Plasma matrix metalloproteinase-3 predicts mortality in acute respiratory distress syndrome: a biomarker analysis of a randomized controlled trial
Abstract Background Matrix metalloproteinase-3 (MMP-3) is a proteolytic enzyme involved in acute respiratory distress syndrome (ARDS) pathophysiology that may serve as a lung-specific biomarker in ARDS. Methods This study was a secondary biomarker analysis of a subset of Albuterol for the Treatment...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-023-02476-5 |
| _version_ | 1797795522536275968 |
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| author | Timothy W. Jones Sultan Almuntashiri Aaron Chase Abdullah Alhumaid Payaningal R. Somanath Andrea Sikora Duo Zhang |
| author_facet | Timothy W. Jones Sultan Almuntashiri Aaron Chase Abdullah Alhumaid Payaningal R. Somanath Andrea Sikora Duo Zhang |
| author_sort | Timothy W. Jones |
| collection | DOAJ |
| description | Abstract Background Matrix metalloproteinase-3 (MMP-3) is a proteolytic enzyme involved in acute respiratory distress syndrome (ARDS) pathophysiology that may serve as a lung-specific biomarker in ARDS. Methods This study was a secondary biomarker analysis of a subset of Albuterol for the Treatment of Acute Lung Injury (ALTA) trial patients to determine the prognostic value of MMP-3. Plasma sample MMP-3 was measured by enzyme-linked immunosorbent assay. The primary outcome was the area under the receiver operating characteristic (AUROC) of MMP-3 at day 3 for the prediction of 90-day mortality. Results A total of 100 unique patient samples were evaluated and the AUROC analysis of day three MMP-3 showed an AUROC of 0.77 for the prediction of 90-day mortality (95% confidence interval: 0.67–0.87), corresponding to a sensitivity of 92% and specificity of 63% and an optimal cutoff value of 18.4 ng/mL. Patients in the high MMP-3 group (≥ 18.4 ng/mL) showed higher mortality compared to the non-elevated MMP-3 group (< 18.4 ng/mL) (47% vs. 4%, p < 0.001). A positive difference in day zero and day three MMP-3 concentration was predictive of mortality with an AUROC of 0.74 correlating to 73% sensitivity, 81% specificity, and an optimal cutoff value of + 9.5 ng/mL. Conclusions Day three MMP-3 concentration and difference in day zero and three MMP-3 concentrations demonstrated acceptable AUROCs for predicting 90-day mortality with a cut-point of 18.4 ng/mL and + 9.5 ng/mL, respectively. These results suggest a prognostic role of MMP-3 in ARDS. |
| first_indexed | 2024-03-13T03:19:15Z |
| format | Article |
| id | doaj.art-87c37b325ed5421d9d97fd044e279372 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-13T03:19:15Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-87c37b325ed5421d9d97fd044e2793722023-06-25T11:25:22ZengBMCRespiratory Research1465-993X2023-06-012411910.1186/s12931-023-02476-5Plasma matrix metalloproteinase-3 predicts mortality in acute respiratory distress syndrome: a biomarker analysis of a randomized controlled trialTimothy W. Jones0Sultan Almuntashiri1Aaron Chase2Abdullah Alhumaid3Payaningal R. Somanath4Andrea Sikora5Duo Zhang6Department of Pharmacy, Augusta University Medical CenterDepartment of Clinical and Administrative Pharmacy, University of Georgia College of PharmacyDepartment of Pharmacy, Augusta University Medical CenterDepartment of Clinical and Administrative Pharmacy, University of Georgia College of PharmacyDepartment of Clinical and Administrative Pharmacy, University of Georgia College of PharmacyDepartment of Clinical and Administrative Pharmacy, University of Georgia College of PharmacyDepartment of Clinical and Administrative Pharmacy, University of Georgia College of PharmacyAbstract Background Matrix metalloproteinase-3 (MMP-3) is a proteolytic enzyme involved in acute respiratory distress syndrome (ARDS) pathophysiology that may serve as a lung-specific biomarker in ARDS. Methods This study was a secondary biomarker analysis of a subset of Albuterol for the Treatment of Acute Lung Injury (ALTA) trial patients to determine the prognostic value of MMP-3. Plasma sample MMP-3 was measured by enzyme-linked immunosorbent assay. The primary outcome was the area under the receiver operating characteristic (AUROC) of MMP-3 at day 3 for the prediction of 90-day mortality. Results A total of 100 unique patient samples were evaluated and the AUROC analysis of day three MMP-3 showed an AUROC of 0.77 for the prediction of 90-day mortality (95% confidence interval: 0.67–0.87), corresponding to a sensitivity of 92% and specificity of 63% and an optimal cutoff value of 18.4 ng/mL. Patients in the high MMP-3 group (≥ 18.4 ng/mL) showed higher mortality compared to the non-elevated MMP-3 group (< 18.4 ng/mL) (47% vs. 4%, p < 0.001). A positive difference in day zero and day three MMP-3 concentration was predictive of mortality with an AUROC of 0.74 correlating to 73% sensitivity, 81% specificity, and an optimal cutoff value of + 9.5 ng/mL. Conclusions Day three MMP-3 concentration and difference in day zero and three MMP-3 concentrations demonstrated acceptable AUROCs for predicting 90-day mortality with a cut-point of 18.4 ng/mL and + 9.5 ng/mL, respectively. These results suggest a prognostic role of MMP-3 in ARDS.https://doi.org/10.1186/s12931-023-02476-5Acute respiratory distress syndromeAcute lung injuryBiomarkerMatrix metalloproteinase-3Mortality prediction |
| spellingShingle | Timothy W. Jones Sultan Almuntashiri Aaron Chase Abdullah Alhumaid Payaningal R. Somanath Andrea Sikora Duo Zhang Plasma matrix metalloproteinase-3 predicts mortality in acute respiratory distress syndrome: a biomarker analysis of a randomized controlled trial Respiratory Research Acute respiratory distress syndrome Acute lung injury Biomarker Matrix metalloproteinase-3 Mortality prediction |
| title | Plasma matrix metalloproteinase-3 predicts mortality in acute respiratory distress syndrome: a biomarker analysis of a randomized controlled trial |
| title_full | Plasma matrix metalloproteinase-3 predicts mortality in acute respiratory distress syndrome: a biomarker analysis of a randomized controlled trial |
| title_fullStr | Plasma matrix metalloproteinase-3 predicts mortality in acute respiratory distress syndrome: a biomarker analysis of a randomized controlled trial |
| title_full_unstemmed | Plasma matrix metalloproteinase-3 predicts mortality in acute respiratory distress syndrome: a biomarker analysis of a randomized controlled trial |
| title_short | Plasma matrix metalloproteinase-3 predicts mortality in acute respiratory distress syndrome: a biomarker analysis of a randomized controlled trial |
| title_sort | plasma matrix metalloproteinase 3 predicts mortality in acute respiratory distress syndrome a biomarker analysis of a randomized controlled trial |
| topic | Acute respiratory distress syndrome Acute lung injury Biomarker Matrix metalloproteinase-3 Mortality prediction |
| url | https://doi.org/10.1186/s12931-023-02476-5 |
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