Genetic susceptibility to acute lung injury.

OBJECTIVE

To review the complex interactions of markers of genetic susceptibility for critical illness and acute lung injury. These may affect the responses of critically ill patients to acute lung injury and acute respiratory distress syndrome and may affect outcome.

DATA SOURCES AND STUDY SELECTION

Published research and review articles related to genetic factors associated with susceptibility to critical illnesses and pulmonary disease.

DATA EXTRACTION AND SYNTHESIS

Critical illness in adults often is followed by acute lung injury, a phenomenon of acute diffuse lung inflammation. Physicians have long known that each patient responds differently to drugs and has a different risk for a particular event or outcome. Now, there is some evidence that cellular and humoral immune responses are subject to polymorphic genetic control, which explains the well-known diversity of clinical manifestations and outcomes in critically ill patients with the same disease. By revealing altered expression of relatively few genes involved in the responses to lung injury and repair, some investigators have found that these responses, and susceptibility to acute lung injury, are heritable. In the last 5 yrs, we have discovered that an individual's risks and cellular responses can be related to his or her own unique DNA.

CONCLUSIONS

The search for an association between functional variants of a gene and clinical phenotype may help to identify key pathophysiological processes of disease. In the future, we will know much about which therapy is best for each individual patient in the intensive care unit.