Matrix metalloproteinase-9 predicts pulmonary status declines in α<sub>1</sub>-antitrypsin deficiency
<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase-9 (MMP-9) may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes.</p> <p>Methods...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-03-01
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| Series: | Respiratory Research |
| Online Access: | http://respiratory-research.com/content/12/1/35 |
| _version_ | 1811318599165411328 |
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| author | Rames Alexis Eisner Mark D Omachi Theodore A Markovtsova Lada Blanc Paul D |
| author_facet | Rames Alexis Eisner Mark D Omachi Theodore A Markovtsova Lada Blanc Paul D |
| author_sort | Rames Alexis |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase-9 (MMP-9) may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes.</p> <p>Methods</p> <p>We utilized data from the placebo arm (n = 126) of a clinical trial of patients with alpha<sub>1</sub>-antitrypsin deficiency (AATD) and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period. Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT), and COPD exacerbations were assessed at regular intervals over 12 months. Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history. A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models.</p> <p>Results</p> <p>At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV<sub>1 </sub>(p = 0.03), FVC (p < 0.001), carbon monoxide transfer factor (p = 0.03), resting oxygen saturation (p = 0.02), and ISWT distance walked (p = 0.02) but were not associated with radiographic lung density or total lung capacity (TLC). In longitudinal analyses, MMP-9 predicted a further decline in transfer factor (p = 0.04) and oxygen saturation (p < 0.001). MMP-9 also predicted worsening lung density (p = 0.003), increasing TLC (p = 0.02), and more frequent COPD exacerbations over follow-up (p = 0.003). Controlling additionally for hs-CRP levels did not substantively change the longitudinal associations between MMP-9 and these outcomes.</p> <p>Conclusions</p> <p>Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema.</p> |
| first_indexed | 2024-04-13T12:28:37Z |
| format | Article |
| id | doaj.art-1997ee6e84a348af870b8acf98c12edf |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-04-13T12:28:37Z |
| publishDate | 2011-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-1997ee6e84a348af870b8acf98c12edf2022-12-22T02:46:55ZengBMCRespiratory Research1465-99212011-03-011213510.1186/1465-9921-12-35Matrix metalloproteinase-9 predicts pulmonary status declines in α<sub>1</sub>-antitrypsin deficiencyRames AlexisEisner Mark DOmachi Theodore AMarkovtsova LadaBlanc Paul D<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase-9 (MMP-9) may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes.</p> <p>Methods</p> <p>We utilized data from the placebo arm (n = 126) of a clinical trial of patients with alpha<sub>1</sub>-antitrypsin deficiency (AATD) and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period. Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT), and COPD exacerbations were assessed at regular intervals over 12 months. Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history. A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models.</p> <p>Results</p> <p>At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV<sub>1 </sub>(p = 0.03), FVC (p < 0.001), carbon monoxide transfer factor (p = 0.03), resting oxygen saturation (p = 0.02), and ISWT distance walked (p = 0.02) but were not associated with radiographic lung density or total lung capacity (TLC). In longitudinal analyses, MMP-9 predicted a further decline in transfer factor (p = 0.04) and oxygen saturation (p < 0.001). MMP-9 also predicted worsening lung density (p = 0.003), increasing TLC (p = 0.02), and more frequent COPD exacerbations over follow-up (p = 0.003). Controlling additionally for hs-CRP levels did not substantively change the longitudinal associations between MMP-9 and these outcomes.</p> <p>Conclusions</p> <p>Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema.</p>http://respiratory-research.com/content/12/1/35 |
| spellingShingle | Rames Alexis Eisner Mark D Omachi Theodore A Markovtsova Lada Blanc Paul D Matrix metalloproteinase-9 predicts pulmonary status declines in α<sub>1</sub>-antitrypsin deficiency Respiratory Research |
| title | Matrix metalloproteinase-9 predicts pulmonary status declines in α<sub>1</sub>-antitrypsin deficiency |
| title_full | Matrix metalloproteinase-9 predicts pulmonary status declines in α<sub>1</sub>-antitrypsin deficiency |
| title_fullStr | Matrix metalloproteinase-9 predicts pulmonary status declines in α<sub>1</sub>-antitrypsin deficiency |
| title_full_unstemmed | Matrix metalloproteinase-9 predicts pulmonary status declines in α<sub>1</sub>-antitrypsin deficiency |
| title_short | Matrix metalloproteinase-9 predicts pulmonary status declines in α<sub>1</sub>-antitrypsin deficiency |
| title_sort | matrix metalloproteinase 9 predicts pulmonary status declines in α sub 1 sub antitrypsin deficiency |
| url | http://respiratory-research.com/content/12/1/35 |
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