Background Recent guidelines differ in how fractional exhaled nitric oxide (FeNO) is used to diagnose school-age asthma, either as one of several tests with a cut-off at 25 ppb or as a single rule-in test at 35 ppb. Evidence on its diagnostic performance and clinical utility in subgroups remain limited.

Methods We analysed data from 1,979 school-age children in the Swiss Paediatric Airway Cohort referred for suspected asthma. We investigated FeNO performance with diagnosis by paediatric pulmonologists as reference standard using receiver operating characteristics curves, selected cut-offs and simulated predictive values across different prevalence. Subgroup analyses considered allergic sensitisation with allergic rhinitis and current inhaled corticosteroid (ICS) use.

Results In the overall cohort (asthma diagnosis 70%), FeNO showed poor discrimination for asthma (AUC 0.66; 95% CI 0.64–0.68) with an optimal cut-off at 22 ppb. At 25 and 35 ppb, sensitivity was low (43%, 95% CI 40–46; 31%, 95% CI 29–34) and specificity moderate to high (84%, 95% CI 77–84; 90%, 95% CI 87–92). Positive predictive value at 35 ppb was 88% and was 57% when simulated at a prevalence of 30%. FeNO had no diagnostic value in non-sensitised children and lower performance in sensitised children with allergic rhinitis than in those without (AUC 0.59 vs 0.68). Current ICS use did not influence performance.

Conclusion FeNO has limited diagnostic performance as a stand-alone test for school-age asthma, and underlying asthma prevalence and allergic characteristics should be considered in the interpretation.

MS, MG, CdeJ, PH and CK have nothing to disclose. AM reports personal fees and grants from Vertex, all outside the submitted work. NR reports personal fees from OM Pharma, Schwabe Pharma, Vertex, and Sanofi, all outside the submitted work.

This study was funded by the Swiss National Science Foundation (SNF 212519).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Bern Cantonal Ethics Committee (Kantonale Ethikkommission Bern 2016-02176) approved the study; written informed consent was obtained from parents and patients aged ≥ 14 years.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes