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Ambulatory oxygen: now and in the future

Supplemental oxygen is used by many patients with a variety of long-term respiratory illnesses (for example, cardiac failure, cancer and end-stage cardiorespiratory disease), although the majority of evidence comes from the use of oxygen in patients with chronic obstructive pulmonary disease (COPD). Indeed, in the population of patients with resting hypoxaemic chronic respiratory failure (CRF) due to COPD, the use of supplemental oxygen for at least 15 hours per day has been shown to improve blood arterial oxygen tension and to reduce the risk of secondary correlated events (for example, pulmonary hypertension or cardiac failure). So far, this pharmacological intervention has proven to be effective in reducing mortality in these patients in the long term.1,2 This particular approach has been defined as long-term oxygen therapy (LTOT). 
 
Notwithstanding, many more respiratory patients may develop hypoxaemia during exercise (namely, a fall in SaO2 of 4 points below the level of 90%). Overall, ambulatory oxygen (AO) is generally administered to patients under LTOT who have a better degree of independence, to increase their chance of achieving the optimal daily duration of oxygen.3 However, in mobile patients who do not qualify for LTOT but do desaturate on exercise, AO is often prescribed outside the guideline recommendations in order to improve quality of life. While these patients report improved breathlessness and tiredness, AO does not appear to fully improve the patients ability to exercise, increase survival4 nor quality of life.5 The functional limitations of the oxygen delivery (for example, portability of cylinders) may contribute to this, but providing AO to patients who will not benefit has even cost implications, both for patients and for the healthcare system. 
 
A large, randomised trial in North America has investigated whether the use of supplemental oxygen among patients with COPD and moderate resting desaturation or moderate exercise-induced desaturation, may lead to a longer time to death or first hospitalisation, for any cause, as compared with no use of supplemental oxygen.6 The results showed no consistency in differences between the two groups both in terms of functions and perception of health quality, thus authors have concluded that supplemental oxygen is not beneficial in this subgroup of COPD patients. This study has limitations that do not allow a unique and solid conclusion against the wider use of AO in the COPD population. For example, lack of masking, the use of different devices to deliver oxygen, the lack of testing any acute effect of oxygen on exercise performance, and the limitation of enrolment only to the least severe patients (according to the pre-specified criteria of oxygen desaturation) might have restricted the results for application in a small subset of patients.
 
The current guidelines recommend that AO should not be routinely prescribed for all patients needing stationary oxygen supplementation. It should be offered to improve mobility and performance (walking and exercise) within a pulmonary rehabilitation course, particularly ‘oxygen responders’ – patients who have demonstrated to improve their endurance (to >10% from baseline assessment).3
 
For this reason, patient selection for AO is still an important issue. Among several criteria proposed to physiologically test candidates, an easy-to-use scoring system (including lung function and resting oxygen saturation) has been developed and validated to identify patients at risk of walking-induced desaturation.7 The current guidelines recommend a formal assessment of SaO2 during any ambulation test, to set the minimum supplied oxygen flow from portable systems, able to compensate. However, the type of exercise used for testing desaturation may also be a contributory factor,8 because different tests (for example, walking or cycling) have differing oxygen requirements following the drop in arterial oxygenation. Moreover, the patient’s oxygen needs should ideally be evaluated at home, specifically during daily living activities.3
 
Therefore, the lack of uniform criteria for defining exertional desaturation and standardised exercise protocols requires further clarification and research to identify patients who will benefit from supplemental oxygen.
 
Portable oxygen systems
Supplemental oxygen by means of portable systems is mandatory for active patients who can leave their home and are or aiming to be able to perform several daily activities. Since the early beginnings of LTOT, technical advances in portable devices have been steadily focused on improving this facility.
 
Oxygen administration, which is usually delivered by easy-to-use and well tolerated tubing and nasal cannulae while performing activities (for example, eating, drinking or walking), can usually be provided by three main commercially available sources: compressed gas cylinders, oxygen concentrators, and liquid oxygen containers. Each of these sources are static or portable. The choice of appropriate system is not based on specific individual’s characteristics, but the patient’s preference and adherence (for example, the ability to overcome an individual’s disability by using that specific device), and correlating costs.
 
Gas cylinders
Compressed oxygen cylinders, are widely used in almost all countries, and are available in four different sizes. A pressure manometer with a valve system and a flow meter are required to adjust the amount of gas delivered to the patient; for a correct use, the valve system must be opened slowly with caution, anticlockwise turning, and regulating the flow rate to that prescribed.
 
At present, due to the costs and relatively wider availability (even in remote areas) compared with other systems, compressed oxygen cylinders are more often prescribed for short periods at home or hospital use. The use of compressed oxygen cylinders for AO is significantly limited.
 
Oxygen concentrators
An oxygen transportable concentrator is an electrical device that provides oxygen from the atmospheric air. The device concentrates and separates oxygen from nitrogen through a series of molecular filters, directly to the patient’s airways through a control flow device. The performance of the oxygen concentrator progressively reduces with the increase of the delivered flow rate.9,10 For this reason, it is not recommended for use in patients with a severe chronic hypoxaemia when the patient’s oxygen flow requirement is greater than 4l/min. 
 
The most important advantage of an oxygen concentrator is that it can operate independently on the base systems (oxygen cylinders need to be refilled periodically from a base unit). However, this portable system needs to be connected to the main electricity supply.
 
Recently, portable concentrators, wearable machines of small size and weight (3–5kg), have been developed. The majority of portable concentrators provide pulsed oxygen only, to function as ‘on-demand’ delivery systems for low-concentration oxygen therapy that can provide the same oxygen saturation to patients at a much lower volume per minute than continuous-flow oxygen. Pulsed-dose systems aim to increase the oxygen tank duration and battery life of the concentrator and allow adjustable delivery. Delivering the oxygen bolus early in inspiration provides patients with the similar oxygen concentration as with continuous-flow.11 Moreover, with a constant flow of oxygen, it is estimated that the final third of inspired volume remains in ‘dead space’ and does not reach the alveolar region. 
 
Previous studies have shown that pulsed-dose oxygen during exercise can provide similar oxygen saturation to continuous flow.12 By contrast, a significant variability in effectiveness between individual patients has been shown earlier on a practical basis. It is possible that this depends on disease differences (that is, COPD or interstitial lung disease) and coexisting pathological conditions, thus prescriptions should be individualised and validated by a specific ambulatory walk test.13 Regardless of the oxygenation variability provided by concentrators, patients prefer them due to their ease of use and practical when travelling.14
 
Liquid oxygen container
This widely used system allows for the storage of oxygen in a liquid form, while the gas form is delivered through coils where it vaporises. The system is an economic and simple oxygen source for ambulatory patients in a clinical practice. There are two important aspects to this mode of oxygen delivery: 1) a large storage volume in the base unit; 2) a portable and refillable unit (also known as a ‘stroller’) with a capacity between 0.5l and 1.2l and lightweight (3kg when full) for ambulation.
 
Even if this lightweight portable unit can be carried by the patient for outdoor activities, it has limited capacity and time-limited usage, especially at flow rates over 6l/min. This limitation can be only partly resolved by adding conserving devices such as flow-economisers.
 
Health economic aspects
In 2013, the National Oxygen Project (NOP) was established in Scotland to provide a nationally coordinated service with a contracted service provider. This replaced the previous pharmacy-led, regionally organised system, offering both pre-filled oxygen cylinders and home refillable cylinders (the HomeFill system). This more robust system, established to be more cost-effective, and involved clinicians to ensure a patient-centred service. The reform included development of a single, consistent care pathway. The NOP aimed to benefit patients by providing an accurate diagnosis, ensuring prescription of the most appropriate mode of treatment, offering equal access to treatment for all, focusing treatment on the patient’s needs with planned follow-up, and improving the patient’s perceived health quality. The system also benefitted the clinician offering electronic prescribing and a range of simplified modalities. A survey following NOP action has shown that all patients found the new system easy-to-use and rated the quality of service “as good as or better than the previous oxygen service”. In patients who left the home more than four times a week, there was a 50% increase in time spent away, and 92% of patients reported an increase in quality of life. Finally, the cost reduction compared with the previous system was estimated at 77%.15
 
Conclusions 
In many respiratory patients, the presence of even mild oxygen desaturation during exercise or activities of daily living can be corrected with the use of an AO regimen. This can be provided by different portable devices and specific equipment carried by the patients. Even if the clinical benefits of AO still remain uncertain, a common consensus exists among the respiratory specialists for implementing this regimen with the final aim to improve the patient’s level of independence, perceived health status and functionality, especially in the most disabled individuals. The most recent guidelines recommend that AO is useful and feasible, but it should not be routinely offered to patients who are not eligible for LTOT. 
 
Future research is still needed to answer further queries in the field. There is a lack of uniform criteria for defining exertional desaturation and testing and outcomes of ongoing clinical studies in this area are awaited with the hope that they may solve this problem.
 
References
1 Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxaemic chronic obstructive lung disease. Ann Intern Med 1980;93:391–8.
2 Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet 1981;1:1681–6.
3 Hardinge M et al. British Thoracic Society Home Oxygen Guideline Development Group; British Thoracic Society Standards of Care Committee.  British Thoracic Society Home Oxygen Guideline Development Group; British Thoracic Society Standards of Care Committee. British Thoracic Society guidelines for home oxygen use in adults. Thorax 2015;70 Suppl1:1–43.
4 Ameer F et al. Ambulatory oxygen for people with chronic obstructive pulmonary disease who are not hypoxaemic at rest. Cochrane Database Syst Rev 2014;6:CD000238.
5 Ekström M et al. Oxygen for breathlessness in patients with chronic obstructive pulmonary disease who do not qualify for home oxygen therapy (Review) Cochrane Database Syst Rev 2016;11:CD006429.
6 Albert RK et al. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med 2016;375(17):1617–27.
7 Crisafulli E et al. Predicting walking-induced desaturations in COPD patients: a statistical model. Resp Care 2013;58(9):1495–503.
8 Poulain M et al. 6-minute walk testing is more sensitive than maximal incremental cycle testing for detecting oxygen desaturation in patients with COPD. Chest 2003;123(5):1401–7.
9 Johns DP et al. Evaluation of six oxygen concentrators. Thorax 1985;10(11):806–10.
10 Kacmarek R. Delivery systems for long-term oxygen therapy. Respir Care 2000;45:84–92.
11 Zhou S, Chatburn RL. Effect of the anatomic reservoir on low-flow oxygen delivery via nasal cannula: constant flow versus pulse flow with portable oxygen concentrator. Respir Care 2014;59(8):1199–209.
12 Garrod R et al. Evaluation of pulsed dose oxygen delivery during exercise in patients with severe chronic obstructive pulmonary disease. Thorax 1999;54(3):242–4.
13 Couillard A et al. Oxygen therapy by a portable concentrator with a demand valve: a randomised controlled study of its effectiveness in patients with COPD. Rev Mal Respir 2010;27(9):1030–8. 
14 Yáñez AM et al. Oxygenation with a single portable pulse-dose oxygen-conserving device and combined stationary and portable oxygen delivery devices in subjects with COPD. Respir Care 2015;60(3):382–7. 
15 Murphie P et al. National Homefill survey in Scotland. Eur Respir J 2014;44(58):P3700.
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