Table 1_Lymphocyte-to-high-density lipoprotein ratio and mortality in asthma patients: a novel immunoinflammatory biomarker with nonlinear association.docx

BackgroundThe 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.
MethodsThis 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.
ResultsOver 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).
ConclusionLHR 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.

背景：淋巴细胞-高密度脂蛋白比值（lymphocyte-to-high-density lipoprotein ratio, LHR）是一项反映全身炎症与免疫状态的新型生物标志物，已在多种疾病中得到广泛研究。然而，其与哮喘患者死亡风险的关联尚未被探索。
方法：本研究使用了1999-2018年全国健康与营养检查调查（National Health and Nutrition Examination Survey, NHANES）的数据，共纳入5323名成年哮喘患者。通过与截至2019年12月31日的国家死亡索引（National Death Index, NDI）进行关联匹配，确定受试者的死亡结局。采用Cox比例风险模型与Fine-Gray竞争风险模型，探究LHR与死亡风险之间的关联；通过限制性立方样条分析评估剂量-反应关系。
结果：在平均106.95个月的随访期内，共记录到724例全因死亡（占比13.6%）。经多变量校正后，对数转换后的LHR每升高1个单位，死亡风险均显著降低：全因死亡风险降低18%（风险比HR=0.82，95%置信区间CI: 0.74–0.91），心血管疾病（cardiovascular disease, CVD）相关死亡风险降低21%（HR=0.79，95%CI: 0.65–0.96），慢性下呼吸道疾病（chronic lower respiratory disease, CLRD）相关死亡风险降低41%（HR=0.59，95%CI: 0.45–0.77）。限制性立方样条分析显示，LHR与全因死亡及CLRD相关死亡呈L型关联，拐点分别为1.78和1.52；而与CVD相关死亡则呈线性关联。竞争风险模型进一步证实，LHR升高与CLRD相关死亡风险降低存在关联（亚分布风险比SHR=0.64，95%CI: 0.46–0.88），但与CVD相关死亡的关联不再具有统计学意义（SHR=0.85，95%CI: 0.70–1.03）。
结论：LHR与全因死亡及CLRD相关死亡呈非线性关联，且与CLRD相关死亡风险呈显著负相关。竞争风险模型进一步验证了上述研究结果，证实本研究结论具有稳健性。