It is unclear what effect biological sex has on the 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 (LPS) administration, the most common ALI model, and 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 (CI). Risk of bias was assessed using the 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 to 2.69). Meta-analysis demonstrated significantly elevated albumin levels (SMD 2.17, 95% CI 0.63 to 3.70) and total cell counts (SMD 0.80, 95% CI 0.27 to 1.33) in bronchoalveolar lavage fluid from male mice compared to females. 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.
Keywords: ALI; ARDS; acute lung injury; acute respiratory distress syndrome; biological sex.