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Automated O2 titration improves exercise capacity in patients with hypercapnic chronic obstructive pulmonary disease: a randomised controlled cross-over trial
  1. Isabelle Vivodtzev1,2,
  2. Erwan L’Her3,
  3. Gabrielle Vottero4,
  4. Claire Yankoff4,
  5. Renaud Tamisier1,
  6. François Maltais5,
  7. François Lellouche5,
  8. Jean-Louis Pépin1
  1. 1 Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, Grenoble Alps University, 38000 Grenoble, France
  2. 2 Cardiovascular Research Laboratory, dept. of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Cambridge, Massachusetts, USA
  3. 3 LATIM Inserm UMR1101, Université de Bretagne Occidentale, Brest, France
  4. 4 Rehabilitation center, Clinique de Pneumologie Les Rieux, ATRIR, Nyons, France
  5. 5 Centre de recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Qc, Canada
  1. Correspondence to Dr Isabelle Vivodtzev, Cardiovascular laboratory, Spaulding Cambridge Hospital, Cambridge MA 02138, USA; ivivodtzev{at}


Automatically titrated O2 flows (FreeO2) was compared with constant O2 flow on exercise capacity, O2 saturation and risk of hyperoxia-related hypercapnia in patients with severe COPD with baseline hypercapnia and long-term oxygen therapy (LTOT). Twelve patients were enrolled in a randomised double-blind cross-over study to perform exercise with either FreeO2 or constant flow. Endurance time (primary outcome) and SpO2 were both significantly improved with FreeO2compared with constant flow (p<0.04), although pCO2 was similar in both conditions. Automated titration of O2 significantly and clinically improved endurance walking time in patients with severe COPD receiving LTOT, without worsening of pCO2.

Trial registration number Results , NCT01575327

  • ambulatory oxygen therapy
  • copd ÀÜ mechanisms
  • exercise

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  • Contributors Study concept and design: IV, FL, J-LP. Acquisition of data: IV, GV, CY, RT. Analysis and interpretation of data: IV, J-LP. Drafting of the manuscript: IV, J-LP. Critical revision of the manuscript for important intellectual content: IV, E L’H, RT, FM, FL, J-LP. Study supervision: IV, J-LP.

  • Funding Endowment fund ‘Fondation de l’Avenir’, France; Endowment fund ‘Agir pour les Maladies chroniques’, France; French National Research Agency (framework of the ‘Investissements d’avenir’ program) (ANR-15-IDEX-02).

  • Competing interests The authors declare that IV, GV and CY have no financial interests that may be relevant to the submitted work. FL is co-inventor of the FreeO2 system. FL is co-founder of Oxynov, a R&D company to develop automated systems for respiratory support. No support from this company was provided for the study; EL’H is co-inventor of the FreeO2 system. ELH is co-founder of Oxynov, a R&D company to develop automated systems for respiratory support. He received grants for participation to expert boards or speaking at conferences sponsored by Smiths Medical, Air Liquide Medical Systems, Sedana Medical and General Electrics. No support from this company was provided for the study; FM participates in Innovair, a company that owns shares in OxyNov; FM reports grants for participating in multicentre trials sponsored by GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca and Novartis; and unrestricted research grants from Boehringer Ingelheim, Novartis and Grifols; others from Boehringer Ingelheim, Novartis and Grifols. FM holds a CIHR/GlaxoSmithKline research chair on COPD. No support from those companies was provided for the study; J-LP has received lecture fees from Resmed, Perimetre, Philips, Fisher and Paykel, JAZZ pharmaceutical, AstraZeneca and SEFAM. J-LP has received conference travelling grant from Agiradom and Teva. J-LP has also received unrestricted research funds from ResMed, Philips, GSK, Fondation de la recherche medicale, Direction de la recherche Clinique du CHU de Grenoble, Fond de dotation ‘Agir pour les maladies chroniques’. No support from those companies was provided for the study; RT reports grants from Resmed, grants from Philips, other from Resmed and other from Agiradom. No support from those companies was provided for the study.

  • Patient consent Obtained.

  • Ethics approval CPP Sud Est V, 11-AGIR-01.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Unpublished data are available: exercise parameters: HR, pH, HCO3 (earlobe blood samples). Please contact Isabelle Vivodtzev at

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