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Background: Telemonitoring trials for early detection of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have provided mixed results. Day-to-day variations in lung function measured by the forced oscillation technique (FOT) may yield greater insight. We evaluated the clinical utility of home telemonitoring of variability in FOT measures in terms of 1) the relationship with symptoms and quality of life (QoL); and 2) the timing of variability of FOT measures and symptom changes prior to AECOPD., Methods: Daily FOT parameters at 5 Hz (resistance (R) and reactance (X); Resmon Pro Diary, Restech Srl, Milan, Italy), daily symptoms (COPD Assessment Test (CAT)) and 4-weekly QoL data (St George's Respiratory Questionnaire (SGRQ)) were recorded over 8-9 months from chronic obstructive pulmonary disease (COPD) patients. Variability of R and X was calculated as the standard deviation (sd) over 7-day running windows and we also examined the effect of varying window size. The relationship of FOT versus CAT and SGRQ was assessed using linear mixed modelling, daily changes in FOT variability and CAT prior to AECOPD using one-way repeated measures ANOVA., Results: Fifteen participants with a mean±sd age of 69±10 years and a % predicted forced expiratory volume in 1 s (FEV 1 ) of 39±10% had a median (interquartile range (IQR)) adherence of 95.4% (79.0-98.8%). Variability of the inspiratory component of X (indicated by the standard deviation of inspiratory reactance (SDX insp )) related to CAT and weakly to SGRQ (fixed effect estimates 1.57, 95% CI 0.65-2.49 (p=0.001) and 4.41, 95% CI -0.06 to 8.89 (p=0.05), respectively). SDX insp changed significantly on the same day as CAT (1 day before AECOPD, both p=0.02) and earlier when using shorter running windows (3 days before AECOPD, p=0.01; accuracy=0.72 for 5-day windows)., Conclusions: SDX insp from FOT telemonitoring reflects COPD symptoms and may be a sensitive biomarker for early detection of AECOPD., Competing Interests: Conflict of interest: S.C. Zimmermann reports a project grant (1049560) from the National Health and Medical Research Council (NHMRC), a Lung Foundation Australia/Boehringer Ingelheim COPD Research Top Up Grant 2016 and an NHMRC grant for a postgraduate scholarship (1074630), during the conduct of the study; non-financial support for travel and accommodation from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Menarini and Novartis Pharmaceuticals, outside the submitted work. The forced oscillation technique (FOT) devices used in the study were provided on loan from Restech Srl. Conflict of interest: J. Huvanandana has nothing to disclose. Conflict of interest: C.D. Nguyen has nothing to disclose. Conflict of interest: A. Bertolin has nothing to disclose. Conflict of interest: J.C. Watts has nothing to disclose. Conflict of interest: A. Gobbi owns stocks and serves as a board member of Restech Srl, a spin-off company of the Politecnico di Milano University involved in the design, manufacturing and commercialisation of medical devices based on the forced oscillation technique (FOT), outside the submitted work. Conflict of interest: C.S. Farah reports personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim and Sanofi Genzyme, outside the submitted work. Conflict of interest: M.J. Peters has nothing to disclose. Conflict of interest: R.L. Dellacà reports grants from Acutronic and personal fees for scientific committee work from Restech srl, outside the submitted work. They have a patent on the detection of expiratory flow limitation (EFL) by the forced oscillation technique (FOT) with royalties paid to Philips Respironics and Restech srl, a patent on monitoring lung volume recruitment by FOT with royalties paid to Vyaire and a patent on early detection of exacerbations by home monitoring of FOT with royalties paid to Restech. They are a co-founder and shareholder of Restech srl, a spin-off company of the Politecnico di Milano University producing medical devices for lung function testing based on FOT. Conflict of interest: G.G. King reports a bridging grant from the University of Sydney and non-financial support (provision of forced oscillation technique (FOT) devices) from Restech srl, during the conduct of the study; grants, personal fees for advisory board work, lectures and consultancy, and support for meeting attendance from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Menarini and MundiPharma, as well as grants from the National Health and Medical Research Council (NHMRC) and the Asthma Foundation, outside the submitted work. They are co-chair of the American Thoracic Society (ATS)/European Respiratory Society (ERS) task force on technical standards for the FOT. Conflict of interest: C. Thamrin has a patent (WO 2006130922 A1) issued and is a member of a current international task force committee on FOT technical standards. They have intellectual property arrangements with THORASYS Thoracic Medical Systems and Restech srl relating to research collaborations, but do not have any financial relationships with either company., (Copyright ©ERS 2020.)

Oscillometry (also known as the forced oscillation technique) measures the mechanical properties of the respiratory system (upper and intrathoracic airways, lung tissue and chest wall) during quiet tidal breathing, by the application of an oscillating pressure signal (input or forcing signal), most commonly at the mouth. With increased clinical and research use, it is critical that all technical details of the hardware design, signal processing and analyses, and testing protocols are transparent and clearly reported to allow standardisation, comparison and replication of clinical and research studies. Because of this need, an update of the 2003 European Respiratory Society (ERS) technical standards document was produced by an ERS task force of experts who are active in clinical oscillometry research.The aim of the task force was to provide technical recommendations regarding oscillometry measurement including hardware, software, testing protocols and quality control.The main changes in this update, compared with the 2003 ERS task force document are 1) new quality control procedures which reflect use of "within-breath" analysis, and methods of handling artefacts; 2) recommendation to disclose signal processing, quality control, artefact handling and breathing protocols ( e.g. number and duration of acquisitions) in reports and publications to allow comparability and replication between devices and laboratories; 3) a summary review of new data to support threshold values for bronchodilator and bronchial challenge tests; and 4) updated list of predicted impedance values in adults and children., Competing Interests: Conflict of interest: G.G. King reports grants from American Thoracic Society and European Respiratory Society, during the conduct of the study; a collaborative research agreement and IP agreement with Restech, grants and personal fees for lectures from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Menarini, MundiPharma and Cyclomedica, grants from NH&MRC, Philanthropic Societies, Sydney University, outside the submitted work. Conflict of interest: J. Bates is a minor shareholder and received personal fees for advisory board work from Oscillavent, LLC, outside the submitted work; and has a patent (patent application US 20160007882 A1; proposes the use of oscillometry in ventilated patients) pending to none, and a patent PCT application WO2015127377 A1 (proposes variable tidal volume ventilation as a means of performing oscillometry in ventilated patients) pending to none. Conflict of interest: K.I. Berger has nothing to disclose. Conflict of interest: P. Calverley has advised Philips Respironics about the clinical application of FOT and spoken on this topic at meetings supported by this company. Conflict of interest: P.L. de Melo has a patent 28727 issued. Conflict of interest: R.L. Dellacà has a patent on the detection of EFL by FOT with royalties paid to Philips Respironics and Restech srl, a patent on monitoring lung volume recruitment by FOT with royalties paid to Vyaire, and a patent on early detection of exacerbations by home monitoring of FOT with royalties paid to Restech, and is co-founder and shareholder of Restech srl, a spin-off company of the Politecnico di Milano University producing medical devices for lung function testing based on FOT. Conflict of interest: R. Farré reports contracts for bench assessment of CPAP devices from Resmed and ANTADIR, outside the submitted work. Conflict of interest: G.L. Hall reports grants from American Thoracic Society and European Respiratory Society, during the conduct of the study. Conflict of interest: I. Ioan has nothing to disclose. Conflict of interest: C.G. Irvin reports other for advisory board work from Methapharm, personal fees and non-financial support for advisory board work from Medical Graphics Corp, grants from NIH and American Lung Association, outside the submitted work. Conflict of interest: D.W. Kaczka reports grants from US Department of Defense (W81XWH-16-1-0434) and National Institutes of Health (R01-HL112986, R01-HL126838 and R41-HL140640), and is co-founder and shareholder from OscillaVent, Inc., during the conduct of the study; grants from ZOLL Medical Corporation, and is shareholder and member of an advisory board for Monitor Mask, Inc., outside the submitted work; and has a patent Systems and methods for multi-frequency oscillator ventilation pending to OscillaVent, Inc. (US20160339191A1), a patent Treatment of respiratory condition using targeted delivery pending (US20150290418A1), a patent System and method for setting positive end expiratory pressure during mechanical ventilation based on dynamic lung function (US20070240717A1, abandoned), a patent Enhanced ventilation waveform device issued (US 6,435,182 B1), and a patent Servo-controlled pneumatic pressure oscillator for respiratory impedance measurements and high-frequency ventilation (US20070006924A1, abandoned). Conflict of interest: D.A. Kaminsky reports personal fees for lectures from MGC Diagnostics, Inc., outside the submitted work. Conflict of interest: H. Kurosawa reports grants and personal fees from Chest M.I. Inc., during the conduct of the study; personal fees from Nippon Boehringer Ingelheim Co. Ltd, outside the submitted work; and has a patent US2012101400 with royalties paid to Tohoku University. Conflict of interest: E. Lombardi reports personal fees from Angelini, Boehringer, GSK, Omron and Vifor, grants and personal fees from Chiesi, Lusofarmaco and Novartis, grants and non-financial support from ResTech, personal fees and non-financial support from Vertex, outside the submitted work. Conflict of interest: G.N. Maksym reports financial support from Thorasys, Thoracic Medical Systems Inc, prior to the submitted work and non-financial support from Thorasys during the submitted work; and has a patent Respiratory Device (design patent) issued to Thorasys, a patent Respiratory Device filter issued to Thorasys, a patent Piezoelectric beam bending actuated Device for measuring respiratory system impedance issued to Thorasys, and a patent Method of assessment of airway variability in airway hyperresponsiveness issued to Thorasys. Conflict of interest: F. Marchal has nothing to disclose. Conflict of interest: B.W. Oppenheimer has nothing to disclose. Conflict of interest: S.J. Simpson has nothing to disclose. Conflict of interest: C. Thamrin has a patent WO 2006130922 A1 issued which is broadly relevant to the work, and has intellectual property arrangements with Thorasys Medical Systems and Restech srl relating to research collaborations, but does not have any financial relationships with either company. Conflict of interest: M. van den Berge reports grants paid to the university from AstraZeneca, TEVA, GSK and Chiesi, outside the submitted work. Conflict of interest: E. Oostveen has nothing to disclose., (Copyright ©ERS 2020.)

Inert gas washout tests, performed using the single- or multiple-breath washout technique, were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests, such as spirometry, as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence based, where possible, but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed. Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.

In cystic fibrosis (CF), tests for ventilation inhomogeneity are sensitive but not established for clinical routine. We assessed feasibility of a new double-tracer gas single-breath washout (SBW) in school-aged children with CF and control subjects, and compared SBW between groups and with multiple-breath nitrogen washout (MBNW). Three SBW and MBNW were performed in 118 children (66 with CF) using a side-stream ultrasonic flowmeter setup. The double-tracer gas containing 5% sulfur hexafluoride and 26.3% helium was applied during one tidal breath. Outcomes were SBW phase III slope (SIII(DTG)), MBNW-derived lung clearance index (LCI), and indices of acinar (S(acin)) and conductive (S(cond)) ventilation inhomogeneity. SBW took significantly less time to perform than MBNW. SBW and MBNW were feasible in 109 (92.4%) and 98 (83.0%) children, respectively. SIII(DTG) differed between children with CF and controls, mean±sd was -456.7±492.8 and -88.4±129.1 mg·mol·L(-1), respectively. Abnormal SIII(DTG) was present in 36 (59%) children with CF. SIII(DTG) was associated with LCI (r= -0.58) and S(acin) (r= -0.58), but not with S(cond). In CF, steeply sloping SIII(DTG) potentially reflects ventilation inhomogeneity near the acinus entrance. This tidal SBW is a promising test to assess ventilation inhomogeneity in an easy and fast way.

Despite association with lung growth and long-term respiratory morbidity, there is a lack of normative lung function data for unsedated infants conforming to latest European Respiratory Society/American Thoracic Society standards. Lung function was measured using an ultrasonic flow meter in 342 unsedated, healthy, term-born infants at a mean ± sd age of 5.1 ± 0.8 weeks during natural sleep according to the latest standards. Tidal breathing flow-volume loops (TBFVL) and exhaled nitric oxide (eNO) measurements were obtained from 100 regular breaths. We aimed for three acceptable measurements for multiple-breath washout and 5-10 acceptable interruption resistance (R(int)) measurements. Acceptable measurements were obtained in ≤ 285 infants with high variability. Mean values were 7.48 mL·kg⁻¹ (95% limits of agreement 4.95-10.0 mL·kg⁻¹) for tidal volume, 14.3 ppb (2.6-26.1 ppb) for eNO, 23.9 mL·kg⁻¹ (16.0-31.8 mL·kg⁻¹) for functional residual capacity, 6.75 (5.63-7.87) for lung clearance index and 3.78 kPa·s·L⁻¹ (1.14-6.42 kPa·s·L⁻¹) for R(int). In males, TBFVL outcomes were associated with anthropometric parameters and in females, with maternal smoking during pregnancy, maternal asthma and Caesarean section. This large normative data set in unsedated infants offers reference values for future research and particularly for studies where sedation may put infants at risk. Furthermore, it highlights the impact of maternal and environmental risk factors on neonatal lung function.

The response to beta(2)-agonists differs between asthmatics and has been linked to subsequent adverse events, even death. Possible determinants include beta(2)-adrenoceptor genotype at position 16, lung function and airway hyperresponsiveness. Fluctuation analysis provides a simple parameter alpha measuring the complex correlation properties of day-to-day peak expiratory flow. The present study investigated whether alpha predicts clinical response to beta(2)-agonist treatment, taking into account other conventional predictors. Analysis was performed on previously published twice-daily peak expiratory flow measurements in 66 asthmatic adults over three 6-month randomised order treatment periods: placebo, salbutamol and salmeterol. Multiple linear regression was used to determine the association between alpha during the placebo period and response to treatment (change in the number of days with symptoms), taking into account other predictors namely beta(2)-adrenoceptor genotype, lung function and its variability, and airway hyperresponsiveness. The current authors found that alpha measured during the placebo period considerably improved the prediction of response to salmeterol treatment, taking into account genotype, lung function or its variability, or airway hyperresponsiveness. The present study provides further evidence that response to beta(2)-agonists is related to the time correlation properties of lung function in asthma. The current authors conclude that fluctuation analysis of lung function offers a novel predictor to identify patients who may respond well or poorly to treatment.