Background. Observational researches reported the underlying correlation of plasma myeloperoxidase (MPO) concentration with respiratory tract infections (RTIs), but their causality remained unclear. Here, we examined the cause–effect relation between plasma MPO levels and RTIs. Materials and Methods. Datasets of plasma MPO levels were from the Folkersen et al. study (n = 21,758) and INTERVAL study (n = 3,301). Summarized data for upper respiratory tract infection (URTI) (2,795 cases and 483,689 controls) and lower respiratory tract infection (LRTI) in the intensive care unit (ICU) (585 cases and 430,780 controls) were from the UK Biobank database. The primary method for Mendelian randomization (MR) analysis was the inverse variance weighted approach, with MR-Egger and weighted median methods as supplements. Cochrane’s Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers global test, funnel plots, and leave-one-out analysis were used for sensitivity analysis. Results. We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011–1.274; ) and LRTI (ICU) (OR = 1.323; 95% CI = 1.006–1.739; ). The consistent impact direction is shown when additional plasma MPO level genome-wide association study datasets are used (URTI: OR = 1.158; 95% CI = 1.072–1.251; ; LRTI (ICU): OR = 1.216; 95% CI = 1.020–1.450; ). There was no evidence of a causal effect of URTI and LRTI (ICU) on plasma MPO concentration in the reverse analysis (). The sensitivity analysis revealed no violations of MR presumptions. Conclusions. Plasma MPO levels may causally affect the risks of URTI and LRTI (ICU). In contrast, the causal role of URTI and LRTI (ICU) on plasma MPO concentration was not supported in our MR analysis. Further studies are needed to identify the relationship between RTIs and plasma MPO levels.

中文翻译：

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血浆髓过氧化物酶水平与呼吸道感染之间的因果关系：双向孟德尔随机研究

背景。观察性研究报告了血浆髓过氧化物酶（MPO）浓度与呼吸道感染（RTI）的潜在相关性，但其因果关系仍不清楚。在这里，我们研究了血浆 MPO 水平与 RTI 之间的因果关系。材料和方法。血浆 MPO 水平的数据集来自 Folkersen 等人。研究 ( n  = 21,758) 和 INTERVAL 研究 ( n  = 3,301)。重症监护病房 (ICU) 中上呼吸道感染 (URTI)（2,795 例病例和 483,689 名对照）和下呼吸道感染 (LRTI)（585 例病例和 430,780 名对照）的汇总数据来自英国生物银行数据库。孟德尔随机化（MR）分析的主要方法是逆方差加权法，并以MR-Egger法和加权中位数法作为补充。采用Cochrane Q检验、MR-Egger截距检验、MR多效性残差和和异常值全局检验、漏斗图和留一分析进行敏感性分析。结果。我们发现血浆 MPO 水平与 URTI 呈正相关（比值比 (OR) = 1.135；95% 置信区间 (CI) = 1.011–1.274；）和 LRTI（ICU）（OR = 1.323；95% CI = 1.006–1.739；）。当使用额外的血浆 MPO 水平全基因组关联研究数据集时，显示了一致的影响方向（URTI：OR = 1.158；95% CI = 1.072–1.251；; LRTI（ICU）：OR = 1.216； 95% CI = 1.020–1.450；）。反向分析中没有证据表明 URTI 和 LRTI (ICU) 对血浆 MPO 浓度有因果影响（）。敏感性分析显示没有违反 MR 假设。结论。血浆 MPO 水平可能会影响 URTI 和 LRTI (ICU) 的风险。相反，我们的 MR 分析不支持 URTI 和 LRTI (ICU) 对血浆 MPO 浓度的因果作用。需要进一步研究来确定 RTI 与血浆 MPO 水平之间的关系。