The relationship between inflammatory levels prior to lung cancer diagnosis and all-cause mortality after diagnosis

Background The relationship between pre-diagnostic inflammatory levels and all-cause mortality risk following a diagnosis of lung cancer remains unclear, with heterogeneity across different pathological types warranting further investigation. Objective To explore in patients with lung cancer the association between pre-diagnostic inflammatory levels and all-cause mortality, analyzing differences across pathological types. Methods Based on health examination data from the Kailuan Group obtained between 2006 and 2020, 2,111 patients with newly diagnosed lung cancer (mean age 65.04 ± 9.93 years) were included and followed for up to 12 years. Multivariable Cox regression and Fine-Gray competing risk models were used to estimate inflammatory markers and all-cause mortality hazard ratios. Stratified and sensitivity analyses were also conducted. Results A total of 1,804 deaths occurred, for a cumulative incidence of 70.3%. After multivariate adjustment, each Z-score increase of one in white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, systemic immune-inflammation index (SII), and aggregate inflammation systemic index (AISI) was associated with a 6.9%, 7.8%, 7.9%, 8.5%, and 6.0% increase, respectively, in overall lung cancer mortality risk. This association exhibited heterogeneity across pathological types: lung adenocarcinoma was significantly associated with neutrophil count, AISI, and lymphocyte-to-high-density lipoprotein cholesterol ratio; lung squamous cell carcinoma was primarily associated with SII and neutrophil-to-high-density lipoprotein cholesterol ratio; and no consistent positive association was observed in small cell lung cancer (SCLC). Stratified analyses revealed that inflammation-related mortality risk was higher in males, individuals aged ≥ 60 years, those with higher education, those with low income, current smokers, and those with a family history of cancer. In lung adenocarcinoma, a higher risk was observed in females, individuals aged < 60 years, those with higher education, and those without hypertension. For lung squamous cell carcinoma, those at higher risk included males, individuals with higher education, and those with diabetes. In SCLC, higher risks were observed in individuals with a family history of cancer or a history of diabetes. Conclusion Pre-diagnostic inflammatory levels are an independent risk factor for all-cause mortality in lung cancer, with specific impact varying depending on pathological type and individual characteristics.