Principal Investigator: Edwin Blalock
Funding Mechanism: National Institutes of Health- Grant
ID number: 1R01HL114439-01
Award Date: 9/12/2012
Institution: University of Alabama at Birmingham
The body controls lung inflammation via a natural mechanism that interrupts the production of a neutrophil chemokine called proline-glycine-proline (PGP); when acute inflammation occurs, the enzyme leukotriene A4 hydrolase (LTA4H) becomes activated and terminates the PGP inflammatory pathway. Cigarette smoking and chronic obstructive pulmonary disease (COPD) prevent this natural mechanism from occurring, causing a self-propagating multi-step pathway of PGP-mediated inflammation. Once a chronic inflammatory environment is established, elevated acetyl PGP (N--PGP) levels persist in COPD patients even after smoking cessation; elevated N--PGP levels may be associated with COPD exacerbations and may define a subpopulation of patients who experience frequent COPD exacerbations. This study will evaluate body fluid samples from a large cohort of COPD patients to determine whether disturbances in the anti-inflammatory mechanism and increased PGP levels are biomarkers for COPD exacerbations and disease progression. The study population will include 600 patients with severe COPD, 1,800 patients with mild to moderate COPD, 600 healthy smokers and 200 non-smokers. The study aims are: (1) to correlate PGP and LTA4H in COPD patients’ sputum, plasma, and urine with disease parameters such as exacerbations, degree of emphysema and disease progression; (2) to test whether aberrant LTA4H triaminopeptidase (TAP) activity continues in COPD even after smoking cessation, and whether this defect is associated with PGP levels; (3) to correlate baseline sputum PGP levels with those of plasma and urine; and (4) to assess whether plasma and urine PGP levels change over time and associate with particular COPD subpopulations and/or disease parameters. Together, these data will evaluate whether PGP levels can be used as biomarkers for COPD exacerbation associated with tobacco use.