The Structure of Large and Small Airways in Nonfatal and Fatal Asthma

Abstract

Asthma is characterized by excessive airway narrowing and airway wall inflammation. In cases of fatal asthma, increased thickness of the airway wall is observed and may account for excessive airway narrowing when smooth muscle contracts. This study was undertaken to examine airway dimensions in large and small airways in both fatal and nonfatal cases of asthma. Airway wall areas (total, inner, and outer relative to smooth muscle layer), epithelial integrity, smooth muscle shortening, and the areas of smooth muscle, cartilage, and mucous glands were compared in transverse sections of large and small airways of subjects dying of asthma (fatal asthma, n = 11), those dying suddenly of nonrespiratory diseases and having a definite history of asthma (nonfatal asthma, n = 13), and those dying suddenly without any history of respiratory illness (control, n = 11). Airways were grouped by size using the basement membrane perimeter for comparison. All areas were expressed as areas per millimeter of basement membrane. In cartilaginous airways, the cases of fatal asthma had greater (p < 0.05) total wall, inner wall, outer wall, smooth muscle, mucous gland and cartilage areas than did control and nonfatal cases. The inner wall area was greater in the fatal and nonfatal cases than in the control cases (p < 0.05) in the small cartilaginous airways and membranous bronchioles (MB). In small MB (perimeter < 2 mm), the total and outer wall areas were greater (p < 0.05) in cases of fatal and nonfatal asthma than in control cases. In large MB (perimeter, 2 to 4 mm), the area of smooth muscle was greater in fatal and nonfatal cases than in control cases (p < 0.05), but there were no differences between fatal and nonfatal cases of asthma. Smooth muscle shortening and epithelial disruption varied greatly between cases, but there were no significant differences between groups in large or small airways. It is concluded that structural changes that may increase airway responsiveness occur in large and small airways in fatal asthma, but they occur predominantly in the small airways in nonfatal cases of asthma. Whether these changes, when widespread, predispose to death from asthma or result from more severe disease is unknown.