Respiratory failure, caused by progressive damage to the airways, is a common consequence of chronic obstructive pulmonary disease (COPD). Chronic respiratory failure is classified as hypoxemic, which is characterised by low blood oxygen levels, or hypercapnic, which is a build-up of CO2. The latter is particularly problematic because it is associated with an increased risk of death, and patients with chronic hypercapnia are more likely to be admitted to hospital.1,2 Reducing hospital stays is an important treatment goal in COPD, because hospitalisation tends to have a negative impact on prognosis, with only 50% of patients still alive 5 years after hospital admission for COPD.3
Non-invasive ventilation (NIV) has been found to be effective in life-threatening situations when a patient suffers hypercapnic respiratory failure.4 However, the role of NIV used at home for the long-term management of COPD is less established, leading to confusion about whether it should be used at all. Therefore, a European Respiratory Society (ERS) Task Force has published a guideline providing evidence-based recommendations for the use of NIV at home.5 The main recommendations are summarised here and in Table 1.
Question 1: Should long-term home NIV be used in stable patients with COPD?
Recommendation: The ERS Task Force suggests that long-term home NIV should be used in patients with chronic stable hypercapnic COPD.
Despite the fact that no guidelines to date recommend the routine use of home NIV in patients with chronic stable hypercapnic COPD, it is increasingly being used in this setting.6 Early studies investigating its effectiveness had inconsistent findings, probably due to differences in study populations and variances in ventilator settings and usage.5 More recent studies have used high-intensity NIV, which appears to be more effective.7,8 Beneficial effects on survival, shortness of breath, exercise capacity and quality of life (QoL) have been reported.8,9 The use of NIV in these patients also appears to be cost-effective because it reduces exacerbations and hospitalisation.10
Question 2: Should long-term home NIV be used after an episode of acute hypercapnic respiratory failure in patients with COPD rather than not using NIV?
Recommendation: The ERS Task Force suggests that long-term home NIV can be used in patients with COPD following a life-threatening episode of acute hypercapnic respiratory failure requiring acute NIV, if hypercapnia persists following the episode.
Patients with chronic respiratory failure who experience an acute episode of respiratory failure are likely to have a repeat episode requiring hopitalisation.10 Some studies have shown that the use of NIV after hospital discharge can reduce re-hospitalisation rates, and can improve breathlessness and some physiological parameters, including arterial partial pressures of CO2 (PaCO2) and oxygen, and mean pulmonary artery pressure.11 However, other studies have not demonstrated an advantage.12
Question 3: When using long-term home NIV in patients with COPD, should the settings be adjusted to normalise or at least significantly reduce PaCO2?
Recommendation: The ERS Task Force suggests titrating NIV to normalise or reduce PaCO2 levels in patients with COPD.
No clinical trials have specifically targeted PaCO2 as an endpoint, so the task force considered a subgroup analysis of a larger study.13 These data were not sufficient to provide definitive recommendations about benefit, but there was minimal evidence of harm. Therefore, the task force decided the balance of evidence was in favour of the intervention.
Question 4: When using long-term home NIV in patients with COPD, should clinicians use fixed-pressure support mode as first choice, rather than adaptive or auto-titrating pressure modes?
Recommendation: The ERS Task Force suggests using fixed-pressure support mode as the first-choice ventilator mode in patients with COPD using home NIV.
Classical modes of operating NIV are comprised of both pressure-targeted and volume-targeted modes. In the former, the inspiratory pressure is fixed, while the volumes delivered can vary. In the latter, the volume is fixed while the pressure can vary. Both modes have been found to be equally effective, although pressure-targeted NIV tends to be better tolerated by patients.14 Recent advances in NIV devices have enabled adaptive or auto-titrating modes that aim to combine the advantages of volume- and pressure targeted NIV. However, no advantages in terms of QoL or patient-reported outcomes have been demonstrated.15,16 Importantly, there is a risk of harm in the event of an air leak, which could potentially lead to inappropriate low volumes being delivered.17 Since there is currently insufficient data to assess this potential risk, the task force cannot recommend the use of adaptive or auto-titrating modes at present.
Discussion
Because of the lack of strong evidence from clinical studies, all these recommendations were classified as weak and conditional, with the evidence being low or very low certainty (Table 1). This highlights the need for more well-designed clinical studies.
The guideline also discusses factors that may affect the benefits of long-term home NIV in patients with COPD. The task force reached the following conclusions:5
- Age, while being associated with a poor prognosis, should not limit the use of long-term home NIV.
- Mental and physical disability are barriers to the effective use of NIV. Caregivers are needed to assist patients with disabilities.
- Comorbidities, such as cancer, heart disease, obesity, cachexia and obstructive sleep apnoea, are not contraindications to the use of NIV.
- Adherence is key to the effectiveness of NIV. Patients should aim to use NIV for 5 hours a day.
- Humidification may be useful for patients with mucosal dryness.
- Supplemental oxygen can be used in patients with hypoxaemia. The dose of oxygen required during the day may be insufficient at night.
- Pulmonary rehabilitation may increase exercise capacity and QoL.
- It is reasonable to prescribe mucolytics to patients with airway secretions that might be a barrier to NIV.
Finally, the guideline considered monitoring and follow-up of patients during long-term home NIV. Improvements in NIV software have allowed for improved monitoring, and can provide details on adherence, respiratory rate and leakages. A small study found that parameters recorded by NIV devices can even predict exacerbations.18 The task force recommended that clinical evaluation should focus on symptoms of nocturnal hypoventilation and patient discomfort.5
In summary, the ERS guideline supports the use of long-term NIV in targeting a reduction in CO2 in COPD patients with persistent hypercapnic respiratory failure.
Table 1: ERS recommendations for long-term NIV use
| Question | Recommendation | Level of recommendation/evidence |
| Should LTH-NIV be used in stable patients with COPD? | LTH-NIV should be used for patients with chronic, stable, hypercapnic COPD | Conditional, low certainty evidence |
| Should LTH-NIV be used after an episode of acute hypercapnic respiratory failure in patients with COPD? | LTH-NIV should be used in patients with COPD after a life-threatening episode of acute hypercapnic respiratory failure in patients requiring acute NIV, if hypercapnia persists after the episode | Conditional, low certainty evidence |
| When using LTH-NIV in COPD patients, should NIV settings be titrated to normalise or at least cause a significant reduction in PaCO2? | LTN-NIV should be titrated to normalise or reduce PaCO2levels in patients with COPD | Conditional, very low certainty evidence |
| When using LTH-NIV in COPD patients, should we use fixed pressure modes rather than adaptive or auto-titrating pressure modes? | Fixed pressure support mode should be the first choice ventilator mode in patients with COPD using LTH-NIV | Conditional, very low certainty evidence |
COPD = chronic obstructive pulmonary disease; LTH-NIV = long-term home non-invasive ventilation; PaCO2 = arterial partial pressure of carbon dioxide
References
1. Connors AF, Jr., Dawson NV, Thomas C, et al., Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments), Am J Respir Crit Care Med, 1996;154:959-67.
2. Ahmadi Z, Bornefalk-Hermansson A, Franklin KA, et al., Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease: a population-based prospective study, Respir Res, 2014;15:30.
3. Hoogendoorn M, Hoogenveen RT, Rutten-van Molken MP, et al., Case fatality of COPD exacerbations: a meta-analysis and statistical modelling approach, Eur Respir J, 2011;37:508-15.
4. Rochwerg B, Brochard L, Elliott MW, et al., Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure, Eur Respir J, 2017;50:.
5. Ergan B, Oczkowski S, Rochwerg B, et al., European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD, Eur Respir J, 2019;54:.
6. Crimi C, Noto A, Princi P, et al., Domiciliary Non-invasive Ventilation in COPD: An International Survey of Indications and Practices, Copd, 2016;13:483-90.
7. Dreher M, Storre JH, Schmoor C, et al., High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial, Thorax, 2010;65:303-8.
8. Kohnlein T, Windisch W, Kohler D, et al., Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial, Lancet Respir Med, 2014;2:698-705.
9. Murphy PB, Rehal S, Arbane G, et al., Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial, Jama, 2017;317:2177-86.
10. Tuggey JM, Plant PK, Elliott MW, Domiciliary non-invasive ventilation for recurrent acidotic exacerbations of COPD: an economic analysis, Thorax, 2003;58:867-71.
11. Xiang PC, Zhang X, Yang JN, et al., [The efficacy and safety of long term home noninvasive positive pressure ventilation in patients with stable severe chronic obstructive pulmonary disease], Zhonghua Jie He He Hu Xi Za Zhi, 2007;30:746-50.
12. Struik FM, Sprooten RT, Kerstjens HA, et al., Nocturnal non-invasive ventilation in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure: a randomised, controlled, parallel-group study, Thorax, 2014;69:826-34.
13. Duiverman ML, Maagh P, Magnet FS, et al., Impact of High-Intensity-NIV on the heart in stable COPD: a randomised cross-over pilot study, Respir Res, 2017;18:76.
14. Windisch W, Storre JH, Sorichter S, et al., Comparison of volume- and pressure-limited NPPV at night: a prospective randomized cross-over trial, Respir Med, 2005;99:52-9.
15. Ekkernkamp E, Storre JH, Windisch W, et al., Impact of intelligent volume-assured pressure support on sleep quality in stable hypercapnic chronic obstructive pulmonary disease patients: a randomized, crossover study, Respiration, 2014;88:270-6.
16. Nilius G, Katamadze N, Domanski U, et al., Non-invasive ventilation with intelligent volume-assured pressure support versus pressure-controlled ventilation: effects on the respiratory event rate and sleep quality in COPD with chronic hypercapnia, Int J Chron Obstruct Pulmon Dis, 2017;12:1039-45.
17. Arellano-Maric MP, Gregoretti C, Duiverman M, et al., Long-term volume-targeted pressure-controlled ventilation: sense or nonsense?, Eur Respir J, 2017;49:.
18. Borel JC, Pelletier J, Taleux N, et al., Parameters recorded by software of non-invasive ventilators predict COPD exacerbation: a proof-of-concept study, Thorax, 2015;70:284-5.
