Value of Exhaled Nitric Oxide and FEF(25–75) in Identifying Factors Associated With Chronic Cough in Allergic Rhinitis

PURPOSE: Chronic cough in allergic rhinitis (AR) patients is common with multiple etiologies including cough variant asthma (CVA), non-asthmatic eosinophilic bronchitis (NAEB), gastroesophageal reflux-related cough (GERC), and upper airway cough syndrome (UACS). Practical indicators that distinguish these categories are lacking. We aimed to explore the diagnostic value of the fraction of exhaled nitric oxide (FeNO) and forced expiratory flow at 25% and 75% of pulmonary volume (FEF(25–75)) in specifically identifying CVA and NAEB in these patients. METHODS: Consecutive AR patients with chronic cough were screened and underwent induced sputum, FeNO, nasal nitric oxide, spirometry, and methacholine bronchial provocation testing. All patients also completed gastroesophageal reflux disease questionnaires. RESULTS: Among 1,680 AR patients, 324 (19.3%) were identified with chronic cough, of whom 316 (97.5%) underwent etiology analyses. Overall, 87 (27.5%) patients had chronic cough caused by NAEB, 78 (24.7%) by CVA, 16 (5.1%) by GERC, and 81 (25.6%) by UACS. Patients with either NAEB or CVA (n = 165, in total) were further assigned to a common group designated as CVA/NAEB, because they both responded to corticosteroid therapy. Receiver operating characteristic curves of FeNO revealed obvious differences among CVA, NAEB, and CVA/NAEB (area under the curve = 0.855, 0.699, and 0.923, respectively). The cutoff values of FeNO at 43.5 and 32.5 ppb were shown to best differentiate CVA and CVA/NAEB, respectively. FEF(25–75) was significantly lower in patients with CVA than in those with other causes. A FEF(25–75) value of 74.6% showed good sensitivity and specificity for identifying patients with CVA. CONCLUSIONS: NAEB, CVA, and UACS are common causes of chronic cough in patients with AR. FeNO can first be used to discriminate patients with CVA/NAEB, then FEF(25–75) (or combined with FeNO) can further discriminate patients with CVA from those with CVA/NAEB.