Performance of fractional exhaled nitric oxide in predicting response to inhaled corticosteroids in chronic cough: a meta-analysis

Background. Chronic cough is a disabling condition with a high proportion of diagnostic and therapeutic failures. Fractional exhaled nitric oxide (FeNO) has been considered a useful biomarker for predicting inhaled corticosteroids (ICS) response. We evaluated the relationship between FeNO and ICS response in chronic cough by performing a systematic review with meta-analysis. Methods. PubMed, Web of Science, Scopus and EMBASE databases were systematically searched. Differences were expressed as Odds Ratio (OR) with 95% confidence intervals (95%CI). Pooled sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), and area under the hierarchical summary receiver operating characteristic curve (HSROCAUC) were estimated. Results. Nine articles on 740 chronic-cough patients showed that the response rate to ICS was 87.4% (95%CI: 83.8–91.0) in 317 patients with a high FeNO and 46.3% (95%CI: 41.6–51.0) in 423 controls, with an attributable proportion of 47.0% and a diagnostic OR of 9.1 (95%CI: 3.7–22.4, p <.001). The pooled estimate of diagnostic indexes resulted in a sensitivity of 68.5% (95%CI: 46.7–84.4) and specificity of 81.9% (95%CI: 63.0–92.3), with a HSROCAUC of 0.82 (95%CI: 0.64–0.90). In a realistic scenario with a pre-test probability set at 30%, based on a pooled PLR of 3.79 (95%CI: 1.24–7.47) and NLR of 0.38 (95%CI: 0.22–0.66), the post-test probability was 62% with a high FeNO and 14% if the test was negative. Subgroup analyses confirmed a better performance for the recommended FeNO cut-off greater than 25 ppb. Meta-regression and sensitivity analyses showed no impact of major demographic and clinic variables on results. Conclusions. A high FeNO before starting ICS therapy may help identify chronic-cough patients responding to treatment, with a better performance ofhigher cut-off values. Further studies are needed to evaluate the real usefulness of this biomarker to guide cough therapy and optimise strategies in different healthcare settings (community, hospital, rehabilitation).Key messages Chronic cough is a disabling condition with a high proportion of diagnostic and therapeutic failures. Fractional exhaled nitric oxide (FeNO) may be a useful biomarker for identifying chronic cough patients who respond to steroid treatment. A FeNO cut-off lower than 25 ppb should be considered irrelevant for this clinical application.