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

Fractional exhaled nitric oxide (F_ENO) has been proposed as a non-invasive marker of inflammation in the lungs. Measuring F_ENO 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.

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.

From 1137 identified studies, 33 were included in the meta-analysis. All NO-parameters (alveolar NO concentration (C_ANO), bronchial flux of NO (J_awNO), bronchial mucosal NO concentration (C_awNO) and bronchial wall NO diffusion capacity (D_awNO)) were found increased in glucocorticoid-treated and glucocorticoid-naïve asthma. J_awNO and C_ANO were most notably increased in both study groups. Elevation of D_awNO and C_awNO seemed less prominent in both asthma groups.

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 C_awNO and D_awNO 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.