Abstract
Introduction: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with increased morbidity and mortality. The novel inflammatory biomarker, systemic immune-inflammation index (SII), may have prognostic value. This study aimed to assess the association between SII and short-term and long-term adverse outcomes among AECOPD inpatients. Methods: This was a multicenter, retrospective analysis of a prospectively collected cohort of AECOPD inpatients. We initially compared SII and other clinical characteristics between survivors and non-survivors during hospitalization, adjusting for primary comorbidities using propensity score matching (PSM). We assessed the short-term and long-term adverse outcomes, particularly focusing on in-hospital mortality and 2-year all-cause mortality, across different levels of SII. Multivariate Cox analysis was employed to evaluate the associations of SII, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) with in-hospital mortality of AECOPD patients. Restricted cubic spline (RCS) models investigated the nonlinear relationships between these biomarkers and in-hospital mortality. To compare the predictive values of SII, NLR, and PLR for in-hospital mortality, receiver operating characteristic (ROC) curve analysis was performed. Subgroup analysis was carried out to further determine the predictive capacity of SII among diverse subgroups. Results: The study included 12,551 AECOPD inpatients, among whom 180 (1.4%) died in hospital. Whether before or after PSM adjusting for comorbidities, the levels of SII, NLR, and PLR in non-survivors were significantly higher than those in survivors (all P < 0.001). Elevated SII levels (divided into quartiles) were associated with increased in-hospital mortality (Q1 vs. Q2 vs. Q3 vs. Q4: 0.6% vs. 0.8% vs. 1.5% vs. 2.8%) and 2-year all-cause mortality (15.4% vs. 22.6% vs. 22.2% vs. 27.8%), as well as other adverse outcomes (all P < 0.05). After adjusting for covariates, higher levels of SII and NLR consistently remained associated with increased in-hospital mortality. RCS analysis revealed a consistent linear relationship between SII and in-hospital mortality, while NLR and PLR exhibited nonlinear relationships. Furthermore, ROC curve analysis indicated that SII showed inferiority to NLR but superiority to PLR in predicting in-hospital mortality among AECOPD patients (area under the curve for SII vs. NLR vs. PLR: 0.670 vs. 0.731 vs. 0.609). Subgroup analysis revealed that the association between SII and in-hospital mortality varied across different subgroups. Conclusion: Elevated SII is associated with increased risks of short-term and long-term adverse outcomes in AECOPD inpatients, making it potential prognostic factor used to identify high-risk patients and guide the management of AECOPD.