Identification and validation of a mirna as a diagnostic biomarker of diffuse alveolar damage in an animal model of acute lung injury and adult respiratory distress syndrome in mechanically ventilated patients

Autor: Cardinal Fernández, Pablo, Ferruelo, Antonio, Rego, N., Rojas, Yeny, Ballén Barragán, A., Granados Carreño, Rosario, Jaramillo, C., López Hernández, E., Martínez Caro, Leticia, Nin, Nicolás, Herrero, Raquel, Cal, Miguel A. de la, Esteban, Andrés, Lorente Balanza, José Ángel
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: ABACUS. Repositorio de Producción Científica
Universidad Europea (UEM)
Popis: The objective is to discover a miRNA with diagnostic characteristics for diffuse alveolar damage (DAD) in an animal of acute lung injury (ALI) and in patients with the ARDS. Male rats (325-372 gr) underwent mechanical ventilation for 2.5 h with VT=9 ml/kg + PEEP=5 cm H2O (low VT, LV, n=10); or VT=25 ml/kg + PEEP=0 cm H2O (high VT, HV, n=19) (11 of 19 developed DAD at histological examination). Whole miRNA expression (RNA-seq-Single Read, 72 cycles, Illumina GaIIx) was analyzed in lung parenchyma. miRNA expression in LV vs. HV and in HV-DAD vs. HV-no-DAD was compared. We used a data mining strategy to prioritize the most relevant miRNA within the miRNAs differentially expressed. Prioritized miRNAs were validated in (1) serum from the same group of rats (RT-PCR); (2) human lung tissue (preserved at -80º after sampling) from autopsies of patients with ARDS (RT-PCR and in situ hybridization) (n=20); (3) human serum from mechanically ventilated patients obtained during the first 24 hours of ICU admission (n=66, 14 nonsurvivors). A p value < 0.05 was considered statistically significant. Results are median (IQR), and odds ratio (OR [95% confidence interval]). RT-PCR results were expressed x10-4. Categorical and continuous variables were compared with χ2 and Mann-Whitney, respectively. Predictive multivariate logistic analysis was used to identify independent risk factors. The area under ROC curve (AUROC, mean±SEM) was used to assess the discriminatory capacity. Multiple-comparison was adjusted by FDR. The local Ethics Committee approved this study. 7.214 JCR (2014) Q1, 3/27 Critical care medicine UEM
Databáze: OpenAIRE
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