Diagnostic utility of fractional exhaled nitric oxide in prolonged and chronic cough according to atopic status

Abstract

Background: Cough-variant asthma (CVA) and cough-predominant asthma (CPA) are the major causes of persistent cough in Japan. The utility of fractional exhaled nitric oxide (FeNO) measurement in the differential diagnosis of persistent cough has been reported, but the influence of atopic status, which is associated with higher FeNO levels, on the diagnostic utility of FeNO has been unknown.

Methods: We retrospectively analyzed 105 non-smoking patients with prolonged and chronic cough that were not treated with corticosteroids and anti-leukotrienes.

Results: CPA was diagnosed in 37 patients, CVA in 40, and non-asthmatic cough (NAC) in 28. FeNO levels were significantly higher in the CPA [35.8 (7.0-317.9) ppb] and CVA [24.9 (3.1-156.0) ppb] groups than in the NAC group [18.2 (6.9-49.0) ppb] (p < 0.01 by Kruskal-Wallis test). The optimal cut-off for distinguishing asthmatic cough (AC; CPA and CVA) from NAC was 29.2 ppb [area under the curve (AUC) 0.74, p < 0.01]. Ninety-one percent of subjects with FeNO levels ≥29.2 ppb had AC. Meanwhile, 40% of AC patients had FeNO levels <29.2 ppb. Stratified cut-off levels were 31.1 ppb (AUC 0.83) in atopic subjects vs. 19.9 ppb (AUC 0.65) in non-atopic subjects (p = 0.03 for AUC).

Conclusions: Although high FeNO levels suggested the existence of AC, lower FeNO levels had limited diagnostic significance. Atopic status affects the utility of FeNO levels in the differential diagnosis of prolonged and chronic cough.

Keywords: Atopy; Chronic cough; Cough-predominant asthma; Cough-variant asthma; Fractional exhaled nitric oxide.