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.