Asthma, a chronic disease characterized by airway hyperreactivity, occurs in 5-8% of the U.S. population and is an extraordinarily common cause of pul monary impairment. Despite considerable research effort, asthma mortality rates continue to rise and the primary defects that underlie airway hyperreac tivity are unknown, although an intrinsic abnormality of airway smooth muscle (ASM) has been postulated (1-3). Increased smooth muscle mass in airways of patients with chronic severe asthma is a well-documented pathological finding. Studies have reported that this increased ASM mass is due to an in creased number of airway myocytes (4-7). Some information is available with respect to factors that promote ASM cell proliferation; however, few studies to date have addressed cellular mechanisms that regulate ASM cell growth. Such studies are critical for an understanding of the pathogenesis of chronic severe asthma. We postulate that frequent stimulation of ASM by contractile
agonists, inflammatory mediators, and growth factors induces chronic adaptive alterations in the airways that result in myocyte proliferation and airway re modeling. Such alterations may have important consequences in determining airway caliber and airway smooth muscle contractility. Proliferation of smooth muscle as described above significantly alters force generation by the muscle (8-10). Compelling evidence suggests that smooth muscle cells undergo pro liferation in response to a variety of chemical and trophic stimuli, and these alterations profoundly affect the force-generation of the muscle (8-10).
