. 2017 Aug 30;5(1):38.

doi: 10.1186/s40635-017-0155-0.

Whole blood microRNA markers are associated with acute respiratory distress syndrome

Zhaozhong Zhu¹, Liming Liang^{2

3}, Ruyang Zhang^{1

4}, Yongyue Wei^{1

4}, Li Su¹, Paula Tejera¹, Yichen Guo¹, Zhaoxi Wang¹, Quan Lu¹, Andrea A Baccarelli¹, Xi Zhu⁵, Ednan K Bajwa⁶, B Taylor Thompson⁶, Guo-Ping Shi⁷, David C Christiani^{8

9}

Affiliations

¹ Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, USA.
² Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴ Department of Environmental Health, Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
⁵ Department of Critical Care Medicine, Peking University Third Hospital, Beijing, China.
⁶ Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, USA. dchris@hsph.harvard.edu.
⁹ Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. dchris@hsph.harvard.edu.

PMID: 28856588
PMCID: PMC5577350
DOI: 10.1186/s40635-017-0155-0

Whole blood microRNA markers are associated with acute respiratory distress syndrome

Zhaozhong Zhu et al. Intensive Care Med Exp. 2017.

. 2017 Aug 30;5(1):38.

doi: 10.1186/s40635-017-0155-0.

Authors

Affiliations

¹ Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, USA.
² Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴ Department of Environmental Health, Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
⁵ Department of Critical Care Medicine, Peking University Third Hospital, Beijing, China.
⁶ Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, USA. dchris@hsph.harvard.edu.
⁹ Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. dchris@hsph.harvard.edu.

PMID: 28856588
PMCID: PMC5577350
DOI: 10.1186/s40635-017-0155-0

Abstract

Background: MicroRNAs (miRNAs) can play important roles in inflammation and infection, which are common manifestations of acute respiratory distress syndrome (ARDS). We assessed if whole blood miRNAs were potential diagnostic biomarkers for human ARDS.

Methods: This nested case-control study (N = 530) examined a cohort of ARDS patients and critically ill at-risk controls. Whole blood miRNA profiles and logistic regression analyses identified miRNAs correlated with ARDS. Stratification analysis also assessed selected miRNA markers for their role in sepsis and pneumonia associated with ARDS. Receiver operating characteristic (ROC) analysis evaluated miRNA diagnostic performance, along with Lung Injury Prediction Score (LIPS).

Results: Statistical analyses were performed on 294 miRNAs, selected from 754 miRNAs after quality control screening. Logistic regression identified 22 miRNAs from a 156-patient discovery cohort as potential risk or protective markers of ARDS. Three miRNAs-miR-181a, miR-92a, and miR-424-from the discovery cohort remained significantly associated with ARDS in a 373-patient independent validation cohort (FDR q < 0.05) and meta-analysis (p < 0.001). ROC analyses demonstrated a LIPS baseline area-under-the-curve (AUC) value of ARDS of 0.708 (95% CI 0.651-0.766). Addition of miR-181a, miR-92a, and miR-424 to LIPS increased baseline AUC to 0.723 (95% CI 0.667-0.778), with a relative integrated discrimination improvement of 2.40 (p = 0.005) and a category-free net reclassification index of 27.21% (p = 0.01).

Conclusions: miR-181a and miR-92a are risk biomarkers for ARDS, whereas miR-424 is a protective biomarker. Addition of these miRNAs to LIPS can improve the risk estimate for ARDS.

Keywords: ARDS; LIPS; MicroRNA; Whole blood.

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Conflict of interest statement

Ethics approval and consent to participate

The institutional review boards of the MGH, BIDMC, and Harvard T.H. Chan School of Public Health approved this study.

Consent for publication

We confirm that we have obtained consent from participants (or legal parent/guardian for children) to report individual patient data.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Study design of discovery cohort, validation cohort, and gene set enrichment analysis (GSEA). *One control sample was excluded due to few detectable miRNAs. **Discovery cohort ARDS and at-risk controls were matched by age (± 5 years) and gender

See this image and copyright information in PMC

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Whole blood microRNA markers are associated with acute respiratory distress syndrome

Affiliations

Whole blood microRNA markers are associated with acute respiratory distress syndrome

Authors

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources