Fractional exhaled nitric oxide at multiple flow rates in chronic cough: association with lung function and airway hyperresponsiveness

Background: The relationship between airway inflammation and airflow obstruction in patients with chronic cough remains unclear. This study aimed to evaluate the relationships between multi-flow fractional exhaled nitric oxide parameters (FeNO₅₀, FeNO₂₀₀, and CaNO) and lung function, and to assess their utility in predicting airway hyperresponsiveness (AHR) in this population. Materials and methods: This retrospective study enrolled 2205 chronic cough outpatients who underwent spirometry and multiple-flow FeNO measurements. Patients were stratified by airway function and FeNO levels for group comparisons, and Spearman’s rank correlation was used. In a subgroup (n = 582) who underwent methacholine bronchial provocation test (BPT), the diagnostic accuracy of these parameters for AHR was evaluated. Results: Among 2014 patients with normal ventilation or airflow obstruction, FeNO₅₀ and FeNO₂₀₀ were significantly higher in outpatients with airflow obstruction than those with both normal ventilation and normal small airway function (p < 0.01). Weak but significant negative correlations were found between FeNO₅₀ or FeNO₂₀₀ and lung function parameters (all coefficients ∼0.1), which were slightly stronger in females. FeNO₅₀ and FeNO₂₀₀ showed moderate diagnostic value (AUCs: 0.775 and 0.721, Cut-off: 31.5 and 14.5 ppb, respectively), while CaNO showed none. Combining FeNO₅₀ with small airway parameter (FEF₅₀%pred) yielded the highest predictive accuracy (AUC: 0.895). Conclusions: FeNO₅₀ and FeNO₂₀₀ are associated with the severity of airflow obstruction and moderately predict AHR in chronic cough, whereas CaNO does not. Combining FeNO with lung function parameters enhances predictive performance. Despite statistical significance, the weak correlations between FeNO and lung function parameters warrant cautious clinical interpretation.