Article Text

other Versions

Download PDFPDF
Original research
Oral nitrate supplementation to enhance pulmonary rehabilitation in COPD: ON-EPIC a multicentre, double-blind, placebo-controlled, randomised parallel group study
  1. Matthew J Pavitt1,
  2. Rebecca Jayne Tanner1,
  3. Adam Lewis1,
  4. Sara Buttery1,
  5. Bhavin Mehta2,
  6. Helen Jefford3,
  7. Katrina J Curtis1,
  8. Winston A S Banya1,
  9. Syed Husain4,
  10. Karnan Satkunam3,
  11. Dinesh Shrikrishna5,
  12. William Man1,2,
  13. Michael I Polkey1,2,
  14. Nicholas S Hopkinson1
  1. 1National Heart and Lung Institute, Royal Brompton Campus, Imperial College London, London, UK
  2. 2Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, UK
  3. 3Greenwich Adult Community Health Service, Oxleas NHS Foundation Trust, Dartford, Kent, UK
  4. 4Respiratory Medicine, Maidstone and Tunbridge Wells NHS Trust, Maidstone, Kent, UK
  5. 5Musgrove Park Hospital, Taunton and Somerset NHS Foundation Trust, Taunton, Somerset, UK
  1. Correspondence to Dr Nicholas S Hopkinson, National Heart and Lung Institute, Royal Brompton Campus, Imperial College London, London SW3 6HP, UK; n.hopkinson{at}


Rationale Dietary nitrate supplementation has been proposed as a strategy to improve exercise performance, both in healthy individuals and in people with COPD. We aimed to assess whether it could enhance the effect of pulmonary rehabilitation (PR) in COPD.

Methods This double-blind, placebo-controlled, parallel group, randomised controlled study performed at four UK centres, enrolled adults with Global Initiative for Chronic Obstructive Lung Disease grade II–IV COPD and Medical Research Council dyspnoea score 3–5 or functional limitation to undertake a twice weekly 8-week PR programme. They were randomly assigned (1:1) to either 140 mL of nitrate-rich beetroot juice (BRJ) (12.9 mmol nitrate), or placebo nitrate-deplete BRJ, consumed 3 hours prior to undertaking each PR session. Allocation used computer-generated block randomisation.

Measurements The primary outcome was change in incremental shuttle walk test (ISWT) distance. Secondary outcomes included quality of life, physical activity level, endothelial function via flow-mediated dilatation, fat-free mass index and blood pressure parameters.

Results 165 participants were recruited, 78 randomised to nitrate-rich BRJ and 87 randomised to placebo. Exercise capacity increased more with active treatment (n=57) than placebo (n=65); median (IQR) change in ISWT distance +60 m (10, 85) vs +30 m (0, 70), estimated treatment effect 30 m (95% CI 10 to 40); p=0.027. Active treatment also impacted on systolic blood pressure: treatment group −5.0 mm Hg (−5.0, –3.0) versus control +6.0 mm Hg (−1.0, 15.5), estimated treatment effect −7 mm Hg (95% CI 7 to −20) (p<0.0005). No significant serious adverse events or side effects were reported.

Conclusions Dietary nitrate supplementation appears to be a well-tolerated and effective strategy to augment the benefits of PR in COPD.

Trial registration number ISRCTN27860457.

  • COPD pharmacology
  • pulmonary rehabilitation

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Twitter @DrMattPav, @apl104, @toplungdoc, @COPDdoc

  • Contributors NSH and MIP developed the original idea for the research study. NSH, MJP and RJT wrote the study protocol. WASB designed the statistical analysis plan. MJP, KJC, RJT, SB, AL, BM and HJ undertook patient visits and collected trial data. WM, SH, KS and DS were local site primary investigators. MJP analysed the data and wrote the first draft of the manuscript. All authors edited and contributed to the final manuscript.

  • Funding Moulton Charitable Foundation Grant.

  • Disclaimer The Moulton Charitable Foundation played no role in the conduct or analysis of this study.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval All participants provided written informed consent prior to enrolment in the study, which was approved by the London Bridge Health Research and Ethics Committee (Ref: 14/LO/1474) and conducted in line with the principles of the Declaration of Helsinki.

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

  • Data availability statement Data are available upon reasonable request. Individual participant data that underlie the results in the article, after deidentification (text, tables, figures and appendices), will be available. The study protocol and statistical analysis plan will be available. Data will be made immediately available following publication; no end date. Data will be available to anyone who wishes to access the data, for any purpose. Data will be available indefinitely.

Linked Articles

  • Airwaves
    The Triumvirate