Diagnostic accuracy of FeNO in asthma and predictive value for inhaled corticosteroid responsiveness: A multicentre

Background Fractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and could replace bronchial provocation (BP). To date, cut-off values have been derived by post hoc analysis only. The aim was to validate the diagnostic accuracy for predefined FeNO cut-off values and the predictive value for responsiveness to inhaled cortico-steroids (ICS). Methods We conducted a prospective, diagnostic, multicentre study with patients attending three private practices of pneumologists in Upper Bavaria, Germany, from July 3, 2020 to Jan 21, 2022. Index test was FENO measure-ment. Reference standard was Tiffeneau ratio (FEV1/VC) or airway resistance as assessed by whole body plethysmog-raphy, with additional BP or bronchodilation test. Follow-up was performed after 12 weeks. Analyses of Receiver Operating Characteristics curves were conducted to determine the diagnostic accuracy and predictive value of FeNO. Findings 308 patients with complete follow-up were recruited, 186 (60.4%) were female, average age was 44.7 years, 161 (52.3%) had asthma. Regarding diagnostic accuracy, the area under the curve (AUC) was 0.718 (95% CI 0.661-0.775; p < 0.001). Sensitivity at FeNO > 50 ppb was 0.24 (95% CI 0.18-0.32), specificity 0.99 (0.95 -1.0), positive predictive value (PPV) 0.95 (0.84-0.99), negative predictive value (NPV) 0.54 (0.48-0.60). In 66 patients with'wheezing'and'allergic rhinitis,' the sensitivity at FeNO > 33 ppb was 0.49 (0.34-0.64), specificity 0.88 (0.64-0.99), PPV 0.92 (0.75-0.99), NPV 0.38 (0.23-0.54). In 68 patients with ICS medication, responsiveness was predicted at the cut-off > 43 ppb, with a sensitivity of 0.55 (95%CI 0.36-0.74), specificity 0.82 (0.66-0.92), PPV 0.70 (0.47-0.87), NPV 0.71 (0.56-0.84). Interpretation FeNO measurement allows a valid ruling-in of an asthma diagnosis, whereas ruling-out of asthma is not possible. Enhanced probability of ICS responsiveness is also given with increased FeNO values.

Automated summary

This study validates the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) for diagnosing asthma, and finds that higher FeNO values are associated with increased responsiveness to inhaled corticosteroids (ICS).