Diagnostic accuracy of baseline spirometry indices for predicting airway hyperresponsiveness in symptomatic patients with normal spirometry: a cross-sectional diagnostic study

Airway hyperresponsiveness (AHR) refers to an exaggerated airway response to stimuli, leading to asthma-like symptoms in individuals without meeting the spirometric criteria for asthma. The bronchoprovocation test, typically using methacholine, is considered the gold standard for diagnosing AHR. In this study, we aim to evaluate commonly used spirometry indices, which are non-invasive and widely available, as potential diagnostic tools for AHR. In this cross-sectional diagnostic accuracy study, 148 consecutive adults with symptoms suggestive of AHR and normal baseline spirometry underwent pre-bronchodilator spirometry followed by MCT. The diagnostic performance of spirometric indices for predicting MCT positivity was evaluated using receiver operating characteristic (ROC) analysis. Multivariable logistic regression and five-fold cross-validation were performed to assess independent predictors and model performance. From a total of 148 patients, 46 patients had a positive MCT result, and 102 had a negative MCT result. Patients with positive MCT had significantly lower forced vital capacity (FVC) values than those with negative MCT (3.52 vs. 3.96 L, adjusted q = 0.035). Among all spirometric parameters, FVC z-score demonstrated the highest diagnostic accuracy (AUC 0.652, 95% CI 0.554–0.749), followed by FVC percent predicted (AUC: 0.650) and FVC Absolute value (AUC: 0.647). An FVC percent-predicted cutoff of ≤ 96% yielded 58.7% sensitivity and 73.5% specificity. FEV1/FVC ratio also showed significant discriminatory ability (AUC: 0.642, 95% CI: 0.543–0.740). In multivariable analysis, higher FVC independently predicted lower odds of MCT positivity (adjusted OR: 0.373, 95% CI: 0.208–0.669; p < 0.001). The cross-validated AUC of the combined model was 0.656, providing no meaningful improvement over FVC alone. Baseline spirometric indices, particularly FVC, demonstrate significant ability to identify patients with AHR despite normal spirometry. Although insufficient to replace MCT, these measures may assist in preliminary screening and reducing unnecessary bronchoprovocation testing. Not applicable.