Introduction: Uncontrolled or severe asthma results in symptomatic usage of short-acting ß2-agonist usage (SABA). MicroRNAs (miRNAs) are post-translational regulators that can influence asthma biology. This study aims to identify miRNAs that are associated with increased SABA usage. Methods: Small RNA sequenced from blood serum of 1,132 asthmatic children aged 6 to 14 years in the Genetics of Asthma in Costa Rica Study (GACRS) was used for this analysis. Logistic regression identified miRNAs in patients who required increased SABA usage. These miRNA were validated for association with SABA induced BDR. Gene target pathway analysis was performed on validated miRNAs. Results: 21 miRNAs were significantly associated with increased SABA usage with OR ranging from 0.87 to 1.23. Two miRNAs, miR-378a-3p and miR-144-3p, had odds ratio 1.14 (1 - 1.29, p=0.05) and 1.11 (1.01-1.22, p = 0.035), respectively for increased SABA usage and were also significantly associated with bronchodilator response. Furthermore, a linear regression analysis involving these miRNA and bronchodilator response revealed that increased miR-378a-3p correlated with decreased BDR and increased expression of miR-144-3p correlated with improving pulmonary function with bronchodilators. In gene target KEGG pathway analysis, the erythroblastosis viral oncogene (ErbB) signaling pathway had among one of the highest fold enrichment and p-value. Conclusion: Increased expression miR-378a-3p and miR-144-3p was seen in this patient population who required increased SABA usage. There were different bronchodilatory effects seen in these two miRNAs, suggesting different potential mechanisms underlying increased SABA usage.