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Future Research Directions in Acute Lung Injury

Summary of a National Heart, Lung, and Blood Institute Working Group

Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California; Program in Human Molecular Biology and Genetics and Department of Human Genetics, University of Utah, Salt Lake City, Utah; Cardiovascular and Biological Research Program, Howard Hughes Medical Institute, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; Critical Care Service, Mayo Clinic and Foundation, Rochester; Laboratory of Biomedical Science, North Shore-LIJ Research Institute, Manhasset; Department of Medicine and Physiology, Columbia University College of Physicians and Surgeons; Department of Blood and Vascular Biology, Rockefeller University, New York, New York; Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio; Department of Cellular and Molecular Physiology and Pediatrics, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania; Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC; Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama; Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, Texas; Department of Pulmonary and Critical Care Medicine, University of Vermont, Fletcher Allen Healthcare, Burlington, Vermont; Department of Pathology, University of Michigan, School of Medicine, Ann Arbor, Michigan; and Division of Lung Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland; and Interdepartmental Division of Critical Care Medicine and Department of Medicine, University of Toronto, St. Michael's Hospital, Toronto, Ontario, Canada

Correspondence and requests for reprints should be addressed to Andrea L. Harabin, Ph.D., Division of Lung Diseases, National Heart, Lung, and Blood Institute, Bethesda, MD. E-mail: harabin{at}nih.gov

ABSTRACT

Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are syndromes of acute respiratory failure that result from acute pulmonary edema and inflammation. The development of ALI/ARDS is associated with several clinical disorders including direct pulmonary injury from pneumonia and aspiration as well as indirect pulmonary injury from trauma, sepsis, and other disorders such as acute pancreatitis and drug overdose. Although mortality from ALI/ARDS has decreased in the last decade, it remains high. Despite two major advances in treatment, low VT ventilation for ALI/ARDS and activated protein C for severe sepsis (the leading cause of ALI/ARDS), additional research is needed to develop specific treatments and improve understanding of the pathogenesis of these syndromes. The NHLBI convened a working group to develop specific recommendations for future ALI/ARDS research. Improved understanding of disease heterogeneity through use of evolving biologic, genomic, and genetic approaches should provide major new insights into pathogenesis of ALI. Cellular and molecular methods combined with animal and clinical studies should lead to further progress in the detection and treatment of this complex disease.

Key Words: pulmonary inflammation • critical care • genomics • pulmonary edema • acute respiratory distress syndrome

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