Abstract Rationale Asthma is a common chronic airway disease affecting about 10% of the global population. Early and accurate diagnosis is crucial, but remains challenging. Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of type 2 inflammation, used for monitoring, endotyping and furthermore, in some countries, for diagnosis. However, data is limited, particularly in children, and the diagnostic accuracy and optimal thresholds of this biomarker is unclear. Aim To determine the diagnostic accuracy and optimal thresholds of FeNO for identifying asthma in adults and children. Methods We performed a systematic review of studies evaluating FeNO for asthma diagnosis in adults and children 5-18 years old. Asthma was defined by bronchial provocation testing (BPT positive when methacholine-equivalent PC20 8 mg·mL−¹ or PD20 200 μg), which is gold standard for the analysis. Meta-analyses used multiple-threshold models for FeNO. The area under the receiver operating characteristic curve (AUC) and thresholds achieving specificity 90% and positive likelihood ratios (LR+) were calculated with 95% confidence intervals (CI). The review adhered to PRISMA guidelines. Results Of 3,957 studies, 17 (n = 4,520) assessed FeNO in adults and 4 (n = 547) in children. In adults, the meta-analysis showed an AUC of 0.80 95% CI: 0.75-0.84; at FeNO 46 ppb, specificity was 96% 95-98 and LR + 10.1 6.3-16.3, supporting FeNO as a reliable diagnostic tool to ‘rule in’ asthma. In children, diagnostic accuracy was moderate (AUC 0.76 0.50-0.92); the optimal threshold 38 ppb achieved specificity 0.90 0.62-1.0 and LR + 3.6 2.2-8.4. Performance was not improved in the subgroup of atopic children with an AUC of 0.54 0.42; 0.56. Conclusions FeNO demonstrates good diagnostic accuracy for asthma in adults and moderate accuracy in children, achieving high specificity at 46 ppb and 38 ppb, respectively. In adults, values above this cutoff may be sufficient to rule in asthma without bronchial provocation, but not in children. These results emphasize the need for larger, high-quality pediatric studies and the development of composite clinical plus biomarker-based strategies to improve asthma diagnosis across all age groups. PROSPERO#CRD42023489738; FUNDING: FRQS;APQ This abstract is funded by: APQ; FRQS
Couillard et al. (Fri,) studied this question.