Pathophysiology of chronic obstructive pulmonary disease

Chronic airflow obstruction (CAO) is a syndrome that is produced by a variety of lesions which may occur in bronchi (large airways), bronchioles (small airways), and lung parenchyma (gas exchanging lung). These lesions frequently occur together in various combinations because of a common etiologic agent, tobacco smoke. Occasionally, one lesion or another may play a dominant role. The major disease of the large airways is chronic bronchitis, or chronic sputum production, and it is defined clinically. Its morphologic counterpart is mucous gland enlargement. Mucous gland enlargement is poorly related to CAO. Other lesions of the large airways--inflammation, smooth muscle hyperplasia, cartilage atrophy, and bronchial wall thickening--have also been described, but their functional consequences are uncertain. Bronchiolar lesions are well recognized in CAO, but their relative importance may differ in patients with mild CAO, compared to patients with severe CAO. In mild CAO, inflammation is a very important lesion, and its probable consequences--narrowing, fibrosis, and goblet cell metaplasia--have all been found to be important. In severe CAO, inflammation and fibrosis do not appear to be important, but goblet cell metaplasia, bronchiolar tortuosity, and narrowing do. Emphysema is a subset of airspace enlargement. Emphysema is defined anatomically and is the most important component of severe CAO. Several forms of emphysema can be recognized morphologically and may have specific clinical associations. However, in the usual patient with severe CAO, it is the severity, rather than the type, of emphysema, that is most significant. The diagnosis of emphysema depends on a combined approach. Significant factors include the clinical history (age, sex, smoking, chronic bronchitis, dyspnea), radiologic evidence of overinflation, and diminished diffusing capacity for carbon monoxide.