Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2020

01-12-2020 | Idiopathic Pulmonary Fibrosis | Research article

The impact of high-flow nasal cannula oxygen therapy on exercise capacity in fibrotic interstitial lung disease: a proof-of-concept randomized controlled crossover trial

Authors: Atsushi Suzuki, Masahiko Ando, Tomoki Kimura, Kensuke Kataoka, Toshiki Yokoyama, Eiichi Shiroshita, Yasuhiro Kondoh

Published in: BMC Pulmonary Medicine | Issue 1/2020

Login to get access

Abstract

Background

Patients with fibrotic interstitial lung disease (FILD) often experience gas exchange abnormalities and ventilatory limitations, resulting in reduced exercise capacity. High-flow nasal cannula (HFNC) oxygen therapy is a novel treatment, whose physiological beneficial effects have been demonstrated in various clinical settings. We hypothesized that HFNC oxygen therapy might be superior to conventional oxygen therapy for improving exercise capacity in FILD patients.

Methods

We performed a prospective randomized controlled crossover trial with a high-intensity constant work-rate endurance test (CWRET) using HFNC (50 L/min, FiO2 0.5) and a venturi mask (VM) (15 L/min, FiO2 0.5) for oxygen delivery in FILD patients. The primary outcome variable was endurance time. The secondary outcome variables were SpO2, heart rate, Borg scale (dyspnea and leg fatigue), and patient’s comfort.

Results

Seven hundred and eleven patients were screened and 20 eligible patients were randomized. All patients completed the trial. The majority of patients were good responders to VM and HFNC compared with the baseline test (VM 75%; HFNC 65%). There was no significant difference in endurance time between HFNC and VM (HFNC 6.8 [95% CI 4.3–9.3] min vs VM 7.6 [95% CI 5.0–10.1] min, p = 0.669). No significant differences were found in other secondary endpoints. Subgroup analysis with HFNC good responders revealed that HFNC significantly extended the endurance time compared with VM (VM 6.4 [95%CI 4.5–8.3] min vs HFNC 7.8 [95%CI 5.8–9.7] min, p = 0.046), while no similar effect was observed in the VM good responders.

Conclusions

HFNC did not exceed the efficacy of VM on exercise capacity in FILD, but it may be beneficial if the settings match. Further large studies are needed to confirm these findings.

Trial registration

UMIN-CTR: UMIN000021901.
Appendix
Available only for authorised users
Literature
1.
go back to reference Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ. et al; American Thoracic Society, European Respiratory Society, Japanese respiratory Society, and Latin American Thoracic Society. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198:e44–68.CrossRef Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ. et al; American Thoracic Society, European Respiratory Society, Japanese respiratory Society, and Latin American Thoracic Society. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198:e44–68.CrossRef
2.
go back to reference Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al. ATS/ERS Committee on Idiopathic Interstitial Pneumonias An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188:733–48.CrossRef Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al. ATS/ERS Committee on Idiopathic Interstitial Pneumonias An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188:733–48.CrossRef
3.
go back to reference Nishiyama O, Taniguchi H, Kondoh Y, Kimura T, Kato K, Kataoka K, et al. A simple assessment of dyspnoea as a prognostic indicator in idiopathic pulmonary fibrosis. Eur Respir J. 2010;36:1067–72.CrossRef Nishiyama O, Taniguchi H, Kondoh Y, Kimura T, Kato K, Kataoka K, et al. A simple assessment of dyspnoea as a prognostic indicator in idiopathic pulmonary fibrosis. Eur Respir J. 2010;36:1067–72.CrossRef
4.
go back to reference Flaherty KR, Andrei AC, Murray S, Fraley C, Colby TV, Travis WD, et al. Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test. Am J Respir Crit Care Med. 2006;174:803–9.CrossRef Flaherty KR, Andrei AC, Murray S, Fraley C, Colby TV, Travis WD, et al. Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test. Am J Respir Crit Care Med. 2006;174:803–9.CrossRef
5.
go back to reference Fell CD, Liu LX, Motika C, Kazerooni EA, Gross BH, Travis WD, et al. The prognostic value of cardiopulmonary exercise testing in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2009;179:402–7.CrossRef Fell CD, Liu LX, Motika C, Kazerooni EA, Gross BH, Travis WD, et al. The prognostic value of cardiopulmonary exercise testing in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2009;179:402–7.CrossRef
6.
go back to reference Nishiyama O, Miyajima H, Fukai Y, Yamazaki R, Satoh R, Yamagata T, et al. Effect of ambulatory oxygen on exertional dyspnea in IPF patients without resting hypoxemia. Respir Med. 2013;107:1241–6.CrossRef Nishiyama O, Miyajima H, Fukai Y, Yamazaki R, Satoh R, Yamagata T, et al. Effect of ambulatory oxygen on exertional dyspnea in IPF patients without resting hypoxemia. Respir Med. 2013;107:1241–6.CrossRef
7.
go back to reference Visca D, Mori L, Tsipouri V, Fleming S, Firouzi A, Bonini M, et al. Effect of ambulatory oxygen on quality of life for patient with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomized controlled trial. Lancet Respir Med. 2018;6:759–70.CrossRef Visca D, Mori L, Tsipouri V, Fleming S, Firouzi A, Bonini M, et al. Effect of ambulatory oxygen on quality of life for patient with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomized controlled trial. Lancet Respir Med. 2018;6:759–70.CrossRef
8.
go back to reference Edvardsen A, Jarosch I, Grongstad A, Wiegand L, Gloeckl R, Kenn K, et al. A randomized cross-over trial on the direct effects of oxygen supplementation therapy using different devices on cycle endurance in hypoxemic patients with interstitial lung disease. PLoS One. 2018;13:e0209069.CrossRef Edvardsen A, Jarosch I, Grongstad A, Wiegand L, Gloeckl R, Kenn K, et al. A randomized cross-over trial on the direct effects of oxygen supplementation therapy using different devices on cycle endurance in hypoxemic patients with interstitial lung disease. PLoS One. 2018;13:e0209069.CrossRef
10.
go back to reference Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. FLORALI study group; REVA network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372:2185–96.CrossRef Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. FLORALI study group; REVA network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372:2185–96.CrossRef
11.
go back to reference Stéphan F, Barrucand B, Petit P, Rézaiguia-Delclaux S, Médard A, Delannoy B, BiPOP Study Group, et al. High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial. JAMA. 2015;313:2331–9.CrossRef Stéphan F, Barrucand B, Petit P, Rézaiguia-Delclaux S, Médard A, Delannoy B, BiPOP Study Group, et al. High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial. JAMA. 2015;313:2331–9.CrossRef
12.
go back to reference Maggiore SM, Idone FA, Vaschetto R, et al. Nasal high-flow versus venturi mask oxygen therapy after extubation. Effects on oxygenateon, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190:282–8.CrossRef Maggiore SM, Idone FA, Vaschetto R, et al. Nasal high-flow versus venturi mask oxygen therapy after extubation. Effects on oxygenateon, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190:282–8.CrossRef
13.
go back to reference Fraser JF, Spooner AJ, Dunster KR, Anstey CM, Corley A. Nasal high flow oxygen therapy in patients with COPD reduces respiratory rate and tissue carbon dioxide while increasing tidal and end-expiratory lung volumes; a randomized crossover trial. Thorax. 2016;71:759–61.CrossRef Fraser JF, Spooner AJ, Dunster KR, Anstey CM, Corley A. Nasal high flow oxygen therapy in patients with COPD reduces respiratory rate and tissue carbon dioxide while increasing tidal and end-expiratory lung volumes; a randomized crossover trial. Thorax. 2016;71:759–61.CrossRef
14.
go back to reference Puente-Maestu L, Palange P, Casaburi R, Laveneziana P, Maltais F, Neder JA, et al. Use of exercise testing in the evaluation of interventional efficacy: an official ERS statement. Eur Respir J. 2016;47:479–60.CrossRef Puente-Maestu L, Palange P, Casaburi R, Laveneziana P, Maltais F, Neder JA, et al. Use of exercise testing in the evaluation of interventional efficacy: an official ERS statement. Eur Respir J. 2016;47:479–60.CrossRef
15.
go back to reference Arizono S, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, et al. Endurance time is the most responsive exercise measurement in idiopathic pulmonary fibrosis. Respir Care. 2014;59:1108–15.CrossRef Arizono S, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, et al. Endurance time is the most responsive exercise measurement in idiopathic pulmonary fibrosis. Respir Care. 2014;59:1108–15.CrossRef
16.
go back to reference Chatila W, Nugent T, Vance G, Gaughan J, Criner GJ. The effects of high-flow vs low-flow oxygen on exercise in advanced obstructive airways disease. Chest. 2004;126:1108–15.CrossRef Chatila W, Nugent T, Vance G, Gaughan J, Criner GJ. The effects of high-flow vs low-flow oxygen on exercise in advanced obstructive airways disease. Chest. 2004;126:1108–15.CrossRef
17.
go back to reference Bianchi L, Foglio K, Pagani M, Vitacca M, Rossi A, Ambrosino N. Effects of proportional assist ventilation on exercise tolerance in COPD patients with chronic hypercapnia. Eur Respir J. 1998;11:422–7.CrossRef Bianchi L, Foglio K, Pagani M, Vitacca M, Rossi A, Ambrosino N. Effects of proportional assist ventilation on exercise tolerance in COPD patients with chronic hypercapnia. Eur Respir J. 1998;11:422–7.CrossRef
18.
go back to reference American Thoracic Society, American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003;167:211–77.CrossRef American Thoracic Society, American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003;167:211–77.CrossRef
19.
go back to reference Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46:903–75.CrossRef Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46:903–75.CrossRef
20.
go back to reference Nathan SD, Shlobin OA, Barnett SD, Saggar R, Belperio JA, Ross DJ, et al. Right ventricular systolic pressure by echocardiography as a predictor of pulmonary hypertension in idiopathic pulmonary fibrosis. Respir Med. 2008;102:1305–10.CrossRef Nathan SD, Shlobin OA, Barnett SD, Saggar R, Belperio JA, Ross DJ, et al. Right ventricular systolic pressure by echocardiography as a predictor of pulmonary hypertension in idiopathic pulmonary fibrosis. Respir Med. 2008;102:1305–10.CrossRef
21.
go back to reference Bräunlich J, Beyer D, Mai D, Hammerschmidt S, Seyfarth HJ, Wirtz H. Effects of nasal high flow on ventilation in volunteers, COPD and idiopathic pulmonary fibrosis patients. Respiration. 2013;85:319–25.CrossRef Bräunlich J, Beyer D, Mai D, Hammerschmidt S, Seyfarth HJ, Wirtz H. Effects of nasal high flow on ventilation in volunteers, COPD and idiopathic pulmonary fibrosis patients. Respiration. 2013;85:319–25.CrossRef
22.
go back to reference McKinstry S, Pilcher J, Bardsley G, Berry J, Van de Hei S, Braithwaite I, et al. Nasal high flow therapy and PtCO2 in stable COPD: a randomized controlled cross-over trial. Respirology. 2017;23:378–84.CrossRef McKinstry S, Pilcher J, Bardsley G, Berry J, Van de Hei S, Braithwaite I, et al. Nasal high flow therapy and PtCO2 in stable COPD: a randomized controlled cross-over trial. Respirology. 2017;23:378–84.CrossRef
23.
go back to reference Chanques G, Constantin JM, Sauter M, Jung B, Sebbane M, Verzilli D, et al. Discomfort associated with underhumidified high-flow oxygen therapy in critically ill patients. Intensive Care Med. 2009;35:996–1003.CrossRef Chanques G, Constantin JM, Sauter M, Jung B, Sebbane M, Verzilli D, et al. Discomfort associated with underhumidified high-flow oxygen therapy in critically ill patients. Intensive Care Med. 2009;35:996–1003.CrossRef
24.
go back to reference Parke RL, Ecceleston ML, McGuinness SP. The effects of flow on airway pressure during nasal high-flow oxygen therapy. Respir Care. 2011;56:1151–5.CrossRef Parke RL, Ecceleston ML, McGuinness SP. The effects of flow on airway pressure during nasal high-flow oxygen therapy. Respir Care. 2011;56:1151–5.CrossRef
26.
go back to reference O’Donnell DE, Sanij R, Younes M. Improvement in exercise endurance in patients with chronic airflow limitation using continuous positive airway pressure. Am Rev Respir Dis. 1988;138:1510–4.CrossRef O’Donnell DE, Sanij R, Younes M. Improvement in exercise endurance in patients with chronic airflow limitation using continuous positive airway pressure. Am Rev Respir Dis. 1988;138:1510–4.CrossRef
27.
go back to reference Keilty SEJ, Ponte J, Fleming TA, Moxham J. Effect of inspiratory pressure support on exercise tolerance and breathlessness in patients with severe stable chronic obstructive pulmonary disease. Thorax. 1994;49:990–4.CrossRef Keilty SEJ, Ponte J, Fleming TA, Moxham J. Effect of inspiratory pressure support on exercise tolerance and breathlessness in patients with severe stable chronic obstructive pulmonary disease. Thorax. 1994;49:990–4.CrossRef
28.
go back to reference Moderno EV, Yamaguti WP, Schettino GP, Kairalla RA, Martins MA, Carvalho CR, et al. Effects of proportional assisted ventilation on exercise performance in idiopathic pulmonary fibrosis patients. Respir Med. 2010;104:134–41.CrossRef Moderno EV, Yamaguti WP, Schettino GP, Kairalla RA, Martins MA, Carvalho CR, et al. Effects of proportional assisted ventilation on exercise performance in idiopathic pulmonary fibrosis patients. Respir Med. 2010;104:134–41.CrossRef
29.
go back to reference Nagata K, Kikuchi T, Horie T, Shiraki A, Kitajima T, Kadowaki T, et al. Domiciliary high-flow nasal cannula oxygen therapy for patients with stable hypercapnic chronic obstructive pulmonary disease. A multicenter randomized crossover trial. Ann Am Thorac Soc. 2018;15:432–9.CrossRef Nagata K, Kikuchi T, Horie T, Shiraki A, Kitajima T, Kadowaki T, et al. Domiciliary high-flow nasal cannula oxygen therapy for patients with stable hypercapnic chronic obstructive pulmonary disease. A multicenter randomized crossover trial. Ann Am Thorac Soc. 2018;15:432–9.CrossRef
30.
go back to reference Storgaard LH, Hockey HU, Laursen BS, Weinreich UM. Long-term effects of oxygen-enriched high-flow nasal cannula treatment in COPD patients with chronic hypoxemic respiratory failure. Int J Chorn Obstruct Pulmon Dis. 2018;13:1195–205.CrossRef Storgaard LH, Hockey HU, Laursen BS, Weinreich UM. Long-term effects of oxygen-enriched high-flow nasal cannula treatment in COPD patients with chronic hypoxemic respiratory failure. Int J Chorn Obstruct Pulmon Dis. 2018;13:1195–205.CrossRef
31.
go back to reference Perez-Bogerd S, Wuyts W, Barbier V, Demeyer H, Van Muylem A, Janssens W, et al. Short and long-term effects of pulmonary rehabilitation in interstitial lung diseases: a randomized controlled trial. Respir Res. 2018;19:182.CrossRef Perez-Bogerd S, Wuyts W, Barbier V, Demeyer H, Van Muylem A, Janssens W, et al. Short and long-term effects of pulmonary rehabilitation in interstitial lung diseases: a randomized controlled trial. Respir Res. 2018;19:182.CrossRef
32.
go back to reference Tonelli R, Cocconcelli E, Lanini B, Romagnoli I, Florini F, Castaniere I, et al. Effectiveness of pulmonary rehabilitation in patients with interstitial lung disease of different etiology: a multicenter prospective study. BMC Pulm Med. 2017;17:130.CrossRef Tonelli R, Cocconcelli E, Lanini B, Romagnoli I, Florini F, Castaniere I, et al. Effectiveness of pulmonary rehabilitation in patients with interstitial lung disease of different etiology: a multicenter prospective study. BMC Pulm Med. 2017;17:130.CrossRef
33.
go back to reference Dowman LM, McDonald CF, Hill CJ, Lee AL, Barker K, Boote C, et al. The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial. Thorax. 2017;72:610–9.CrossRef Dowman LM, McDonald CF, Hill CJ, Lee AL, Barker K, Boote C, et al. The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial. Thorax. 2017;72:610–9.CrossRef
34.
go back to reference Juge PA, Lee JS, Ebstein E, Furukawa H, Dobrinskikh E, Gazal S, et al. MUC5B promoter varian and rheumatoid arthritis with interstitial lung disease. N Encl J Med. 2018;379:2209–19.CrossRef Juge PA, Lee JS, Ebstein E, Furukawa H, Dobrinskikh E, Gazal S, et al. MUC5B promoter varian and rheumatoid arthritis with interstitial lung disease. N Encl J Med. 2018;379:2209–19.CrossRef
35.
go back to reference Ley B, Newton CA, Arnould I, Elicker BM, Henry TS, Vittinghoff E, et al. The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study. Lancet Respir Med. 2017;5:639–47.CrossRef Ley B, Newton CA, Arnould I, Elicker BM, Henry TS, Vittinghoff E, et al. The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study. Lancet Respir Med. 2017;5:639–47.CrossRef
36.
go back to reference Newton CA, Batra K, Torrealba J, Kozlitina J, Glazer CS, Aravena C, et al. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. Eur Respir J. 2016;48:1710–20.CrossRef Newton CA, Batra K, Torrealba J, Kozlitina J, Glazer CS, Aravena C, et al. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. Eur Respir J. 2016;48:1710–20.CrossRef
37.
go back to reference Watanabe F, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, et al. Quadriceps weakness contributes to exercise capacity in nonspecific interstitial pneumonia. Respir Med. 2013;107:622–8.CrossRef Watanabe F, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, et al. Quadriceps weakness contributes to exercise capacity in nonspecific interstitial pneumonia. Respir Med. 2013;107:622–8.CrossRef
Metadata
Title
The impact of high-flow nasal cannula oxygen therapy on exercise capacity in fibrotic interstitial lung disease: a proof-of-concept randomized controlled crossover trial
Authors
Atsushi Suzuki
Masahiko Ando
Tomoki Kimura
Kensuke Kataoka
Toshiki Yokoyama
Eiichi Shiroshita
Yasuhiro Kondoh
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2020
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-020-1093-2

Other articles of this Issue 1/2020

BMC Pulmonary Medicine 1/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.