Some investigators have reported elevations in pulmonary vascular resistance and mPAP in patients with nocturnal desaturation41 but others have not.42 Similarly, results from studies on pulmonary haemodynamics with nocturnal oxygen are conflicting.10,41 In a study of patients with isolated nocturnal desaturation, the HOT group showed a decrease in mPAP with supplemental oxygen therapy compared with an increase in the group without oxygen.41 By contrast, another study found no change in mPAP of patients with nocturnal desaturation.10

Premature ventricular contractions occur during sleep in 64% of patients with COPD43,44 and are particularly frequent in those with nocturnal hypoxaemia.43 However, one study found that supplemental oxygen did not decrease the average number of ventricular premature beats in the treated group, although 4 of the 10 subjects experienced a 50% decrease in the frequency of premature ventricular contractions.41

Sleep quality is poor in patients with COPD.41,45–47 The results of studies investigating the effects of NOTT on sleep quality are limited and conflicting, with one study showing an improvement in sleep quality45 and another not finding this benefit.48

In patients with COPD and respiratory failure at rest, oxygen therapy produces increased survival when administered at least 15h a day, including at night. There is no evidence that this positive effect on survival occurs in other aetiologies of respiratory failure or in COPD patients with more moderate hypoxaemia.

Indications for continuous HOT in respiratory disease

Oxygen therapy is the only intervention, in addition to smoking cessation, that reduces mortality in patients with COPD and severe hypoxaemia (consistent recommendation, high quality of evidence). It also attenuates right heart failure caused by cor pulmonale, improves neuropsychological function, and increases exercise tolerance and ability to perform routine activities (consistent recommendation, moderate quality of evidence).

Oxygen administration corrects hypoxaemia only during application, and has no residual effect. When supplemental oxygen is discontinued, hypoxaemia reappears, so for a sustained effect, administration time must be extended for more than 15h a day.

The indication for oxygen therapy in patients with severe hypoxaemia is determined by its effect on survival. As previously discussed, the NOTT7 and MRC6 studies showed that oxygen therapy increases the median survival of patients with COPD when used for a minimum of 15h per day and with a sufficient flow to obtain PaO2 of 60mmHg, which corresponds to SpO2 ≥92%, without increasing PaCO2. These two studies show that HOT improves survival of patients with COPD and PaO2 <55mmHg (7.3kPa).1 The selection criteria of the NOTT study also allowed the inclusion of patients with PaO2 between 55 and 60mmHg with evidence of cor pulmonale, right heart failure or polycythaemia: a beneficial effect of oxygen therapy on survival was also demonstrated in these patients.7

Several studies have evaluated the use of supplemental oxygen in patients with PaO2 between 56 and 65mmHg (7.4–8.7kPa), and the results are uniformly poor.11,12 Górecka et al.11 did not identify increased survival at three years between a group of patients with PaO2 of 56–65mmHg treated with oxygen therapy and a control group. Similarly, Haidl et al.12 did not find better survival at three years in a small group of patients with COPD and mild to moderate hypoxaemia treated with oxygen compared to a control group, despite the detection of a slight improvement in tolerance exercise and dyspnoea. Therefore, according to the information available to date, continuous oxygen therapy does not improve survival in patients with COPD and mild to moderate hypoxaemia.1 However, the above studies have several limitations. They lack sufficient power to rule out a beneficial effect and, moreover, a longer use of oxygen may possibly be required for achieving beneficial effects (in all of these studies the average was less than 15h per day). The existence of subgroups of patients responding to oxygen therapy cannot be ruled out in these cohorts and patients with COPD and comorbidities, especially cardiovascular and cerebrovascular diseases, which may be more sensitive to the effect of this intervention, are not evaluated.

In the absence of a demonstrated effect on survival in this group of patients, more information on the effect of oxygen therapy on other clinical variables is needed.49,50 Despite the great heterogeneity of the clinical trials analysed, a recent meta-analysis showed that oxygen therapy produces a significant improvement in dyspnoea.51 Moreover, very partial data suggest that it may improve health-related quality of life, increased exercise tolerance, decreased frequency of hospitalisations, and improve depression and cognitive function of these patients.49,52 Its hypothetical role in stabilising pulmonary hypertension and in reducing arrhythmias and electrocardiographic changes suggestive of myocardial ischaemia has not yet been convincingly established.13,14 The LOTT study (NCT00692198) may provide relevant information on these issues in the coming years.

Accordingly, continuous oxygen therapy is indicated in patients with COPD who, at rest and breathing room air, maintain PaO2 less than or equal to 55mmHg (consistent recommendation, high quality of evidence), and in those patients who have PaO2 between 55 and 59mmHg, but also show clinical or electrocardiographic evidence of pulmonary hypertension, haematocrit higher than 55% or signs of right heart failure (consistent recommendation, moderate quality of evidence). Continuous oxygen therapy in patients with COPD and moderate hypoxaemia is not recommended (consistent recommendation, low quality of evidence) (Table 4).53–56

In all cases, the indication for oxygen therapy should be established from a duplicate blood gas quantification within a period of three weeks, during a phase of clinical stability (3months without exacerbation) and on appropriate drug therapy. The oxygen supply should be monitored to ensure that the necessary flow for effectively increasing PaO2 does not trigger acute hypercapnia or acidosis. Finally, the indication for oxygen therapy should be reconsidered in patients who, despite complying with the necessary requirements, continue to smoke, have a clear history of poor compliance or are unable to handle the oxygen supply systems correctly.

Patients with baseline PaO2 above 60mmHg may develop severe hypoxaemia in certain circumstances, especially during exercise and sleep, suggesting the need for oxygen administration.

COPD with exercise-induced hypoxaemia. A varying percentage of patients with COPD and mild to moderate hypoxaemia experience desaturation during exercise, which can be identified by a reading of SpO2 ≤88% for at least 2min in the 6MWT.57,58

Reversal of exercise-induced hypoxaemia by oxygen therapy improves peripheral oxygen delivery, reduces ventilatory demand, reduces dynamic hyperinflation and improves right cardiac function.59 Administration of oxygen during exercise in patients who desaturate provides a short-term benefit, with increased exercise tolerance and reduced dyspnoea.60–63 This benefit may be maintained over the medium term, with improvement in health-related quality of life38 and increased exercise capacity.58 However, although exercise desaturation in patients with COPD who remain normoxaemic at rest is a poor prognostic factor, oxygen therapy has not been shown to alter their survival.58

In the absence of more specific information, oxygen therapy during exercise may be considered for increasing the quality of life of patients with exercise-induced hypoxaemia if hypoxaemia correction (SpO2 ≥90%) and improvement in dyspnoea or exercise tolerance by oxygen administration (increase of the distance in at least 25–30m64,65) can be demonstrated (weak recommendation, low quality of evidence).

In patients with exercise limitations due to hypoxaemia, oxygen administration during exercise may allow an increase in effort intensity, and reduce dyspnoea; this should facilitate rehabilitation, the effectiveness of which is amply demonstrated.55,56 The effect of training with supplemental oxygen versus air in patients without severe hypoxaemia has been evaluated in several short-term studies. It has been shown that oxygen increases peak power and endurance time in a constant load exercise, while decreasing isotime respiratory rate,36 and also dyspnoea.62 A meta-analysis of the effect of oxygen therapy during a training programme confirms that it improves endurance time and reduces dyspnoea during constant load exercise, and during the shuttle walking test, whereas no effect was identified on the progressive cardiopulmonary exercise test or on 6MWT.37 However, there are no studies showing that patients performing rehabilitation without oxygen have worse outcomes than patients receiving oxygen. Therefore, administration of oxygen during exercise in patients with exercise desaturation included in rehabilitation programmes is recommended in order to increase the duration and intensity of training (weak recommendation, moderate quality of evidence) (Table 4).

COPD with nocturnal hypoxaemia. There are several criteria for the identification of nocturnal hypoxaemia, including an episode of desaturation of at least 5min duration with minimum SpO2 ≤85% observed at least once during the night, preferably during REM sleep.39 Although the most operational definition consists of SpO2 <90% for a duration ≥30% of the total recording time,66 patients with COPD and moderate hypoxaemia during wakefulness have been shown to have worse survival at three years if they have nocturnal desaturation than those without it.39

There is still little information available on the effect of NOTT. Two small studies have detected no effect on survival or on the indication of continuous oxygen therapy.10,39 Although their sample sizes are inadequate for assessing the incidence of these episodes, currently available evidence suggests that NOTT does not improve survival of patients with COPD who have only nocturnal desaturation. Results from the evaluation of other possible effects of NOTT are controversial and provide no consistent information about its impact on the quality of sleep and the development of arrhythmias or pulmonary hypertension.58 While some authors describe a minimum effect on increased pulmonary pressure,40 another study did not detect an impact on pulmonary haemodynamics.10 In coming years, the INOX study (NCT01044628) is expected to provide more solid information for determining whether NOTT affects mortality or the future need for oxygen therapy in patients with COPD associated with moderate hypoxaemia and nocturnal desaturation.

NOTT can be considered in patients with demonstrated nocturnal oxyhaemoglobin desaturation (SpO2 <90% for at least 30% of total recording time) and hypoxia-related sequelae (polycythaemia or signs of right heart failure) (weak recommendation, low quality evidence). In this situation, CPAP or mechanical ventilation should be considered for replacing or supplementing oxygen therapy (consistent recommendation, moderate quality of evidence) (Table 4).

Other special situations. Patients with severe COPD and moderate hypoxaemia at sea level may require oxygen supplementation during air travel, especially during overseas flights. Assessment of the oxygen needs and the flow titre needed during air travel should be made according to specific recommendations.67,68

The concept of increased survival in COPD patients treated with oxygen therapy has been extended by analogy to chronic respiratory failure caused by other conditions.69 While this concept seems reasonable, it should be remembered that it is based on the hypothesis that the beneficial effect of oxygen is due to hypoxaemia correction, regardless of its cause, but this has not been demonstrated. Preliminary information is available on the role of oxygen therapy in some diseases.

There are no consistent data on the long-term effects of oxygen therapy in patients with pulmonary hypertension.70 Although an improvement in pulmonary hypertension with low oxygen flow has been described in some patients with pulmonary arterial hypertension,13,71 this has not been confirmed in controlled studies. In a controlled study in patients with Eisenmenger syndrome, NOTT showed no effect on haematological variables, quality of life or survival,72 while a previous study suggested increased survival.73

In these patients, oxygen therapy is indicated if PaO2 is less than 60mmHg, and the aim is to maintain SpO2 >90% (consistent recommendation, low quality of evidence).74–76 Oxygen therapy during exercise can be considered when symptomatic benefit of the exercise desaturation correction is demonstrated (weak recommendation, low quality of evidence).76

Hypoxaemia at rest and desaturation during exercise in patients with IPF are factors of poor prognosis,77,78 so reversal may be of clinical interest. Moreover, oxygen therapy may attenuate the component of pulmonary hypertension caused by hypoxaemia and help improve exercise tolerance and quality of life of these patients.79 However, oxygen administration has not been shown to improve the survival of IPF patients.80,81

In the absence of specific data, HOT is recommended in case of severe hypoxaemia at rest (PaO2 <60mmHg) or desaturation during exercise (consistent recommendation, quality of evidence very low).82

NOTT has shown no effect on mortality, hospitalisations and disease progression in patients with cystic fibrosis, although it reduces school and workplace absenteeism.83 In turn, oxygen administration during exercise seems to improve respiratory and cardiovascular work, increased exercise capacity, and reduced oxyhaemoglobin desaturation.27,84 The wide heterogeneity of the studies is evident in a meta-analysis confirming that oxygen therapy shows no effect on survival but reduces absenteeism.85 In addition, it shows that oxygen therapy during exercise can increase its duration.85

Therefore, in the absence of more specific information, oxygen therapy is recommended for severe hypoxaemia (PaO2 <60mmHg), with special emphasis on the need for correct titration of the oxygen flow required during exercise (consistent recommendation, quality low evidence).

Once oxygen therapy is indicated, re-evaluation after a month or two months from prescription is recommended in order to verify compliance, ensure that the patient continues to refrain from smoking, and to evaluate the clinical impact, both in perception of subjective benefit, and the effect on patients’ quality of life. Baseline blood gas assessment is required to rule out sham severe hypoxaemia, which can cause up to 30% of unnecessary prescriptions during hospital discharge.86,87 In addition, blood gas assessment with the prescribed oxygen flow is recommended to verify that PaO2 is maintained at >60mmHg.

Although there is no consensus recommendation on the frequency of periodic reviews, at least one annual visit seems reasonable.

The recommendations and available evidence for the use of oxygen in other clinical situations are discussed below.

Data from randomised controlled studies on the role of HOT in patients with congestive heart failure show no benefits on survival or functional status of patients (consistent recommendation, very low quality of evidence).

Up to 33–82% of patients with chronic heart failure have been reported to possibly have central apnoea with Cheyne-Stokes periodic breathing.88,89 Suppression of nocturnal hypoxaemia with oxygen therapy improves Cheyne-Stokes respiration,89–93 reducing sympathetic activity and increasing exercise tolerance.89 In these patients, nocturnal oxygen has been shown to improve sleep parameters, left ventricular function and health-related quality of life.89,94,95

Therefore, in patients with heart failure (left ventricular ejection fraction <45%) and Cheyne–Stokes respiration, NOTT should be considered, once correction of sleep parameters has been verified. It should be used preferably in combination with forced ventilation (consistent recommendation, high quality of evidence).

The hepatopulmonary syndrome (HPS) is characterised by an increased alveolar–arterial oxygen gradient caused by pulmonary vasodilation. Initially, it may present without hypoxaemia and occurs in the context of liver disease, both acute and chronic, particularly liver cirrhosis. The cause of hypoxaemia in HPS is the dilation of precapillary and postcapillary lung vessels that allow the quick passage of desaturated venous blood to the pulmonary veins, resulting in decreased oxygenation of arterial blood. Most studies have found that cirrhotic patients with HPS have higher mortality than patients without HPS with a similar degree of liver dysfunction. The prognosis is worse in those with a PaO2 <60mmHg.96

HPS intensity is established whenever an important alveolar–arterial O2 gradient is found (>15mmHg), depending on the degree of hypoxaemia: mild when PaO2 >80mmHg, moderate between 60 and 80mmHg; severe from <60 and more than 50mmHg, and very severe when less than 50mmHg. The treatment of choice is liver transplantation.96

Administration of O2 has been shown to provide symptomatic relief in isolated cases, although no evidence for widespread use is available. Improved liver function has been described in two patients treated with oxygen, reinforcing the concept that hypoxia can directly alter liver function and regeneration. The recommendations of scientific societies establish that HOT should be indicated in patients with PaO2 between 50 and 60mmHg, whereas the indication must be individualised in those with severe hypoxaemia (consistent recommendation, very low quality of evidence).97

This entity is listed as one of the most excruciating pains that a human being can experience. Pharmacological treatment of choice during crises is the triptans (sumatriptan). This medication is subcutaneously injected and takes effect in only 15min. However, it is contraindicated in patients with ischaemic heart disease, and its use should be confined to two injections per day. The alternative is inhalation of 100% O2.98 The great advantages of O2 is that it can be combined with drug therapy, it can be used several times a day, it has no side effects, and can be used in patients in whom triptans are contraindicated.99 Controlled studies have shown that administration of 100% O2 for 15min at the beginning of the episode is a safe and effective treatment in terms of aborting the crisis, and this has been reflected in practice guidelines.100 Results of a double-blind, placebo-controlled, crossover study providing strong scientific evidence on the superiority of the O2 administration versus air in the elimination of pain at 15min and a significant improvement in pain in this period have been recently published.101 The door remains open to studies for establishing the best way to administer O2 and the domiciliary dose for patients with cluster headaches (consistent recommendation, moderate quality of evidence).

It is assumed that oxygen administration to cancer patients with dyspnoea may partially alleviate their symptomatology.102 Consequently, oxygen therapy is considered a palliative treatment in various guidelines.103,104

However, two meta-analyses failed to verify the effectiveness of oxygen as symptomatic treatment of refractory dyspnoea in cancer patients without severe hypoxaemia.105,106 Neither did Abernethy et al.107 demonstrate the superiority of oxygen versus air in the control of symptoms in cancer patients with limited life expectancy, refractory dyspnoea and PaO2 >55mmHg. A recent meta-analysis evaluating the efficacy of various treatments for symptomatic dyspnoea secondary to cancer confirms the beneficial effect of opioids, while no benefit is detected for oxygen.108

Therefore, oxygen is less effective than opiates for the symptomatic treatment of secondary dyspnoea in cancer (consistent recommendation, high quality of evidence), and it may be considered only if an additional effect is identified in a short therapeutic trial (weak recommendation, low quality of evidence).

Oxygen treatment is somewhat different in children compared to adults.109 Most clinical situations that require the administration of oxygen to children are unique to paediatric patients, although there is occasionally some overlap between older children and young adults. Prognosis is usually good and many children need oxygen only for a limited period, determined by growth and neurodevelopment. Furthermore, many children only require oxygen at night, usually for less than 15h.110,111

Specific indications for oxygen therapy in children are limited to three conditions: severe hypoxaemia (3 standard deviations below expected values with the child in a stable condition on room air); nocturnal desaturation (total time with SpO2 <90% for longer than 20% of the recording time); or presence of pulmonary hypertension, right ventricular hypertrophy or polycythaemia secondary to chronic hypoxaemia (consistent recommendation, moderate quality of evidence).110,111

Oxygen therapy reduces or prevents pulmonary hypertension in neonatal chronic lung disease. It reduces intermittent desaturations, decreases airway resistance and promotes growth (consistent recommendation, low quality of evidence). It is also beneficial for neurodevelopment (consistent recommendation, very low quality of evidence), may reduce the associated risk of sudden death (consistent recommendation, very low quality of evidence) and decreases hospitalisation (consistent recommendation, low quality of evidence).110,111 In children with cystic fibrosis, oxygen therapy improves school attendance (consistent recommendation, moderate quality of evidence), and produces symptomatic improvement (consistent recommendation, very low quality of evidence).111

NOTT should be recommended for patients with congestive heart failure and diagnosed Cheyne-Stokes respiration, and preferably associated with forced ventilation. Indication of HOT in patients with HPS should be considered in those with respiratory failure. Administration of 100% oxygen has proved efficacy in patients with cluster headaches. Palliative use of oxygen therapy in cancer patients with dyspnoea has proved less effective than opioid administration.

HOT should not be interrupted when patients need to leave their home for a few hours. Therefore, patients require portable oxygen delivery systems as part of their prescription.113,114

A classic method is the use of an oxygen gas cylinder the size of a small backpack (size M-6) that, if necessary, can be transported in a trolley. However, its small capacity comprises a limitation, as a patient with a HOT prescription of 2l/min depletes an M-6 (164l of oxygen gas) cylinder in just over an hour. Larger cylinders are extremely unwieldy and difficult to transport.

The second option is a portable backpack that can be attached to the aforementioned liquid oxygen mother unit. This can be filled and used by active patients with demonstrated reduction in oxyhaemoglobin saturation (SpO2) during exercise who want to use it away from home.115–117 Usage time will depend on the flow used. It is useful for short trips by patients who need high flows of more than 3l/min during exercise.

Concentrator with cylinder transfer. This is an adaptation of the traditional concentrator. This module transfers O2 to a portable cylinder, and requires several hours for filling and daily refilling. It is useful for patients who sporadically leave home, although this system is rare in our country.

Portable oxygen concentrator. This has the advantage of being adaptable to any power outlet or car battery. This device has led to the technology called “non-delivery/delivery-less”, because it does not need gas to be delivered to the home, but it does require servicing every three months. Portable concentrators should weigh a maximum of 4kg, although some continuous-flow systems weigh 9kg and produce 90±3% oxygen, providing at least 2 litres of oxygen for at least 4h. They are useful in patients who make long journeys and frequently participate in activities away from the home.117

On-demand valve. The so-called “pulse dose systems”, “demand flow”, “demand oxygen delivery system” and/or “oxygen-conserving devices”, unlike continuous flow therapy, supply oxygen intermittently. Instead of a continuous flow, the on-demand oxygen storage technology (OST) provides a pre-set volume or oxygen bolus, measured in millilitres per breath. The bolus is delivered when the patient makes an inspiratory effort (or demand), during the first 60% of inspiration. Hence, oxygen is not wasted for the remainder of each breathing cycle, allowing a longer duration of the supply source. Importantly, the numerical setting of a continuous flow metre, expressed in litres/min, is not equivalent to the numerically different configuration of an OST, which depends on the model, and indicates the relative volumes of bolus delivered. Two systems can be used: liquid oxygen and concentrator. The first supplies between 1.5 and 5 pulses (pulse of ±15ml), refilling from the corresponding mother unit. Also, some models capable of functioning both with pulse or continuous flow are available. Pulses vary depending on models in the case of portable oxygen concentrators (1–6 pulses), with different pulses. These have the advantage of being easily refilled and used at home and on travel. Some models can be used for both continuous flow and demand. They are useful in patients capable of triggering the valve in whom correct saturations during ambulation have been verified118 (Fig. 3).

Fig. 3.

Portable systems with on-demand valve: concentrators. (A) Respironics, Murrysville, Pennsylvania, (B) Invacare, Elyria, Ohio; (C) Inogen, Goleta, California, (D) AirSep, Buffalo, New York, (E) SeQual Technologies, San Diego, California, and (F) DeBillviss Igo.

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On-demand devices are sensitive to variables such as the patient's respiratory rate, which may affect the SpO2 figures obtained. Therefore, alarms should be set to trigger when SpO2 is lower than 85%. For the prescription of all portable systems, evaluation of the patient during exercise for proper dose adjustment is required.119

The transtracheal catheter delivers oxygen directly into the trachea through a small catheter 1.6–2mm in diameter that is introduced percutaneously between the second and third tracheal rings. This results in oxygen saving of 50% at rest and 30% during exercise. It is indicated for patients using portable sources for ambulation. The drawbacks are that it is an invasive method, requiring training and education for care, and it must be replaced every 60–90 days in a hospital setting.50 Current use is limited.120

The fraction of inspired O2 (FiO2) is regulated by opening the side windows of the “Venturi effect” mask. It provides a fixed, constant supply of FiO2, irrespective of the patient's breathing pattern. As home treatment, this is only used in patients with hypercapnia, and applied overnight.

This is the commonly used system at home. It consists of two small, flexible tubes 0.5–1cm in diameter that are inserted in the nostrils and adjusted behind the ears. FiO2 is completely variable, depending on the patient's tidal volume. Since it is recognised that standard nasal prongs are inefficient (only 15–20% of the administered oxygen participates in the gas exchange), oxygen-saving systems have been designed for a more efficient use of oxygen, with an increase in autonomy of up to 3 times longer than continuous oxygen supplied with conventional nasal prongs.

Washing with soap and water of the part of the delivery systems in contact with the patient (e.g. nasal prongs, reservoir cannulas or masks) every morning is recommended. Extensions and tubes should be washed once a week, and replacement of nasal prongs and face-masks every 15 days is recommended. In the case of reservoir cannulas, the manufacturer recommends replacement every 3 weeks.

With regard to the supply systems, oxygen is not combustible, but activates combustion of flammable materials, so the general recommendations of the suppliers must be adhered to.117

Specific recommendations according to source of oxygen

Liquid oxygen is extremely cold, so the icy parts should not be touched. Backpack filling should be performed in a well-ventilated room with a solid floor. The reservoir should not be left unattended during refilling. If leaks occur while disconnecting the mother unit and the backpack, the pack should be connected again and, if this is not possible, the room should be ventilated. Do not touch the source of the leaks, and do not smoke or cause sparks or flames. In case of leakage, it is recommended to stay away from the outflow. If it comes into contact with the eyes, wash with plenty of water for more than 15min. If liquid oxygen comes into contact with the skin, do not rub the area, remove clothing if necessary, thaw the affected areas with moderate heat and, in both cases, seek medical care.122

Deducing the cost of oxygen therapy is a complex task. It is more complicated than merely assessing the costs indicated in current agreements with various health authorities, whether listed by cost per daily treatment, per capita cost, or alternative cost estimates. The cost of additional technologies and technological innovation must be added to this basic expenditure. Then the benefits of this treatment modality must be subtracted from the costs. To this equation must be added the consideration that the indications are correct, compliance with prescription optimal, and adherence complete. Only then can we be certain that investment in home oxygen therapy is beneficial.

The report from Fenin and PricewaterhouseCoopers in 2011 has provided some data on the efficiency and benefits of home oxygen therapy in Spain.135 In this report, the cost-utility analysis of treating COPD with oxygen shows that the annual treatment of a patient with stage IV COPD (by spirometric obstruction) represents an average saving of 1372euros (€), while improving the patient's quality of life by 0.15 years in quality-adjusted life years per patient. Another important point in this report is that the cost of a patient with stage III COPD represents approximately 70% of the cost of a patient with stage IV COPD. These data indicate that the weighted average cost estimate of a treated stage III-IV patient would be €3178, while the average cost of an untreated patient would be €4079. Overall, 79000 COPD patients are estimated to have received treatment with oxygen in Spain in 2010, representing a cost of 100 million euros, while 42000 patients that should have received this therapy did not, generating an associated cost of 172 million euros.

No data on the cost-effectiveness of specific equipment for oxygen therapy, such as portable oxygen concentrators or liquid oxygen, are available.

Oxygen flow should be adjusted using the same source the patient will use at home. Adjustment of the flow with a pulse-oximeter until achieving SpO2 ≥90% is recommended, and arterial blood gases should be obtained at this point to ensure adequate hypoxaemia correction without causing hypercapnia. In patients with normocapnic respiratory failure, adjustment can be made using only the pulse-oximeter. Adjustment of oxygen flow during sleep should be performed with continuous SpO2monitoring during sleep, aimed at maintaining SpO2 ≥90%. During exercise, adjustment of oxygen flow for an average SpO2 ≥90% during the 6MWT is recommended. The choice of the oxygen source should be adapted to the patient profile.

Like any drug, oxygen therapy has its side effects and risks,136,137 although it is generally a safe treatment if the basic guidelines are followed. The main adverse effects are derived from equipment misuse.

The side effect that most impacts on the clinical management of patients requiring HOT is hypercapnia. The main mechanisms of this phenomenon are worsening of the V/Q balance secondary to inhibition of hypoxic vasoconstriction and inhibition of hypoxic stimulus. This occurs particularly during sleep127,129 and may worsen if oxygen flow is increased to correct nocturnal hypoxaemia as recommended by various guidelines, as recently demonstrated in COPD patients in stable phase and chronic hypercapnic respiratory failure132 (Fig. 5).

Fig. 5.

Evolution of PaCO2 (A) and pH (B) during sleep with flow adjusted during waking (solid line) and after increasing it by 1l/min during sleep (dotted line). From Samolski et al.132

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The clinical impact of nocturnal hypercapnia secondary to oxygen therapy is not known. However, presence of daytime hypercapnia has been considered a factor for poor prognosis in the outcome of COPD patients who require HOT.138–140 Hypercapnia may enhance muscle dysfunction, reduce diaphragm contractility and lead to muscle fatigue.141,142 It may also influence cardiac contractility, leading to arrhythmias and structural injuries in the myocardium.143–145 Other known effects of hypercapnia are decreased cerebral vascular resistance with increased intracranial pressure, enhancing cerebral tissue hypoxia.

In the case of concurrent SAHS and COPD, oxygen therapy may prolong the duration of obstructive events, even with low flows.146,147 As a result of these phenomena, the sleep quality of these patients could be affected.148

Another side effect of oxygen therapy is pulmonary toxicity. Oxygen can cause direct lung injury by causing absorption atelectasis, since the intra-alveolar nitrogen concentration is reduced, and diffuse lung injury (acute and chronic) caused by release of free radicals. These complications are typical of prolonged oxygen administration at high concentrations. Such alterations are dose-dependent, and related both to partial pressure of oxygen and exposure time. Lesions are irreversible only in cases of chronic lung injury (capillary proliferation, interstitial fibrosis, epithelial hyperplasia and bleeding). Although HOT uses low O2 flows and exposures to FiO2 <0.5 that can be tolerated for weeks, cases of patients receiving HOT who have presented histological changes related to oxygen toxicity have been described.149

Finally, other adverse effects that may influence treatment compliance are congestion and irritation of nasal mucosa and epistaxis, contact eczema from the nasal prong material, and psychological and social effects.

There is also a risk of fire and explosions that is much more acute when the patient continues to smoke. Liquid oxygen can cause burns when handling the supply source or when there are leaks in the system.