Small Airway Dysfunction and Type 2 Biomarkers Predict Exacerbations in Mild, Well-Controlled Asthma: A Retrospective Cohort Study

Background Small airway dysfunction (SAD) plays a pivotal but often overlooked role in asthma pathophysiology. Its contribution to exacerbation risk among patients with mild, well-controlled asthma remains unclear. Objective This study aimed to assess the prevalence and clinical significance of SAD and type 2 inflammation biomarkers in mild, well-controlled asthma, and to determine their independent and combined predictive value for acute exacerbations. Methods A retrospective cohort study was conducted in 250 adults with mild, well-controlled asthma. Lung function indices, blood eosinophil counts, and fractional exhaled nitric oxide (FeNO) levels were analyzed. Logistic regression and receiver operating characteristic (ROC) analyses were performed to evaluate predictors of exacerbations. Results SAD was identified in 40.4% of patients and was strongly associated with a higher exacerbation rate (73.3% vs. 32.9%, p  < 0.001). SAD (adjusted OR = 17.91, 95% CI 7.03–49.39) and elevated eosinophils (aOR = 4.97, 95% CI 2.54–10.12) were independent predictors of exacerbations. Combined models incorporating FEF25–75%pred and eosinophil count achieved the highest discriminative performance (AUC = 0.769), surpassing any single biomarker. Conclusions Even in mild, well-controlled asthma, SAD and type 2 inflammation markers identify a high-risk phenotype susceptible to exacerbations. Integrating small airway function with inflammatory biomarkers enhances risk stratification, supporting precision monitoring and tailored therapeutic strategies in asthma management.