Short-burst oxygen therapy for COPD patients: a 6-month randomised, controlled study

Short-burst oxygen therapy (SBOT) is defined as the “intermittent use of oxygen for the relief of breathlessness, before exercise or for recovery after exercise” 1. There is no evidence from acute studies that SBOT provides clinically meaningful benefit for patients with chronic obstructive pulmonary disease (COPD) 2–4. Despite this, the use of SBOT appears to be common practice for distressed dyspnoeic COPD patients 1, 5. This has considerable financial implications. In the UK, cylinder prescriptions almost doubled in the last decade with annual costs >£10 million 6.

COPD is a leading cause of morbidity and mortality in many countries, including New Zealand, where it is the fourth most common cause of hospital admission 7. Readmission rates are high. A comprehensive study from the USA of patient outcomes following an exacerbation reported 50% of patients were readmitted within 6 months 8. A recent large international survey conducted in Canada and the USA, and Europe emphasised the high economic impact of COPD with the majority of healthcare costs accounted for by hospitalisations 9.

Over half the referrals to the present authors' oxygen service originate from COPD patients following a recent admission 10. These patients often do not fulfil criteria for other modes of oxygen prescription, such as long-term or ambulatory oxygen, where a more secure evidence-base exists 11–13. A report from the Royal College of Physicians observed that “despite extensive prescription of SBOT, there is no adequate evidence available for firm recommendations and further research is required” 1. This is an important patient group, not only in terms of high consumption of scarce healthcare resource, but also with regard to personal burden of chronic disease with distressing levels of dyspnoea and poor health-related quality of life (HRQL), which declines inexorably over time 8, 14–17. The original landmark clinical oxygen studies 11, 12 concentrated on survival as the primary outcome. The significance of other measures, including symptom relief, HRQL and acute healthcare utilisation, is now better appreciated. There are no previous randomised long-term studies of domiciliary SBOT in COPD patients and no studies have specifically addressed the impact of SBOT on either HRQL or acute healthcare utilisation.

The aim of this study was to determine whether the availability of SBOT to dyspnoeic but not hypoxic COPD patients following hospital discharge from an acute exacerbation improves HRQL and reduces acute healthcare utilisation.

METHODS

A 6-month prospective, randomised, double-blind, placebo-controlled, parallel group study of cylinder oxygen versus cylinder air versus usual care was performed. Patient recruitment and study design are outlined in figure 1⇓. Consecutive patients admitted to (Auckland and Green Lane Hospitals, Auckland, New Zealand) between November 2001 and December 2003 with an acute exacerbation of COPD were recruited.

RESULTS

DISCUSSION

This is the first randomised, double-blind, placebo-controlled, parallel group home-based study of SBOT for COPD patients recently discharged from hospital following an acute exacerbation. The availability of SBOT neither improved HRQL nor reduced acute healthcare utilisation.

SBOT continues to be widely prescribed 1, 5, 6, despite a number of acute studies that provide little evidence of meaningful clinical benefit 2–4. In an evaluation of SBOT pre- and post-exercise in COPD patients, SBOT neither reduced dyspnoea nor improved performance 3, consistent with the results of Nandi et al. 4. Furthermore, the reproducibility of any response is poor 3, 29. Oxygen provided to COPD patients during recovery from maximal symptom-limited exercise had no effect on either dyspnoea or recovery time 2. In this present study, these findings were extended to demonstrate that the longer-term availability of SBOT did not improve HRQL or reduce acute healthcare utilisation.

One of this study's strengths is that it reflects the real-life prescription and use of SBOT in the domiciliary setting, as opposed to the more proscriptive instructions enforced in the acute gym-based studies. Furthermore, the acute SBOT studies did not necessarily recruit the patient group for which SBOT is prescribed in clinical practice 2–4 and the mode(s) of exercise employed was (were) not clinically relevant 2–4. A recent study concluded that “evidence-based treatment decisions for obstructive lung disease are based on studies which include a very small highly selected fraction of this patient population” and “it is questionable whether such data scan be extrapolated to a larger, real life population of patients with obstructive lung disease 30.”

The present authors believe that their patients more accurately reflect the population currently prescribed domiciliary SBOT. Hence, the results reported herein are likely to be more generalisable. The present study population was elderly (mean age 77 yrs), often frail and vulnerable, and with chronic severe disease associated with distressing dyspnoea, poor HRQL and considerable comorbidities. It is salutary that their HRQL was comparable with previously reported HRQL of COPD patients fulfilling the criteria for LTOT 17 and rather worse than COPD patients not fulfilling the criteria for LTOT but suitable for ambulatory oxygen 13. Acute healthcare utilisation was high; these patients had just required admission for an acute exacerbation of COPD and the majority another admission in the preceding 6 months.

Study of COPD patients following an acute exacerbation was deliberate, recognising that, not only do they represent the majority of referrals to the present authors' oxygen service 10, but also that this is the group for whom any impact on HRQL and acute healthcare utilisation might be expected to be greatest. Further study is required to definitively address domiciliary SBOT in a chronic stable population. Nonetheless, the present study population, by definition, had important dyspnoea limiting daily activity, as reflected by the CRQ dyspnoea domain both at baseline and 6 months. Accordingly, given the present results in conjunction with the largely negative results of the acute gym-based studies, similar results would be expected.

There are considerable practical difficulties in conducting such a study. The baseline patient characteristics bear testament to some of the potential difficulties. These factors were likely to be influential in the comparatively high rate (39%) of eligible patients declining to participate. Although patients were excluded only where strictly necessary; nevertheless, 204 (62%) proved ineligible, largely due to current smoking or inability to complete HRQL questionnaires. Mortality (10%) over the 6-month study period was high. Such patients represent a challenge both to recruit and maintain in clinical studies.

The negative impact of COPD on HRQL is substantial 8, 14–17. Management should be concentrated on symptom relief and improving HRQL. Modest, but clinically meaningful, improvement in HRQL for COPD patients following the introduction of LTOT 17 is reported. Modest improvements in HRQL have also been shown for COPD patients provided with a domiciliary supply of ambulatory oxygen 13. However, in this present study of SBOT, there were no significant differences between patient groups in any of the HRQL measures (CRQ, SF-36, HAD), apart from improvement in the CRQ emotion domain in the usual care group.

It must be emphasised that the present study design was pragmatic and intended to reflect the real-life clinical prescription of SBOT, as outlined in the Royal College of Physicians Report 1, i.e. availability and use as required. The present authors recognise that patients recovering from an acute exacerbation would be expected to improve in time with some effect on usage. This only serves to emphasise the importance of a randomised controlled design such as this, which allowed us to demonstrate that there was no significant difference over time between cylinder oxygen, cylinder air and usual care groups. However, notwithstanding this, the present study population continued with important dyspnoea, as reflected by the CRQ domain at 6 months. Thus, it seems improbable that a therapeutic effect was missed. Any benefit would be perceived promptly, providing immediate positive feedback such that, on the next occasion, the patient would again use the cylinder, resulting in a sustained pattern of use. Whilst acknowledging the limitations of patient diaries, the striking decay in use after an initial burst lends confidence that patients did not perceive sufficient clinical benefit to warrant continued use. It was felt that 6 months would be sufficient to prove a clinically meaningful benefit. Given the results reported herein, it is clear that a longer or indeed larger study would have been futile. The low-level use of SBOT could conceivably have contributed to a failure to show benefit from SBOT; however, analysis of results was on the basis of “intention-to-treat” and such an analysis failed to show clinical benefit. Furthermore, there was no evidence of benefit in terms of HRQL at 2 months, i.e. during a period of relatively higher use of cylinder gas. In line with the present findings, a review of domiciliary cylinder use in the UK also reported low use 5.

The failure to show a HRQL benefit does not exclude a potential separate benefit from SBOT, e.g. the concept of a security blanket, where the presence of a cylinder might be influential in an acute episode. The present study did not support this hypothesis, in that the usual care group performed best with a significantly longer time to first admission and trend towards less acute unscheduled events than the cylinder groups. The patient groups were very well matched, not only for demography, physiological measures and HRQL, but also for potential social confounders. The exception was that more of the usual group lived alone, but this only just reached statistical significance and should not be overemphasised. It is recognised, however, that patients who live alone may be less likely to be readmitted than those with a spouse, who may call emergency services. Using validated measures of social supports 19–21, it was found that patients virtually universally reported that they were very or extremely satisfied with their general social support. This contrasts with a lack of disease-specific social support, a similar finding to asthma studies 20. This emphasises the importance of separate assessment of general and disease-specific social supports and the development of disease-specific support systems as part of the comprehensive management of COPD. The usual group may have developed alternative coping strategies, unlike the cylinder groups, who may have “relied” on cylinder availability. Mastery plays a considerable role in attenuating acute healthcare utilisation however there was no difference between patient groups. The only statistically significant difference in HRQL was improvement in the CRQ emotion domain in the usual care group. The cylinder may have served as a constant reminder of their disease severity with a potential effect on mood.

Management options for severe COPD are often unsatisfactory, hence the ongoing interest and lingering expectations as to the role of SBOT. SBOT continues to be widely prescribed 1, 5, 6, seemingly driven by expectations as opposed to evidence-based guidelines. The potential for a powerful placebo effect underscores the importance of randomised, controlled studies.

In conclusion, in a 6-month randomised, double-blind, placebo-controlled, parallel group study, availability of short-burst oxygen therapy to chronic obstructive pulmonary disease patients following discharge after an exacerbation was not associated with differences in health-related quality of life or acute healthcare utilisation. These results, in conjunction with recent results of acute studies of short-burst oxygen therapy, provide no support for the widespread use of this form of oxygen prescription. Scarce health resources would be better directed to proven modalities, such as pulmonary rehabilitation.