Diagnostic value of fractional exhaled nitric oxide in predicting cough variant asthma in children with chronic cough: a systematic review and meta-analysis

Abstract

Objective·To evaluate the values of fractional exhaled nitric oxide (FeNO) for the diagnosis of cough variant asthma (CVA) in children with chronic cough by systematic review and meta-analysis.Methods·PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database (SinoMed), China National Knowledge Infrastructure (CNKI), and Wanfang Database were systematically searched for cohort studies and case-control studies to March 1, 2022. Two researchers independently screened the studies according to the inclusion and exclusion criteria, and the number of true positive, false positive, true negative, and false negative patients and the cut-off value of FeNO were extracted from the studies. Diagnostic accuracy studies tool version 2 (QUADAS-2) was used to evaluate the quality of the included literature in terms of risk bias and clinical applicability. Revman 5.4 was used to draw the quality evaluation chart. A meta-analysis was performed by the midas and spearman commands of Stata 17.0. Spearman correlation coefficients of sensitivity logarithm and (1-specificity) logarithm were used to test the threshold effect. The substantial heterogeneity caused by non-threshold effect was tested by bivariate box plot and I2 statistic. The effect size was pooled by bivariate random effect model. Publication bias was evaluated by Deek´s Funnel plot.Results·One thousand and ninety-nine studies were retrieved in total and 9 were finally included. The diagnostic criteria of the included study were all from expert consensus or guidelines. The QUADAS-2 showed that the quality of the included study was low. The Spearman correlation coefficient of sensitivity and (1-specificity) was 0.05 (P=0.90), indicating that there was no heterogeneity caused by threshold effect. The results of bivariate box plot and I2=0 showed that there was no heterogeneity caused by non-threshold effect. Combined effect showed that the sensitivity was 0.82 (95%CI 0.78－0.85), the specificity was 0.93 (95%CI 0.89‒0.95), the positive likelihood ratio was 11.30 (95%CI 7.40‒17.10), the negative likelihood ratio was 0.19 (95%CI 0.16‒0.24), the diagnostic odds ratio was 58 (95%CI 34‒101), and the area under the summary receiver operating characteristic (SROC) curve was 0.89 (95%CI 0.86‒0.92). The result of Deek´s Funnel plot showed that there was no publication bias.Conclusion·FeNO test has a moderate diagnostic value in prediciting CVA in children with chronic cough. However, the results of the study need to be interpreted with caution due to the low quality of the original evidence.

Keywords

• fractional exhaled nitric oxide (feno)
• cough variant asthma (cva)
• child
• diagnosis