Development of a diagnostic score using FeNO and symptoms to predict asthma

Background: Fractional exhaled nitric oxide (FeNO) is known as effective for ruling-in asthma. The diagnostic value might be increased in combination with clinical signs and symptoms (CSS). The aim was to develop a new model for ruling-in and ruling-out asthma. Methods: Diagnostic multi-centre study in three practices of pneumologists in Germany. Whole-body plethysmography was combined with bronchodilation tests or bronchial provocation as diagnostic reference standard. Follow-up was performed after 3 months. An expert committee evaluated test results, symptoms, and course of disease for the final diagnosis. Relevant CSS known from guidelines were used to enable combinatorial development of decision rules. Outcomes of multiple logistic regression modeling were translated into a diagnostic score and internally validated by ten-fold cross validation. Results: 308 patients with complete follow-up were included. 186 (60.4%) were female, average age was 44.7 years and 161 (52.5%) had asthma. The average area under the receiver operating curve (AUC) of the diagnostic score was 0.755 (interquartile range 0.721–0.814). Allergic rhinitis, wheezing, dyspnea on exertion, coughing attacks at night, and awakening by shortness of breath were leading symptoms for ruling-in asthma. Frequent coughing and frequent respiratory infections were leading symptoms for ruling-out. The combination of FeNO and CSS allowed ruling-in asthma with a probability of up to 99%, and ruling-out with a post-test probability down to 9%. Conclusion: The diagnostic scoring model increased the diagnostic value of FeNO in combination with CSS. The new decision rule allowed to rule-in asthma with high certainty, and also to rule-out with acceptable certainty.