Flow-independent nitric oxide parameters in asthma: a systematic review and meta-analysis

Introduction. Fractional exhaled nitric oxide (FENO) has been proposed as a non-invasive marker of inflammation in the lungs. Measuring FENO at several flow rates enables the calculation of flow independent NO-parameters that describe the NO-exchange dynamics of the lungs more precisely. The purpose of this study was to compare the NO-parameters between asthmatics and healthy subjects in a systematic review and meta-analysis. Methods. A systematic search was performed in Ovid Medline, Web of Science, Scopus and Cochrane Library databases. All studies with asthmatic and healthy control groups with at least one NO-parameter calculated were included. Results. From 1137 identified studies, 33 were included in the meta-analysis. All NO-parameters (alveolar NO concentration (CANO), bronchial flux of NO (J(aw)NO), bronchial mucosal NO concentration (CawNO) and bronchial wall NO diffusion capacity (DawNO)) were found increased in glucocorticoid-treated and glucocorticoid-naive asthma. J(aw)NO and CANO were most notably increased in both study groups. Elevation of DawNO and CawNO seemed less prominent in both asthma groups. Discussion. We found that all the NO-parameters are elevated in asthma as compared to healthy subjects. However, results were highly heterogenous and the evidence on CawNO and DawNO is still quite feeble due to only few studies reporting them. To gain more knowledge on the NO-parameters in asthma, nonlinear methods and standardized study protocols should be used in future studies.