A comparative study on the value of lower airway exhaled nitric oxide combined with small airway parameters for diagnosing cough-variant asthma

BACKGROUND: The diagnosis of cough-variant asthma (CVA) is based on bronchial provocation test, which is challenging to be conducted. Most CVA patients have type 2 airway inflammation and small airway dysfunction. FeNO(200), reflecting small airway inflammation, may be used to diagnose CVA. OBJECTIVE: This study aimed to explore and compare the value of lower airway exhaled nitric oxide (FeNO(50), FeNO(200), and CaNO) combined with small airway parameters for diagnosing CVA. METHODS: Chronic cough patients who attended the clinic from September 2021 to August 2022 were enrolled and divided into CVA group (n = 71) and non-CVA (NCVA) group (n = 212). The diagnostic values of FeNO(50), FeNO(200), concentration of alveolar nitric oxide (CaNO), maximal mid-expiratory flow (MMEF), forced expiratory flow at 75% of forced vital capacity (FEF(75%)) and forced expiratory flow at 50% of forced vital capacity (FEF(50%)) for CVA were evaluated. RESULTS: FeNO(50) [39(39) ppb versus 17(12) parts per billion (ppb), p < 0.01], FeNO(200) [17(14) ppb versus 8(5) ppb, p < 0.01] and CaNO [5.0(6.1) ppb versus 3.5(3.6) ppb, p < 0.01] in CVA group were significantly higher than those in NCVA group. The optimal cut-off values of FeNO(50), FeNO(200), and CaNO for diagnosis of CVA were 27.00 ppb [area under the curve (AUC) 0.88, sensitivity 78.87%, specificity 79.25%], 11.00 ppb (AUC 0.92, sensitivity 88.73%, specificity 81.60%) and 3.60 ppb (AUC 0.66, sensitivity 73.24%, specificity 52.36%), respectively. For diagnosing CVA, the value of FeNO(200) was better than FeNO(50) (p = 0.04). The optimal cut-off values of MMEF, FEF(75%), and FEF(50%) for the diagnosis of CVA were 63.80% (AUC 0.75, sensitivity 53.52%, specificity 86.32%), 77.9% (AUC 0.74, sensitivity 57.75%, specificity 83.49%) and 73.50% (AUC 0.75, sensitivity 60.56%, specificity 80.19%), respectively. The AUCs of FeNO(50) combined with MMEF, FEF(75%), and FEF(50%) for the diagnosis of CVA were all 0.89. The AUCs of FeNO(200) combined with MMEF, FEF(75%), and FEF(50%) for the diagnosis of CVA were all 0.93. CONCLUSION: FeNO(200) > 11 ppb contributed strongly for differentiating CVA from chronic cough, especially in patients with small airway dysfunction.