Lymphocyte-to-high-density lipoprotein ratio and mortality in asthma patients: a novel immunoinflammatory biomarker with nonlinear association.

Background: The lymphocyte-to-high-density lipoprotein ratio (LHR), a novel biomarker reflecting systemic inflammation and immune status, has been widely studied in various diseases. However, its association with mortality risk among asthma patients remains unexplored. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2018, including 5,323 adult asthma patients. Mortality outcomes were ascertained through linkage with the National Death Index (NDI) up to December 31, 2019. Cox proportional hazards models and Fine-Gray competing risk models were employed to examine the association between LHR and mortality risks. Dose-response relationships were assessed using restricted cubic spline analyses. Results: Over a mean follow-up period of 106.95 months, 724 all-cause deaths (13.6%) were recorded. After multivariable adjustment, a one-unit increase in log-transformed LHR was associated with reduced risks of mortality: 18% for all-cause (HR = 0.82, 95% CI: 0.74-0.91), 21% for cardiovascular disease (CVD) (HR = 0.79, 95% CI: 0.65-0.96), and 41% for chronic lower respiratory disease (CLRD) (HR = 0.59, 95% CI: 0.45-0.77). Restricted cubic spline analyses showed an L-shaped association of LHR with all-cause and CLRD mortality, with inflection points at 1.78 and 1.52, respectively. For CVD mortality, a linear association was observed. Competing risk models further confirmed the association of LHR with reduced CLRD mortality (SHR = 0.64, 95% CI: 0.46-0.88), while the association with CVD mortality was no longer significant (SHR = 0.85, 95% CI: 0.70-1.03). Conclusion: LHR is nonlinearly associated with all-cause and CLRD mortality and shows a significant inverse association with CLRD mortality risk. These findings were further validated using competing risk models, highlighting the robustness of the results.