Abstract：
It is unclear what effect biological sex has on outcomes of acute lung injury (ALI). Clinical studies are confounded by their observational design. We addressed this knowledge gap with a preclinical systematic review of ALI animal studies. We searched MEDLINE and Embase for studies of intratracheal/intranasal/aerosolized lipopolysaccharide administration (the most common ALI model) that reported sex-stratified data. Screening and data extraction were conducted in duplicate. Our primary outcome was histological tissue injury and secondary outcomes included alveolar-capillary barrier alterations and inflammatory markers. We used a random-effects inverse variance meta-analysis, expressing data as standardized mean difference (SMD) with 95% confidence intervals (CIs). Risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. We identified six studies involving 132 animals across 11 independent experiments. A total of 41 outcomes were extracted, with the direction of effect suggesting greater severity in males than females in 26/41 outcomes (63%). One study reported on lung histology and found that male mice exhibited greater injury than females (SMD: 1.61, 95% CI: 0.53-2.69). Meta-analysis demonstrated significantly elevated albumin levels (SMD: 2.17, 95% CI: 0.63-3.70) and total cell counts (SMD: 0.80, 95% CI: 0.27-1.33) in bronchoalveolar lavage fluid from male mice compared with female mice. Most studies had an \"unclear risk of bias.\" Our findings suggest sex-related differences in ALI severity. However, these conclusions are drawn from a small number of animals and studies. Further research is required to address the fundamental issue of biological sex differences in LPS-induced ALI.
摘要：
目前尚不清楚生物性别对急性肺损伤（ALI）的结局有何影响。临床研究被其观察设计所混淆。我们通过对ALI动物研究的临床前系统评价来解决这一知识差距。我们搜索MEDLINE和Embase的气管内/鼻内/雾化脂多糖（LPS）给药的研究，最常见的ALI模型，并报告性别分层数据。筛选和数据提取一式两份进行。我们的主要结果是组织学组织损伤，次要结果包括肺泡-毛细血管屏障改变和炎症标志物。我们使用了随机效应逆方差荟萃分析，将数据表示为标准平均差(SMD)，95%置信区间(CI)。使用SYRCLE工具评估偏倚风险。我们在11个独立实验中确定了涉及132只动物的6项研究。总共提取了41个结果，效果方向表明，在26/41结局中，男性比女性更严重(63%)。一项研究报道了肺组织学，发现雄性小鼠比雌性小鼠表现出更大的损伤（SMD1.61，95％CI0.53至2.69）。荟萃分析表明，与雌性相比，雄性小鼠支气管肺泡灌洗液中白蛋白水平（SMD2.17，95％CI0.63至3.70）和总细胞计数（SMD0.80，95％CI0.27至1.33）显着升高。大多数研究都有“不清楚的偏倚风险”。我们的研究结果表明ALI严重程度存在性别相关差异。然而,这些结论是从少数动物和研究中得出的。需要进一步的研究来解决LPS诱导的ALI中生物学性别差异的基本问题。
