The Emphysema Biology and Lung Imaging Research Program is focused on the investigation of fundamental biologic concepts in advanced chronic obstructive lung disease, particularly emphysema. The program utilizes advanced tools in molecular, biochemical, physiologic and radiographic assessment for research investigations which are predominantly based in clinical medicine.
The Emphysema Research Center (ERC) is the core specialty program, run by Dr. Frank Sciurba. This program has been a national leader in the field of lung reduction surgery, pulmonary rehabilitation, and transtracheal oxygen therapy.
The center relies on successful basic science collaborations with the departments of clinical pharmacology and biochemistry, and with other local and international collaborators.
The Center maintains an active registry for patient participation in clinical research trials of novel treatments for patients with advanced COPD.
The Emphysema Biology and Lung Imaging Research Program is also focused on the use of advanced imaging to study lung disease. PACCM investigators in a collaborative effort with Dr. Jim Hogg and Dr. Harvey Coxson at the University of British Columbia. have used volumetric CT scans to assess the density of lung tissue.
This technique, termed Computed Tomographic Morphometry (CTM) uses attenuation data to estimate the inflation of the lung, in terms of volume of gas per gram of tissue, the volumes of the specific lung components (tissue, airspace) as well as the surface area per volume of the parenchyma and has been validated using quantitative histopathology of resected lung tissue in the patients on whom the CT scans were performed. This method is very sensitive to minor changes in lung anatomy and will allow patients to be followed longitudinally, as demonstrated in a study of patients undergoing Lung Volume Reduction Surgery (LVRS).
The available facilities include a pulmonary/exercise physiology research laboratory and the pulmonary rehabilitation unit, which occupy over 9,000 sq feet of clinical and research space, contain an oval 188 foot rubberized track, 11 pulmonary function rooms (including four research and clinical exercise rooms and a pulmonary mechanics room), 2 patient examination rooms, and a large conference room.
There is a dedicated database coordinator and 8.5 Research and clinical pulmonary technologists and exercise physiologists. The Emphysema Biology and Lung Imaging Research Program has a working relationship with the General Clinical Research Center, an inpatient and outpatient research support facility, which is useful when more complex protocols involving overnight stays are needed.
The Division's Emphysema Center has participated in three of the largest NIH sponsored studies in patients with COPD.
The PACCM Division has been a leading center in the NIH sponsored Lung Health Study since 1989. The original Lung Health Study (called LHS I) was a 10-center randomized clinical trial of 5,887 middle-aged smokers (35-59 yrs of age) with spirometric evidence of early chronic obstructive pulmonary disease (COPD), who were initially recruited from November, 1986, through January, 1989. The objective was to determine whether an intervention program combining smoking cessation and an inhaled bronchodilator could slow the decline in the forced expired volume in 1 sec (FEV 1) over a 5-yr. follow-up period. In addition to lung function, extensive data on respiratory symptoms, medication use, and smoking status were also obtained at baseline and annually by questionnaire. Five-yr follow-up rates in all LHS I groups were very high (~ 90% at all annual visits and ~ 95% at the fifth annual visit), and sustained smoking cessation rates in the special intervention groups (~ 22%) were substantially higher than in the usual care control group (~ 5%). Data from LHS I have yielded a large number of publications. The major findings were that smoking cessation had a marked beneficial effect, increasing FEV 1 initially, and then slowing the rate of decline to approximately that seen in nonsmokers, whereas an inhaled bronchodilator had no effect on the decline in FEV 1.
Lung Health Study II (LHS II) was carried out between the end of LHS I and the beginning of LHS III (1994-99). The recently completed LHS II was a randomized clinical trial conducted in 1,116 LHS participants at the 10 LHS clinical centers to determine whether intervention with an inhaled corticosteroid can slow the rate of FEV 1 decline over a 4-yr follow-up period. The main findings were that the inhaled corticosteroid did not alter the FEV 1 rate of decline but did have a modest benefit in reducing airway reactivity, respiratory symptoms and health care use for respiratory problems (Lung Health Study Research Group, 2000).
The University of Pittsburgh is one of 17 centers that participated in the National Emphysema Treatment Trial (NETT). This multicenter trial was a unique cooperation between the NIH (science) and the Agency for Medicare and Medicaid (funding), to study the effectiveness of lung volume reduction surgery compared to maximal medical therapy in subjects with advanced emphysema. Comprehensive physiologic, radiologic and cardiac evaluations were performed on subjects at baseline and at 6 months, 1, 2, 3 and 4 years following intervention. Our team provided sentinel publications in this field preceding the NETT, including a New England Journal of Medicine article documenting the physiological basis of this procedure.
The University of Pittsburgh is one of 5 national centers participating in the Feasibility of Retinoid Therapy in Emphysema (FORTE) clinical trial. This trial examines the feasibility and efficacy of all-trans and 13-cis retinoic acid in subjects with mild to severe emphysema. In this trial the University of Pittsburgh will be be performing core or unique investigator initiated substudies including: 1) the evaluation of cytochrome P450 peripheral and regional lung response to retinoid administration, 2) detailed pharmacokinetic assessment of retinoids in COPD, 3) advanced exercise and pulmonary mechanical response to retinoids, and 4) histologically based quantitative CT analysis of retinoid response in emphysema patients.