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

Abstract

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. The objective of this study was to investigate whether small-airway function tests can predict BHR in adult patients with chronic cough. 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. Patients with chronic cough with BHR showed lower forced expiratory flow between 25% and 75% (FEF25%-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 FEF25%-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 FEF25%-75%, with negative predictive values of 85.38% and 81.34%, respectively. The combined use of FENO and FEF25%-75% increased the AUC to 0.843 (95% CI, 0.794-0.892), significantly higher than either FENO (P= .012) or FEF25%-75% (P < .0001) alone. Small-airway dysfunction is present in patients with chronic cough and BHR. FEF25%-75% has value as a negative predictive parameter for BHR, especially when combined with FENO. FENO > 43 ppb and FEF25%-75% <78.5% strongly predicted a positive bronchial provocation test.