FeNO Outperforms Blood Eosinophils for Diagnosing Suspected Asthma: Study
Fractional exhaled nitric oxide (FeNO) effectively predicted airway hyper-responsiveness in adults and children with suspected asthma, providing clinically useful rule-in and rule-out thresholds. Blood eosinophil count (BEC) performed poorly when used alone and did not add diagnostic value to FeNO. The findings were replicated in adults in primary care, supporting FeNO-guided diagnostic algorithms, while accounting for recent inhaled corticosteroid use. The study was published in The Lancet Respiratory Medicine by Marc-Andre and colleagues.
To assess diagnostic accuracy, databases were screened up to June 4, 2024, to identify 30 studies suitable for the analysis, which involved 22 adult studies (7,141 patients) and nine pediatric studies (989 patients aged 5–17 years), using FeNO or BEC compared with BPT or bronchodilator reversibility combined with BPT. For prospective validation of the meta-analysis results, the DIVE cohort study, carried out at a single center, included 123 adults with suspected asthma and negative bronchodilator reversibility who were referred from primary care for methacholine BPT. Subjects received a point-of-care test of FeNO and BEC followed by BPT challenge. ROC curves and AUC statistics analyzed biomarker accuracy, while post-hoc subgroup analyses examined the influence of recent ICS exposure on the results.
Key findings:
- Meta-analysis established good diagnostic accuracy for FeNO in adults (AUC, 0.80; 95% CI, 0.73–0.85), validated by the DIVE cohort (AUC, 0.77; 95% CI, 0.65–0.89).
- Meta-analysis demonstrated fair diagnostic accuracy for FeNO in children aged 5–17 years (AUC, 0.75; 95% CI, 0.65–0.82).
- Standalone BEC showed weak diagnostic accuracy in adults across meta-analysis (AUC, 0.65; 95% CI, 0.59–0.71) and DIVE validation (AUC, 0.67; 95% CI, 0.53–0.80), providing zero added diagnostic value when combined with FeNO.
- A FeNO threshold of 48 ppb or higher achieved a positive likelihood ratio of 10.1 (95% CI, 8.9–11.2).
- At a 20% primary care disease prevalence, FeNO of 65 ppb or higher achieved an 80% positive predictive value (PPV; 95% CI, 72–86), validated in DIVE with a 73% PPV (95% CI, 39–94).
- A FeNO threshold of less than 20 ppb yielded a 93% negative predictive value (NPV; 95% CI, 91–94) with an 18% missed diagnosis rate at 20% prevalence, replicated in DIVE with a 92% NPV (95% CI, 82–97).
- At a 56% aggregated pediatric study prevalence, a FeNO threshold of 30 ppb or higher achieved an 80% PPV (95% CI, 73–84).
- In the DIVE cohort (22 of 123 patients BPT-positive [18%]), FeNO rule-in and rule-out cutoffs demonstrated an overall diagnostic classification accuracy of 89%.
Fractional exhaled nitric oxide is a useful and clinically meaningful biomarker for assessing possible cases of asthma in patients with normal spirometry. From the results of the study, it can be concluded that the threshold values in determining whether to include or exclude a subject from having airway hyper-reactivity can effectively predict airway hyper-responsiveness without unnecessary invasive procedures but not the number of eosinophils in the bloodstream.
Reference:
Roy, M.-A., Gronnier, M., Désy, L., Pouliot, L., Lemaire-Paquette, S., Lemieux, S.-È., Ramphul, M., Vézina, F.-A., Philippe, L., Duval, M., Mathieu, B., Li, J., He, Y., Schleich, F., Mare, S., Lopez-Campos, J. L., Muñoz-Sanchez, B., Alvarez-Gutierrez, F. J., Romero-Falcon, A., … Couillard, S. (2026). Accuracy of type 2 inflammatory biomarkers to diagnose asthma in adults and children: a meta-analysis of 30 studies with prospective validation in an adult primary care cohort. The Lancet Respiratory Medicine. https://doi.org/10.1016/S2213-2600(26)00228-6
