Approach to the genetic epidemiology of acute lung injury

Since the initial description of ARDS in 1967(1), much research has been focused on defining the pathogenesis, clinical presentation, course, and outcome of the syndrome. Initially, early studies investigated the role of complement and endotoxin in lung injury (2). In the past decade, research has focused more on the role of pro-inflammatory and anti-inflammatory response in the pathogenesis and course of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) (3). At the same time, clinical studies were conducted evaluating variables that influence the development and outcome of ALI/ARDS. While many of the animal studies have been consistent, many of the in vivo studies have been heterogeneous. Consequently, efforts to find clinical factors or biomarkers to predict, diagnose, or prognosticate outcomes in ARDS have often been disappointing. Our current understanding of why some patients develop and die from ARDS while others do not is incomplete. For example, while major risk factors for ARDS have been identified, the majority of patients with these risk factors do not develop ARDS. Only 3.8% of patients with documented bacteremia, 41.2% of patients with sepsis syndrome, and 11.9% of intensive care unit patients with pneumonia developed ARDS (4, 5). While smoking has been found to be associated with an increased risk of ARDS in one study, more than half of the ARDS patients were never or ex-smokers (6). Other clinical factors in ARDS have mixed results in the literature. While some studies report an increased risk of developing or dying from ARDS with older age, comorbid conditions such as alcohol-related diseases, and severity of illness, other studies did not find the same (5, 7–10).