Chronic Obstructive Pulmonary Disease is Associated with Lung Cancer Mortality in a Prospective Study of Never Smokers

Rationale: Several studies have suggested that previous lung disease may increase the risk of lung cancer. It is important to clarify the association between previous lung disease and lung cancer risk in the general population.

Objectives: The association between self-reported physician-diagnosed chronic bronchitis and emphysema and lung cancer mortality was examined in a U.S. prospective study of 448,600 lifelong nonsmokers who were cancer-free at baseline.

Methods: During the 20-year follow-up period from 1982 to 2002, 1,759 lung cancer deaths occurred. Cox proportional hazards models were used to obtain adjusted hazard ratios (HRs) for lung cancer mortality associated with chronic bronchitis and emphysema as well as for both of these diseases together.

Measurements And Main Results: Lung cancer mortality was significantly associated with both emphysema (HR, 1.66; 95% confidence interval [CI], 1.06, 2.59) and with the combined endpoint of emphysema and chronic bronchitis (HR, 2.44; 95% CI, 1.22, 4.90) in analyses that combined men and women. No association was observed with chronic bronchitis alone (HR, 0.96; 95% CI, 0.72, 1.28) in the overall analysis, although the association was stronger in men (HR, 1.59; 95% CI, 0.95, 2.66) than women (HR, 0.82; 95% CI, 0.58, 1.16; p for interaction, 0.04). The association between emphysema and lung cancer was stronger in analyses that excluded early years of follow-up.

Conclusions: This large prospective study strengthens the evidence that increased lung cancer risk is associated with nonmalignant pulmonary conditions, especially emphysema, even in lifelong nonsmokers.