Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomised controlled trial

doi:10.1016/S2213-2600(18)30289-3

The Lancet Respiratory Medicine

Volume 6, Issue 10, October 2018, Pages 759-770

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https://doi.org/10.1016/S2213-2600(18)30289-3 Get rights and content

Summary

Background

In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia.

Methods

AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the King's Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed.

Findings

Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p<0·0001), and scores in breathlessness and activity (mean difference 8·6 [95% CI 4·7 to 12·5]; p<0·0001) and chest symptoms (7·6 [1·9 to 13·2]; p=0·009) subdomains. However, the effect on the psychological subdomain was not significant (2·4 [–0·6 to 5·5]; p=0·12). The most common adverse events were upper respiratory tract infections (three in the oxygen group and one in the no-treatment group). Five serious adverse events, including two deaths (one in each group) occurred, but none were considered to be related to treatment.

Interpretation

Ambulatory oxygen seemed to be associated with improved HRQOL in patients with interstitial lung disease with isolated exertional hypoxia and could be an effective intervention in this patient group, who have few therapeutic options. However, further studies are needed to confirm this finding.

Funding

UK National Institute for Health Research.

Introduction

Fibrotic interstitial lung diseases are associated with substantially reduced health-related quality of life (HRQOL) and survival. In idiopathic pulmonary fibrosis (IPF), the most common and deadly of the idiopathic interstitial pneumonias,¹ antifibrotic therapy lessens decline in lung function but does not improve HRQOL.2, 3 As pulmonary fibrosis advances, exertional breathlessness is triggered by simple activities of daily life. Breathlessness is the strongest determinant of HRQOL in patients with fibrotic interstitial lung disease,4, 5 and can be difficult to manage, both for patients and for their informal carers.

Oxygen desaturation contributes to exercise intolerance in patients with interstitial lung disease. However, few data exist for supplemental ambulatory oxygen use in this group, with most studies done in patients with chronic obstructive pulmonary disease (COPD). Although improved survival was noted in patients with COPD and resting hypoxaemia who used supplemental oxygen for at least 15 h per day compared with patients who used nocturnal supplemental oxygen only,⁶ ambulatory oxygen had no effect on mortality or HRQOL in patients with COPD and isolated exertional desaturation.⁷ However, interstitial lung diseases are characterised by more frequent and severe exercise-induced desaturation than is COPD,⁸ suggesting that studies specifically of interstitial lung disease are needed.⁵ The paucity of data for ambulatory oxygen in interstitial lung diseases means that there is no guidance on use of the treatment in national and international guidelines.1, 9, 10

Research in context

Evidence before this study

The 2011 idiopathic pulmonary fibrosis guidelines did not provide guidance on the use of supplemental oxygen in patients with isolated exertional hypoxia, and although the 2015 British Thoracic Society guidelines state that ambulatory oxygen should not be routinely offered to patients who are not hypoxic at rest, no specific reference to patients with interstitial lung disease was made (except to mention the possible benefit of ambulatory oxygen for individual patients with severe exertional breathlessness). We searched PubMed with the terms “ambulatory oxygen”, “supplemental oxygen”, “portable oxygen”, “exercise/exertion”, and “interstitial lung disease” for systematic reviews and randomised controlled trials published up to March 1, 2018, with no language restrictions. Neither a 2016 Cochrane review nor a systematic review published in early 2017 had shown evidence of a consistent effect of supplemental oxygen during short bursts of exercise on dyspnoea. However, many of the reviewed studies were deemed low quality because they were retrospective or uncontrolled, or included only small numbers of patients. Two controlled studies published subsequently showed significant benefits of high-flow oxygen compared with placebo air on endurance time and breathlessness during a cycle ergometer test in the laboratory setting. However, the acute effects of high-flow supplemental oxygen on exercise in a laboratory setting might not translate to benefits of ambulatory oxygen in day-to-day life. We identified no studies of the effect of ambulatory oxygen on quality of life in patients with interstitial lung disease.

Added value of this study

Our findings suggests that, compared with no treatment, ambulatory oxygen improves day-to-day health-related quality of life (HRQOL) in patients with isolated exertional hypoxia. Although further studies are needed to confirm this finding, as the first prospective assessment of ambulatory oxygen in the daily lives of patients with interstitial lung diseases, this study represents a crucial stepping stone towards the delineation of guidelines specific to interstitial lung disease.

Implications of all the available evidence

To our knowledge, the AmbOx study is the first prospective randomised controlled trial of the effect of ambulatory oxygen on HRQOL in patients with interstitial lung disease. The results of this trial, if supported by further studies, will enable delineation of specific guidelines for ambulatory oxygen use in interstitial lung disease. However, further larger studies are required to confirm this finding, to enable further understanding of the predictors of long-term uptake of ambulatory oxygen, and to assess whether long-term ambulatory oxygen use is associated with improvements in survival.

Both a systematic review¹¹ and a Cochrane review¹² of studies specifically assessing use of supplemental oxygen during exercise tests in patients with interstitial lung disease were inconclusive, although two studies13, 14 published subsequently showed significant benefits of high-flow oxygen compared with placebo air in terms of performance and breathlessness during cycle endurance testing in the laboratory. However, immediate benefits in the test setting do not necessarily translate into improvements in day-to-day HRQOL. Drawbacks of ambulatory oxygen include the weight of the portable oxygen equipment, logistic difficulties of replenishment, travel limitations, and the psychological and social burden of the intervention on patients and their caregivers.15, 16 The effects of high-flow oxygen, used in a pulmonary rehabilitation setting, on exercise performance and breathlessness are under investigation.¹⁷ We investigated whether portable ambulatory oxygen was associated with improved HRQOL compared with no intervention in patients with fibrotic interstitial lung disease.

Section snippets

Study design and participants

AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled trial done at three interstitial lung disease centres (Royal Brompton Hospital, Aintree University Hospital, and North Bristol NHS Trust) in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest (transcutaneous arterial oxygen saturation ≥94% on room air) but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening

Results

Between Aug 26, 2014, and Sept 22, 2016, 269 patients were screened. 84 of these screened patients were randomly assigned between Sept 10, 2014, and Oct 5, 2016, 41 to ambulatory oxygen first and 43 to no oxygen first (figure 2). One patient withdrew a few hours after being randomly assigned and did not complete the 6MWT. 37 patients assigned to oxygen first and 39 assigned to no oxygen first completed the trial (figure 2). Baseline characteristics were well balanced between groups (table 1).

Discussion

To our knowledge, this study is the first randomised controlled trial of the effects of ambulatory oxygen on day-to-day HRQOL in patients with fibrotic interstitial lung disease. Ambulatory oxygen was associated with improvements in total K-BILD scores compared with no treatment. Ambulatory oxygen use was also associated with significant improvements in scores on the breathlessness and activity and chest symptoms subdomains of K-BILD, in UCSDSOBQ scores, and in global assessments of change in

References (43)

O Nishiyama et al.
Health-related quality of life in patients with idiopathic pulmonary fibrosis. What is the main contributing factor?
Respir Med
(2005)
JJ Swigris et al.
Health-related quality of life among patients with idiopathic pulmonary fibrosis
Chest
(2005)
BA Graney et al.
Looking ahead and behind at supplemental oxygen: a qualitative study of patients with pulmonary fibrosis
Heart Lung
(2017)
EG Eakin et al.
Validation of a new dyspnea measure: the UCSD Shortness of Breath Questionnaire. University of California, San Diego
Chest
(1998)
PW Jones et al.
The St George's Respiratory Questionnaire
Respir Med
(1991)
I Bjelland et al.
The validity of the Hospital Anxiety and Depression Scale. An updated literature review
J Psychosom Res
(2002)
AS Patel et al.
The minimal important difference of the King's Brief Interstitial Lung Disease Questionnaire (K-BILD) and forced vital capacity in interstitial lung disease
Respir Med
(2013)
Y Wang et al.
Intermittent hypoxia simulating obstructive sleep apnea causes pulmonary inflammation and activates the Nrf2/HO-1 pathway
Exp Ther Med
(2017)
AP Abernethy et al.
Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial
Lancet
(2010)
G Raghu et al.
An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management
Am J Respir Crit Care Med
(2011)

TE King et al.

A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis

N Engl J Med

(2014)

L Richeldi et al.

Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis

N Engl J Med

(2014)

Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group

Ann Intern Med

(1980)

RK Albert et al.

A randomized trial of long-term oxygen for COPD with moderate desaturation

N Engl J Med

(2016)

JP Du Plessis et al.

Exertional hypoxemia is more severe in fibrotic interstitial lung disease than in COPD

Respirology

(2018)

M Hardinge et al.

Guideline update: the British Thoracic Society Guidelines on home oxygen use in adults

Thorax

(2015)

HE Jo et al.

Diagnosis and management of idiopathic pulmonary fibrosis: Thoracic Society of Australia and New Zealand and Lung Foundation Australia position statements summary

Med J Aust

(2018)

EC Bell et al.

Oxygen therapy for interstitial lung disease: a systematic review

Eur Respir Rev

(2017)

C Sharp et al.

Ambulatory and short-burst oxygen for interstitial lung disease

Cochrane Database Syst Rev

(2016)

MR Schaeffer et al.

Effects of hyperoxia on dyspnoea and exercise endurance in fibrotic interstitial lung disease

Eur Respir J

(2017)

LM Dowman et al.

Greater endurance capacity and improved dyspnoea with acute oxygen supplementation in idiopathic pulmonary fibrosis patients without resting hypoxaemia

Respirology

(2017)

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Because new evidence had accumulated, we formulated the “Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition).” While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress.
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Determinar los efectos de un programa de rehabilitación pulmonar en la capacidad funcional y calidad de vida relacionada con la salud en pacientes con enfermedad pulmonar intersticial difusa con y sin uso de oxígeno domiciliario.
Estudio cuasiexperimental en el que todos los pacientes, por conveniencia, firmaron el consentimiento informado. Se dividieron en 2 grupos: con y sin oxígeno domiciliario, evaluados antes y después de la rehabilitación pulmonar en variables clínicas, capacidad funcional y calidad de vida.
Se vincularon 31 pacientes que se dividieron en 2 grupos con oxígeno y sin oxígeno domiciliario, la mayor participación fue de hombres, edad promedio de 56 años, y se obtuvo que la mayoría había acudido a urgencias. Ambos grupos presentaron mejorías en la distancia recorrida y en la ansiedad: valor-p < 0,05. La calidad de vida presentó mejorías significativas por dominio en ambos grupos: valor-p < 0,05.
El grupo de EPID con uso de oxígeno domiciliario presenta mayores cambios en la capacidad funcional. En cuanto a la calidad de vida el grupo EPID sin uso de oxígeno domiciliario mejoró significativamente el dominio actividades del SGRQ, y el grupo EPID con uso de oxígeno domiciliario presentó mejoría en los dominios síntomas e impacto.
Diffuse Interstitial Pulmonary Disease is a group of diseases that cause a disorder of aerobic capacity and quality of life, also cause a high rate of morbidity and mortality for this population. The use of home oxygen therapy has benefits that have not yet been compared in pulmonary rehabilitation programs.
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Quasi-experimental study, all patients for convenience who signed the informed consent. They were divided into two groups: with and without home oxygen, evaluated before and after pulmonary rehabilitation in clinical variables, functional capacity and quality of life.
31 patients were linked, divided into two groups with oxygen and without home oxygen, the largest participation was men, average age 56 years, it was obtained that the majority had gone to the emergency room. Both groups presented improvements in the distance traveled and in anxiety p-value ≤ 0.05. The quality of life presented significant improvements by domain in both groups p-value ≤ 0.05.
The ILD group with home oxygen use presents greater changes in functional capacity. Regarding quality of life, the ILD group without home oxygen use significantly improved the activities domain of the SGRQ and the ILD group with home oxygen use showed improvement in the symptoms and impact domains.
A retrospective study of crossover ambulatory oxygen walk testing in patients with fibrotic lung disease
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Fibrotic interstitial lung disease (ILD) comprises a group of lung conditions that are often progressive, debilitating, and life-shortening. Ambulatory oxygen therapy (AOT) is regularly prescribed to manage symptoms in patients with fibrotic ILD. In our institution, the decision to prescribe portable oxygen is made on the basis of oxygen improving exercise capacity, measured with the single-blinded, crossover ambulatory oxygen walk test (AOWT). This study aimed to investigate the characteristics and survival rates of patients with fibrotic ILD who have either positive or negative results on the AOWT.
This retrospective cohort study compared the data from 99 patients with fibrotic ILD who underwent the AOWT. These patients were classified into two groups based on whether they showed improvement in the AOWT with supplemental oxygen (positive group) or no improvement (negative group). Patient demographics for both groups were compared to determine any significant differences. A multivariate Cox proportional hazards model was used to analyze the survival rates of the two groups.
Out of the 99 patients, 71 were in the positive group. We compared the measured characteristics between the positive and negative groups and found no significant difference, wherein the adjusted hazard ratio was 1.33 (95% confidence interval 0.69–2.60, P = 0.40).
The AOWT can be used to rationalize AOT, but there was no significant difference in baseline characteristics or survival rates between patients whose performance was improved or not in the AOWT.
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^†: These authors contributed equally

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ArticlesEffect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomised controlled trial

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design and participants

Results

Discussion

Respir Med

Chest

Heart Lung

Chest

Respir Med

J Psychosom Res

Respir Med

Exp Ther Med

Lancet

An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management

Am J Respir Crit Care Med

A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis

N Engl J Med

Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis

N Engl J Med

Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group

Ann Intern Med

A randomized trial of long-term oxygen for COPD with moderate desaturation

N Engl J Med

Exertional hypoxemia is more severe in fibrotic interstitial lung disease than in COPD

Respirology

Guideline update: the British Thoracic Society Guidelines on home oxygen use in adults

Thorax

Diagnosis and management of idiopathic pulmonary fibrosis: Thoracic Society of Australia and New Zealand and Lung Foundation Australia position statements summary

Med J Aust

Oxygen therapy for interstitial lung disease: a systematic review

Eur Respir Rev

Ambulatory and short-burst oxygen for interstitial lung disease

Cochrane Database Syst Rev

Effects of hyperoxia on dyspnoea and exercise endurance in fibrotic interstitial lung disease

Eur Respir J

Greater endurance capacity and improved dyspnoea with acute oxygen supplementation in idiopathic pulmonary fibrosis patients without resting hypoxaemia

Respirology

Articles
Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomised controlled trial