From left, Julie Bastarache, M.D., Lorraine Ware, M.D., and Ling Wang, M.D., go over data in the lab.
photo by Dana Johnson
Grant bolsters Acute Lung Injury research
Lorraine Ware, M.D, has been puzzled for many years by Acute Lung Injury, a common syndrome in critically ill patients.
What causes the syndrome and how can physicians better diagnose and predict its outcome?
With a $6 million grant from the Heart Lung and Blood Institute of the National Institutes of Health, Ware, an assistant professor of Medicine at Vanderbilt University Medical Center, and her colleagues are hoping to discover a protein biomarker for the syndrome that will facilitate in diagnosis, timely treatment and improved understanding of the pathogenesis of the disease.
Acute Lung Injury and its more severe form, Acute Respiratory Distress Syndrome (ARDS), involve severe inflammation of the lung that lead to respiratory failure and complicate a variety of critical conditions including severe trauma, sepsis, pneumonia, pancreatitis and aspiration of gastric contents into the lungs.
“This is a severe problem,” said Ware. “Even though the clinical definitions of Acute Lung Injury are easy to apply, it is frequently not diagnosed. In addition, there are a lot of conditions that look like this syndrome, especially fluid overload in the lungs. It can be a real challenge to diagnose, which is why we have to find identifying markers.”
The incidence of Acute Lung Injury is estimated at 150,000 a year with a mortality rate of at least 30 percent to 50 percent. The available treatment is underutilized and as the population ages, the numbers will escalate, Ware said.
The grant will allow Ware to establish a multi-disciplinary Clinical Proteomics Program, one that reflects a bench-to-bedside approach. The program is the result of a request from the NIH's Heart Lung and Blood Institute. After establishing a network of basic proteomic programs to develop novel methods, it needed groups who were clinically oriented to apply the new methodologies to clinical problems.
“Vanderbilt will serve as the coordinating center for a national network of four Clinical Proteomics programs. Our program will focus on Acute Lung Injury in adult patients,” Ware said.
Massachusetts General Hospital will have a cardiology program, the Mayo Clinic will serve as the vascular biology site and the University of Colorado in Denver will have a pediatric pulmonary program.
Ware plans to study patients at risk for Acute Lung Injury who have been admitted to Vanderbilt's intensive care units as well as examine existing blood samples from the ARDS Network, which is an NIH-funded multi-center clinical trials network. The four-year grant will see more than 2,500 enrollees at Vanderbilt.
“We hope to accomplish several things,” Ware said. “By developing tests that are useful for diagnosis and prognosis, we can better identify and stratify patients for future clinical trials. In addition, we are hoping to use this funding opportunity to build a state-of-the-art clinical proteomics program at Vanderbilt that can also be applied to lung diseases other than Acute Lung Injury and that will be a resource to investigators outside of the pulmonary field.”
In building a program, Ware said that another important goal is to improve training in the field of clinical proteomics. The funding will allow for a higher level of instruction in the lab, fellowship programs, visiting professors and educational opportunities.
“It is because of this funding mechanism that we are able to initiate a large-scale multi-disciplinary study that includes a multi-faceted educational program.”
Others involved with the study include co investigator Gordon Bernard, M.D., Melinda Owen Bass Professor of Medicine, director, Division of Allergy, Pulmonary and Critical Care and assistant vice chancellor for Research; Addison May, M.D., associate professor of Surgery and Anesthesiology; Dean Billheimer, Ph.D., assistant professor of Biostatistics; Richard Caprioli, M.D., Stanley Cohen Professor of Biochemistry, professor of Pharmacology, Chemistry and director, Center in Mass Spectrometry, who will identify novel markers for the condition; Ray Mernaugh, Ph.D., research associate professor of Biochemistry; and Constantin Aliferis, M.D., Ph.D., assistant professor of Biomedical Informatics.