Incremental Diagnostic Value of Small Airway Dysfunction and Inflammatory Markers in Asthma: Development and Validation of a Nomogram-based Predictive Model

<title>Abstract</title> <p> Background Asthma diagnosis is challenging in symptomatic patients with preserved spirometry. We investigated whether peripheral inflammatory markers and small airway dysfunction could improve diagnostic accuracy. Methods We prospectively enrolled 143 symptomatic adults, including 71 with asthma and 72 without asthma. Asthma was diagnosed by bronchial provocation and/or bronchodilator reversibility testing. Preserved spirometry was defined by GLI-2012 z-scores. A diagnostic model incorporating age, gender, body mass index (BMI), eosinophil-to-monocyte ratio (EMR), and FEF ₂₅₋₇₅ was developed and validated using ROC analysis, calibration, decision curve analysis, and reclassification metrics. Results Patients with asthma were older and had higher rates of abnormal EMR and FEF ₂₅₋₇₅ status than controls. In multivariable analysis, age (OR 1.043, 95% CI 1.017–1.070), abnormal EMR (OR 3.898, 95% CI 1.759–8.637), and abnormal FEF ₂₅₋₇₅ (OR 7.223, 95% CI 1.999–26.099) were independently associated with asthma. The combined model achieved the best discrimination (AUC 0.78), outperforming the baseline, inflammation, and small airway models. Calibration and decision curve analyses supported good model performance and clinical utility. Conclusions In patients with preserved spirometry, the combination of EMR and FEF ₂₅₋₇₅ improves asthma discrimination and enables individualized risk estimation. </p>