Investigating Biological Sex Differences in a Preclinical Model of Acute Lung Injury

Abstract

Despite decades of research, Acute Respiratory Distress Syndrome (ARDS) remains a leading cause of mortality in critically patients, with treatments limited to supportive care. Biological sex is increasingly recognized as a key variable influencing disease progression and therapeutic outcomes, but its role in ARDS is underexplored. Clinical findings have been inconsistent, highlighting the need for robust preclinical research. This thesis addresses these gaps through two studies: 1) a systematic review revealing that few studies of LPS-induced acute lung injury (ALI) models report sex stratified data, but the available data suggests males tend to fare worse; and 2) experimental studies refining the LPS administration routes in this model. These refinements reduced unwanted variability and enhanced the detection of meaningful biological differences, finding that male mice exhibited more severe lung injury. Together, these findings lay the groundwork future research (e.g., a multilaboratory studies) that can further address these gaps.