Serum miRNAs are crucial for prediction of Asthma Exacerbations in Costa Rica

Principal Investigator: Michael J. McGeachie

Authors: Anshul Tiwari, Alvin T Kho, Juan C Celedón, Scott T Weiss, Kelan G Tantisira, Michael J McGeachie
Lay Abstract

Introduction: MicroRNAs (miRs) are small non-coding RNA molecules that have emerged as key regulators of inflammatory processes and have showed promise as non-invasive biomarkers and disease predictors. We anticipated that miRs would be strongly associated to asthma exacerbation in a pediatric asthma cohort.

Objective: The purpose of this study was to investigate if there was a link between circulating miRs and asthma exacerbation.

Methods: Using blood samples from 1165 Costa Rican children with asthma, we performed small RNA sequencing. For replication, we utilized 492 children with asthma from the CAMP clinical trial. Our primary outcome was severe asthma exacerbations, defined as >2 emergency room or urgent care visits in GACRS and the presence or absence of asthma-related hospitalizations in the prior year in CAMP.

Results & Conclusions: Using statistics, we found there were 29 micro RNAs with unusual patterns of expression in cases compared with controls. Further four of these miRs showed the same patterns in CAMP. These miRNAs regulate biological pathways associated with asthma. These microRNAs might have a significant and important function in asthma exacerbation. This will be investigated further as a potential biomarker and therapeutic target in the future.

Funding: R01 HL139634, R01 HL127332, R01 HL129935, P01 HL132825

Scientific Abstract

Introduction: MicroRNAs (miRs) are small non-coding RNA molecules that have emerged as non-invasive biomarkers and disease predictors. We anticipated that miRs would be strongly associated to asthma exacerbation in a pediatric asthma cohort.

Objective: The purpose of this study was to investigate if there was a link between circulating miRs and asthma exacerbation.

Methods: On 1165 serum samples from the Genetics of Asthma in Costa Rica Study (GACRS), we performed small RNA sequencing. The DESeq2 program in R was used to identify differentially expressed miRs in subjects with and without severe asthma exacerbations, using a 10% FDR and adjustments for age, gender, and (ICS) usage.

Results: We found 10 upregulated and 19 downregulated miRs. These were assessed for replication in CAMP, where 4 miRs was downregulated between exacerbation (n=298) and non-exacerbation subjects (n=194). Pathway enrichment analysis showed MAPK, PI3-Akt, RAS, and cAMP signaling pathways were strongly enriched for DE miR target genes.

Conclusion: In our discovery cohort, 29 DE miRNAs were associated with asthma exacerbation. In an independent cohort, four miRs were replicated. These microRNAs might have a significant and important function in asthma exacerbation. This will be investigated further as a potential biomarker and therapeutic target in the future.

Clinical Implications
miRNAs were associated with asthma exacerbation and involved in four major asthma pathways. These microRNAs might have a significant and important function in asthma exacerbation. This will be investigated further as a potential biomarker and therapeutic target in the future.

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