Plasma TIMP-1 as a sex-specific biomarker for acute lung injury.
Plasma TIMP-1 as a sex-specific biomarker for acute lung injury.
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DOI：
10.1186/s13293-022-00481-9
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发表时间：
2022-12-08
影响因子：
7.9
通讯作者：
Zhang, Duo
中科院分区：
文献类型：
--
作者：
Almuntashiri, Sultan;Jones, Timothy W.;Wang, Xiaoyun;Sikora, Andrea;Zhang, Duo
急性呼吸窘迫综合征（ARDS）是一种高发病率和高死亡率的疾病，死亡率高达40%。临床前和临床研究已经将性别特异性激素作为不同免疫反应的关键贡献者。因此，需要探索性和性激素在肺损伤和ARDS发展中的作用。金属蛋白酶组织抑制剂-1（TIMP-1）是最早发现的天然胶原酶抑制剂，仅定位于X染色体。本研究旨在评估循环TIMP-1的预后作用，以及男性和女性之间的浓度差异是否与ARDS患者的死亡率相关。对随机化当天入组沙丁胺醇治疗急性肺损伤（阿尔塔）试验的100例ARDS患者的人血浆样本进行了评价。使用酶联免疫测定法（ELISA）测量TIMP-1的量。计算受试者工作特征下面积（AUROC），以评估TIMP-1对30天和90天死亡率的预测能力。计算卡方检验和Kaplan-Meier曲线以评估不同变量和生存率。女性中TIMP-1和30天死亡率的AUROC分析显示，TIMP-1的AUC为0.87（95%置信区间[CI] 0.78至0.97; P = 0.0014），最佳截止值为159.7 ng/mL，产生100%灵敏度和74%特异性。对于90天死亡率，AUROC分析显示AUC为0.82（95%置信区间[CI] 0.67至0.97; P = 0.0016），具有相似的临界值，产生90%的灵敏度和76.47%的特异性。将受试者按TIMP-1浓度分为高（≥ 159.7 ng/mL）或低（< 159.7 ng/mL），表明高TIMP-1与30和90天死亡率增加相关（均P < 0.0001）。TIMP-1高浓度组无呼吸机天数、无ICU天数均较低（P均< 0.05）。循环TIMP-1似乎是女性ARDS患者死亡率的一个有前景的生物标志物。高TIMP-1组显示更差的VFD和无ICU天数。循环TIMP-1可能是ARDS患者性别特异性的生物标志物，可以改善ARDS表型，并为女性提供新的治疗靶点。血浆TIMP-1水平在ARDS患者中显著升高。男性和女性ARDS患者血浆TIMP-1水平无差异。考虑到30天和90天的死亡率，与女性幸存者相比，女性非幸存者具有显著更高的血浆TIMP-1水平。然而，在男性组中，非幸存者和幸存者之间没有差异。血浆TIMP-1水平对女性ARDS患者死亡率的预测具有很好的鉴别能力。高TIMP-1水平组显示其他相关临床结局、VFD和无ICU天数更差。
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. 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. 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). 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. 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.
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DOI：
10.3390/diagnostics11091643
发表时间：
2021-09-08
期刊：
Diagnostics (Basel, Switzerland)
影响因子：
--
作者：
Almuntashiri S;James C;Wang X;Siddiqui B;Zhang D
通讯作者：
Zhang D
影响因子：
3.3
作者：
Kubota, Yukihiko;Nishiwaki, Kiyoji;Sugimoto, Asako
通讯作者：
Sugimoto, Asako
DOI：
10.1097/ta.0b013e31822c0d31
发表时间：
2011-10-01
影响因子：
--
作者：
Heffernan, Daithi S.;Dossett, Lesly A.;May, Addison K.
通讯作者：
May, Addison K.
影响因子：
1.6
作者：
Chen, Guobing;Ge, Dandan;Ma, Qilin
通讯作者：
Ma, Qilin
DOI：
10.1097/shk.0000000000000386
发表时间：
2015-08
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Hsu AT;Barrett CD;DeBusk GM;Ellson CD;Gautam S;Talmor DS;Gallagher DC;Yaffe MB
通讯作者：
Yaffe MB