A preclinical systematic review and meta-analysis assessing the effect of biological sex in lipopolysaccharide-induced acute lung injury.
A preclinical systematic review and meta-analysis assessing the effect of biological sex in lipopolysaccharide-induced acute lung injury.
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临床前系统评价和荟萃分析，评估生物性别对脂多糖诱导的急性肺损伤的影响。
DOI：
10.1152/ajplung.00336.2023
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Lalu,ManojM
中科院分区：
文献类型：
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作者：
Kuhar,Eva;Chander,Nikesh;Stewart,DuncanJ;Jahandideh,Forough;Zhang,Haibo;Kristof,ArnoldS;Bastarache,JulieA;Schmidt,EricP;Taljaard,Monica;Thébaud,Bernard;Engelberts,Doreen;Fergusson,DeanA;Lalu,ManojM
目前尚不清楚生物性别对急性肺损伤（ALI）的结局有何影响。临床研究受到其观察性设计的混淆。我们通过对ALI动物研究的临床前系统综述解决了这一知识缺口。我们在MEDLINE和Embase中检索了报告了性别分层数据的经鼻内/鼻内/雾化脂多糖给药（最常见的ALI模型）研究。筛选和数据提取一式两份进行。我们的主要结局是组织学组织损伤，次要结局包括肺泡-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，将数据表示为标准化均值差（SMD）和95%置信区间（CI）。使用实验动物实验系统评价中心（SYRCLE）工具评估偏倚风险。我们确定了6项研究，涉及132只动物，11项独立实验。共提取了41个结局，在26/41个结局（63%）中，作用方向表明男性的严重程度高于女性。一项研究报告了肺组织学，发现雄性小鼠的损伤大于雌性小鼠（SMD：1.61，95% CI：0.53-2.69）。荟萃分析显示，与雌性小鼠相比，雄性小鼠支气管肺泡灌洗液中的白蛋白水平（SMD：2.17，95% CI：0.63-3.70）和总细胞计数（SMD：0.80，95% CI：0.27-1.33）显著升高。大多数研究都有“不明确的偏倚风险”。我们的研究结果表明，性别相关的差异，急性肺损伤的严重程度。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的生物学性别差异的基本问题。
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.