The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS.

TitleThe matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS.
Publication TypePublication
Year2019
AuthorsJ Wells M, Xing D, Viera L, Burkes RM, Wu Y, Bhatt SP, Dransfield MT, Couper DJ, O'Neal W, Hoffman EA, Gaggar A, Barjaktarevic I, Curtis JL, Labaki WW, Han MLan K, Freeman CM, Putcha N, Schlange T, J Blalock E
Corporate AuthorsSPIROMICS Investigators,
JournalRespir Res
Volume20
Issue1
Pagination254
Date Published2019 Nov 12
ISSN1465-993X
KeywordsAged, biomarkers, Cohort Studies, Female, Glycine, Humans, Male, Middle Aged, Proline, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Spirometry, Sputum
Abstract

BACKGROUND: Pulmonary and systemic inflammation are central features of chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated relationships between biologically active extracellular matrix components, or matrikines, and COPD pathogenesis. We studied the relationships between the matrikine acetyl-proline-glycine-proline (AcPGP) in sputum and plasma and clinical features of COPD.METHODS: Sputum and plasma samples were obtained from COPD participants in the SPIROMICS cohort at enrollment. AcPGP was isolated using solid phase extraction and measured by mass spectrometry. Demographics, spirometry, quality of life questionnaires, and quantitative computed tomography (CT) imaging with parametric response mapping (PRM) were obtained at baseline. Severe COPD exacerbations were recorded at 1-year of prospective follow-up. We used linear and logistic regression models to measure associations between AcPGP and features of COPD, and Kaplan-Meier analyses to measure time-to-first severe exacerbation.RESULTS: The 182 COPD participants in the analysis were 66 ± 8 years old, 62% male, 84% White race, and 39% were current smokers. AcPGP concentrations were 0.61 ± 1.89 ng/mL (mean ± SD) in sputum and 0.60 ± 1.13 ng/mL in plasma. In adjusted linear regression models, sputum AcPGP was associated with FEV/FVC, spirometric GOLD stage, PRM-small airways disease, and PRM-emphysema. Sputum AcPGP also correlated with severe AECOPD, and elevated sputum AcPGP was associated with shorter time-to-first severe COPD exacerbation. In contrast, plasma AcPGP was not associated with symptoms, pulmonary function, or severe exacerbation risk.CONCLUSIONS: In COPD, sputum but not plasma AcPGP concentrations are associated with the severity of airflow limitation, small airways disease, emphysema, and risk for severe AECOPD at 1-year of follow-up.TRIAL REGISTRATION: ClinicalTrials.gov: NCT01969344 (SPIROMICS).

DOI10.1186/s12931-019-1230-8
Alternate JournalRespir Res
PubMed ID31718676
PubMed Central IDPMC6852714
Grant ListU24 HL141762 / HL / NHLBI NIH HHS / United States
S10 OD018526 / OD / NIH HHS / United States
P30 ES005605 / ES / NIEHS NIH HHS / United States
I01BX001756 / / U.S. Department of Veterans Affairs /
K24 HL140108 / HL / NHLBI NIH HHS / United States
K08 HL123940 / HL / NHLBI NIH HHS / United States
I01 CX000911 / CX / CSRD VA / United States
HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C, U01 HL137880 / / National Heart, Lung, and Blood Institute (US) /
R01 HL102371 / HL / NHLBI NIH HHS / United States
K24 HL137013 / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
R35 HL135710 / HL / NHLBI NIH HHS / United States
P30 DK054759 / DK / NIDDK NIH HHS / United States
R01HL114439, R01HL126596,and R35HL135710 / / National Heart, Lung, and Blood Institute (US) /
I01 CX001553 / CX / CSRD VA / United States
MS#: 
MS198
Manuscript Full Title: 
The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS.
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: Birmingham (University of Alabama at Birmingham)
ECI: 
Manuscript Status: 
Published and Public