Objective: Bronchial asthma is a heterogeneous chronic inflammatory airway disease driven by T helper 2 (Th2) immunopolarization. The objective assessment of asthma severity remains clinically challenging, particularly in settings with limited access to spirometry, necessitating the identification of reliable, non-invasive molecular biomarkers. This study aimed to evaluate serum expression levels of miR-21-5p and miR-155-5p in adult patients with bronchial asthma; determine their correlation with total serum immunoglobulin E (IgE), blood eosinophil count (BEC), and disease severity; assess their diagnostic accuracy, and examine the independence of these associations from potential demographic and clinical confounders.

Materials and Methods: A case-control study design was employed involving the participation of 120 adults at Al-Diwaniyah Teaching Hospital, Iraq (October 2025-March 2026), consisting of 60 asthmatic patients and 60 healthy controls. Disease severity was confirmed based on disease duration, exacerbation rate, and responsiveness to corticosteroids. Quantification of serum levels of miR-21-5p and miR-155-5p was accomplished using the stem-loop qRT-PCR technique; total IgE was measured through the ELISA test; BEC was estimated based on the CBC test.

Results: Serum miR-21-5p and miR-155-5p were significantly elevated in asthmatic patients versus controls (P<0.001), with stepwise increases across severity groups. Both correlated positively with total IgE (r=0.672; r=0.719) and BEC (r=0.579; r=0.756), and inversely with FEV1% (r=−0.705; r=−0.812). Asthma severity independently predicted both miRNAs after multivariate adjustment (β=2.12 and β=2.52; p<0.001). ROC analysis yielded AUCs of 0.97 for miR-155-5p (sensitivity 96.7%, specificity 95.0%), 0.97 for total IgE, and 0.96 for miR-21-5p.

Conclusion: Serum miR-21-5p and miR-155-5p were robust, non-invasive biomarkers for diagnosing bronchial asthma and objectively stratifying its severity in an adult Iraqi cohort. Their severity-dependent upregulation is independent of key demographic confounders and is biologically anchored in the Th2-mediated, eosinophilic inflammatory cascade, underscoring their potential utility in resource- limited clinical settings.