Airway remodeling: Potential contributions of subepithelial fibrosis and airway smooth muscle hypertrophy/hyperplasia to airway narrowing in asthma

Recently, much attention has been focused on the airway structural changes accompanying chronic, severe asthma, and the potential ramifications of the se changes for airway function and medical management. Airway remodeling ma y exaggerate airway narrowing by: (i) thickening of the aint airway wall in ternal to the smooth muscle, thereby increasing the luminal obstruction gen erated by a given degree of smooth muscle shortening; (ii) increasing the a mount of smooth muscle, thereby increasing shortening; and/or (iii) reducin g the load on the smooth muscle, either by increasing the compliance of the airway wall or by reducing airway-parenchymal interdependence. The possibi lity also exists that airway remodeling represents a protective mechanism a gainst excessive airway narrowing. The major airway structural changes occu rring in asthma are subepithelial protein deposition and increased airway s mooth muscle mass (hypertrophy: hyperplasia. or both). Several investigator s have found correlations between the magnitudes of subepithelial thickenin g and smooth muscle hypertrophy/hyperplasia and the severity of airways dis ease, though interpretation has been made difficult by study differences in patient population, treatment, indices of disease severity, and morphometr ic technique. Taken together, these data suggest that increases in airway r emodeling may contribute significantly to the airflow obstruction observed in patients with asthma. However, data proving a causal relationship betwee n airway remodeling and asthma severity remain elusive.