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: In the same way that COPD increases the risk of lung cancer, could PRISm be a risk factor for developing lung cancer? 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 to FVC ratio ≥ 0.70 and FEV₁ < 80% predicted), mild COPD (FEV₁ to FVC ratio < 0.70 and FEV₁ ≥ 80%), and moderate to severe COPD (FEV₁ to FVC ratio < 0.70 and FEV₁ < 80%). Patients with incident lung cancer 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 HRs (sHRs), adjusting for confoundings. Results: During a median follow-up of 13 years, 2,058 patients with incident lung cancer 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 the mild COPD group, and 2.92 (95% CI, 2.62-3.25) in the moderate to severe COPD group compared with that among individuals with normal spirometry findings. Results from the competing risk model were consistent, with an sHR of 1.55 (95% CI, 1.35-1.79) in the PRISm group. Interpretation: Our results show that PRISm is associated independently with an increased risk of lung cancer. It is necessary to improve risk stratification and potential early screening strategies in populations with PRISm.