RT Journal Article SR Electronic T1 Controlled versus free breathing for multiple breath nitrogen washout in healthy adults JF ERJ Open Research JO erjor FD European Respiratory Society SP 00435-2020 DO 10.1183/23120541.00435-2020 A1 Blake M. Handley A1 Edward Jeagal A1 Robin E. Schoeffel A1 Tanya Badal A1 David G. Chapman A1 Catherine E. Farrow A1 Gregory G. King A1 Paul D. Robinson A1 Stephen Milne A1 Cindy Thamrin YR 2020 UL http://openres.ersjournals.com/content/early/2020/10/22/23120541.00435-2020.abstract AB Multiple breath nitrogen washout (MBNW) quantifies ventilation heterogeneity. Two distinct protocols are currently used for MBNW testing: “controlled breathing”, with targeted tidal volume (VT) and respiratory rate (RR); and “free breathing”, with no constraints on breathing pattern. Indices derived from the two protocols (functional residual capacity [FRC], lung clearance index [LCI], Scond, Sacin) have not been directly compared in adults. We aimed to determine whether MBNW indices are comparable between protocols, to identify factors underlying any between-protocol differences, and to determine the between-session variabilities of each protocol.We performed MBNW testing by both protocols in 27 healthy adult volunteers, applying the currently-proposed correction for VT to Scond and Sacin derived from free breathing. To establish between-session variability, we repeated testing in 15 volunteers within 3 months.While FRC was comparable between controlled versus free breathing (3.17(0.98) versus 3.18(0.94) L,p=0.88), indices of ventilation heterogeneity derived from the two protocols were not, with poor correlation for Scond (r=0.18,p=0.36) and significant bias for Sacin (0.057(0.021)L−1 versus 0.085(0.038)L−1,p=0.0004). Between-protocol differences in Sacin were related to differences in the breathing pattern, i.e. VT (p=0.004) and RR (p=0.01), rather than FRC. FRC and LCI showed good between-session repeatability, but Scond and Sacin from free breathing showed poor repeatability with wide limits of agreement.These findings have implications for the ongoing clinical implementation of MBNW, as they demonstrate that Scond and Sacin from free breathing, despite VT correction, are not equivalent to the controlled breathing protocol. The poor between-session repeatability of Scond during free breathing may limit its clinical utility.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. 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 ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Mr. Handley has nothing to disclose.Conflict of interest: Mr. Jeagal has nothing to disclose.Conflict of interest: Ms. Schoeffel has nothing to disclose.Conflict of interest: Ms. Badal has nothing to disclose.Conflict of interest: Dr. Chapman has nothing to disclose.Conflict of interest: Dr. Farrow has nothing to disclose.Conflict of interest: G.G. King reports fees for consultancy services (which include lectures and advisory board services), conference attendance support and unrestricted research grants from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini and MundiPharma, and research grants and fellowships from theNational Health & Medical Research Council and the Asthma Foundation, outside the submitted work.Conflict of interest: Dr. Robinson has nothing to disclose.Conflict of interest: Dr. Milne reports personal fees from Novartis, personal fees from Boehringer-Ingelheim, outside the submitted work; and is supported by the MITACS Accelerate program.Conflict of interest: Dr. Thamrin has nothing to disclose.