Am J Respir Crit Care Med. Dec 15, 2010; 182(12): 1554–1562.
Strategic Plan for Lung Vascular Research
An NHLBI-ORDR Workshop Report
1Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio; 2Department of Medicine, Providence Veterans Affairs Medical Center, Warren Alpert Medical School of Brown University, Providence, Rhode Island; 3University of South Alabama, Center for Lung Biology, Mobile, Alabama; 4Genomic Medicine, Cleveland Clinic, Cleveland, Ohio; 5Division of Pulmonary, Sleep, and Critical Care Medicine, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island; 6Section of Cardiology, Department of Medicine, University of Chicago, Chicago, Illinois; 7Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, Bethesda, Maryland; 8Department of Medicine and Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York City, New York; 9Division of Pulmonary and Critical Care Medicine, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia; 10Department of Internal Medicine and Center for Pharmacogenomics, Washington University School of Medicine, St. Louis, Missouri; 11Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Texas Health Science Center at Houston Medical School, Houston, Texas; 12Translational Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland; 13Department of Medicine, University of Colorado at Denver, Denver, Colorado; 14Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; 15Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland; 16Université Paris-Sud 11, Hôpital Antoine Béclère, Paris, France; 17Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; 18Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 19Department of Anatomy, University of California San Francisco, San Francisco, California; 20Department of Allergy, Pulmonary, and Critical Medicine, Vanderbilt School of Medicine, Nashville, Tennessee; 21Division of Pulmonary and Critical Care, Department of Medicine, Stanford University School of Medicine, Stanford, California; 22Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, California; 23Department of Medicine/Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, California; 24Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts; 25Novartis Institutes for Biomedical Research, Cambridge, Massachusetts; 26Department of Pediatrics, Northwestern University, Chicago, Illinois; 27Department of Pediatrics, University of Colorado at Denver, Denver, Colorado; 28United Therapeutics, Silver Spring, Maryland; 29Department of Molecular Pharmacology and Experimental Therapeutics and Medicine, Mayo Medical School-Mayo Clinic, Rochester, Minnesota; 30Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; 31Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois; and 32Division of Lung Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland
Received June 7, 2010; Accepted September 9, 2010.
AT A GLANCE COMMENTARY
Scientific Knowledge on the Subject
Basic lung vascular research is progressing and novel translational and clinical study opportunities are emerging, particularly for pulmonary arterial hypertension. The investigative community is assessing how to move forward to acquire new knowledge, apply new technologies, and develop new tools to conduct modern studies in lung vasculature research so that lung health may be improved.
What This Study Adds to the Field
This report represents a collective body of scientific expert opinion provided to the National Heart, Lung, and Blood Institute for use in strategic support planning. The recommendations given here will be of interest to the general cardiopulmonary community because they constitute a summary of the directions lung vascular research may take in the near future.
Lung perfusion is accomplished by the pulmonary circulation, which originates from the right ventricle, and the bronchial circulation, which originates from the aorta. The low-resistance characteristics of the pulmonary circulation allow it to accommodate the entire cardiac output while maintaining low pulmonary vascular pressures, thereby preventing hydrostatic damage to the delicate alveolar blood–gas barrier. The bronchial circulation is approximately 3% of total lung perfusion and provides most of the nutrients and oxygen to the airways and the large pulmonary vessels via the vasa vasorum. In addition, the lung lymphatic vessels remove extravascular water and protein.
Despite significant discoveries in vascular biology, there remain gaps in our knowledge of lung diseases characterized by vascular remodeling, proliferative vessel growth, and/or loss of the pulmonary vascular bed. One lung vascular disease is pulmonary arterial hypertension (PAH), which is now described as a panvasculopathy of elastic, muscular, and nonmuscular pulmonary arteries and arterioles. Although a rare disorder (1
), major improvements in the lives of patients with PAH have directly resulted from basic lung vascular research. However, without disease-modifying therapies, PAH remains a progressive and rapidly fatal disease. Furthermore, a report from the Centers for Disease Control and Prevention (Atlanta, GA) indicated that during 1980–2002, death rates and hospitalization rates significantly increased for “pulmonary hypertension” as either any contributing cause of death or as any listed hospital diagnosis (2
). The etiology of this observation was hypothesized to be multifactorial, but the economic impact of this trend was clear, as was the need to further advance our scientific understanding of lung vascular health and disease, particularly in an aging U.S. population.
To expedite progress in lung vascular research, an invitational workshop of leading experts in laboratory, translational, and clinical studies was held. The objectives of the workshop were to review the state of science in lung vascular biology, identify emerging opportunities, define research directions, and make recommendations to the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH, Bethesda, MD) to use for strategic planning. Emphasis on PAH emerged, because several translational research opportunities were identified specific to this clinical condition. Although a primary focus on the pulmonary circulation is presented here, we acknowledge that key areas for investigation exist specific to the bronchial and lung lymphatic networks, but time constraints did not allow for open discussion of all topics. Selected slides presented at the meeting are included in the online supplement.