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We recently developed a model-based method for analyzing multiple breath nitrogen washout data that does not require identification of Phase-III. In the present study, we assessed the effect of irregular breathing patterns on the intra-subject variabilities of the model parameters. Nitrogen fraction at the mouth was measured in 18 healthy and 20 asthmatic subjects during triplicate performances of multiple breath nitrogen washout, during controlled (target tidal volume 1 L at 8-12 breaths per minute) and free (unrestricted) breathing. The parameters S cond , S acin and functional residual capacity (FRC) were obtained by conventional analysis of the slope of Phase-III. Fitting the model to the washout data provided functional residual capacity (FRC M ), dead space volume (V D ), the coefficient of variation of regional specific ventilation ([Formula: see text]), and the model equivalent of S acin (S acin-M ). Intra-participant coefficients of variation for the model parameters for both health and asthma were FRC M  < 5.2%, V D  < 5.4%, [Formula: see text] < 9.0%, and S acin-M  < 45.6% for controlled breathing, and FRC M  < 4.6%, V D  < 5.3%, [Formula: see text] < 13.2%, and S acin-M  < 103.2% for free breathing. The coefficients of variation limits for conventional parameters were FRC < 6.1%, with S cond  < 73.6% and S acin  < 49.2% for controlled breathing and S cond  < 35.0% and S acin  < 74.4% for free breathing. The model-fitting approach to multiple breath nitrogen washout analysis provides a measure of regional ventilation heterogeneity in [Formula: see text] that is less affected by irregularities in the breathing pattern than its corresponding Phase-III slope analysis parameter S cond ., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The lack of comparability in indices of ventilation heterogeneity between free- and controlled-breathing MBNW protocols is confirmed in asthma https://bit.ly/3lmri4A., Competing Interests: Provenance: Submitted article, peer reviewed. Conflicts of interest: B.M. Handley has nothing to disclose. Conflicts of interest: J. Bozier has nothing to disclose. Conflicts of interest: E. Jeagal has nothing to disclose. Conflicts of interest: S. Rutting has nothing to disclose. Conflicts of interest: R.E. Schoeffel has nothing to disclose. Conflicts of interest: P.D. Robinson has nothing to disclose. Conflicts of interest: G.G. King reports fees for consultancy services, conference attendance support and unrestricted research grants from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini, MundiPharma. G.G. King also reports NHMRC research grants and fellowships. Conflicts of interest: S. Milne has nothing to disclose. Conflicts of interest: C. Thamrin reports supply of equipment for an unrelated study from Restech SRL. C. Thamrin also reports funded research collaboration for an unrelated project., (Copyright ©The authors 2021.)

Multiple breath nitrogen washout (MBNW) quantifies ventilation heterogeneity. Two distinct protocols are currently used for MBNW testing: "controlled breathing", with targeted tidal volume ( V T ) 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), S cond , S acin ) 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 V T to S cond and S acin 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 S cond (r=0.18, p=0.36) and significant bias for S acin (0.057 (0.021) L -1 versus 0.085 (0.038) L -1 , p=0.0004). Between-protocol differences in S acin were related to differences in the breathing pattern, i.e. V T (p=0.004) and RR (p=0.01), rather than FRC. FRC and LCI showed good between-session repeatability, but S cond and S acin 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 S cond and S acin from free breathing, despite V T correction, are not equivalent to the controlled breathing protocol. The poor between-session repeatability of S cond during free breathing may limit its clinical utility., Competing Interests: Conflict of interest: B.M. Handley has nothing to disclose. Conflict of interest: E. Jeagal has nothing to disclose. Conflict of interest: R.E. Schoeffel has nothing to disclose. Conflict of interest: T. Badal has nothing to disclose. Conflict of interest: D.G. Chapman has nothing to disclose. Conflict of interest: C.E. 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 the National Health & Medical Research Council and the Asthma Foundation, outside the submitted work. Conflict of interest: P.D. Robinson has nothing to disclose. Conflict of interest: S. Milne reports personal fees from Novartis and Boehringer Ingelheim outside the submitted work, and is supported by the MITACS Accelerate programme. Conflict of interest: C. Thamrin has nothing to disclose., (Copyright ©ERS 2021.)

The forced oscillation technique (FOT) is gaining clinical acceptance, facilitated by more commercial devices and clinical data. However, the effects of variations in testing protocols used in FOT data acquisition are unknown. We describe the effect of duration of data acquisition on FOT results in subjects with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls. FOT data were acquired from 20 healthy, 22 asthmatic and 18 COPD subjects for 60 s in triplicate. The first 16, 30 and 60 s of each measurement were analysed to obtain total, inspiratory and expiratory resistance of respiratory system ( R rs ) and respiratory system reactance ( X rs ) at 5 and 19 Hz. With increasing duration, there was a decrease in total and expiratory R rs for healthy controls, total and inspiratory R rs for asthmatic subjects and magnitude of total and inspiratory X rs for COPD subjects at 5 Hz. These decreases were small compared to the differences between clinical groups. Measuring for 16, 30 and 60 s provided ≥3 acceptable breaths in at least 90, 95 and 100% of subjects, respectively. The coefficient of variation for total R rs and X rs also decreased with duration. Similar results were found for R rs and X rs at 19 Hz. FOT results are statistically, but likely minimally, impacted by acquisition duration in healthy, asthmatic or COPD subjects., Competing Interests: can be found alongside this article at openres.ersjournals.com