Acute respiratory distress syndrome (ARDS) is a major clinical problem with high morbidity and mortality. Diffuse alveolar damage (DAD) is considered the histological hallmark for the acute phase of ARDS. DAD is characterized by an acute phase with edema, hyaline membranes, and inflammation, followed by an organizing phase with alveolar septal fibrosis and type II pneumocyte hyperplasia. Given the difficulties in obtaining a biopsy in patients with ARDS, the presence of DAD is not required to make the diagnosis. However, biopsy and autopsy studies suggest that only one-half of patients who meet the clinical definition of ARDS also have DAD. The other half are found to have a group of heterogeneous disorders, including pneumonia. Importantly, the subgroup of patients with ARDS who also have DAD appears to have increased mortality. It is possible that the response of these patients to specific therapies targeting the molecular mechanisms of ARDS may differ from patients without DAD. Therefore, it may be important to develop noninvasive methods to identify DAD. A predictive model for DAD based on noninvasive measurements has been developed in an autopsy cohort but must be validated. It would be ideal to identify biomarkers or imaging techniques that help determine which patients with ARDS have DAD. We conclude that additional studies are needed to determine the effect of DAD on outcomes in ARDS, and whether noninvasive techniques to identify DAD should be developed with the goal of determining whether this population responds differently to specific therapies targeting the molecular mechanisms of ARDS.

Objective: The objective of this study was to analyze the association between candidate gene polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) in patients with severe sepsis. Methods: Patients older than 18 years admitted to the intensive care unit (ICU) with the diagnosis of severe sepsis were prospectively included. A blood sample was drawn on the first day of ICU admission, and DNA was extracted. We genotyped the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene (polymerase chain reaction) and the following single-nucleotide polymorphisms (TaqMan SNP genotyping assay): tumor necrosis factor α -376 G/A, -308 G/A, and -238 G/A; interleukin 8 -251 T/A; pre–B cell colony-enhancing factor -1001 G/T; and vascular endothelial growth factor +405 C/G and +936 C/T. Polymorphisms were selected based on reports on their association with ARDS. Variables associated in univariate analysis (P < 0.1) with the diagnosis of ARDS were included in a multiple logistic regression analysis. Results: We studied 149 patients, of whom 35 presented ARDS. Variables included in the maximal multivariate model were male sex, chronic alcoholism, use of ACE inhibitors or angiotensin-receptor blockers, Simplified Acute Physiology Score II score, serum glucose concentration at ICU admission, and the presence of the allele D of the ACE gene. After adjustment for those variables, the presence of the allele D of the ACE gene (odds ratio, 4.75; 95% confidence interval, 1.02–22.20; P = 0.048) was significantly associated with the diagnosis of ARDS. Conclusion: The presence of the allele D of the ACE gene is associated with ARDS in patients with severe sepsis.