Lung Cancer Risk in Preserved Ratio Impaired Spirometry and Airway Obstruction: A UK Biobank Study.

BACKGROUND Preserved ratio impaired spirometry (PRISm) has emerged as a distinct pulmonary pattern with potential clinical significance, but its association with lung cancer risk remains unclear. RESEARCH QUESTION This study compared the risk of incident lung cancer among individuals with PRISm to that among those with normal spirometry and chronic obstructive pulmonary disease (COPD). STUDY DESIGN AND METHODS We analyzed data from 267,222 UK Biobank participants who underwent spirometry at baseline and had no history of cancer before enrollment. Lung function was categorized as normal, PRISm (FEV1/FVC ≥ 0.70 and FEV1 < 80% predicted), mild COPD (FEV1/FVC < 0.70 and FEV1 ≥ 80%), and moderate-to-severe COPD (FEV1/FVC < 0.70 and FEV1 < 80%). Incident lung cancer cases were identified through linkage to national cancer registries. Cox proportional hazards and Fine-Gray competing risk models were used to estimate hazard ratios (HRs) and subdistribution hazard ratios (sHRs), adjusting for confoundings. RESULTS During a median follow-up of 13 years, 2,058 incident lung cancer cases were identified. In multivariate models, the adjusted HR for lung cancer was 1.59 (95% CI 1.38-1.82) in the PRISm group, 1.75 (95% CI 1.51-2.02) in mild COPD, and 2.92 (95% CI 2.62-3.25) in moderate-to-severe COPD, compared to that among individuals with normal spirometry. Results from the competing risk model were consistent, with an sHR of 1.55 (95% CI 1.35-1.79) in PRISm. INTERPRETATION PRISm is independently associated with an increased risk of lung cancer. It is necessary to improve risk stratification and potential early screening strategies in PRISm populations. CLINICAL TRIALS REGISTRATION NA.