Objective: There has been increasing evidence that angiotensin II may play an important role in the pathogenesis and in the evolution of acute lung injury. It was therefore hypothesized that polymorphisms of the angiotensin-converting enzyme gene affects the risk and outcome of acute respiratory distress syndrome (ARDS).

Design: Prospective, observational study.

Patients and settings: The ARDS group consisted of 101 patients treated at the medical intensive care unit; the control groups consisted of 138 "at-risk" patients treated at the medical intensive care unit due to acute respiratory failure but did not meet the ARDS criteria throughout the hospital course, and 210 non-at-risk subjects.

Intervention: None.

Measurements and main results: The ARDS patients and control subjects were genotyped for the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene. Association of the polymorphism and the risk and the outcome of ARDS was analyzed. There was no significant difference in the frequencies of the genotypes between the ARDS, at-risk, and non-at-risk groups. The 28-day mortality rates were significantly different between the three angiotensin-converting enzyme genotypes (42%, 65%, and 75% for II, ID, and DD, respectively; p = .036). Survival analysis showed that the II genotype favorably affected 28-day survival (hazard ratio, 0.46; 95% confidence interval, 0.26-0.81; p = .007), whereas ARDS caused by hospital-acquired pneumonia had a negative effect (hazard ratio, 2.34; 95% confidence interval, 1.25-4.40; p = .008). The II genotype (hazard ratio, 0.53; 95% confidence interval, 0.32-0.87; p = .012) and ARDS caused by hospital-acquired pneumonia (hazard ratio, 2.13; 95% confidence interval, 1.24-3.68; p = .006) were also significant prognostic factors for the in-hospital mortality.

Conclusions: The angiotensin-converting enzyme I/D polymorphism is a significant prognostic factor for the outcome of ARDS. Patients with the II genotype have a significantly better chance of survival. This study did not show an increased risk for ARDS in Chinese patients with the D allele.