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 (FEV1), 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 FEV1 values: 2037 were included in the discovery set and 2376 were included in the validation set. The effect of low FEV1 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 FEV1 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 FEV1 of more than 90% and CRP up to 2 mg/l, 0.05 with only FEV1 of up to 90% or CRP above 2 mg/l, and 0.12 with FEV1 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 FEV1 could be used to select higher-risk individuals for future LDCT screening and preventive programs.
Thoracic Surgery Unit.
Ugo
U
Pastorino
Biochemical Laboratory.
Daniele
D
Morelli
Department of Radiology.
Alfonso
A
Marchianò
Thoracic Surgery Unit.
Stefano
S
Sestini
Thoracic Surgery Unit.
Paola
P
Suatoni
Immuno-haematology and Transfusion Medicine Unit.
Francesca
F
Taverna
Tumour Genomics Unit, Fondazione IRCCS Istituto Nazionale Tumori.
Mattia
M
Boeri
Tumour Genomics Unit, Fondazione IRCCS Istituto Nazionale Tumori.
Gabriella
G
Sozzi
Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy.
Anna
A
Cantarutti
Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy.
Giovanni
G
Corrao
D002097:C-Reactive Protein / Q000378:metabolism*; D055088:Early Detection of Cancer / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
D018836:Inflammation Mediators; D002097:C-Reactive Protein