Question 1. How is HOT currently administered and followed up?

In Sweden, oxygen services are provided mainly within respiratory or internal medicine clinics and are publicly funded [14]. All 48 clinics that prescribe LTOT have agreed to comply with guidelines from the Swedevox Registry and the Swedish Respiratory Society [25], which are in line with international guidelines [1, 12]. HOT is prescribed by specialists in pulmonary medicine, internal medicine or palliative medicine after clinical assessment and evaluation of the indication for HOT. It is conducted as an inpatient in the ward or at an outpatient clinic. To assess the level of chronic hypoxaemia and HOT eligibility, arterial blood gas (ABG) analysis under steady-state conditions while breathing room air should be performed. The procedure for the use of HOT is explained to the patient, including potential benefits and risks. The decision whether to prescribe HOT involves a comprehensive review of a patient's comorbidities, clinical status, attitude towards oxygen therapy and ability to adhere to the treatment and follow-up.

The oxygen equipment is supplied to the patient by specialised oxygen nurses or sometimes by oxygen technicians at each clinical unit. The equipment is publicly funded (through taxes) and free to the patient. Oxygen nurses provide detailed information regarding oxygen therapy and its follow-up (which may include home visits) to the patient and informal caregivers and enter data into the national Swedevox registry, which has maintained a stable coverage of about 85% of patients starting LTOT in Sweden since 1987 [14].

Safety aspects should be considered before initiation of HOT. Patients are informed about the increased risk of burn injuries during any interaction with potential sources of open flames, such as cigarettes, e-cigarettes, toasters, etc., emphasising the importance of avoiding such situations. The risk of fire and explosion may vary by type of oxygen equipment. Continual oxygen therapy with oxygen concentrators (which only enrich oxygen from room air and include no oxygen storage) are considered safe. As reported to the Swedevox registry in 2021, about 86% of patients were also prescribed portable oxygen equipment, most often a portable oxygen concentrator (89%) and in some cases cylinders of compressed gas (7%) or liquid oxygen (4%) [25].

According to Swedish guidelines, contraindications for HOT in order to decrease the risk of burn injuries and fire hazards include inadequate collaboration and adherence to the therapy, severe dementia (which could lead to insufficient daily duration of HOT and increased risk of fall injuries on the oxygen tubes), active smoking (including e-cigarettes), and other contact with fire (such as gas or wood stoves and heating) [25]. Occupational therapists from the municipality can assist with home adaptions as needed.

Patients prescribed HOT should optimally be followed up within a few weeks to check adherence, eligibility (including ABG and safety issues), side-effects and the need for portable oxygen equipment and then regularly about twice a year. Treatment is ended after individual assessment if the HOT eligibility criteria are not met, at which time the oxygen equipment is returned.

Remarks

A national structured approach to the prescription, management and follow-up of HOT has facilitated standardisation of the management and adherence to the eligibility criteria for oxygen therapy in Sweden. The TF advocates for the prescription and management of HOT by healthcare professionals with adequate knowledge of oxygen therapy and that follow-up of the therapy should be carried out by specialised oxygen staff, preferably complemented by home visits to assess the patent's interaction with the treatment in their home environment. A national oxygen registry (Swedevox) effectively monitors the adherence to the eligibility criteria. The presented structure might also be suitable for implementation in other settings for improved and sustained validity of HOT prescription and management. We acknowledge that conducting adequate follow-up, particularly through home visits, may pose additional challenges in resource-limited settings, depending on the structure of healthcare systems.

Question 2: What are the potential benefits of HOT in people that meet the eligibility criteria but who continue to smoke?

LTOT is standard of care for patients with severe chronic resting room air hypoxaemia [1, 3, 4, 12]. Chronic hypoxaemia is defined as hypoxaemia that persists despite the patient being in a stable clinical condition and having optimal treatment of underlying disease [1]. The eligibility criteria for HOT vary between countries [22]. HOT assessment using pulse oximetry might misclassify hypoxaemia and repeated ABG analysis under steady-state conditions while breathing room air is recommended to confirm chronic severe hypoxaemia [26, 27]. Severe hypoxaemia was defined in the landmark LTOT trials as meeting either of the following criteria: 1) arterial carbon dioxide tension (PaO2) ≤ 55 mmHg (7.3 kPa) or 2) PaO2 56–59 mmHg (7.5–7.9 kPa) together with oedema, haematocrit ≥55% or the presence of cor pulmonale [1, 3, 4, 12]. The two landmark randomised clinical trials from the 1970s (the NOTT and MRC trials) included a total of 290 people with COPD and severe chronic hypoxaemia, defined according with the criteria above. The studies showed that LTOT decreased 2-year and 5-year mortality [3, 4].

Although the findings from the NOTT and MRC trials have been widely adopted into clinical practice guidelines [22], the generalisability of the findings for current practice is diminished by the fact that they included mostly men younger than 70 years without significant comorbidity [3, 4]. In addition, treatment for COPD, cardiovascular disease and other comorbidities has significantly improved in recent decades.

A survival benefit of HOT has not been shown in COPD patients with moderate or mild resting hypoxaemia or hypoxaemia only during exercise or at sleep [7]. In the Long-term Oxygen Therapy Trial (LOTT), 738 patients with COPD and moderate resting hypoxaemia (defined in the trial as a peripheral oxygen saturation of 89–93%), exertional hypoxaemia, or both, were randomised to LTOT or no oxygen [5]. The LOTT did not find any differences between the oxygen and no oxygen groups in the primary composite outcome of death or requirement for LTOT. There were also no differences in secondary outcomes including 6-min walk distance, lung function or health-related quality of life (HRQoL). In a recently published trial, nocturnal oxygen did not have any effect on survival or progression to HOT in COPD [28], findings that are in line with previous studies [29, 30]. Ambulatory oxygen, in the setting of isolated hypoxaemia during exertion, has shown acute beneficial effects in terms of exercise capacity and breathlessness during laboratory-based exercise tests in COPD [31] and pulmonary fibrosis [32]. However, evidence for its effect in the context of pulmonary rehabilitation or for daily life (home) treatment is less consistent [31]. Trials of palliative oxygen for relief of breathlessness or reduction of respiratory distress near death have not reported any clear benefits with oxygen compared with breathing air or no treatment [33, 34].

Trials on the efficacy of HOT in chronic conditions other than COPD, such as interstitial lung disease (ILD), are lacking. However, clinical guidelines recommend HOT for other conditions using the same criteria as in COPD [1, 16]. For people with ILD and exertional hypoxaemia, one crossover trial with a 2-week treatment period reported improvements in HRQoL, but the long-term impact on HRQoL is unknown [35]. In laboratory studies, there were small improvements in exercise capacity with ambulatory oxygen [36].

Most patients evaluated for HOT in clinical practice are former or active smokers, which poses an ethical dilemma for healthcare professionals [37]. Data from the oxygen register in Denmark, where smoking is not a strict contraindication for HOT, indicate that 20–25% of patients on HOT continue to smoke [38]. In the MRC trial, which showed a survival benefit with oxygen therapy in hypoxaemic COPD, approximately 40% of the study population were smokers at the start of the trial and smoking was not regarded as a contraindication; however, they were encouraged to quit smoking [3]. Smokers were also eligible for the NOTT. Although no mention of smoking was made in the original paper, a secondary publication indicated that 38% of participants were actively smoking at study entry [39]. The effectiveness of oxygen therapy in smokers with hypoxaemia and secondary polycythaemia was evaluated in some early studies [40, 41]. Smoking may contribute to secondary polycythaemia in hypoxic COPD patients due to the strong binding of CO to haemoglobin, which could also attenuate the effect of the supplemental oxygen [40]. However, no trial has specifically compared the benefit of HOT between smokers and nonsmokers.

The risk–benefit assessment is affected by the type of oxygen equipment used, as the risk of smoking-related harm is probably more significant in LTOT compared to ambulatory oxygen therapy. In addition, the potential benefits, including improved survival, is also likely to be greater in LTOT.

Remarks

The TF concludes that HOT is likely to improve survival in people with chronic severe hypoxaemia and may improve breathlessness and well-being in some patients. The benefit of oxygen therapy is likely to be greater in people with more severe hypoxaemia, whereas a benefit has not been shown in mild to moderate hypoxaemia. Smokers were included in the original efficacy trials. Although the benefit of HOT among smokers is uncertain due to a lack of robust evidence in the field, a positive effect among smokers cannot be precluded. Further research on the benefit of HOT among smokers is difficult to perform due to ethical issues; however, national registries could be used to improve the existing evidence base.

Question 3: What are the potential risks of adverse effects of HOT in people who otherwise meet the eligibility criteria but continue to smoke?

HOT provides oxygen-enriched air within the home setting, which, together with smoking or another heat source, provides the necessary elements to ignite and magnify fires and cause burn injuries and fire hazards [42]. Tobacco smoking is the main cause of burn injuries during HOT [43–46]. The incidence of burn injuries during LTOT is reported at 85/100 000 person-years in Sweden (where smoking is a strong contraindication) compared with 170/100 000 person-years in Denmark (where smoking is allowed in some patients during LTOT) [47]. Burn injuries include head and neck burns, and inhalation injuries. Compared to other burns, burn injuries in relation to HOT are associated with a higher risk of inhalation injury and mortality [45]. The use of e-cigarettes and other vaping devices carries the same risk as regular cigarettes [11]. The risk of burns during HOT also extends to persons surrounding the patient, such as family, home care providers, informal caregivers, as well as neighbours [43, 44]. The risk of fire and explosion likely differs by type of HOT equipment. Cylinders of compressed gas or liquid oxygen can explode after about 20 min of fire. In contrast, oxygen concentrators do not explode and pose fewer safety and health risks. Furthermore, smoking can contaminate and decrease the life span of oxygen concentrators. Although studies are lacking, it is known from clinical practice that smoking (by the patient or others) near the concentrator can lead to the requirement for filters to be cleaned and replaced more frequently; in addition, the concentrator will have a shorter operating time. Therefore, patients and their families must be informed of the risks of burn injuries and fire and how to avoid them. The prescribing physician and the oxygen supplier must assess on case-to-case basis whether HOT can be used safely.

Remarks

The TF concludes that smoking during HOT is associated with several potential adverse effects for patients and caregivers, who need to be adequately informed about the associated risks and safety precautions. Oxygen can increase the risk of fire and burn injuries for the patient and others. The risk of fire accidents depends on the type of oxygen equipment used, where cylinders of compressed oxygen may be associated with a higher risk compared with liquid oxygen and oxygen concentrators (lowest risks). Tobacco smoke exposure reduces the life span of oxygen equipment, thereby increasing HOT-related costs.