Tobacco smoke effects on the small airways can often be measured physiologically as an obstructive change in FEV₁, more specifically in FEF_25%-75% or FEF_75%. When clinically significant, these changes are referred to as small-airway disease. However, FEV₁, FEF_25%-75%, and FEF_75% do not distinguish between proximal (membranous or terminal) and distal (respiratory) bronchioles.

Tobacco smoke causes morphologic changes in both the respiratory bronchioles and the membranous (terminal) bronchioles. These changes may be observed together or in combination with other tobacco-related changes such as emphysema. Bronchiolitis of little or no clinical significance can frequently be observed in lung tissue from many smokers. In patients with clinical chronic obstructive pulmonary disease, physiologic obstruction and severity of clinical disease appear to correlate with the severity of histologic bronchiolitis.

Membranous (terminal) bronchiolitis may be seen in occasional membranous bronchioles of smokers or may be more extensive and accompanied by other smoking-related changes, including emphysema, respiratory bronchiolitis, and/or desquamative interstitial pneumonia. The histopathologic changes of membranous (terminal) bronchiolitis include lymphocytic infiltrates of the bronchiolar wall, smooth-muscle hyperplasia, adventitial fibrosis, and hyperplasia and metaplasia of bronchiolar epithelium. Goblet-cell metaplasia of the membranous bronchiolar epithelium (normally goblet cells are not found in the bronchiolar epithelium) may be accompanied by mucus plugs. Macrophages containing finely granular brown pigment (smoker’s pigment), such as those seen in respiratory bronchiolitis and desquamative interstitial pneumonia, are often seen in the lumens of the membranous bronchioles, as well as in the lumens of adjacent respiratory bronchioles, alveolar ducts, and alveoli. Histiocytes containing the same finely granular brown pigment and/or macrophages containing coarse black anthracotic pigment may also be seen in the fibrotic walls of membranous bronchioles.