Kamis , 10 Sep 2020 16:32:11
Day-to-day variability of forced oscillatory mechanics for early detection of acute exacerbations in COPD


Sabine C. Zimmermann, Jacqueline Huvanandana, Chinh D. Nguyen, Amy Bertolin, Joanna C. Watts, Alessandro Gobbi, Claude S. Farah, Matthew J. Peters, Raffaele L. Dellacà, Gregory G. King, Cindy Thamrin

European Respiratory Journal 2020 56: 1901739; DOI: 10.1183/13993003.01739-2019

Abstract

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 (FEV1) 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 (SDXinsp)) 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). SDXinsp 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 SDXinsp from FOT telemonitoring reflects COPD symptoms and may be a sensitive biomarker for early detection of AECOPD.

Telemonitoring of day-to-day variations in lung function using oscillometry in COPD may help assess symptoms and detect acute exacerbations early https://bit.ly/2RUhn7c

Footnotes

  • Author contributions: S.C. Zimmermann, C.S. Farah, A. Gobbi, G.G. King and C. Thamrin contributed to conception and design of the study. S.C. Zimmermann, A. Bertolin and J.C. Watts contributed to data collection. S.C. Zimmermann, J. Huvanandana, C.D. Nguyen, G.G. King and C. Thamrin contributed to data analysis. S.C. Zimmermann, J. Huvanandana, C.D. Nguyen, A. Gobbi, C.S. Farah, M.J. Peters, R.L. Dellacà, G.G. King and C. Thamrin contributed to interpretation of data. S.C. Zimmermann, J. Huvanandana, G.G. King and C. Thamrin contributed to preparation of the manuscript. All authors have read and approved the final manuscript.

  • This article has an editorial commentary: https://doi.org/10.1183/13993003.01815-2020

  • This article has supplementary material available from erj.ersjournals.com

  • This study was registered at www.clinicaltrials.gov as part of a larger trial NCT 01552031.

  • 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.

  • Support statement: This study was funded by a National Health and Medical Research Council (NHMRC) project grant (1049560) and a Lung Foundation Australia/Boehringer Ingelheim COPD Research Top-Up Grant 2016. S.C. Zimmermann was funded by an NHMRC postgraduate scholarship (1074630). Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received September 4, 2019.
  • Accepted April 17, 2020.
  • Copyright ©ERS 2020