Abstract: Asthma is a heterogeneous inflammatory airway disease characterized by diverse endotypes, variable clinical severity, and differential treatment responses driven by genetic, epigenetic, and environmental influences. MicroRNAs (miRNAs), as post-transcriptional regulators of gene expression, are central modulators of airway inflammation, remodeling, and immune dysregulation and represent promising candidates for biomarker development and therapeutic targeting. Despite the growing literature on dysregulated miRNAs in asthma, findings remain inconsistent and frequently lack independent validation. Using a structured search strategy covering 2009– 2025, we identified 299 records and applied predefined replication criteria to prioritize reproducible associations. Two complementary validation Criteria were implemented: cross-study replication across independent cohorts and discovery–replication study designs addressing clinical heterogeneity. This approach yielded 49 cross-study replicated and 10 discovery–replication validated journal articles, substantially narrowing the field to a focused set of high-confidence miRNA candidates. Among the most consistently replicated miRNAs, miR-146a and miR-1246 emerged as central regulators linked to NF- κ B signaling, epithelial dysfunction, and corticosteroid responsiveness. Replicated miRNAs demonstrated compartment-specific expression across airway epithelium, smooth muscle, immune cells, and circulating fractions, and were associated with clinically relevant dimensions including disease severity, exacerbation frequency, lung function variability, and treatment response. Genetic, epigenetic, and environmental influences further support their biological plausibility. By consolidating independent replication evidence, this review defines a curated set of robust asthma-associated miRNAs supported by convergent data across populations and phenotypes. These findings provide a basis for future efforts in endotype-aware biomarker development and inform future strategies toward miRNA-guided precision diagnostics and therapeutic interventions in asthma. Keywords: asthma, MicroRNAs, epigenetic regulation, biomarkers, asthma severity, airway inflamma-tion, asthma endotypes
Hadikhani et al. (Fri,) studied this question.