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Bronchoalveolar fluid and plasma inflammatory biomarkers in contemporary ARDS patients.

ABSTRACT: Purpose: Bronchoalveolar fluid (BALF) and plasma biomarkers are often endpoints in early phase randomized trials (RCTs) in acute respiratory distress syndrome (ARDS). With ARDS mortality decreasing, we analyzed baseline biomarkers in samples from contemporary ARDS patients participating in a prior RCT and compared these to historical controls. Materials and methods: Ninety ARDS adult patients enrolled in the parent trial. BALF and blood were collected at baseline, day 4?±?1, and day 8?±?1. Interleukins-8/-6/-1?/-1 receptor antagonist/-10; granulocyte colony stimulating factor; monocyte chemotactic protein-1; tumour necrosis factor-?; surfactant protein-D; von Willebrand factor; leukotriene B4; receptor for advanced glycosylation end products; soluble Fas ligand; and neutrophil counts were measured. Results: Compared to historical measurements, our values were generally substantially lower, despite our participants being similar to historical controls. For example, our BALF IL-8 and plasma IL-6 were notably lower than in a 1999 RCT of low tidal volume ventilation and a 2007 biomarker study, respectively. Conclusions: Baseline biomarker levels in current ARDS patients are substantially lower than 6-20?years before collection of these samples. These findings, whether from ICU care changes resulting in less inflammation or from variation in assay techniques over time, have important implications for design of future RCTs with biomarkers as endpoints.

SUBMITTER: Stapleton RD

PROVIDER: S-EPMC7147943 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Bronchoalveolar fluid and plasma inflammatory biomarkers in contemporary ARDS patients.

Stapleton Renee D RD Suratt Benjamin T BT Neff Margaret J MJ Wurfel Mark M MM Ware Lorraine B LB Ruzinski John T JT Caldwell Ellen E Hallstrand Teal S TS Parsons Polly E PE

Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 20190304 4

<b>Purpose:</b> Bronchoalveolar fluid (BALF) and plasma biomarkers are often endpoints in early phase randomized trials (RCTs) in acute respiratory distress syndrome (ARDS). With ARDS mortality decreasing, we analyzed baseline biomarkers in samples from contemporary ARDS patients participating in a prior RCT and compared these to historical controls. <b>Materials and methods:</b> Ninety ARDS adult patients enrolled in the parent trial. BALF and blood were collected at baseline, day 4 ± 1, and da ...[more]

PMID: 30744430

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Project description:Micro RNAs (MiRNAs) act as a key regulator participating in various biological process, and the roles of that play in chronic obstructive pulmonary disease (COPD) are discovered. However, recent pharmacological treatment for COPD focus on alleviating symptoms and reducing the risk events. The heterogeneous COPD causes variable responses to pharmacological interventions. COPD treatment has gradually developed into precision medicine, integrating clinical and biomarker information to optimize personalized therapy. Thus, targeting miRNAs represents a promising strategy for COPD individual therapy. Twelve COPD patients, 7 community-acquired pneumonia and 4 normal people were recruited. Total RNAs were collected from the bronch alveolar lavage cells and peripheral blood plasma of each participant. miRNAs were profiled by microarray and systematically compared between patients with different groups. Bioinformatic analysis identified pathways relevant to the pathogenesis of COPD. Next, the target pathway networks were mapped. Compared different groups, we obtain differential expression of miRNAs (Q value (Adjusted P value) < .05 and |log2FC| >2). Gene ontology enrichment analyses showed that differentially expressed miRNAs function as regulators in different modules of cellular component, molecular function and biological process. Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that signals, such as MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway and oxidative stress may participate in the pathogenesis of COPD. In the miRNAs target pathway networks, novel-hsa-miR26-3p or hsa-miR-3529-3p/CDC42/MAPK signaling pathway may play a role in regulating COPD. Our findings demonstrate critical roles of the miRNAs in COPD molecular pathology. The data support a plausible mechanism that miRNAs may be involved in the development of COPD by affecting the inflammatory and oxidative stress. Moreover, hsa-miR-4748/CDC42/MAPK signaling pathway may contribute to the pathogenesis of COPD, providing a potential novel therapeutic strategy in COPD.

Dataset Information

Bronchoalveolar fluid and plasma inflammatory biomarkers in contemporary ARDS patients.

Publications

Bronchoalveolar fluid and plasma inflammatory biomarkers in contemporary ARDS patients.

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