Supplemental oxygen for symptomatic relief in people with serious respiratory illness: a systematic review and meta-analysis

Zainab Ahmadi; Natasha E Smallwood; Anne-Marie Russell; Ravijyot Saggu; Lorena Romero; Anne E Holland; Magnus Ekström

doi:10.1183/16000617.0025-2024

. 2025 Mar 5;34(175):240025. doi: 10.1183/16000617.0025-2024

Supplemental oxygen for symptomatic relief in people with serious respiratory illness: a systematic review and meta-analysis

Zainab Ahmadi ^1,^✉, Natasha E Smallwood ^2,³, Anne-Marie Russell ^4,⁵, Ravijyot Saggu ⁶, Lorena Romero ⁷, Anne E Holland ^3,^8,⁹, Magnus Ekström ¹

PMCID: PMC11880903 PMID: 40044186

Abstract

Background

People with serious respiratory illness frequently have a high symptom burden and may be prescribed supplemental oxygen therapy with the aims of reducing the severity of breathlessness and improving health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to assess the effectiveness of oxygen therapy versus no oxygen on 1) breathlessness, 2) HRQoL and 3) adverse events.

Methods

A comprehensive search was performed in Embase, Medline and the Cochrane Central Register of Controlled Trials for randomised controlled trials published prior to June 2022. We used the Cochrane Risk of Bias Tool for appraising the studies and conducted random-effect meta-analyses when appropriate. We pooled effects recorded on different scales as standardised mean differences (SMDs) with 95% confidence intervals. Lower SMDs indicated decreased breathlessness or HRQoL. We assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.

Results

We found that supplemental oxygen (compared with sham air or no treatment), reduced breathlessness intensity during laboratory exercise testing (SMD −0.75, 95% CI −1.23–−0.28, 12 randomised control trials (RCTs), 245 participants), but had no shown effect on breathlessness measured in daily life (SMD −0.08, 95% CI −0.41–0.26, one RCT, 213 participants) or HRQoL (SMD −0.06, −0.17–0.05, 14 RCTs, 1062 participants). Few or no adverse events related to oxygen therapy were reported. For all the outcomes, the certainty of evidence was low.

Conclusions

Oxygen improved exertional breathlessness in laboratory-based exercise studies but was not shown to improve breathlessness or HRQoL in daily life.

Shareable abstract

This review found no evidence that supplemental oxygen provides symptomatic relief of breathlessness in a daily-life setting for people with serious respiratory illness. https://bit.ly/3DIRcv1

Introduction

People with serious respiratory illness frequently experience burdensome respiratory symptoms including chronic breathlessness [1–3]. Breathlessness is a major cause of physical limitations and reduced quality of life [4]. Fear of exertional breathlessness may cause a vicious cycle of deconditioning, increased symptom burden and social isolation, leading to negative health outcomes [5, 6]. Chronic breathlessness is associated with a high utilisation of healthcare resources [7]. Although the impact of chronic breathlessness is increasingly recognised, there are limited options for its optimal treatment and management. The cornerstone of breathlessness management remains nonpharmacological interventions such as breathing techniques, fan therapy, pulmonary rehabilitation and regular physical activity and exercise [8, 9]. Pharmacological treatments for chronic breathlessness, including low-dose opioids and oxygen therapy, have shown efficacy under controlled conditions in laboratory settings, whereas in real-life settings the effects have been inconsistent or absent [10–12].

Supplemental oxygen therapy may be prescribed in clinical practice to treat moderate hypoxaemia and/or exertional desaturation [13]. However, a Cochrane review in 2016 reported limited, low-quality evidence regarding any effectiveness of oxygen therapy to improve breathlessness or health-related quality of life (HRQoL) in daily life [10]. Qualitative studies provide an insight into the lived experience of oxygen therapy with reported benefits such as symptom relief, increased self-confidence and a sense of security, but also concerns such as fears of social stigma, dependence on oxygen therapy and adverse effects [14]. Furthermore, oxygen therapy, after hospitalisation, is the second-largest cost driver for patients with COPD in high-income countries [15]. Whilst oxygen therapy is expensive, eligible individuals who do not use domiciliary oxygen therapy may experience increased costs due to increased hospitalisations, reduced quality of life and lower productivity [16].

There is currently limited guidance concerning the net clinical benefit of oxygen therapy in terms of relief from breathlessness and improving quality of life in people with serious respiratory illness. As resources are limited, there is a need to maximise health outcomes at a societal level and provide evidence-based treatments that are clinically meaningful.

The aim of this systemic review and meta-analysis was to synthesise current evidence regarding the effectiveness of oxygen therapy versus no oxygen on breathlessness, HRQoL and adverse effects in people with serious respiratory illness not requiring long-term oxygen therapy.

Methods

This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines [17]. This review was conducted as part of the 2024 European Respiratory Society (ERS) clinical practice guideline on symptom management for adults with serious respiratory illness [9].

The protocol was developed a priori but was not published, due to the confidentiality requirements of the ERS clinical practice guideline development process. Instead, the protocol was submitted to the European Respiratory Review editorial office in April 2023 to be held in confidence and made available to reviewers. The protocol can be found in the online supplement (appendix 1).

Search strategy for identification of studies

Literature searches were designed and conducted by a medical librarian (L.R.). Embase, Medline and the Cochrane Central Register of Controlled Trials databases were searched from inception to 6 June 2022. Where a high-quality, relevant systematic review was previously published, it was utilised to increase the efficiency of the guideline development process. If a previous systematic review was judged to cover the search scope up to that point, searches were conducted from the last search date of that systematic review to identify any additional clinical trials published afterwards. The AMSTAR-2 checklist was used to appraise the quality of the existing systematic reviews [18]. Full search strategies for the databases are provided in the online supplement (appendix 2). Citations retrieved from searches were uploaded into Covidence (www.covidence.org), where duplicates were removed before titles and abstracts were screened independently by two reviewers (Z.A. and M.E.), with any conflicts resolved through discussion. Any additional relevant articles identified by the authors or sourced from the reference list of identified studies were also included. Full texts of potentially eligible studies were retrieved and independently assessed against the inclusion/exclusion criteria by two reviewers (Z.A. and M.E.) with conflicts resolved by discussion. The screening process was documented using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) study flow diagram [17].

Inclusion and exclusion criteria

We included studies that met the following inclusion criteria: 1) study design: randomised controlled trial, including both parallel and crossover trials; 2) participants: adults ≥18 years of age with serious respiratory illness; 3) intervention: supplemental oxygen, delivered either at rest or during exercise by a noninvasive method (mask or nasal prongs) in any dose; 4) comparator: no oxygen therapy including sham treatment (with air) or usual care.

Serious respiratory illness was defined as a condition that carries a high risk of mortality, negatively impacts quality of life and daily function, and/or is burdensome in symptoms, treatments or caregiver stress [19]. In this systematic review, we included asthma, bronchiectasis, COPD, cystic fibrosis, interstitial lung diseases, other obstructive lung diseases and pulmonary arterial hypertension. For mixed studies, we included studies with at least 80% of participants having nonmalignant lung disease.

Studies were excluded if study participants were treated with supplemental oxygen at the time of randomisation or met the criteria for long-term oxygen or ambulatory oxygen therapy [13]. We did not include trials of short-burst oxygen therapy delivered only before or after exertion. Studies were also excluded if the comparator was other types of oxygen therapy, such as using high-flow nasal cannulae, or if intervention data were not provided or could not be calculated.

Outcomes

The critical outcome of interest was breathlessness measured on any validated scale in a laboratory setting or in a domiciliary setting. However, exercise measures obtained before and after an intervention must have been recorded at iso-workload. In the domiciliary setting, daily life measures included measures of breathlessness “right now”, such as those recorded in symptom diaries. Important outcomes included in this review were HRQoL, using any validated scale, and adverse events, defined according to the investigators’ definition.

Quality assessments

The Cochrane Risk of Bias Tool version 1 was used for assessing risk of bias at the study level to be consistent with an identified previous systematic review [20]. External ERS methodologists assessed the risk of bias in terms of allocation sequence generation, allocation concealment, blinding of participants and outcome assessors, handling of missing data, selective outcome reporting and other threats to the validity of studies, in line with recommendations provided in the Cochrane Handbook for Systematic Reviews of Interventions [20]. We carried forward the appraisal of the other studies as reported in the original reviews [10, 21]. The unit of analysis was the individual trial participant, with no cluster randomised control trials (RCTs) included in the analysis. We used the I² statistic to measure heterogeneity. The certainty of the body of evidence per outcome was evaluated following Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology [22], taking into consideration the risk of bias, imprecision, inconsistency, indirectness and publication bias. The certainty was categorised as “high”, “moderate”, “low” or “very low” according to GRADE [22]. Any disagreements or uncertainties were resolved through discussion within the authors.

Data extraction, synthesis and analysis

Data were extracted using a standardised data extraction template by the ERS methodologists. Information concerning year of publication, title, study design, sample size, participant characteristics, interventions and outcome measures were extracted. We performed meta-analyses using Review Manager software version 5.4. We analysed outcomes on different scales as standardised mean differences (SMDs) for continuous data or odds ratios for dichotomous data (adverse events) with corresponding 95% confidence intervals using random-effects models. SMD estimates were interpreted using thresholds for effect sizes according to Cohen [23] as follows: SMD≈0.20: small effect; SMD≈0.50: moderate effect; SMD≈0.80: large effect. Prediction intervals were calculated to reflect the range of observed effect sizes across studies. We compared within-patient effects from both periods of crossover trials. Meta-analyses included post scores only. For studies for which post scores were not available, we reported changes from baseline scores separately. For breathlessness during exercise, we used only scores measured at a similar time-point in both groups (iso-scores). For studies evaluating different oxygen doses, we included only the lowest dose in the analysis. Breathlessness was analysed separately 1) during exertion at iso-time in a laboratory setting and 2) “right now” in daily life at home. If meta-analysis was not performed, a narrative summary of the outcome was conducted.

Results

A total of 1710 records were identified by the search for systematic reviews, of which 21 were screened in full text. Two relevant systematic reviews were identified [10, 21], which included 31 reports on 26 eligible studies. The search for additional RCTs published from July 2016 onwards yielded 2530 records. After removal of duplicates, 1967 records were screened, 17 were selected for full-text review and 11 eligible studies were identified. Overall, a total of 42 reports describing 37 studies were included in the present systematic review (figure 1).

Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram.

Characteristics of included studies

Of the 37 included studies (table 1), 25 were laboratory-based exercise studies (including 796 participants) and 12 were studies of daily-life measures at home (1696 participants). The study populations comprised adults diagnosed with COPD (28 studies), interstitial lung disease (seven studies) or people with various other respiratory illnesses (two studies) including pulmonary arterial hypertension. One study included people in a palliative care setting [24].

TABLE 1.

Characteristics of the included 42 reports on 37 studies in the systematic review

First author, [ref.], year	Country	Study design	Study setting	Population	Sample size (intervention/comparator)	% Women	Age (years)	Intervention	Comparator	Included outcomes
Abernethy [24] 2010^#	Australia, USA, England	Parallel	At-home daily life measures	COPD	239 (120/119)	32	Mean±sd: 73.2±9.9	Domiciliary oxygen (2 L·min⁻¹) delivered continuously from concentrator by a nasal cannula, at least 15 h·day⁻¹ for 7 days	Room air (2 L min⁻¹) delivered continuously from concentrator by a nasal cannula; at least 15 h·day⁻¹ for 7 days	Breathlessness: NRS intensity “right now” Quality of life: McGill Quality of Life Questionnaire score Adverse events: data collected on day 3 via telephone contact
Alison [36] 2019	Australia	Parallel	Laboratory-based exercise measures	COPD	111 (58/53)	45	Mean±sd: 69±7	Oxygen (5 L·min⁻¹) via nasal prongs during exercise training with treadmill and cycle exercise for 8 weeks	Air (5 L·min⁻¹) via nasal prongs during exercise training with treadmill and cycle exercise for 8 weeks	Breathlessness: Dyspnoea-12 Questionnaire Quality of life: CRQ total score, CRQ subdomains
Arizono [43] 2020	Japan	Crossover	Laboratory-based exercise measures	IPF	72	33	Median (IQR): 66.5 (63.5–67.5)	Oxygen (4 L·min⁻¹) given via a nasal cannula during a symptom-limited CPET	Air (4 L·min⁻¹) via a nasal cannula during a symptom-limited CPET	Breathlessness: mBorg intensity at iso-time
Bruni [44] 2012^#	Italy	Crossover	Laboratory-based exercise measures	COPD, “hyperinflators”	10	0	Mean±sd: 68.1±6.6	Oxygen (F_IO₂ 0.5) delivered through a mouthpiece during a symptom-limited CPET	Room air delivered through a mouthpiece during a symptom-limited cycle CPET	Breathlessness: mBorg intensity at iso-time
Bruni [44] 2012^#	Italy	Crossover	Laboratory-based exercise measures	COPD, “non hyperinflators”	6	0	Mean±sd: 68.1±6.6	Oxygen (F_IO₂ 0.5) delivered through a mouthpiece during a symptom-limited CPET	Room air delivered through a mouthpiece during a symptom-limited cycle CPET	Breathlessness: mBorg intensity at iso-time
Davidson [56] 1988^#	England	Crossover	Laboratory-based exercise measures	COPD	17	NA	Mean±sem: 64.4±2.1	Oxygen (2, 4 or 6 L·min⁻¹) delivered through a nasal cannula or valve during 6MWT, cycle ergometer test or endurance shuttle walk test	Compressed air (4 L·min⁻¹ delivered through a nasal cannula or valve during 6MWT, cycle ergometer test or endurance shuttle walk test	Breathlessness: 10 cm VAS intensity at end of exercise
Dean [45] 1992^#	USA	Crossover	Laboratory-based exercise measures	COPD	12	0	Not reported	Oxygen (F_IO₂ 0.40) delivered through a mouthpiece during a symptom-limited CPET	Compressed air (F_IO₂ 0.21) delivered through a mouthpiece during a symptom-limited CPET	Breathlessness: mBorg intensity at iso-time
Dipla [46] 2021	Greece	Crossover	Laboratory-based exercise measures	IPF	13	15.4	Mean±sd: 63.4±9.6	Oxygen (F_IO₂ 0.40) via a Venturi mask during a symptom-limited CPET	Medical air (F_IO₂ 0.21) via a Venturi mask during a symptom-limited CPET	Breathlessness: 0–10 scale at iso-time
Eaton [25] 2002^#	New Zealand	Crossover	At-home daily life measures	COPD	50	30	Mean±sd: 57.1±9.3	Oxygen (4 L·min⁻¹) given via a nasal cannula during 6MWT after a 6-week domiciliary programme	Compressed air given via a nasal cannula during 6MWT after a 6-week domiciliary programme	Breathlessness: mBorg intensity at end of exercise Quality of life: CRQ total score, CRQ subdomains, SF-36 Adverse events: number of dropouts
Emtner [37] 2003^#	USA	Parallel	Laboratory-based exercise measures	COPD	15	16.7	Mean±sd: 67±10	Oxygen (F_IO₂ 0.30) via mouthpiece during a symptom-limited CPET after 7 weeks of training	Compressed air via mouthpiece during a symptom-limited CPET after 7 weeks of training	Breathlessness: mBorg intensity at end of exercise Quality of life: CRQ total score, CRQ subdomains, SF-36 Adverse events: number of dropouts
Emtner [37] 2003^#	USA	Parallel	Laboratory-based exercise measures	COPD	14	20	Mean±sd: 66±7	Oxygen (F_IO₂0.30) via mouthpiece during a symptom-limited CPET after 7 weeks of training	Compressed air via mouthpiece during a symptom-limited CPET after 7 weeks of training	Breathlessness: mBorg intensity at end of exercise Quality of life: CRQ total score, CRQ subdomains, SF-36 Adverse effects: number of dropouts
Eves [47] 2006^#	Canada	Crossover	Laboratory-based exercise measures	COPD	10	0	Mean±sd: 65±11	Oxygen (F_IO₂ 0.40) via mouthpiece during a symptom-limited CPET	Medical air via mouthpiece during a symptom-limited CPET	Breathlessness: mBorg intensity at iso-time
Harris-Eze [57] 1994^¶	Canada	Crossover	Laboratory-based exercise measures	ILD	7	14.3	49	Oxygen (F_IO₂ 0.60) during incremental exercise test	Room air during incremental exercise test	Breathlessness: mBorg intensity at end of exercise
Jolly [58] 2001^#	Argentina	Crossover	Laboratory-based exercise measures	COPD, “nondesaturators”	9	0	Mean±sem: 70±3	Oxygen (3, 6, 9 or 12 L·min⁻¹) given via a nasal cannula during 6MWT	Compressed air (3, 6, 9 or 12 L·min⁻¹) given via a nasal cannula during 6MWT	Breathlessness: mBorg intensity at end of exercise
Jolly [58] 2001^#	Argentina	Crossover	Laboratory-based exercise measures	COPD, “desaturators”	11	9.1%	Mean±sem: 67±2	Oxygen (3, 6, 9 or 12 L·min⁻¹) given via a nasal cannula during 6MWT	Compressed air (3, 6, 9 or 12 L·min⁻¹) given via a nasal cannula during 6MWT	Breathlessness: mBorg intensity at end-exercise
Khor [26] 2020	Australia	Parallel	At home daily life measures	ILD	30 (15 / 15)	26.7	Mean±sd: O₂ 70.3±7.8 Air 73.3±8.4	Oxygen via portable concentrators during 6MWT after 12 weeks exercise	Air via portable concentrators during 6MWT after 12 weeks exercise	Breathlessness: UCSD SOBQ Quality of life: HADS, SGRQ total, SGRQ subdomains
Knebel [59] 2000^#	USA	Crossover	Laboratory-based exercise measures	COPD	33	37%	Mean±sd: 47±7	Oxygen (4 L·min⁻¹) delivered by a nasal cannula during 6MWT	Compressed air (4 L·min⁻¹) delivered by a nasal cannula during 6MWT	Breathlessness: 10 cm VAS intensity Adverse events: number of dropouts
Lacasse [64] 2020	Canada, Portugal, Spain, France	Parallel	At-home daily life measures	COPD	243 (123/120)	35 (34.1/35.8)	Mean±sd: O₂ 69±8 Air 69±8	Nocturnal oxygen (1–4 L·min⁻¹) delivered from concentrator by a nasal cannula	Ambient air delivered from concentrator by a nasal cannula	Quality of life: SGRQ total, SGRQ subdomains, SF-36
Laude [60] 2006^#	UK	Crossover	Laboratory-based exercise measures	COPD	82 (78/76)	NA	Mean age (range): 69.7 (46–84)	Oxygen (0.28) via face mask and an inspiratory demand valve during endurance shuttle walking test	Medical air via a face mask and an inspiratory demand valve during endurance shuttle walking test	Breathlessness: mBorg intensity at end of exercise Adverse events: number of dropouts
Lellouche [55] 2016	Canada	Crossover	Laboratory-based exercise measures	COPD	15	19	Mean±sd: 69±9	Oxygen (2 L·min⁻¹) delivered through a nasal cannula during endurance shuttle walk tests	Air (2 L·min⁻¹) delivered through a nasal cannula during endurance shuttle walk tests	Breathlessness: mBorg intensity (only reported in supplement, no longer available)
Ltottrg [28] 2016	USA	Parallel	At-home daily life measures	COPD	738 (368/370)	26.6 (28/25)	Mean±sd: O₂ 68.3±7.5 Air 69.3±7.4	Supplemental oxygen (2 L·min⁻¹) delivered continuously from concentrator by a nasal cannula, prescribed either 24 h·day⁻¹ or only during exercise and sleep	No supplemental oxygen	Quality of life: SGRQ total, SGRQ subdomains, SF-36
McDonald [29] 1995^#	Australia	Crossover	At-home daily life measures	COPD	33	7.69	Mean±sd: 73±6	Oxygen (4 L·min⁻¹) via a nasal cannula from portable gas cylinders after 6-week period of training	Compressed air (4 L·min⁻¹) via a nasal cannula from portable gas cylinders after 6-week period of training	Breathlessness: mBorg intensity at end of exercise Quality of life: CRQ subdomains
Miki [48] 2012^#	Japan	Crossover	Laboratory-based exercise measures	COPD	35	0	Mean±sd: 70.4±5.7	Oxygen (F_IO₂ 0.24) via face mask during a symptom-limited CPET	Compressed air (F_IO₂ 0.21) via face mask during a symptom-limited CPET	Breathlessness: mBorg intensity at iso-time
Moore [30] 2011^#	Australia	Parallel	At-home daily life measures	COPD	143	31	Mean±sd: 71.8±9.8	Domiciliary oxygen (6 L·min⁻¹) delivered through nasal prongs during 6MWT after 12 weeks exercise	Air (6 L·min⁻¹) delivered through nasal prongs during 6MWT after 12 weeks exercise	Breathlessness: CRQ dyspnoea domain Quality of life: CRQ total score, CRQ subdomains Adverse events: number of dropouts
Nishiyama [61] 2013^¶	Japan	Crossover	Laboratory-based exercise measures	IPF	20	20	Mean: 73.5	Ambulatory oxygen (4 L·min⁻¹) via a nasal cannula during 6MWT	Ambulatory air (4 L·min⁻¹) via a nasal cannula during 6MWT	Breathlessness: mBorg intensity at end of exercise
Nonoyama [31] 2007^#	Canada	Crossover	At-home daily life measures	COPD	38	37	Mean±sd: 69±10	Ambulatory oxygen (1–3 L·min⁻¹) delivered through nasal prongs after 2 weeks exercise	Medical air (2 L·min⁻¹) delivered through nasal prongs after 2 weeks exercise	Breathlessness: mBorg intensity at end of exercise and CRQ dyspnoea domain Quality of life: CRQ subdomains, SGRQ total Adverse events: number of dropouts
O’Donnell [49] 1997^#	Canada	Crossover	Laboratory-based exercise measures	COPD	11	36.4	Mean±sem: 68±2	Oxygen (F_IO₂ 0.60) given through a mouthpiece during a symptom-limited CPET	Room air (F_IO₂ 0.21) through a mouthpiece during a symptom-limited CPET	Breathlessness: mBorg intensity at iso-time
Oliveira [62] 2012^#	UK	Crossover	Laboratory-based exercise measures	COPD, “desaturators”	8	0	Mean±sd: 66.7±7.9	Hyperoxia (F_IO₂ 0.40) through a face mask connected to a low-resistance Douglas bag during incremental cycle testing	Normoxia (F_IO₂ 0.21) through a face mask connected to a low-resistance Douglas bag during incremental cycle testing	Breathlessness: mBorg intensity at end of exercise
Oliveira [62] 2012^#	UK	Crossover	Lab-based exercise measures	COPD, “non-desaturators”	12	0	Mean±sd: 60.3±5.9	Hyperoxia (F_IO₂ 0.40) through a face mask connected to a low-resistance Douglas bag during incremental cycle testing	Normoxia (F_IO₂ 0.21) through a face mask connected to a low-resistance Douglas bag during incremental cycle testing	Breathlessness: mBorg intensity at end-exercise
Ringbaek [32] 2013^#	Denmark	Parallel	At-home daily life measures	COPD	45	46.7	Mean±sd: 69.0±8.7	Ambulatory oxygen (2 L·min⁻¹) delivered through a portable oxygen concentrator during exercise for up to 33 weeks, measured during an endurance shuttle walk test	Room air without use of a sham concentrator, measured during an endurance shuttle walk test	Breathlessness: mBorg intensity at end of exercise after 7 weeks of training Quality of life: SGRQ total Adverse events: COPD exacerbations, all hospital admissions, deaths at study end
Rooyackers [38] 1997^#	Netherlands	Parallel	Laboratory-based exercise measures	COPD	12	16.7	Mean±sd: 59±13	Oxygen (4 L·min⁻¹) given during 6MWT, incremental and symptom-limited CPET after 10 weeks exercise	Room air given during 6MWT, incremental and symptom-limited CPET after 10 weeks exercise	Breathlessness: mBorg intensity at end of exercise Quality of life: CRQ total, CRQ subdomains
Rooyackers [38] 1997^#	Netherlands	Parallel	Laboratory-based exercise measures	COPD	12	16.7	Mean±sd: 63±5	Oxygen (4 L·min⁻¹) given during 6MWT, incremental and symptom-limited CPET after 10 weeks exercise	Room air given during 6MWT, incremental and symptom-limited CPET after 10 weeks exercise	Breathlessness: mBorg intensity at end of exercise Quality of life: CRQ total, CRQ subdomains
Schaeffer [50] 2017	Canada	Crossover	Laboratory-based exercise measures	ILD	20	NA	Mean±sd: 66±9	Oxygen (F_IO₂ 60%) during a symptom-limited CPET	Room air (F_IO₂ 21%) during a symptom-limited CPET	Breathlessness: mBorg intensity at iso-time
Scorsone [51] 2010^#	Italy	Parallel	Laboratory-based exercise measures	COPD	20	30	Mean±sd: O₂ 67±9 Air 68±7	Oxygen (F_IO₂ 0.4) delivered by mouthpiece during a symptom-limited CPET after from an 8-week training programme	Air delivered by mouthpiece during a symptom-limited CPET after from an 8-week training programme	Breathlessness: mBorg intensity at iso-time
Somfay [52] 2001^#	USA	Crossover	Laboratory-based exercise measures	COPD	10	40	Mean±sd: 67±7	Oxygen (30%, 50%, 75% or 100%) delivered by mouthpiece during a symptom-limited CPET	Compressed air delivered by mouthpiece during a symptom-limited CPET	Breathlessness: mBorg intensity at iso-time
Spielmanns[41] 2015^#	Germany	Parallel	Laboratory-based exercise measures	COPD	85 (42/43)	NA	Mean±sd: O₂ 65±8.7 Air 64±8.4	Oxygen (4 L·min⁻¹) via a nasal cannula during 6MWT after 24 weeks training	Compressed air (4 L·min⁻¹) via a nasal cannula during 6MWT after 24 weeks training	Quality of life: SF-36 subdomains Adverse events
Swinburn [53] 1991^¶	UK	Crossover	Laboratory-based exercise measures	COPD	10	40	56.3	Oxygen (4 L·min⁻¹) via face mask at rest	Air (4 L·min⁻¹) via face mask at rest	Breathlessness: VAS (1–100) at iso-time
Ulrich [33] 2015	Switzerland	Crossover	At-home daily life measures	PH	23	15	Median (IQR): 66 (56–71)	Nocturnal oxygen therapy (NOT) via a nasal cannula (3 L·min⁻¹) from concentrator Acetazolamide: 2×250 mg·day⁻¹ with breakfast and dinner	Sham NOT via nasal cannulae (3 L·min⁻¹) from concentrator Placebo: capsule with breakfast and dinner	Quality of life: SF-36 subdomains
Ulrich [34] 2019	Switzerland	Crossover	At-home daily life measures	PAH/CTEPH	30	66.7	Mean±sd: 60±15	Domiciliary oxygen therapy (3 L·min⁻¹) via a nasal cannula from a concentrator during 6MWT	Ambient air via domiciliary oxygen therapy (3 L·min⁻¹) via a nasal cannula from a concentrator during 6MWT	Breathlessness: mBorg intensity at end of exercise Quality of life: SF-36 subdomains
Visca [35] 2018	UK	Crossover	At-home daily life measures	ILD	84 (41/43)	31 (37/26)	Mean±sd: 67.9±10.4	Oxygen (titrated up to 6 L·min⁻¹) via a nasal cannula from cylinders after 2 weeks training	Air via nasal cannulae from cylinders after 2 weeks training	Breathlessness: UCSD SOBQ Quality of life: K-BILD, SGRQ
Voduc [54] 2010^#	Canada	Crossover	Lab-based exercise measures	COPD	24	30	Mean±sd: 65.9±6.6	Oxygen (F_IO₂ 0.5) via a face mask during a symptom-limited CPET	Room air via a face mask during a symptom-limited CPET	Breathlessness: mBorg intensity at iso-time Adverse events: number of dropouts
Woodcock [63] 1981^#	UK	Crossover	Laboratory-based exercise measures	COPD	10	10	Mean (range): 62 (43–70)	Oxygen (4 L·min⁻¹) during treadmill test and 6MWT	Compressed air (4 L·min⁻¹) during treadmill test and 6MWT	Breathlessness: 10cm VAS intensity at end of exercise

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^#: Data from Ekström et al. [10] and supplemented from original study as necessary. ^¶: Data from Bell et al. [21] and supplemented from original study as necessary. 6MWT: 6-min walk test; CPET: cardiopulmonary exercise test; CRQ: Chronic Respiratory Questionnaire; CTEPH: chronic thromboembolic pulmonary hypertension; F_IO₂: inspiratory oxygen fraction; HADS: Hospital Anxiety and Depression Scale; ILD: interstitial lung disease; IPF: idiopathic pulmonary fibrosis; IQR: interquartile range; K-BILD: King's Brief Interstitial Lung Disease Questionnaire; LTOTTRG: Long-Term Oxygen Treatment Trial Research Group; mBORG: the modified 0–10 Borg category ratio (Borg CR10) scale; NA: not available; NRS: Numerical Rating Scale; PAH: pulmonary arterial hypertension; PH: pulmonary hypertension; SF-36: 36-item Short-Form Health Survey; SGRQ: St George's Respiratory Questionnaire; UCSD SOBQ: University of California, San Diego Shortness of Breath Questionnaire; VAS: Visual Analogue Scale.

Intervention characteristics

Most included studies provided continuous oxygen during exercise testing, mainly symptom-limited cardiopulmonary cycle exercise tests, 6-min walk tests, endurance shuttle walk tests or incremental shuttle walk tests. 11 studies provided domiciliary oxygen during daily life activities [24–35], including nocturnal oxygen administration [24, 27, 28, 33]. There were a variety of administration devices (nasal cannulae, mouthpieces/valves or masks), oxygen flow rates, concentrations used, as well as in the durations and frequency of oxygen administered (table 1). Most of the studies compared oxygen versus air, which was delivered using the same noninvasive method in both groups. The comparator was mainly room air (table 1). Most of the studies compared supplemental oxygen to room air administered via nasal cannulae or masks, whilst some studies compared with compressed air. The one domiciliary trial on breathlessness in daily life compared a continuous flow rate of 2 L·min⁻¹ of double-blind oxygen or air, prescribed to be used at least 15 h·day⁻¹ for 1 week [24].

Outcome characteristics

Breathlessness was measured using a variety of different validated scales, predominantly the modified 0–10 Borg category ratio scale, which was used in 21 studies. For HRQoL, eight studies [25, 29, 30, 36–38] used the Chronic Respiratory Disease Questionnaire [39], six studies [26–28, 31, 32, 35] used St. George's Respiratory Questionnaire (SGRQ) [40], three studies [33, 34, 41] used the 36-item Short-Form Health Survey [42] and one study used the McGill Quality of Life Questionnaire [24]. The way in which the scales were administered was inconsistent and over varying durations ranging from baseline, days to 33 weeks.

Risk of bias

We have provided risk of bias judgements for each study in table 2. Methods were poorly reported in most of the included studies. For individual RCTs, we assessed risk of bias as low for more than half of the studies in the domains of blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective reporting.

TABLE 2.

Risk of bias assessment for randomised studies on PICO (population, intervention, comparison and outcome) framework: should supplemental oxygen be used to reduce symptoms in people with serious illness related to lung disease?

First author, [ref.], year	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Other bias
Abernethy [24] 2010^#	Low	Low	Low	Low	Unclear	Low	Low
Alison [36] 2019	Low	Low	Low	Low	Low	Low	Low
Arizono [43] 2020	Low	Low	Low	High	Low	Low	Low
Bruni [44] 2012^#	Unclear	Unclear	Low	Low	Low	Low	Unclear
Bruni [44] 2012^#	Unclear	Unclear	Low	Low	Low	Low	Unclear
Davidson [56] 1988^#	Unclear	Unclear	Unclear	Unclear	Unclear	Unclear	Unclear
Dean [45] 1992^#	Unclear	Unclear	Low	Low	Low	Low	Unclear
Dipla [46] 2021	Low	Unclear	Low	High	Low	Low	Low
Eaton [25] 2002^#	Unclear	Unclear	Low	Low	Low	Low	Unclear
Emtner [37] 2003^#	Low	Low	Low	Low	Low	Low	Low
Emtner [37] 2003^#	Low	Low	Low	Low	Low	Low	Low
Eves [47] 2006^#	Unclear	Unclear	Low	Low	Low	Low	Unclear
Harris-Eze [57] 1994^¶	Low	Low	Low	Unclear	Low	Low	Unclear
Jolly [58] 2001^#	Unclear	High	Low	Low	Low	Low	Unclear
Jolly [58] 2001^#	Unclear	High	Low	Low	Low	Low	Unclear
Khor [26] 2020	Low	Low	Low	Low	Low	Low	Low
Knebel [59] 2000^#	Unclear	Unclear	Low	Low	Unclear	Low	Unclear
Lacasse [64] 2020	Low	Unclear	Low	Low	Low	Low	Low
Laude [60] 2006^#	Unclear	Unclear	Low	Unclear	Unclear	Low	Unclear
Lellouche [55] 2016	Unclear	High	Low	Low	Low	Low	Low
LTOTTRG [28] 2016	Unclear	High	High	High	High	Low	High
McDonald [29] 1995^#	Unclear	Unclear	Low	Low	Unclear	Unclear	Unclear
Miki [48] 2012^#	Unclear	Unclear	Unclear	Unclear	Unclear	Low	Unclear
Moore [30] 2011^#	Unclear	Unclear	Low	Low	Low	Low	Unclear
Nishiyama [61] 2013^¶	Low	Low	Low	Low	Low	Low	Low
Nonoyama [31] 2007^#	Low	Low	Low	Low	Unclear	Low	Unclear
O’Donnell [49] 1997^#	Unclear	Unclear	Low	Low	Low	Low	Unclear
Oliveira [62] 2012^#	Unclear	Unclear	Low	Low	Low	Low	Low
Oliveira [62] 2012^#	Unclear	Unclear	Low	Low	Low	Low	Low
Ringbaek [32] 2013^#	Low	Low	High	High	High	Low	Low
Rooyackers [38] 1997^#	Unclear	Unclear	High	High	Low	Low	Unclear
Rooyackers [38] 1997^#	Unclear	Unclear	High	High	Low	Low	Unclear
Scorsone [51] 2010^#	Unclear	Unclear	Low	Low	Low	Low	Unclear
Schaeffer [50] 2017	Unclear	High	High	High	Low	Low	Low
Somfay [52] 2001^#	Unclear	Unclear	High	High	Low	Low	Unclear
Spielmanns [41] 2015^#	Low	Low	Unclear	Unclear	High	Low	Low
Swinburn [53] 1991^¶	Low	Low	Low	Low	Low	Low	Unclear
Ulrich [33] 2015	Low	Low	Low	Low	Low	Low	Low
Ulrich [34] 2019	Low	Unclear	Unclear	Unclear	Low	Low	Low
Visca [35] 2018	Low	Low	Low	High	Low	Low	Low
Voduc [54] 2010^#	Unclear	Unclear	Low	Low	High	Low	Unclear
Woodcock [63] 1981^#	Unclear	Unclear	Low	Low	Low	Low	Low

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^#: Risk of bias assessment from Ekström et al. [10]. ^¶: Risk of bias assessment from Bell et al. [21]. New studies were appraised using Cochrane Risk of Bias v1.0 in order to be comparable with the systematic reviews we were updating. We carried forward the appraisal of the other studies as reported in the original reviews (Ekström et al. [10] and Bell et al. [21]). LTOTTRG: Long-Term Oxygen Treatment Trial Research Group.

Although all studies were described as randomised, there was insufficient information on allocation procedures and we assessed the risk of bias as mostly unclear regarding random sequence generation, allocation concealment and other biases. We assessed risk of bias as high for some studies mainly in the domains of blinding of participants and personnel and blinding of outcome assessment.

Effects of interventions

Critical outcome: breathlessness

A meta-analysis of 12 laboratory-based exercise studies (n=245 participants) [43–54] measuring breathlessness at iso-time demonstrated a moderate and statistically significant treatment effect in favour of supplemental oxygen (SMD −0.75, 95% CI −1.23–−0.28, I²=66%) (figure 2).

Forest plot for the critical outcome of breathlessness measured at iso-time. HK: Hoffman–Kringle; SMD: standardised mean difference.

In the one trial in a daily life setting, oxygen (compared with air) had no statistically significant effect on breathlessness “right now” over 1 week (SMD −0.08, 95% CI −0.41–0.26, one RCT, 213 participants) [24].

Some studies were not included in the meta-analysis of breathlessness, as analysis of the exertion level could not be standardised due to insufficient reports [35, 55] or that breathlessness was measured at end of exercise and not iso-time [24–26, 29–32, 34, 36–38, 41, 56–63]. In the analysis, lower scores indicated reduced breathlessness intensity.

Important outcome: HRQoL

A meta-analysis of 14 studies (n=1062 participants) [25–28, 31–36, 38, 41] showed that oxygen (compared with sham air or no treatment) had no statistically or clinically significant treatment effect on the important outcome of HRQoL (SMD −0.06, −0.17–0.05, I²=0%, figure 3). In the analysis, lower scores indicated reduced HRQoL intensity.

Forest plot for the important outcome of health-related quality of life measured with a validated tool. LTOTTRG: Long-Term Oxygen Treatment Trial Research Group; HK: Hoffman–Kringle; SMD: standardised mean difference.

Important outcome: adverse events

Adverse events were evaluated by nine studies [24, 25, 30, 32, 37, 41, 54, 59, 60], but assessments and reporting varied markedly, and meta-analysis could therefore not be performed. The reported rate of adverse events varied from none up to 29% of patients receiving the intervention. In several studies, none of the participants withdrew from the study for adverse events and no other adverse events were reported [25, 37, 60]. In the study by Abernethy et al. [24] (n=239), serious adverse events were rare in the domiciliary setting, with no clinically meaningful differences between groups (oxygen versus air), as follows: moderate to extreme drowsiness: 31/65 (47%) versus 36/70 (51%); moderate to extreme nasal irritation: 19/65 (29%) versus 25/70 (35%); moderate to extremely troublesome nosebleeds: 2/65 (3%) versus 2/70 (3%); moderate to extreme anxiousness: 17/65 (26%) versus 28/70 (40%). Moore et al. [30] (n=143) reported in the oxygen group that one participant was deceased and one became unwell. In Ringbaek et al. [32] (n=45), at study end (33 weeks), the mean number of adverse events did not differ significantly between treatment groups in terms of acute COPD exacerbations (p=0.30) or number of participants with hospital admission or dropout (p=0.59). Spielmanns et al. [41] (n=85) reported that five participants discontinued owing to comorbidities in the oxygen group and seven discontinued because of comorbidities in the air group. Adverse events were reported to be unrelated to the intervention in two studies [54, 59]. In Knebel et al. [59] (n=31), two participants were unable to complete all of the walks in the study because of unrelated problems (fever and migraine headache). In Voduc et al. [54] (n=15), three participants developed COPD exacerbations and one developed worsening of arthritis that limited exercise and thus was excluded.

Certainty of evidence

The certainty of evidence for all included outcomes was assessed using the GRADE criteria and was found to be generally of “low” quality (supplementary table S1). For the important outcome of HRQoL, the certainty of evidence was graded as moderate. Reasons for downgrading certainty of evidence included a high proportion of studies with unclear or high risk of bias on one or more domains (selection bias, performance bias, detection bias and attrition bias), a high proportion of studies with small sample sizes and imprecision of evidence. A serious risk of bias was noted by studies that reported varying estimations of the rate of adverse events from none to up to 29% of patients receiving the intervention. This could be explained by inconsistent reporting of the type and severity of adverse events.

Discussion

Main findings

When administered in a laboratory-based setting, supplemental oxygen therapy (compared with air) led to a statistically and clinically significant improvement in exertional breathlessness measured at iso-time or iso-load, with a moderate effect size. There were no statistically significant effects of oxygen therapy on breathlessness or HRQoL when measured in the daily life (home) setting. However, only one study of breathlessness in home treatment could be included and the quality of evidence was considered low because of imprecision in the effect estimates for the critical and important outcomes. Given the marked heterogeneity in study populations, interventions and duration of therapy, trials measuring outcomes during laboratory exercise tests or in daily life were not combined. The findings from our systematic review and meta-analysis are in line with previous systematic reviews [64, 65].

Adverse events were uncommon in trials of oxygen during laboratory exercise testing but were prevalent in the daily life setting. However, similar rates of adverse events were reported in the oxygen and the comparison group (air or no treatment). In the daily life setting, the adverse events were mainly local symptoms, such dry nose or throat and nosebleeds, and some related to falls over oxygen equipment. A small number of patients required hospitalisation for adverse events.

Mechanisms of effect for oxygen in relieving breathlessness

Mechanisms underpinning the potential effect of oxygen on exertional breathlessness are complex and involve decreased hypoxaemia during exertion, delayed and decreased anaerobic metabolism, lactate accumulation, improved dynamic ventilatory mechanics, delayed increase in ventilatory drive, and critical inspiratory constraints [5, 49, 66, 67]. Furthermore, reduced fatigue in peripheral muscles and possible cardiovascular effects of supplemental oxygen may contribute to breathlessness relief [5, 68]. Airflow to the face and upper airways may relieve breathlessness through increased afferent feedback and reduced imbalance between ventilatory demand and perceived ventilatory work and thus the level of breathlessness [69, 70]. Better understanding of the underlying mechanisms involved in breathlessness regulation might help identify which patients are likely to gain the most benefit from oxygen therapy and under which conditions.

Our finding of no clear treatment effect of oxygen on breathlessness or HRQoL in the daily life setting should be interpreted with caution as it might reflect several relevant factors including 1) insufficient adherence to the therapy in home settings due to issues such as adverse events and perceived limitation and stigma (feelings of shame) related to the oxygen equipment and treatment [71], 2) oxygen flow rates may have been insufficient in some patients in the domiciliary studies, and 3) breathlessness was not assessed in relation to a standardised level of exertion (such as iso-workload). Therefore, a patient who improved from the oxygen therapy may have become able to do more (such as walking faster or for a longer time) before being limited by the symptom [72]. As most patients are not breathless at rest but become symptomatic at varying levels of exertion, failure to account for the level of exertion needed to elicit the patient's breathlessness could lead to false-negative findings [72].

Clinical implementations and practical application

Based on the present findings, supplemental oxygen therapy is not recommended as the initial treatment for patients with breathlessness. Management of underlying disease(s) should be optimised and nonpharmacological interventions offered [73–75]. In the absence of robust evidence of benefit from oxygen therapy, treatment decisions should be informed by patients’ perspectives on the benefits and costs.

In adults with serious respiratory illness, the ERS task force suggest that supplemental oxygen therapy might be offered on a case-by-case basis for selected patients with severe persisting breathlessness who are likely to use the treatment safely [9]. Despite the absence of supportive (positive) evidence in the domiciliary setting, as there was supportive evidence in laboratory (more standardised) trials, the ERS task force decided not to recommend against supplemental oxygen, but instead made a conditional recommendation for either offering or not offering supplemental oxygen to this population [9]. The effect on breathlessness should be measured using validated scales at a standardised level of symptom stimulus (such as iso-load during a standardised exercise testing). The findings of this review are consistent with those of recent American Thoracic Society guidelines giving a conditional recommendation for ambulatory oxygen use in patients with advanced lung disease with severe exertional hypoxaemia [13], despite limited evidence to support the use of oxygen to relieve breathlessness and improve quality of life.

There is limited information on how to screen for potential responders to oxygen treatment during exercise [76–78]. A trial of oxygen versus air during exertion, preferably using a constant work rate test, may provide clinically useful information to identify people more likely to respond to oxygen treatment during exercise [76–78]. Training with oxygen might be useful in the setting of pulmonary rehabilitation where training intensity is limited by breathlessness [36, 79]. An individually tailored approach is recommended. The oxygen equipment and flow rate need to be adapted to the patient's needs and preferences to best support mobility and quality of life [80] and optimally use the lowest concentration of oxygen necessary to achieve a clinical improvement in symptoms. When supplemental oxygen is being considered to try to reduce exertional breathlessness, clear communication and shared decision making are required. This should include the patient's goals, willingness and ability to use the treatment correctly, potential harms and the broader impact on the patient's life. Safety education should be provided to avoid tripping and falls, and to decrease risk of fires and burn injuries by not smoking and to avoid activities around an open flame or sparks [81]. Other clinicians and the patients’ informal caregivers may also require education and support regarding the use of oxygen for symptom management in people with nonmalignant, serious respiratory illness. The need for supplemental oxygen therapy, effectiveness and harms should be monitored and appropriately managed during the treatment, and the oxygen therapy should be discontinued when there is no perceived net clinical benefit [13].

Methodological considerations

Several methodological limitations are worthy of consideration. Limitations of this systematic review and meta-analysis mainly reflect the heterogeneity and methodological limitations of the currently available body of literature. Evidence regarding supplemental oxygen therapy in the home setting is scarce and only one trial was included for breathlessness in daily life [24]. Moreover, for valid measurement, activity-related breathlessness should be assessed at a standardised level of exertion. For HRQoL, SGRQ is more sensitive to changes with interventions than other instruments and assigns health utility values. Perhaps there was a missed opportunity within the studies for health economic evaluation – albeit the study populations were generally small. The majority of evidence has focused predominantly on people with COPD; therefore, it is challenging to extrapolate the true impact of oxygen on symptoms in people with other nonmalignant serious respiratory illnesses. Studies report significant differences in home oxygen needs and experiences across patients with different lung diseases, lifestyles and oxygen requirements [13, 82]. To improve clinical care, there is a need to identify distinct clinical phenotypes which may predict treatment efficacy. A single study included people at the very end of life [24], who are usually highly symptomatic and who may be prescribed oxygen for symptom palliation [83]. Therefore, it is not clear if oxygen is beneficial for symptomatic relief in people with more severe breathlessness occurring at rest. Thus, we cannot rule out a possible effect of supplemental oxygen in an end-of-life palliative care setting. We acknowledge that conducting research in this vulnerable group of patients poses multiple ethical and logistical challenges.

Conclusions

Given the limited evidence base, oxygen therapy might be offered to selected patients with severe persisting breathlessness, rather than large cohorts, to enable assessment of benefit and acceptability and using the lowest concentration possible to achieve clinical and symptomatic improvement. There is limited data regarding any benefits that oxygen therapy may have on symptoms in people with illnesses other than COPD and in people at the very end of life.

Points for clinical practice

In people with serious respiratory illness, oxygen administered during standardised exercise testing in a laboratory setting improved exertional breathlessness; however, domiciliary oxygen therapy was not shown to improve breathlessness experienced in daily life (only one study included) or HRQoL (14 studies).
Adverse events related to oxygen therapy were not prevalent during exercise testing. However, in the domiciliary setting, side-effects were common and included local symptoms from upper airways.
Based on the results of the current systematic review and meta-analysis, performed during the development of the recent ERS guidelines, the ERS clinical practice guideline on symptom management for adults with serious respiratory illness made a conditional recommendation for either administering or not administering supplemental oxygen to reduce symptoms in people with serious respiratory illness.

Supplementary material

Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

Supplementary material ERR-0025-2024.SUPPLEMENT^{(428.1KB, pdf)}

Acknowledgements

We acknowledge the contribution of Jeanette Boyd from the European Lung Foundation and extend our sincere thanks to the consumer partners who participated in the ERS Symptom Management Guideline Task Force: Phil Collis, Tessa Jelen, John Solheim and Chantal Vandendungen. The authors thank Thomy Tonia (ERS senior methodologist) for help with the meta-analysis for this review.

Provenance: Commissioned article, peer reviewed.

Previous articles in this series: No. 1: Smallwood NE, Pascoe A, Wijsenbeek M, et al. Opioids for the palliation of symptoms in people with serious respiratory illness: a systematic review and meta-analysis. Eur Respir Rev 2024; 33: 230265. No. 2: Burge AT, Gadowski AM, Romero L, et al. The effect of graded exercise therapy on fatigue in people with serious respiratory illness: a systematic review. Eur Respir Rev 2024; 33: 240027. No. 3: Burge AT, Gadowski AM, Jones A, et al. Breathing techniques to reduce symptoms in people with serious respiratory illness: a systematic review. Eur Respir Rev 2024; 33: 240012. No. 4: Spathis A, Reilly CC, Bausewein C, et al. Multicomponent services for symptoms in serious respiratory illness: a systematic review and meta-analysis. Eur Respir Rev 2024; 33: 240054.

Number 5 in the Series “Symptom management for advanced lung disease” Edited by Anne E. Holland, Magnus Ekström and Natasha E. Smallwood

Author contributions: All authors contributed significantly to manuscript writing and critical revisions for intellectually important content. All authors have read and approved the final version of the manuscript.

Conflict of Interest: Z. Ahmadi has nothing to disclose. N.E. Smallwood reports grants from NHMRC, MRFF, Cancer Council Australia, Fisher & Paykel Healthcare (FPH), Windermere Foundation, Lung Foundation Australia, Lord Mayor's Foundation Melbourne and Bethlehem Griffiths Foundation; consultancy fees from The Limbic and Orchard Consulting; payment or honoraria for lectures, presentations, manuscript writing or educational events from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, FPH and Health Ed; support for attending meetings from Chiesi and Boehringer Ingelheim; leadership roles with the Thoracic Society of Australia and New Zealand (Board Director and past state president), Victorian Doctors’ Program (Board Director), and European Respiratory Society (Co-chair guidelines committee); and receipt of equipment, materials, drugs, medical writing, gifts or other services from FPH. A-M. Russell reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, Hoffman La Roche, Irish Lung Fibrosis Association and Aerogen; and support for attending meetings from Boehringer Ingelheim, Hoffman La Roche and Interstitial Lung Disease Interdisciplinary Network. R. Saggu reports payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK and TEVA; and participation on a data safety monitoring board or advisory board with GSK, Sanofi, AstraZeneca and TEVA. L. Romero has nothing to disclose. A.E. Holland reports non-financial support from BOC Australia and Air Liquide Australia for oxygen therapy clinical trials, outside the submitted work. M. Ekström has nothing to disclose.

Support statement: M. Ekström was supported by an unrestricted grant from the Swedish Research Council (Dnr: 2019–02081). Z. Ahmadi was supported by grants from Swedish Heart-Lung foundation (ID: 20200295) and Swedish government funding of clinical research (ALF). Funding information for this article has been deposited with the Crossref Funder Registry.

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PERMALINK

Supplemental oxygen for symptomatic relief in people with serious respiratory illness: a systematic review and meta-analysis

Zainab Ahmadi

Natasha E Smallwood

Anne-Marie Russell

Ravijyot Saggu

Lorena Romero

Anne E Holland

Magnus Ekström

Abstract

Background

Methods

Results

Conclusions

Shareable abstract

Introduction

Methods

Search strategy for identification of studies

Inclusion and exclusion criteria

Outcomes

Quality assessments

Data extraction, synthesis and analysis

Results

FIGURE 1.

Characteristics of included studies

TABLE 1.

Intervention characteristics

Outcome characteristics

Risk of bias

TABLE 2.

Effects of interventions

Critical outcome: breathlessness

FIGURE 2.

Important outcome: HRQoL

FIGURE 3.

Important outcome: adverse events

Certainty of evidence

Discussion

Main findings

Mechanisms of effect for oxygen in relieving breathlessness

Clinical implementations and practical application

Methodological considerations

Conclusions

Points for clinical practice

Supplementary material

Acknowledgements

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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