Supplemental oxygen and dypsnoea in interstitial lung disease: absence of evidence is not evidence of absence

We would like to thank M.R. Schaeffer and colleagues for their correspondence regarding our recently published systematic review of oxygen for interstitial lung disease (ILD) [1]. In this review, we found no consistent evidence that oxygen therapy administered during exercise tests reduced the primary outcome of dyspnoea, although randomised crossover trials demonstrated improvements in exercise performance. We also reported that the quality of evidence was very poor, due to the retrospective nature of many studies, the potential for selection bias and lack of blinding.

Short abstract

Current evidence does not provide definitive answers regarding the benefits (or otherwise) of oxygen therapy for ILD http://ow.ly/4qr830dCYm4

From the authors:

We would like to thank M.R. Schaeffer and colleagues for their correspondence regarding our recently published systematic review of oxygen for interstitial lung disease (ILD) [1]. In this review, we found no consistent evidence that oxygen therapy administered during exercise tests reduced the primary outcome of dyspnoea, although randomised crossover trials demonstrated improvements in exercise performance. We also reported that the quality of evidence was very poor, due to the retrospective nature of many studies, the potential for selection bias and lack of blinding.

We welcome the recent study by Schaeffer et al. [2], which adds important evidence regarding the acute effects of supplemental oxygen in ILD during laboratory testing. In a single-blinded randomised crossover study, the authors demonstrated that breathing oxygen at inspiratory oxygen fraction (F_IO2) 60% during a constant load cycle ergometer test resulted in decreased dyspnoea at iso-time (mean 1.9 Borg units), as well as a highly significant increase in endurance time (mean 10.3 min). These results are consistent with our own recent findings in a double-blind randomised crossover study using F_IO2 50% during constant load cycling [3], where we found reduced dyspnoea at maximal workload (mean 1 Borg unit) and increased endurance time (mean 99 s). Unfortunately, neither of these studies was available at the time our systematic search of the literature was conducted in March 2016, which illustrates a limitation of systematic reviews in an evolving field. We also acknowledge that we might have found greater improvements in our study [3] had dyspnoea been measured at iso-time, as suggested by the correspondents, although the improvement in dyspnoea at peak exercise is also an encouraging finding.

It is interesting to note impressive gains in exercise endurance time with supplemental oxygen in both studies [2, 3], which was consistent with our systematic review findings [1]. This is aligned with the patient experience of oxygen therapy. In our recent qualitative study [4], patients with ILD reported that, although they had expected oxygen therapy to reduce breathlessness, more common experiences included increased energy levels, better exercise capacity and enhanced physical activity. Unfortunately, there are no quantitative studies to aid our understanding of the impact of supplemental oxygen during daily life in people with ILD. Tightly controlled studies such as those of Schaeffer et al. [2] and our own [3] provide welcome hints of a possible symptomatic and physiological benefit in the laboratory setting, which could be relevant to the application of oxygen during exercise training in pulmonary rehabilitation, where oxygen delivery and exercise dose can be tightly controlled. However, the relevance of these findings to the use of ambulatory oxygen in daily life remains unclear. Both studies used high levels of inspired oxygen, which are impractical to deliver during free-living physical activity, and were conducted during cycling on an ergometer, an activity which is not representative of daily functioning. More evidence is urgently needed regarding the impact of ambulatory oxygen during day-to-day life on symptoms, physical activity and long-term outcomes in people with ILD.

We agree that the current body of evidence does not provide a definitive answer regarding the benefits (or otherwise) of oxygen therapy for people with ILD, particularly for oxygen therapy during daily life. Ongoing trials may provide useful direction [5, 6]. However, we also note that use of oxygen therapy is not without costs to patients, who describe practical challenges, psychosocial impacts and unmet expectations [4]. Until robust data from clinical trials are available, we would encourage health professionals to actively engage individual patients in treatment decisions, providing the guidance needed to make informed decisions regarding the benefits and the costs of oxygen therapy during daily life.

Disclosures

I. Glaspole ERR-0072-2017_Glaspole ^{(1.2MB, pdf)}

A.E. Holland ERR-0072-2017_Holland ^{(1.2MB, pdf)}