ArticleBiology of sex differences2022
Plasma TIMP-1 as a sex-specific biomarker for acute lung injury.
Article in Biology of sex differences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- Age- and sex-dependent heterogeneity during LPS-induced murine acute lung injury.Immunity & ageing : I & A · 2026Article
- Sex-related differences in lung injury distribution and outcomes in COVID-19 acute respiratory failure: insights from the CT-COVID19 multicenter study group.Intensive care medicine experimental · 2026Article
- Current Insights into Clinical, Molecular, and Therapeutic Approaches to Acute Respiratory Distress Syndrome.Medical sciences (Basel, Switzerland) · 2026Review
- Sex-Specific Pathophysiological Signatures in Allometric Dosing-Controlled Bleomycin Acute Lung Injury Model.bioRxiv : the preprint server for biology · 2026Article
- Analysis of Stratifin Expression and Proteome Variation in a Rat Model of Acute Lung Injury.Journal of proteome research · 2025Article
- Pathophysiological mechanisms of ARDS: a narrative review from molecular to organ-level perspectives.Respiratory research · 2025Review
- Estrogen-dependent gene regulation: Molecular basis of TIMP-1 as a sex-specific biomarker for acute lung injury.Physiological reports · 2024Article
- Club Cell Secretory Protein-16 (CC16) as a Prognostic Biomarker for COVID-19 and H1N1 Viral Infections.Diagnostics (Basel, Switzerland) · 2024Article
- Advances in Biomarkers for Diagnosis and Treatment of ARDS.Diagnostics (Basel, Switzerland) · 2023Review
- TIMP-1 and its potential diagnostic and prognostic value in pulmonary diseases.Chinese medical journal pulmonary and critical care medicine · 2023Article
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundAcute 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.
methodsHuman 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.
resultsAUROC 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).
conclusionCirculating 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.
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