Abstract
OBJECTIVE: To investigate the association between the systemic immune-inflammation index (SII) and all-cause mortality in patients with interstitial lung disease (ILD). METHODS: This retrospective cohort study included 366 patients with ILD. SII was calculated using peripheral blood counts and analyzed as both a continuous and categorical variable based on the optimal cutoff value determined by receiver operating characteristic (ROC) analysis. Kaplan-Meier survival curves were used to compare survival between SII groups. Univariable and multivariable Cox proportional hazards models were applied to evaluate the association between SII and all-cause mortality. Restricted cubic spline (RCS) analysis was performed to assess the dose-response relationship. Subgroup analyses were conducted to examine the robustness of the association. RESULTS: Over a median follow-up of 20.6 months, the primary outcome of all-cause mortality occurred in 91 patients (24.9%). The median SII was significantly higher in deceased patients compared with survivors (1471.14 vs. 1017.21). ROC analysis showed a statistically significant discriminatory ability of SII for mortality prediction (AUC = 0.658, 95% CI 0.594-0.723). Kaplan-Meier analysis demonstrated significantly lower survival in patients with high SII (log-rank p < 0.001). In multivariable Cox models, higher SII remained independently associated with increased all-cause mortality, showing consistent associations across modeling strategies, whether evaluated per standard deviation increase or according to the optimal cutoff value (adjusted HR per standard deviation increase: 1.213, 95% CI 1.048-1.403; adjusted HR for high vs. low SII: 1.717, 95% CI 1.109-2.656; both p < 0.05). RCS analysis revealed a significant linear positive association between SII and mortality risk (P for overall = 0.032; P for nonlinearity = 0.305). Subgroup analyses indicated significant associations between higher SII and all-cause mortality among patients aged ≥60 years, females, and those without anti-synthetase syndrome. CONCLUSION: Elevated SII is independently and linearly associated with increased all-cause mortality in patients with ILD. These findings suggest that SII may have potential clinical value in the assessment and management of patients with ILD.