Normative multiple breath washout data in school-aged children corrected for sensor error

The nitrogen (N2) multiple-breath washout (MBW) technique is a lung function test used to assess ventilation distribution and lung volumes. The lung clearance index (LCI) is a marker of global ventilation inhomogeneity from the technique. It is calculated by the number of functional residual capacity (FRC) turnovers required to washout resident N2 from the lungs by breathing 100% oxygen (O2) [1]. We have previously published normative data for MBW outcomes in healthy, white, school-aged children measured with the commercially available Exhalyzer D MBW device (Eco Medics AG, Duernten, Switzerland) in the European Respiratory Journal [2]. Wyler et al. recently identified an error in the cross-sensitivity correction for the O2 and carbon dioxide (CO2) gas sensors within the Exhalyzer D device [3]. This error results in an overestimation of N2 concentration and MBW outcomes, including LCI and FRC. Correction of this error and reanalysis of MBW data is possible and has now been implemented into an updated software version by the manufacturer (Spiroware version 3.3.1, Eco Medics AG). The aim of this study was to provide updated N2MBW normative data in healthy children collected on the Exhalyzer D device and analysed using Spiroware 3.3.1, and to report the differences in outcomes from the previous version Spiroware 3.2.1 [2]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: A.C. Kentgens reports no other conflicts of interest. Conflict of interest: P. Latzin reports grants from Vertex and Vifor paid to the institution, personal and honoraria paid to the institution from Vertex, Vifor and OM Pharma, and for participation on a Data Safety Monitoring Board or Advisory Board personal from Santhera (DMC) and personal and fees paid to the institution from Polyphor, Vertex, OM pharma and Vifor, all outside the submitted work. Conflict of interest: P. Anagnostopoulou has nothing to disclose. Conflict of interest: R. Jensen has nothing to disclose. Conflict of interest: M. Stahl reports MBW over-reader Service for Vertex Pharmaceuticals and a role as chairman of FGM, Secretary of Group CF ERS and Treasurer of GPP, outside the submitted work. Conflict of interest: A. Harper has nothing to disclose. Conflict of interest: S. Yammine reports a Swiss National Science Foundation grant 179905, outside the submitted work. Conflict of interest: R.E. Foong has nothing to disclose. Conflict of interest: G.L. Hall reports grant funding from the National Health and Medical Research Council of Australia and equipment loan from Niche Medical. Conflict of interest: F. Singer reports honoraria for lectures and presentations from Novartis Pharma Schweiz AG and Vertex Pharmaceuticals (CH) GmbH, outside the submitted work. Conflict of interest: S. Stanojevic reports MBW over-reader Service for Vertex Pharmaceuticals and role as chair of the Global Lung Function Initiative Network of the ERS, and the position of ATS Pulmonary Function Committee Co-Chair, outside the submitted work. Conflict of interest: M.A. Mall reports grants from the German Federal Ministry of Education and Research (Grant # 82DZL004A1) and the Einstein Foundation Berlin (Grant # EP-2017-393) during the conduct of this study, and personal fees advisory board work, consultancy, and lectures from Boehringer Ingelheim and Vertex Pharmaceuticals, and patient recruitment fees in clinical trial from Boehringer Ingelheim, and Vertex Pharmaceuticals (investigator-initiated study), outside the submitted work. Conflict of interest: F. Ratjen reports PI for grants, consulting, or honorarium for CF related activities from Vertex, and reports to have acted as a consultant for CF related activities for Proteostasis, Bayer, Translate, Genentech, Boehringer Ingelheim and Calithera, outside the submitted work. Conflict of interest: K.A. Ramsey reports a grant from Vertex paid to the institution, and a role as co-chair of the ERS MBW GLI taskforce.