Diagnostic accuracy of fractional exhaled nitric oxide (FeNO) with or without blood eosinophils in childhood, adolescent, and adult asthma: protocol for a systematic review and meta-analysis

IntroductionAsthma poses a diagnostic challenge due to its intermittent symptoms and variable airflow obstruction. Diagnostic assessments such as spirometry and bronchodilator response are frequently non-diagnostic, necessitating confirmatory bronchial provocation testing. Biomarkers of type-2 inflammation --exhaled nitric oxide (FeNO) and blood eosinophil counts (BEC)-- are useful in asthma, but their diagnostic values in children and in combination (FeNO+BEC) are unclear. This systematic review will evaluate the diagnostic accuracy of FeNO alone or in combination with BEC in paediatric and adult asthma. Methods and AnalysisThis protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. The review will include studies of any design on the diagnostic accuracy of FeNO with or without BEC in asthma compared to the reference standards bronchodilator response and provocation testing in patients [≥] 5 years old selected from MEDLINE, Embase, and Cochrane CENTRAL databases. Screening, study selection, and data extraction will be independently performed by two reviewers. Risk of bias will be assessed using QUADAS-2 and QUADAS-C. Meta-analysis will be carried out by pooling the sensitivity and specificity of FeNO alone or in combination with BEC in a bivariate random effects model allowing the generation of summarised operating characteristic curves and summary points. Further analysis utilising a multiple thresholds model will enable the computation of diagnostic thresholds for FeNO. Ethics and DisseminationNo patient data will be stored without prior approval from ethics committee. The findings will be submitted in a peer-reviewed publication. RegistrationPROSPERO CRD42023489738 SOCIAL MEDIA MESSAGEDiagnosing asthma is challenging. Spirometry and bronchodilator reversibility are often non-diagnostic, calling for provocation testing. Our systematic review will explore complementary approaches using FeNO with and without the blood eosinophil count.