Gender and Acute Respiratory Distress Syndrome in Critically Injured Adults: A Prospective Study

Abstract

Objective The acute respiratory distress syndrome (ARDS) is a pro-inflammatory condition that often complicates trauma and critical illness. Animal studies have shown that both gender and sex hormones play an important role in inflammatory regulation. Human data is scant regarding the role of gender and sex hormones in developing ARDS. Our objective was to describe gender and hormonal differences in patients who develop ARDS in a large cohort of critically injured adults. Methods A prospective cohort study of adult trauma patients requiring ICU admission for at least 48 hours was performed. Demographic and clinical data was collected prospectively, and sex hormones were assayed at study entry (48 hours). The primary outcome was the development of ARDS. Multivariate logistic regression was used to determine the adjusted odds of death associated with differences in gender. Results 648 patients met entry criteria and 180 patients developed ARDS (31%). Females were more likely to develop ARDS (35 % versus 25%, p=0.02). This association remained after adjusting for age, mechanism of injury, injury severity and blood product transfusion (OR 1.6 95% CI 1.1 – 2.4, p=0.02). Of patients with ARDS, there was no difference in mortality related to gender (22% mortality in females with ARDS versus 20% in males, p=NS). A pro-inflammatory sex hormone profile (low testosterone, high estradiol) was associated with ARDS in both males and females. Conclusion Females are more likely than males to develop ARDS following critical injury. Despite the increased incidence in ARDS, the mortality in patients with ARDS does not differ according to gender. The inflammatory properties of sex hormones may contribute to ARDS, but they do not fully explain observed gender differences.

Acute lung injury and the acute respiratory distress syndrome in the injured patient

“…Despite the higher percentage of ARDS cases in females, the mortality between female and male patients with ARDS after traumatic injury does not appear to differ [38]. This data supports the concept of sex hormones, specifically estrogens, having immunologic properties enabling the development of lung injury.…”

“…For both male and female patients, ARDS increases in incidence with increasing estradiol levels. Additionally, for both male and female patients, ARDS declines with increasing testosterone levels [38]. A recent study by the National Institute of Health in the United States brought awareness to a potential treatment variability [39].…”

Gender-specific Issues in Traumatic Injury and Resuscitation: Consensus-based Recommendations for Future Research

“…Development of ARDS may have more to do with a proinflammatory sex hormone profile (low testosterone and high estradiol) than gender. 57 …”

Acute Respiratory Distress Syndrome in Burn Patients

“…Furthermore, our population was mostly male (84.7%) which may have skewed the prevalence rates, as previous reports have shown higher rates of ARDS in women. 24 Episodes of sepsis, and specifically episodes of CLABSI, CAUTI, and wound sepsis were not tracked for this study, which makes it difficult to definitively identify a clinical insult leading to ARDS development in many of our patients. This represents a limitation as the technical Berlin definition requires ARDS development within 7 days of the presumed clinical insult.…”