Chronic obstructive pulmonary disease: a definition and implications of structural determinants of airflow obstruction for epidemiology.

Chronic obstructive pulmonary disease (COPD) may be defined as a process characterized by the presence of chronic bronchitis or emphysema that may lead to the development of airways obstruction; airways obstruction need not be present at all stage of the process and may be partially reversible. The pathologic changes in the lungs due to smoking affect three regions: the bronchi, bronchioles, and parenchyma. The bronchi show enlargement of the submucosal glands with dilation of their ducts; infiltration with neutrophils and lymphocytes is present but not prominent. Respiratory bronchiolitis is observed in persons smoking for only a few years; the membranous bronchioles show a mix of inflammation, luminal mucus, goblet cell metaplasia, and distortion due to fibrosis and loss of alveolar attachments. The lung parenchyma shows centrilobular emphysema. Bronchial changes are only weakly related to airflow obstruction but bronchiolar changes are also related. The relation between airflow limitation and bronchiolitis is progressively harder to show as the severity of emphysema increases because of the dominant role of emphysema in causing airflow obstruction. Emphysema is the predominant lesion in persons with severe airflow obstruction due to COPD. The diffusing capacity for carbon monoxide is related to the severity of emphysema but is nonspecific and is mildly abnormal in smokers without emphysema. The compliance of the lungs of smokers is decreased even when a emphysema and airflow limitation are mild. Standard epidemiologic tools do not differentiate emphysema from other causes of airflow obstruction. Most persons dying of COPD will have severe emphysema.