التفاصيل البيبلوغرافية
| العنوان: |
Plasma TIMP-1 as a sex-specific biomarker for acute lung injury. |
| المؤلفون: |
Almuntashiri, Sultan1,2 (AUTHOR), Jones, Timothy W.1 (AUTHOR), Wang, Xiaoyun1 (AUTHOR), Sikora, Andrea3,4 (AUTHOR), Zhang, Duo1,5 (AUTHOR) duozhang@uga.edu |
| المصدر: |
Biology of Sex Differences. 12/8/2022, Vol. 13 Issue 1, p1-9. 9p. |
| مصطلحات موضوعية: |
*LUNGS, *ADULT respiratory distress syndrome, *LUNG injuries, *FEMALES, *RECEIVER operating characteristic curves, *PATIENTS |
| مستخلص: |
Background: Acute respiratory distress syndrome (ARDS) confers high morbidity and mortality, with a death rate reaching 40%. Pre-clinical and clinical studies have cited sex-specific sex hormones as a critical contributor to divergent immunologic responses. Therefore, exploration of sex and sex hormone roles following lung injury and ARDS development is needed. Tissue inhibitor of metalloproteinase-1 (TIMP-1) was the first-discovered natural collagenase inhibitor and is located exclusively on the X chromosome. This study aimed to evaluate the prognostic role of circulating TIMP-1, and if concentration differences between males and females correlate with the mortality of ARDS patients. Methods: Human plasma samples from 100 ARDS patients enrolled in Albuterol to Treat Acute Lung Injury (ALTA) trial on the day of randomization were evaluated. The amount of TIMP-1 was measured using an enzyme-linked immunoassay (ELISA). Area under the receiver operating characteristic (AUROC) was computed to assess the predictive power of TIMP-1 for 30 and 90-day mortality. Chi-squared tests and Kaplan–Meier curves were computed to assess different variables and survival. Results: AUROC analysis of TIMP-1 and 30-day mortality among females showed that TIMP-1 exhibited an AUC of 0.87 (95% confidence interval [CI] 0.78 to 0.97; P = 0.0014) with an optimal cut-off value of 159.7 ng/mL producing a 100% sensitivity and 74% specificity. For 90-day mortality, AUROC analysis showed an AUC of 0.82 (95% confidence interval [CI] 0.67 to 0.97; P = 0.0016) with a similar cut-off value producing a 90% sensitivity and 76.47% specificity. Stratifying subjects by TIMP-1 concentration as high (≥ 159.7 ng/mL) or low (< 159.7 ng/mL) indicated that high TIMP-1 was associated with increased 30 and 90-day mortality rates (all P < 0.0001). Lastly, high TIMP-1 group was associated with worse other outcomes including ventilator-free days (VFDs) and ICU-free days (all P < 0.05). Conclusion: Circulating TIMP-1 appeared to be a promising biomarker for mortality among females with ARDS. The high TIMP-1 group showed worse VFDs and ICU-free days. Circulating TIMP-1 may be a sex-specific biomarker in the setting of ARDS and could improve ARDS phenotyping as well as provide a novel therapeutic target in females. Highlights: Plasma TIMP-1 levels are significantly elevated in ARDS patients. Plasma TIMP-1 levels show no difference between female and male ARDS patients. Considering the 30 and 90-day mortality, female non-survivors have significantly higher plasma TIMP-1 levels compared to female survivors. However, there is no difference between non-survivors and survivors in the male group. Plasma TIMP-1 levels demonstrate an excellent discriminating ability for the prediction of mortality among female ARDS patients. The high TIMP-1 level group shows worse other relevant clinical outcomes, VFDs, and ICU-free days. [ABSTRACT FROM AUTHOR] |
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