Gender and acute respiratory distress syndrome in critically injured adults: a prospective study

Abstract

Background: The acute respiratory distress syndrome (ARDS) is a proinflammatory 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 are 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 intensive care unit admission for at least 48 hours was performed. Demographic and clinical data were 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: Six hundred forty-eight patients met entry criteria, and 180 patients developed ARDS (31%). Women were more likely to develop ARDS (35% vs. 25%, p=0.02). This association remained after adjusting for age, mechanism of injury, injury severity, and blood product transfusion (odds ratio, 1.6; 95% confidence interval: 1.1-2.4; p=0.02). Of patients with ARDS, there was no difference in mortality related to gender (22% mortality in women with ARDS vs. 20% in men; p=not significant). A proinflammatory sex hormone profile (low testosterone and high estradiol) was associated with ARDS in both men and women.

Conclusion: Women are more likely than men to develop ARDS after 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.

Trial registration: ClinicalTrials.gov NCT00170560.

Figure 1

The relationship between sex hormones and ARDS stratified by gender. Panel a demonstrates that for both genders, rates of ARDS increase with increasing estradiol. The higher rates of ARDS observed in women are not fully explained by estrogens, however, since for all estradiol levels, the rate of ARDS is higher in females. Panel b demonstrates that for both genders, rates of ARDS decrease with increasing testosterone. Panel c demonstrates the relationship between testosterone and estradiol (testosterone to estradiol ratio) and rates of ARDS. For both genders a higher ratio appears protective, with the lowest rates of ARDS being expected in patients with ratios greater than 50.