Abstract
BACKGROUND: Despite guideline-based therapy, asthma control remains suboptimal in primary care, suggesting initial assessments may overlook key treatable traits. OBJECTIVE: To assess the prevalence of Type 2 (T2) inflammation and small airway dysfunction (SAD) in treatment-naïve uncontrolled asthma, evaluate the utility of Asthma Control Questionnaire-5 (ACQ-5) in their identification. METHODS: This retrospective, single-center study included 171 treatment-naïve adults with uncontrolled asthma (ACQ-5 score ≥ 1.5). A T2-High phenotype was defined as blood eosinophil count ≥ 300 cells/μL and fractional exhaled nitric oxide (FeNO) > 50 ppb. Spirometric categories were defined as: isolated SAD (iSAD) as forced expiratory volume in 1 second (FEV1) ≥ 80% predicted with forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) < 65% predicted, and airflow limitation (AFL) as FEV1 < 80% predicted. Logistic regression and receiver operating characteristic (ROC) analyses were performed. RESULTS: A significant burden of underlying pathology was found, with 48.0% exhibiting a T2-High phenotype and 21.1% having iSAD. While higher ACQ-5 scores strongly associated with AFL (area under the curve [AUC] = 0.802), they were not associated with iSAD and showed poor utility for detecting the T2-High phenotype (AUC = 0.634). CONCLUSION: In treatment-naïve uncontrolled asthma, ACQ-5 scores effectively identify overt AFL but fail to detect underlying iSAD and high-intensity T2 inflammation. These findings highlight a critical discordance between patient-reported symptoms and key pathophysiological domains. Reliance on symptom scores alone creates a diagnostic gap in primary care, underscoring the urgent need for accessible point-of-care tools to achieve precision medicine at the frontline of asthma care.