Airflow Limitation Increases Lung Cancer Risk in Smokers: The Lifelines Cohort Study

BACKGROUND: The relationship between smoking, airflow limitation, and lung cancer occurrence is unclear. This study aims to evaluate the relationship between airflow limitation and lung cancer, and the effect modification by smoking status. METHODS: We included participants with spirometry data from Lifelines, a population-based cohort study from the Northern Netherlands. Airflow limitation was defined as FEV1/FVC ratio < 0.7. The presence of pathology-confirmed primary lung cancer during a median follow-up of 9.5 years was collected. The Cox regression model was used and hazard ratios (HR) with 95% confidence interval (95% CI) were reported. Adjusted confounders included age, sex, educational level, smoking, passive smoking, asthma status and asbestos exposure. The effect modification by smoking status was investigated by estimating the relative excess risk due to interaction (RERI) and the ratio of HRs with 95% CI. RESULTS: Out of 98,630 participants, 14,200 (14.4%) had airflow limitation. In participants with and without airflow limitation, lung cancer incidence was 0.8% and 0.2%, respectively. The adjusted HR between airflow limitation and lung cancer risk was 1.7 (1.4–2.3). The association between airflow limitation and lung cancer differed by smoking status [former smokers: 2.1 (1.4–3.2), current smokers: 2.2 (1.5–3.2)] and never smokers [0.9 (0.4–2.1)]. The RERI and ratio of HRs was 2.1 (0.7–3.4) and 2.5 (1.0–6.5) for former smokers, and 4.6 (95% CI, 1.8–7.4) and 2.5 (95% CI, 1.0–6.3) for current smokers, respectively. CONCLUSIONS: Airflow limitation increases lung cancer risk and this association is modified by smoking status. IMPACT: Ever smokers with airflow limitation are an important target group for the prevention of lung cancer.