The degree of pathological narrowing of the terminal bronchioles is strongly correlated with all physiologic indices of airflow obstruction, including the reduced FEV1. The small airways either are directly narrowed by inflammatory changes or, as in emphysema, lose the tethering effect provided by the surrounding lung parenchyma, which normally limits narrowing during expiration. Lungs of asymptomatic young smokers show clusters of macrophages in and around respiratory bronchioles. Other early pathological lesions include squamous cell metaplasia of the epithelium, chronic inflammation of airway walls, small foci of peribronchiolar fibrosis, and muscular hypertrophy of the bronchiolar wall. As the disease progresses, mural connective tissue, pigment, and muscle become more prominent and goblet cell metaplasia and mucosal ulcerations appear.
Mild bronchiolitis is probably a universal finding in young smokers.
The degree to which these terminal airways are narrowed by the inflammation is highly variable, however, and it is the degree of narrowing that has a strong correlation with obstruction, as measured by spirometry. A low-normal or mildly reduced FEV1 at a young age may indicate narrower terminal bronchioles and does increase the likelihood of symptomatic CAO if the patient continues to be exposed to cigarette smoke over subsequent years and decades. Conversely, if an asymptomatic cigarette smoker has a normal or higher than normal FEV1 at age 40, it is nearly certain that symptomatic CAO will not develop. These so-called nonsusceptible smokers may never suffer from CAO, but of course, they are not protected from lung cancer or from early atherosclerosis. The finding of increased numbers of macrophages in the walls of the respiratory bronchioles of young cigarette smokers may also have a bearing on the early stages of emphysema.