Inhaled Corticosteroids and Risk of Lung Cancer Among Patients with Chronic Obstructive Pulmonary Disease

Rationale And Objectives: Lung cancer is a frequent cause of death among patients with chronic obstructive pulmonary disease (COPD). We examined whether the use of inhaled corticosteroids among patients with COPD was associated with a decreased risk of lung cancer.

Methods: We performed a cohort study of United States veterans enrolled in primary care clinics between December 1996 and May 2001. Participants had received treatment for, had an International Classification of Disease, 9th edition, diagnosis of, or a self-reported diagnosis of COPD. Patients with a history of lung cancer were excluded. To be exposed, patients must have been at least 80% adherent to inhaled corticosteroids. We used Cox regression models to estimate the risk of cancer and adjust for potential confounding factors.

Findings: We identified 10,474 patients with a median follow-up of 3.8 years. In comparison to nonusers of inhaled corticosteroids, adjusting for age, smoking status, smoking intensity, previous history of non-lung cancer malignancy, coexisting illnesses, and bronchodilator use, there was a dose-dependent decreased risk of lung cancer associated with inhaled corticosteroids (ICS dose < 1,200 mug/d: adjusted HR, 1.3; 95% confidence interval, 0.67-1.90; ICS dose >or= 1,200 microg/d: adjusted HR, 0.39; 95% confidence interval, 0.16-0.96). Changes in cohort definitions had minimal effects on the estimated risk. Analyses examining confounding by indication suggest biases in the opposite direction of the described effects.

Interpretation: Results suggest that inhaled corticosteroids may have a potential role in lung cancer prevention among patients with COPD. These initial findings require confirmation in separate and larger cohorts.