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Proteolytic biomarkers are related to prognosis in COPD- report from a population-based cohort

Linder, Robert LU orcid ; Rönmark, Eva ; Pourazar, Jamshid ; Behndig, Annelie F. ; Blomberg, Anders and Lindberg, Anne (2018) In Respiratory Research 19(1).
Abstract

Background: The imbalance between proteases and anti-proteases is considered to contribute to the development of COPD. Our aim was to evaluate the protease MMP-9, the antiprotease TIMP-1 and the MMP-9/TIMP-1-ratio as biomarkers in relation to prognosis. Prognosis was assessed as lung function decline and mortality. This was done among subjects with COPD in a population-based cohort. Methods: In 2005, clinical examinations including spirometry and peripheral blood sampling, were made in a longitudinal population-based cohort. In total, 1542 individuals participated, whereof 594 with COPD. In 2010, 1031 subjects participated in clinical examinations, and 952 subjects underwent spirometry in both 2005 and 2010. Serum MMP-9 and TIMP-1... (More)

Background: The imbalance between proteases and anti-proteases is considered to contribute to the development of COPD. Our aim was to evaluate the protease MMP-9, the antiprotease TIMP-1 and the MMP-9/TIMP-1-ratio as biomarkers in relation to prognosis. Prognosis was assessed as lung function decline and mortality. This was done among subjects with COPD in a population-based cohort. Methods: In 2005, clinical examinations including spirometry and peripheral blood sampling, were made in a longitudinal population-based cohort. In total, 1542 individuals participated, whereof 594 with COPD. In 2010, 1031 subjects participated in clinical examinations, and 952 subjects underwent spirometry in both 2005 and 2010. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbent assay (ELISA). Mortality data were collected from the Swedish national mortality register from the date of examination in 2005 until 31st December 2010. Results: The correlation between biomarkers and lung function decline was similar in non-COPD and COPD, but only significant for MMP-9 and MMP-9/TIMP-1-ratio in non-COPD. Mortality was higher in COPD than non-COPD (16% vs. 10%, p = 0.008). MMP-9 concentrations and MMP-9/TIMP-1 ratios in 2005 were higher among those who died during follow up, as well as among those alive but not participating in 2010, when compared to those participating in the 2010-examination. In non-COPD, male sex, age, burden of smoking, heart disease and MMP-9/TIMP-1 ratio were associated with increased risk for death, while increased TIMP-1 was protective. Among those with COPD, age, current smoking, increased MMP-9 and MMP-9/TIMP-1 ratio were associated with an increased risk for death. Conclusions: The expected association between these biomarkers and lung function decline in COPD was not confirmed in this population-based study, probably due to a healthy survivor effect. Still, it is suggested that increased proteolytic imbalance may be of greater prognostic importance in COPD than in non-COPD.

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author
; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chronic obstructive pulmonary disease (COPD), Matrix metalloproteinases, Mortality, Spirometry, Tissue inhibitor of metalloproteinases, Chronic obstructive pulmonary disease (COPD), KOL, Matrix Metalloproteinases, metalloproteinaser, TIMP, Mortality, mortalitet, Spirometry, spirometri
in
Respiratory Research
volume
19
issue
1
article number
64
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85045389911
  • pmid:29650051
ISSN
1465-9921
DOI
10.1186/s12931-018-0772-5
language
English
LU publication?
no
additional info
Publisher Copyright: © 2018 The Author(s).
id
08451682-265e-40a4-ab30-636bfda480b5
date added to LUP
2025-05-16 10:07:02
date last changed
2025-07-11 14:25:01
@article{08451682-265e-40a4-ab30-636bfda480b5,
  abstract     = {{<p>Background: The imbalance between proteases and anti-proteases is considered to contribute to the development of COPD. Our aim was to evaluate the protease MMP-9, the antiprotease TIMP-1 and the MMP-9/TIMP-1-ratio as biomarkers in relation to prognosis. Prognosis was assessed as lung function decline and mortality. This was done among subjects with COPD in a population-based cohort. Methods: In 2005, clinical examinations including spirometry and peripheral blood sampling, were made in a longitudinal population-based cohort. In total, 1542 individuals participated, whereof 594 with COPD. In 2010, 1031 subjects participated in clinical examinations, and 952 subjects underwent spirometry in both 2005 and 2010. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbent assay (ELISA). Mortality data were collected from the Swedish national mortality register from the date of examination in 2005 until 31st December 2010. Results: The correlation between biomarkers and lung function decline was similar in non-COPD and COPD, but only significant for MMP-9 and MMP-9/TIMP-1-ratio in non-COPD. Mortality was higher in COPD than non-COPD (16% vs. 10%, p = 0.008). MMP-9 concentrations and MMP-9/TIMP-1 ratios in 2005 were higher among those who died during follow up, as well as among those alive but not participating in 2010, when compared to those participating in the 2010-examination. In non-COPD, male sex, age, burden of smoking, heart disease and MMP-9/TIMP-1 ratio were associated with increased risk for death, while increased TIMP-1 was protective. Among those with COPD, age, current smoking, increased MMP-9 and MMP-9/TIMP-1 ratio were associated with an increased risk for death. Conclusions: The expected association between these biomarkers and lung function decline in COPD was not confirmed in this population-based study, probably due to a healthy survivor effect. Still, it is suggested that increased proteolytic imbalance may be of greater prognostic importance in COPD than in non-COPD.</p>}},
  author       = {{Linder, Robert and Rönmark, Eva and Pourazar, Jamshid and Behndig, Annelie F. and Blomberg, Anders and Lindberg, Anne}},
  issn         = {{1465-9921}},
  keywords     = {{Chronic obstructive pulmonary disease (COPD); Matrix metalloproteinases; Mortality; Spirometry; Tissue inhibitor of metalloproteinases; Chronic obstructive pulmonary disease (COPD); KOL; Matrix Metalloproteinases; metalloproteinaser; TIMP; Mortality; mortalitet; Spirometry; spirometri}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Respiratory Research}},
  title        = {{Proteolytic biomarkers are related to prognosis in COPD- report from a population-based cohort}},
  url          = {{http://dx.doi.org/10.1186/s12931-018-0772-5}},
  doi          = {{10.1186/s12931-018-0772-5}},
  volume       = {{19}},
  year         = {{2018}},
}