Inflammatory status and lung function predict mortality in lung cancer screening participants

Low-dose computed tomography (LDCT) screening trials have based their risk selection algorithm on age and tobacco exposure, but never on pulmonary risk-related biomarkers. In the present study, the baseline inflammatory status, measured by C-reactive protein (CRP) level, and lung function, measured by forced expiratory volume in 1 s (FEV(1)), were tested as independent predictors of all-cause mortality in LDCT-screening participants. Between 2000 and 2010, 4413 volunteers were enrolled in two LDCT-screening trials, with evaluable baseline CRP and FEV(1) values: 2037 were included in the discovery set and 2376 were included in the validation set. The effect of low FEV(1) or high CRP alone or combined was evaluated by Kaplan–Meier mortality curves and hazard ratio (HR) with 95% confidence interval (CI) by fitting Cox proportional hazards models. The overall mortality risk was significantly higher in participants with FEV(1) of up to 90% (HR: 2.13, CI: 1.43–3.17) or CRP more than 2 mg/l (HR: 3.38, CI: 1.60–3.54) and was still significant in the fully adjusted model. The cumulative 10-year probability of death was 0.03 for participants with FEV(1) of more than 90% and CRP up to 2 mg/l, 0.05 with only FEV(1) of up to 90% or CRP above 2 mg/l, and 0.12 with FEV(1) of up to 90% and CRP above 2 mg/l. This predictive performance was confirmed in the two external validation cohorts with 10-year mortality rates of 0.06, 0.12, and 0.14, and 0.03, 0.07, and 0.14, respectively. Baseline inflammatory status and lung function reduction are independent predictors of all-cause long-term mortality in LDCT-screening participants. CRP and FEV(1) could be used to select higher-risk individuals for future LDCT screening and preventive programs.