title: Increased matrix metalloproteinase (MMPs) levels do not predict disease severity or progression in emphysema.
abstract: BACKGROUND
  Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema.
  
  
  METHODS
  Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period.
  
  
  RESULTS
  Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline.
  
  
  CONCLUSIONS
  MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease.
authors: Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University Medical Center, New York, New York, United States of America.
authors: Jeanine M
authors: JM
authors: D'Armiento
authors: Monica P
authors: MP
authors: Goldklang
authors: Andrew A
authors: AA
authors: Hardigan
authors: Patrick
authors: P
authors: Geraghty
authors: Michael D
authors: MD
authors: Roth
authors: John E
authors: JE
authors: Connett
authors: Robert A
authors: RA
authors: Wise
authors: Frank C
authors: FC
authors: Sciurba
authors: Steven M
authors: SM
authors: Scharf
authors: Jincy
authors: J
authors: Thankachen
authors: Monirul
authors: M
authors: Islam
authors: Andrew J
authors: AJ
authors: Ghio
authors: Robert F
authors: RF
authors: Foronjy
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018450:Disease Progression; D004646:Emphysema / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D012720:Severity of Illness Index; D012907:Smoking; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases