Extended Data Fig. 4: Association of thymic health, clinical variables, and known diseases prior to trial enrollment with health outcomes in NLST.

a–c, Association analyses between thymic health, the baseline clinical variables body mass index (BMI), smoking status, and pack-years together with diagnosed diseases prior to trial enrollment with a, lung cancer incidence, b, lung cancer-specific mortality, and c, cardiovascular disease (CVD)-specific mortality in NLST, stratified by sex and age. 434 participants were excluded due to missing values in BMI and diagnosed diseases, resulting in 24,597 individuals. Exact cohort sizes after outcome-specific missingness were: overall survival (n = 24,597; 434 missing), lung cancer incidence (n = 22,776; 2,255 missing), and lung cancer and CVD mortality (n = 24,595; 436 missing). d–f, Association analyses between thymic health and the baseline clinical variables BMI, smoking status, and pack-years, stratified by sex and age excluding participants with known diseases or cancer prior to trial enrollment with d, lung cancer incidence, e, lung cancer-specific mortality, and f, CVD-specific mortality in the subgroup of the NLST in which participants with a history of cancer (n = 575), childhood or adult asthma, diabetes, asbestosis, bronchiectasis, lung fibrosis, sarcoidosis, silicosis, or tuberculosis (n = 5,500) were excluded from the analysis (n = 18,619). Exact cohort sizes after outcome-specific missingness were: overall survival (n = 18,565; 54 missing), lung cancer incidence (n = 17,280; 1,339 missing), and lung cancer and CVD mortality (n = 18,564; 55 missing). Cox proportional hazards regression was used to estimate HRs. In the forest plots, the center of each box represents the estimated hazard ratio, and the whiskers denote the corresponding 95% CI; arrowheads indicate that the 95% CI extends beyond the visualized limits; shaded box size is for visualization only and does not encode statistical weight. The overall contribution of thymic health to multivariable models was evaluated using likelihood ratio tests (χ² tests) comparing full models with nested models excluding thymic health (type III test, two-sided). Statistical significance of individual covariate coefficients was assessed using two-sided Wald z-tests with no adjustments for multiple comparisons. CI Confidence Interval, HR Hazard Ratio, NLST National Lung Screening Trial.