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Original research
Oxygen supplementation during exercise improves leg muscle fatigue in chronic fibrotic interstitial lung disease
  1. Mathieu Marillier1,2,
  2. Anne-Catherine Bernard1,2,
  3. Samuel Verges2,
  4. Onofre Moran-Mendoza1,
  5. Denis E O'Donnell1,
  6. José Alberto Neder1
  1. 1Division of Respirology, Department of Medicine, Queen's University, Kingston, Ontario, Canada
  2. 22HP2 Laboratory, INSERM U1042, Grenoble Alpes University, Grenoble, Isere, France
  1. Correspondence to Professor José Alberto Neder, Division of Respirology, Department of Medicine, Queen's University, Kingston, K7L 2V6, Canada; alberto.neder{at}


Background Exercise-induced hypoxaemia is a hallmark of chronic fibrotic interstitial lung disease (f-ILD). It remains unclear whether patients’ severe hypoxaemia may exaggerate locomotor muscle fatigue and, if so, to what extent oxygen (O2) supplementation can ameliorate these abnormalities.

Methods Fifteen patients (12 males, 9 with idiopathic pulmonary fibrosis) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) while breathing medical air. Fifteen age-matched and sex-matched controls cycled up to patients’ Tlim. Patients repeated the exercise test on supplemental O2 (42%±7%) for the same duration. Near-infrared spectroscopy assessed vastus lateralis oxyhaemoglobin concentration ((HbO2)). Pre-exercise to postexercise variation in twitch force (∆Tw) induced by femoral nerve magnetic stimulation quantified muscle fatigue.

Results Patients showed severe hypoxaemia (lowest O2 saturation by pulse oximetry=80.0%±7.6%) which was associated with a blunted increase in muscle (HbO2) during exercise vs controls (+1.3±0.3 µmol vs +4.4±0.4 µmol, respectively; p<0.001). Despite exercising at work rates ∼ one-third lower than controls (42±13 W vs 66±13 W), ∆Tw was greater in patients (∆Tw/external work performed by the leg muscles=−0.59±0.21 %/kJ vs −0.25±0.19 %/kJ; p<0.001). Reversal of exertional hypoxaemia with supplemental O2 was associated with a significant increase in muscle (HbO2), leading to a reduced decrease in ∆Tw in patients (−0.33±0.19 %/kJ; p<0.001 vs air). Supplemental O2 significantly improved leg discomfort (p=0.005).

Conclusion O2 supplementation during exercise improves leg muscle oxygenation and fatigue in f-ILD. Lessening peripheral muscle fatigue to enhance exercise tolerance is a neglected therapeutic target that deserves clinical attention in this patient population.

  • exercise
  • Long Term Oxygen Therapy (LTOT)
  • interstitial fibrosis
  • lung physiology
  • pulmonary rehabilitation
  • respiratory measurement
  • short burst oxygen therapy

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  • Contributors All authors played a role in the content and writing of the manuscript. MM and A-CB collected the data. SV and JAN shared the original idea for the study. MM, A-CB and JAN performed data analysis and prepared it for presentation. MM, A-CB and JAN jointly wrote the first complete draft of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests MM was funded by a European Respiratory Society’s Long Term Fellowship and the John Alexander Stuart Fellowship, Queen’s University. JAN has been funded by the New Clinician Scientist Program from the Southeastern Ontario Academic Medical Association (SEAMO), Canada. His laboratory was established owing to the Canadian Foundation for Innovation’s John R. Evans Leaders Fund, Canada.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Queen’s University Research Ethics Board (DMED-2150–18).

  • Data availability statement Data are available on reasonable request. Data available from the authors on request

    —unidentified patients in excel/SPSS files.

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