The Value of Fractional Exhaled Nitric Oxide and Forced Mid-Expiratory Flow as Predictive Markers of Bronchial Hyperresponsiveness in Adults with Chronic Cough

Background: Bronchial provocation tests are standard for diagnosing the etiology of chronic cough, but they are time consuming and can induce severe bronchospasm. A safer and faster clinical examination to predict bronchial hyperresponsiveness (BHR) is needed.

Objective: The objective of this study was to investigate whether small-airway function tests can predict BHR in adult patients with chronic cough.

Methods: A retrospective, cross-sectional study of diagnoses made using spirometry and bronchial provocation test results was performed in 290 patients with chronic nonproductive cough. BHR-predictive values were analyzed via the area under receiver operating characteristic curves (AUCs). Optimal cutoff values were determined by maximizing the sum of sensitivity and specificity.

Results: Patients with chronic cough with BHR showed lower forced expiratory flow between 25% and 75% (FEF_25%-75%), higher fractional exhaled nitric oxide (FENO), and a higher percentage of eosinophils in blood than patients without BHR (P < .0001 for all). The AUCs of FENO and FEF_25%-75% for a BHR diagnosis were 0.788 (95% CI, 0.725-0.851) and 0.702 (95% CI, 0.641-0.763), respectively. Optimal cutoff values were 43 ppb for FENO and 78.5% for FEF_25%-75%, with negative predictive values of 85.38% and 81.34%, respectively. The combined use of FENO and FEF_25%-75% increased the AUC to 0.843 (95% CI, 0.794-0.892), significantly higher than either FENO (P = .012) or FEF_25%-75% (P < .0001) alone.

Conclusions: Small-airway dysfunction is present in patients with chronic cough and BHR. FEF_25%-75% has value as a negative predictive parameter for BHR, especially when combined with FENO. FENO > 43 ppb and FEF_25%-75% < 78.5% strongly predicted a positive bronchial provocation test.