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Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels
Published on: August 7, 2017
MicroRNA clustering in pediatric asthma reveals differential corticosteroid responsiveness
Minsuk Yang1,2, Upasna Srivastava3, Alvin Kho4
1Division of Pediatric Respiratory Medicine, Department of Pediatrics, University of California san Diego, La Jolla, California, USA.
Background:
Asthma is a heterogeneous disease with variable treatment responses. miRNAs play a critical role in asthma pathogenesis and may serve as biomarkers for distinct asthma endotypes. We tried to identify possible molecular asthma clusters based on miRNA expression profiles in pediatric patients from the Childhood Asthma Management Program (CAMP) cohort.
Methods:
We performed miRNA profiling and k-means clustering on 462 CAMP participants. Differential miRNA expression and pathway enrichment analyses were conducted to characterize cluster-associated molecular features. Clinical characteristics and budesonide-related changes in lung function were compared across clusters, including analyses stratified by peripheral blood eosinophil counts.
Results:
Three possible molecular clusters were identified, each with distinct miRNA expression patterns and enriched biological pathways. All clusters showed enrichment in IL-4/IL-13 signaling and PIP3/AKT pathways. Cluster 1 was characterized by Toll-like receptor-related signaling pathways, Cluster 2 by FOXO-mediated transcription pathways, and Cluster 3 by pathways associated with SCF-KIT signaling. Baseline demographic and clinical characteristics were largely similar across clusters. However, patterns of budesonide-related lung function change differed. Clusters 1 and 3 showed more favorable lung function profiles after budesonide treatment than Cluster 2. In Cluster 1, eosinophilic participants had a higher proportion of moderate asthma, whereas those without eosinophilia were more often classified as having mild asthma. In Cluster 3, eosinophilic participants had greater baseline airway hyperresponsiveness and lower baseline FEV1/FVC but showed greater improvement in FEV1/FVC after budesonide.
Conclusion:
miRNA profiling identified possible molecular asthma clusters with different clinical, physiologic, and treatment-related patterns.
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