Pitt Receives $13M NIH Grant To Help People With Chronic Obstructive Pulmonary Disease

Pitt has been awarded an estimated $13 million grant from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health 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 as a Specialized Center of Clinically Oriented Research (SCCOR) in COPD. Such a center encourages the direction of basic science research findings more rapidly toward clinical problems.

Frank C. Sciurba is principal investigator of the SCCOR grant, which entails three unique projects and three resource cores to support the research. Sciurba is a professor of medicine in Pitt’s School of Medicine and director of the Emphysema Research Center in the school’s Division of Pulmonary, Allergy, and Critical Care Medicine.
The NHLBI estimates that 12 million adults currently have been diagnosed with COPD and that 12 million more are 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,” Sciurba explained. “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.

“With advances in molecular genetics, we may be able to determine that COPD is actually two or more distinct processes,” said Steve Duncan, a professor of medicine in the Pitt medical school’s pulmonary, allergy, and critical care division and a SCCOR coinvestigator. “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.”
Studies to be conducted through the center include the following:

• 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, 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; and

• 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.