High flow nasal oxygen versus usual care in improving pulmonary rehabilitation outcomes of chronic obstructive pulmonary disease patients after an exacerbation

Abstract

Introduction

Early pulmonary rehabilitation (PR) is guideline-recommended for all chronic obstructive pulmonary disease (COPD) patients post-hospitalization for COPD exacerbation but many patients experience difficulties participating in early PR due to significant breathlessness. High flow nasal oxygen (HFO) has been shown to improve ventilatory efficiency in stable COPD patients, but there is little data on HFO use during exercise training in PR post-COPD exacerbation.

Methods

We conducted a pilot randomized controlled trial (RCT) to explore the feasibility of a prospective large-scale RCT to evaluate the impact of HFO in improving PR outcomes of COPD patients post-exacerbation. Patients recently hospitalized for COPD exacerbation were enrolled and randomized to either HFO or usual care during an early 6-weeks, outpatient PR program.

Results

Twenty two patients were randomized between May 2019 to Dec 2019 and 18 patients completed the study. The HFO arm achieved a greater improvement in exercise capacity than the usual care arm, with the mean difference in 6-min walk distance (6MWD) being 30 m (95% CI: −23 m to 84 m), although this was not statistically significant. All 18 patients in both arms were compliant to the pulmonary rehabilitation program (defined by attending ≥75% of exercise sessions). HFO was well tolerated with no adverse events reported.

Conclusion

This pilot RCT has shown preliminary evidence of the feasibility and high patient acceptability of HFO during early PR on improving exercise capacity in COPD patients post-exacerbation These promising results would justify a larger RCT to confirm HFO’s benefits and has the potential to change PR practice.

Keywords

pulmonary rehabilitation high flow nasal oxygen chronic obstructive pulmonary disease

Introduction

Chronic Obstructive Pulmonary Disease (COPD) is the 3^rd leading cause of mortality globally¹ and the 10^th most common cause of mortality in Singapore.² It is a common, progressive, chronic inflammatory lung disease associated with recurrent hospitalizations,³ deteriorating physical function⁴ and poor quality of life,⁵ with the poorest outcomes seen in post-COPD exacerbation patients.^6,7 Globally, there were approximately 384 million cases of COPD in 2010 with an estimated prevalence of 11.7% in adults aged above 30 years⁸

Pulmonary rehabilitation has been shown to enhance exercise tolerance,⁹ decrease breathlessness, improve quality of life,¹⁰ decrease depression and anxiety,¹¹ and reduce COPD readmission rates in COPD patients after an acute COPD exacerbation.⁹ Therefore, early pulmonary rehabilitation is recommended by the Global Initiative for Obstructive Lung Disease (GOLD) guideline for all COPD patients after discharge from hospitalization for acute COPD exacerbation.¹²

Unfortunately, a large majority of post-exacerbation COPD patients are unable to participate in pulmonary rehabilitation nor achieve their target exercise intensity due to significant breathlessness and weakness.¹³ Previous research has explored the possible benefit of supplemental oxygen¹⁴ and non-invasive ventilation^15,16 in enhancing exercise training but the data remains mixed. To date, no single intervention has previously been identified to successfully enhance patient adherence to exercise training and improve pulmonary rehabilitation outcomes.

High Flow Nasal Oxygen (HFO), which involves the delivery of heated and humidified air/oxygen gases at high flow rates via a nasal cannula, is a promising intervention to improve COPD patients’ adherence to pulmonary rehabilitation and enhance clinical outcomes. Physiological studies have suggested that HFO is able to target the pathophysiological mechanisms implicated in exercise intolerance and breathlessness of COPD patients. HFO has been shown to increase mean airway pressure through the delivery of gases at high flow rates,^17,18 ensure more consistent delivery of oxygen to the lungs, improve gas exchange efficiency through continuous washout of carbon dioxide from the airways, and correct the abnormal breathing pattern seen in COPD patients during exercise.¹⁹ In exercise testing studies of stable COPD patients, HFO has been shown to increase exercise endurance time, reduce breathlessness and maintain higher oxygen saturations during the exercise test compared to usual oxygen supplementation.^20,21

Despite the potential benefit of HFO to exercise however, there is little data on the use of HFO during exercise training and its impact on pulmonary rehabilitation outcomes of COPD patients post-hospitalization for COPD exacerbation. Given the high prevalence of COPD, its significant morbidity and mortality, the inability of many patients to reap the benefits of pulmonary rehabilitation and the promising benefits of HFO in enhancing exercise training, there is an urgent need to fill this evidence gap.

Therefore, we conducted a pilot randomized controlled trial (RCT) to explore the feasibility of a prospective large-scale RCT to evaluate the impact of HFO in improving pulmonary rehabilitation outcomes of COPD patients post-exacerbation.

Methods

Study design and subject recruitment

This pilot RCT was conducted at Changi General hospital, a 1000-bed teaching hospital in Singapore. Patients were recruited prior to discharge from a hospital admission for acute COPD exacerbation May 2019 to Dec 2019 and final patient follow-up was completed in Jan 2020. Patient eligibility criteria included a diagnosis of COPD with a post bronchodilator FEV1/FVC ratio on spirometry <0.7, age 21 years and above, currently admitted inpatient for an acute COPD exacerbation, experiencing shortness of breath on exertion, fit to participate in exercise therapy as determined by both physician and physiotherapist and has the mental capacity to follow instructions. Patients were excluded if they had uncontrolled severe medical conditions such as severe chronic heart failure, pulmonary disorder other than COPD, or physical conditions that precluded their ability to participate in exercise or might impair exercise performance. Physicians and respiratory physiotherapists provided a brief description of the study to eligible patients during their hospital admission and enquired if they were keen to be contacted by the study’s research staff for further details. If a patient was agreeable to participate in the study, written informed consent was obtained. This study was approved by the Singhealth Centralised Insitutional Review Board Ref: 2018/2902 (3^rd April 2019) and registered at ClinicalTrials.gov: NCT03940040.

Study interventions, randomisation and masking

Consented patients returned within 1 week of hospital discharge to commence participation in the outpatient pulmonary rehabilitation program. They were randomized on the 1st day of attendance at pulmonary rehabilitation into the intervention arm (HFO) or usual care arm (room air or normal flow oxygen if required) during exercise training (Figure 1). The randomization sequence was generated in blocks by a hospital research unit biostatistician who was independent of study conduct, and allocation concealment was achieved by sequentially numbered, opaque and sealed envelopes. These envelopes were opened consecutively by the study researcher immediately prior to randomization of each patient. Research staff assessing the outcomes of the study and data analyses were masked to the study arm that the participants were allocated to. Given the nature of the two interventions, the patients and medical staff performing the pulmonary rehabilitation program could not be masked.

Figure 1.

Trial flow diagram. PR, pulmonary rehabilitation; HFO, high flow oxygen.

Pulmonary rehabilitation program

Participants attended aerobic and strength training sessions twice weekly for a total of 6 weeks in the pulmonary rehabilitation program. As per routine protocol, each exercise session lasted for an hour with 30 min dedicated to aerobic training and another 30 min to strength training. Aerobic exercises comprise of either walking on a treadmill or cycling on a stationary bike. The intensity for walking exercises (treadmill) was prescribed at 80% of the 6-min walk test speed obtained during baseline assessment. Stationary cycling was commenced at exercise intensity of 5–10 W and the workload was increased until the patient reported a modified Borg dyspnea score of 4-6 (somewhat severe to severe breathlessness). At subsequent sessions, as patient progressed, the speed, duration and/or gradient (in the case of treadmill) of the aerobic exercises were increased. Strength training exercises were performed using the HUR® machines (e.g. leg press, knee extension, knee flexion, chest press, upper limb pull-downs). Strength training was prescribed at two to three sets of 10 Repetitive Maximum (10RM) load. A 10RM load is defined as the maximum weight one can pull or push against repeatedly for 10 times. During exercise, patients’ heart rate and oxygen saturation were continuously monitored with a finger oximeter. Strength training load was increased by 10% when the patient was able to complete 12 repetitions for consecutive two sessions. As a component of the rehabilitation program, patient education was also provided. Topics included the understanding of disease pathophysiology, benefits of exercise, management of dyspnoea and respiratory secretions etc. Patients were encouraged to exercise for another day within the week in order to develop exercise lifestyle habits. For patients in the HFO arm, this additional day of self-directed exercise is performed without HFO.

High flow nasal oxygen

High flow nasal oxygen was administered using the Optiflow nasal cannula (Fisher & Paykel) with the AIRVO two system (Fisher & Paykel, New Zealand). This system allowed the generation of air flow up to 60 L/min. The fractional inspired oxygen (FiO2) delivered to the patient was controlled (FiO2: 0.21 to 1.0) by adjusting the oxygen flow entering the AIRVO two system.

COPD patients who did not require long term oxygen supplementation at baseline commenced exercise at a set flow rate of 30/min with FiO2 0.24. COPD patients who required long term oxygen supplementation at baseline commenced exercise at a set flow rate of 30 L/min with an FiO2 approximately equivalent to their baseline supplemental oxygen requirements. For example, if patients required baseline oxygen of 2 L/min, the AIRVO two FiO2 will be set at FiO2 0.28).

During exercise, oxygen saturation (SpO2) was maintained at or above 90%. If SpO2 fell below 90%, flow rate was increased in a stepwise approach followed by an increase in FiO2 as shown in the titration table below (Table 1). This FiO2 and flow titration protocol was developed by our team as there was no prior published protocol. This titration protocol allowed for patient acclimatization by commencing air flow at a lower rate, and consequently enhanced patient comfort and tolerance. Each level of titration occurred at 15-30 s intervals. The upper limit of the titrated FiO2 was set at 0.4. Exercise was stopped at the point of patient exhaustion.

Table 1.

HFO titration table.

Steps (upward titration)	Flow rate of AIRVO2 (L/min)	FiO₂
1	30	0.24
2	40	0.24
3	50	0.24
4	60	0.24
5	60	0.28
6	60	0.32
7	60	0.36
8	60	0.4

Footnotes: FiO₂, fractional inspired oxygen; HFO, high flow oxygen.

For subsequent sessions, exercise was commenced at the last known high flow oxygen settings required to keep SpO2 above 90% during exercise. However, should SpO2 remain persistently above 98%, settings were decreased stepwise in reverse order of the above table. To ensure comfort, the humidified gas mixture was heated to 34°C for all patients.

Control

Exercise was conducted on room air or normal nasal oxygen supplementation as per usual care. COPD patients who did not require long term oxygen supplementation at baseline commenced exercise on room air. COPD patients who required long term oxygen supplementation at baseline commenced exercise with oxygen supplementation 1 L/min higher than their baseline. For example, if a patient required baseline oxygen of 2 L/min, he commenced exercise with oxygen at 3 L/min.

During exercise, oxygen saturation (SpO2) was maintained at or above 90%. If SpO2 fell below 90%, nasal oxygen was increased by 1 L/min every 15 -30 s. The upper limit of the oxygen supplementation was set at 5 L/min. Exercise was stopped at point of patient exhaustion.

Outcomes

The primary outcome was the change from baseline in exercise capacity, measured by the 6-min walk distance (6MWD) test, compared between the intervention and control arms at the end of a 6-weeks pulmonary rehabilitation program. The 6MWD test was repeated twice, with a 30-min interval between tests and the greatest distance of the two tests was recorded in accordance with the European Society guidelines.²² The 6MWD tests were performed on room air for patients who were not on long term oxygen therapy. For patients on long term oxygen therapy, the 6MWD tests were performed at their baseline oxygen setting. Secondary outcomes were changes from baseline in respiratory symptoms (COPD Assessment test –CAT), lung function and mood (Hospital Anxiety Depression Scale - HADS) compared between the two study arms at completion of the pulmonary rehabilitation program. The lung function tests were performed with a handheld spirometer. As lung function testing is an effort dependent test, three consecutive tests were conducted using the spirometer and the greatest value of the lung function parameters were recorded. In this pilot study where feasibility was the primary focus, treatment completion rates, patient tolerance and adverse events rates were also assessed.

Statistical methods

As this is a pilot study with the primary goal of assessing feasibility, a sample size of 22 patients was selected as a sufficient number to obtain information that would facilitate planning of a future study. The results were analyzed by intention-to-treat. Our primary analysis compares the change in 6MWD distance after 6 weeks of outpatient pulmonary rehabilitation using HFO with usual care, by t test, and we will report the mean difference between the two interventions with 95% confidence limits.

Results

Study participants

A total of 22 patients were randomized and 18 patients completed the study (Figure 1). The 22^nd patient’s trial participation was stopped prematurely due to COVID-19 restrictions at the pandemic onset. Patient baseline characteristics are shown in Table 2. The patient group was all male, current or ex-smokers, and the main ethnicity was Chinese. Two patients in the HFO arm and one patient in the usual care arm required long term oxygen supplementation at baseline.

Table 2.

Patient baseline characteristics.

	PR with HFO group (n = 11)	Usual care PR group (n = 11)
Age, years	75.6 ± 11.7	72.1 ± 6.2
Gender, M (%)	11 (100.0)	11 (100.0)
Race
Chinese, n (%)	10 (90.9)	6 (54.5)
Malay, n (%)	1 (9.1)	1 (9.1)
Indian, n (%)	0 (0.0)	1 (9.1)
Others, n (%)	0 (0.0)	3 (27.3)
Smoking status
Non-smoker, n (%)	0 (0.0)	0 (0.0)
Current smoker, n (%)	6 (54.5)	3 (27.3)
Ex-smoker, n (%)	5 (45.5)	8 (72.7)
Body-mass index, kg/m²	21.7 ± 4.1	20.1 ± 3.4
6MWD, m	348.5 ± 103.0	274.9 ± 113.5
CAT Score	11.7 ± 8.7	7.7 ± 1.8
FEV₁, L	1.4 ± 1.0	0.9 ± 0.1
GOLD stage
I, n (%)	1 (9.1)	0 (0.0)
II, n (%)	6 (54.5)	3 (27.3)
III, n (%)	2 (18.2)	6 (54.5)
IV, n (%)	2 (18.2)	2 (18.2)
HADS (anxiety)	3.18 ± 4.02	1.73 ± 1.42
HADS (depression)	5.55 ± 4.70	3.27 ± 3.80
Baseline O₂ support, n (%)	2 (18.2)	1 (9.1)
Index admission LOS, days	5.3 ± 2.8	3.5 ± 0.7
Comorbidities
Hypertension, n (%)	8 (72.7)	4 (36.4)
Hyperlipidaemia, n (%)	8 (72.7)	6 (54.5)
Diabetes, n (%)	0 (0.0)	3 (27.3)
Heart disease, n (%)	4 (36.4)	3 (27.3)
Stroke, n (%)	1 (9.1)	0 (0.0)
Chronic renal failure, n (%)	1 (9.1)	0 (0.0)
Depression, n (%)	0 (0.0)	0 (0.0)
Psychiatric disorder, n (%)	0 (0.0)	0 (0.0)

Footnotes: CAT: chronic obstructive pulmonary disease assessment test; FEV1: forced expiratory volume in 1 s; GOLD: global obstructive lung disease; HADS: hospital anxiety and depression scale; HFO: high flow oxygen; LOS, hospital length of stay; O₂: oxygen; PR, pulmonary rehabilitation; 6MWD: 6-min walk distance.

Outcomes

For the primary outcome of 6MWD, the HFO arm achieved a greater improvement in 6MWD than the usual care arm, with the difference (unadjusted) between the two arms being 30 m (95% CI:−23 m to 84 m), although this was not statistically significant (Table 3). A minimally clinically significant difference in 6MWD for COPD patients is 30 m, based on broad consensus. For the secondary outcomes of CAT, HADS and FEV1, the difference in their change from pre- to post- rehabilitation program between the two study arms at program completion are shown in Table 4. The findings were not statistically significant, likely due to the small patient numbers.

Table 3.

6MWD (m) at baseline, week six and changes between week six and at baseline.

	PR with HFO group (n = 11)	Usual care PR group (n = 11)	p-value
6MWD at baseline	348.5 (103.0)	274.9 (113.5)	0.127
6MWD at week 6 ^a	283.1 (138.7)	347.4 (101.3)	0.272
6MWD difference between week 6 and baseline ^a	26.4 (50.2)	−4.1 (55.3)	0.244

Footnotes: HFO: high flow oxygen; PR: pulmonary rehabilitation; 6MWD: 6-min walk distance.

^aSample size for PR with HFO Group and Usual Care PR Group are 8 and 10 respectively due to unavailability of post 6-weeks 6MWD data.

Table 4.

Secondary outcome changes between baseline and Week six at pulmonary rehabilitation program completion.

	PR with HFO group (n = 8)	Usual care PR group (n = 10)	p-value
CAT score ^a	−0.25 (5.68)	0.50 (8.94)	0.840
FEV ₁ , litres ^a	−0.28 (0.73)	0.02 (0.17)	0.220
HADS (anxiety) ^a	1.25 (5.01)	1.4 (2.60)	0.935
HADS (depression) ^a	1.63 (3.30)	−0.10 (3.96)	0.338

Footnotes: CAT: chronic obstructive pulmonary disease assessment test; FEV1: forced expiratory volume in 1 s; HADS: hospital anxiety and depression scale; HFO: high flow oxygen; LOS: hospital length of stay; O2: oxygen; PR: pulmonary rehabilitation; 6MWD: 6-min walk distance.

^aunadjusted values.

Patient acceptability and safety of HFO intervention

One patient in the usual care was hospitalized for a surgical condition, and this was unrelated to study conduct. All 18 patients who completed the trial were compliant to their respective treatment arms, defined by attending ≥75% of exercise sessions. HFO was found to be well tolerated by the patients, with no adverse events associated with its implementation.

Discussion

This study confirmed the feasibility of HFO application during exercise training in early pulmonary rehabilitation for COPD patients recently discharged from a hospitalization for COPD exacerbation. HFO was shown to be well tolerated and highly acceptable to patients, with no associated adverse events. Patients in the HFO arm achieved a greater improvement in 6MWD than the usual care arm, with the unadjusted difference between the two arms being 30 m (95% CI: −23 m to 84 m). While this result is not statistically significant due to small patient numbers, it is promising, given that the minimally clinically significant difference in 6MWD for COPD patients is 30 m, based on broad consensus. We believe this preliminary finding provides strong justification for further research and validation in a larger study.

To the best of our knowledge, there is currently no data on the use of HFO during exercise training in an early pulmonary rehabilitation program for COPD patients post-hospitalization for COPD exacerbation, and its impact on pulmonary rehabilitation outcomes in this patient cohort.

We reviewed the literature and found three recently published randomized controlled trials that studied the use of HFO during pulmonary rehabilitation of stable COPD patients, and who did not have any recent COPD exacerbation.

Vitacca et al conducted a recent multicenter randomized controlled trial in Italy comparing the use of HFO to oxygen (delivered via a Venturi mask) during exercise training in COPD patients.²³ The trial inclusion criteria was highly selective as it only included stable advanced COPD patients with chronic respiratory failure requiring long-term oxygen therapy and who did not have any recent COPD exacerbation. The study results demonstrated that the HFO arm achieved a greater improvement in 6-min walk distance (6MWD) after 20 exercise sessions but not in the primary outcome of endurance time. In a similar study, Chihara et al studied 32 stable advanced COPD patients on long-term oxygen therapy in an RCT comparing HFO to oxygen delivered via usual cannula at flow rate of 6 L/min during a 4-weeks inpatient pulmonary rehabilitation program.²⁴ The study demonstrated greater improvement in 6MWD in the HFO arm, but not in the duration of the constant-load exercise test. Regardless, these two studies had limited generalizability as their 1-month, five sessions/week, intensive pulmonary rehabilitation program was conducted inpatient, a high-resource care model that would not be suitable for many healthcare systems including Singapore’s.

In another RCT of 32 moderate to severe stable COPD patients, Fang et al compared the effect of HFO to conventional nasal oxygen supplementation on peripheral muscle oxygenation and hemodynamics during paddling exercise.²⁵ The HFO arm achieved better hemodynamics than the nasal oxygen arm as demonstrated by a higher cardiac index (CI) which was the primary outcome. Another trial in Argentina (ClinicalTrials.gov ID NCT02973945), with an intended 60 COPD patients, comparing the use of HFO against 40% oxygen supplementation via Venturi mask during pulmonary rehabilitation is underway. To highlight, the control arms in the Fang et al and Argentina trials did not reflect usual care in pulmonary rehabilitation, which would limit the interpretation and clinical translation of the trials’ findings. In the study by Fang et al, the control arm was administered nasal oxygen regardless of baseline oxygen status. In the Argentina trial, all the participants in the control arm were administered 40% oxygen through a Venturi mask. Cardiac output, which was the primary outcome in the study by Fang et al, was also not a measure of exercise capacity.

Therefore, these four trials would not inform the effect of HFO on pulmonary rehabilitation outcomes among COPD patients post-hospitalization due to COPD exacerbation, notwithstanding early pulmonary rehabilitation is recommended by the GOLD guidelines¹² for all COPD patients after hospital discharge for an acute exacerbation. In addition, this cohort of patients tend to be frailer and more breathless, posing significant challenges to exercise training in the post-recovery period.

A small study by Prieur et al of 19 moderate to severe COPD patients reported that HFO did not improve exercise tolerance in patients recovering from acute COPD exacerbation.²⁶ However, the confidence interval of the constant work rate exercise test outcome was very wide, likely due to a small number of patients. In addition, this study’s methodology comprised only of a single cycling test session with HFO, with no acclimatization to the very high HFO flow rate applied (at 60 L/min), which possibly accounted for the discomfort reported by half of the patients and likely affected patient tolerance of the intervention. In contrast, our study protocol was designed to allow gradual titration of HFO settings for patient acclimatisation, which likely accounted for the high patient tolerance and acceptability seen.

In another RCT of 44 COPD patients, Tung et al evaluated the use of HFO when pulmonary rehabilitation was commenced during hospitalization for COPD exacerbation.²⁷ However, the methodology was unclear as no details were provided on how oxygen was titrated with HFO or usual care, patient treatment adherence was not reported, and the study’s statistical analysis has been questioned.²⁸

As our study was a pilot RCT, its primary limitation was its small patient numbers. Consequently, confidence intervals of the results were wide, and imbalances in baseline characteristics between the two study arms were observed (length of hospital stay, COPD severity, mean FEV1). Therefore, we were unable to draw any definitive conclusions. Nevertheless, we believe the study had adequately addressed its primary aim of determining feasibility on the use of HFO in early pulmonary rehabilitation post-hospitalization for COPD exacerbation, justifying the conduct of a RCT with larger sample size to confirm the benefits of HFO. Based on the sample standard deviation (SD) of the 6MWD change from baseline in our pilot study of 55 m, we would require a sample size of 128 patients in the next study, with provision for a 15% dropout rate. We were also unable to study patient population subgroups in this pilot study, such as those with chronic hypercapneic respiratory failure in the absence of baseline blood gases, which we hope to further evaluate in a larger, adequately powered study that permits stratification. Another study limitation was the inability to blind patients to the study interventions. However, a placebo cannula and tubing was not applied to the usual care arm for the following reasons: firstly, the study’s aim was a real-world comparison with usual care where patients would not be wearing any device during exercise; secondly, breathing through any tubing increases resistance, which could worsen breathlessness during exercise for an already breathless patient- this might worsen adherence and lead to the result in the usual care arm being worse than the actual usual setting. Finally, the primary outcome of 6MWD was an objective measure test conducted independently of the interventions. Hence, we did not expect a significant influence on the measurement of the primary outcome due to the non-use of placebo in the control (usual care) arm.

The clinical significance of our study is its potential to address a longstanding challenge in COPD pulmonary rehabilitation and change rehabilitation practice. Having demonstrated feasibility in this pilot study, we hope to further this research in a larger, adequately powered RCT to ascertain the benefits of HFO use during exercise training in early pulmonary rehabilitation for COPD patients post-hospitalization for COPD exacerbation.

Footnotes

Ethical Statement

Acknowledgements

We would like to thank our patients for their time and contribution to the study, staff from Changi General Hospital Clinical Trials & Research Unit with special thanks to Nur Shameerah, Geraldine Lim, Carmen Kam. Tan Pei Ting, Department of Physiotherapy, Department of Respiratory and Critical Care Medicine for their support in this trial.

Author contributions

Yingjuan Mok, Hang Siang Wong were involved in the study design, implementation, data analysis and manuscript preparation. Keith Wong was involved in the study design, data analysis and manuscript reviews. Jing Wen Foong, Amanda Soh and Shi Hua Tan were involved in the study design, conduct of the pulmonary rehabilitation program and manuscript reviews. Bryan Choo was involved in data analysis and manuscript reviews.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Changi Hospital Research Fund [CHF2018.04-P].

Informed Consent

Written informed consent was obtained from all participants.

Trial Registration

The trial is registered at ClinicalTrials.gov: NCT03940040.

ORCID iD

Yingjuan Mok

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High flow nasal oxygen versus usual care in improving pulmonary rehabilitation outcomes of chronic obstructive pulmonary disease patients after an exacerbation - a pilot randomized controlled trial

Abstract

Introduction

Methods

Results

Conclusion

Keywords

Introduction

Methods

Study design and subject recruitment

Study interventions, randomisation and masking

Pulmonary rehabilitation program

High flow nasal oxygen

Control

Outcomes

Statistical methods

Results

Study participants

Outcomes

Patient acceptability and safety of HFO intervention

Discussion

Footnotes

Ethical Statement

Acknowledgements

Author contributions

Declaration of Conflicting Interests

Funding

Informed Consent

Trial Registration

ORCID iD

References