PITTSBURGH, January 18, 2007 The University of Pittsburgh has been awarded an estimated $13 million research grant from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) to develop novel approaches that seek to increase our understanding of and improve outcomes for people with chronic obstructive pulmonary disease (COPD), a degenerative breathing disorder that is the fourth leading cause of death and the second leading cause of disability annually in the United States. The five-year grant establishes the University of Pittsburgh as a Specialized Center of Clinically Oriented Research (SCCOR) in COPD. Such a center encourages basic science research findings to be directed more rapidly toward clinical problems.
Frank C. Sciurba, M.D., is principal investigator of the SCCOR grant, which entails three unique projects and three resource cores to support the research. Dr. Sciurba is associate professor of medicine at the University of Pittsburgh School of Medicine and director of the Emphysema Research Center in the division of pulmonary, allergy and critical care medicine.
The grant has important clinical relevance because the NHLBI estimates that 12 million adults currently have a diagnosis of COPD, with an additional 12 million unaware that they have the disorder. COPD is a lung disease commonly related to smoking that diminishes breathing capacity over time and includes conditions such as chronic bronchitis and emphysema.
"COPD damages the lung tissue, expanding and breaking down the walls of air sacs and thickening small airways, which hinders air flow into the lungs and transfer of oxygen into the blood," explained Dr. Sciurba. "These studies will help us to better understand the disease process and possibly devise better treatment options for patients."
Each of the research projects capitalizes on findings of basic science and clinical research performed by the University of Pittsburgh Emphysema Research Center. This SCCOR focuses on advanced cellular and molecular investigations of lung tissue changes involved in COPD to increase understanding of disease progression. One of the projects that could have the most immediate clinical impact uses an inhaled cyclosporine that could potentially slow the inflammation and progression of the disease.
"With advances in molecular genetics, we may be able to determine that COPD is actually two or more distinct processes," said Steve Duncan, M.D., associate professor of medicine in the pulmonary, allergy and critical care division of the University of Pittsburgh School of Medicine and a SCCOR co-investigator. "But using clinical and basic science studies together, looking at the molecular and cellular characteristics of the disease will help us to better define treatments."
In addition to clinicians and scientists from the University of Pittsburgh, the projects are being undertaken with the collaboration of James Hogg, M.D., Ph.D., professor emeritus of pathology at the University of British Columbia in Vancouver, Canada.
Studies to be conducted through the center are:
Seeking peripheral markers of COPD supporting a hypothesis that the disease is not uniform in its presentation, but rather heterogeneous. Researchers believe these differences are definable by anatomic, physiological, molecular and cellular processes to determine disease manifestation and progression. Using quantitative computed tomography (QCT), researchers will study airway remodeling, emphysema and their associations with other functional and physiological indicators of COPD to define unique clinical subcategories related to the interactions of genetic and environmental characteristics in 800 study subjects. Studies will include associated biomarkers in blood and distinctive tissue changes on a molecular level as well as airway mucus content.
Continuing to examine lung tissue for evidence that abnormal immune system responses may contribute to airway injuries that signal COPD progression. For example, Pitt researchers have learned that bronchus-associated lymphoid tissue (BALT), which is part of the mucosal immune system, is found with COPD characterized by advanced airway disease. They will examine possible linkages among cellular organisms called peptides and microbial populations and other antigens that trigger immune response leading to BALT formation and progressive airway damage. Concurrent studies will look at how genetic factors and other molecular mediators affect lung tissue injury by focusing on damage to cellular repair mechanisms related to the inflammatory process. Project leaders are Drs. Duncan and Hogg.
Assessing the efficacy of inhaled cyclosporine in patients with severe COPD to modify immune response and possibly slow disease progression and improve quality of life. Tissue changes characterizing COPD and transplant rejection are similar in many ways, and inhaled cyclosporine is effective in treating organ rejection in lung transplant patients. Studies will include a 28-day clinical safety trial involving particular attention to airway reaction and the risk of infection, as well as a 24-week trial that will examine biomarkers of immune response and changes in symptoms and radiological evidence of the disease. Recruitment for this trial will begin in February. Project leaders are Michael Donahoe, M.D., associate professor of medicine in the division of pulmonary, allergy and critical care medicine; and Robert Branch, M.D., professor of medicine and director of the Center for Clinical Pharmacology, both at the University of Pittsburgh School of Medicine.
University of Pittsburgh SCCOR studies will involve collaboration with other investigators in the departments of radiology, pharmacology and epidemiology and involves study subjects followed for previous research as well as additional patients recruited for SCCOR-specific project studies.
"COPD is a growing epidemic. In fact, the NIH has begun a campaign to raise public awareness of the disease," said Dr. Sciurba. "Even though smoking rates have been decreasing nationwide, rates remain among the highest in western Pennsylvania, where nearly a quarter of people still smoke, and there are millions of people who are at risk because they are former smokers."
Dr. Sciurba added, "Many people with early signs of COPD simply avoid activities they formerly enjoyed because of shortness of breath and other discomfort. Treatment can help, and we hope to find more and better treatments in the future."