The effect of age and duration of disease on airway structure in fatal asthma

We hypothesized that if airway remodeling is related to duration of asthma, that when matched for severity, the airways of older adults should show gr eater alterations than the airways of younger adults. Using standard morpho metric techniques, we compared airways with basement membrane perimeters (P bm) between 2 and 10 mm from young individuals who died of asthma (n = 14, range 17-23 yr), and older individuals with fatal asthma (n = 13, range 40- 49 yr). Comparisons were also made with normal airways from age-matched adu lts. Wall area was increased in old individuals with fatal asthma compared with young individuals with fatal asthma, primarily due to greater adventit ial area, whereas wall area in young individuals with fatal asthma was not different from control subjects. Within muscle bundles the connective tissu e matrix was increased around individual cells in individuals with asthma, unrelated to age. After adjustment for this change, smooth muscle area in b oth asthma groups was still greater than in age-matched control subjects, i n old individuals with fatal asthma 4-fold greater (p = 0.04), and in young individuals with fatal asthma 2-fold greater (p = 0.03). Airway narrowing was increased in old versus young individuals with fatal asthma, with both groups more narrowed than control subjects. Intralumenal obstruction and su bepithelial collagen in the two asthma groups were significantly greater th an in control subjects, but there was no age effect. These data provide sup port for the hypothesis that there is an increase in airway wall area, incl uding smooth muscle, and airway narrowing with increasing duration of sever e asthma or with older age. The observation that total wall thickness was n ot greater in young individuals with young fatal asthma than in control sub jects suggests that factors other than airway wall geometry contribute to t he pathogenesis of fatal attacks in this age group.