Long-term oxygen therapy for patients with chronic obstructive pulmonary disease (COPD): an evidence-based analysis

Abstract

Objective: The objective of this health technology assessment was to determine the effectiveness, cost-effectiveness, and safety of long-term oxygen therapy (LTOT) for chronic obstructive pulmonary disease (COPD).

Clinical Need: Condition and Target Population: Oxygen therapy is used in patients with COPD with hypoxemia, or very low blood oxygen levels, because they may have difficulty obtaining sufficient oxygen from inspired air.

Technology: Long-term oxygen therapy is extended use of oxygen. Oxygen therapy is delivered as a gas from an oxygen source. Different oxygen sources are: 1) oxygen concentrators, electrical units delivering oxygen converted from room air; 2) liquid oxygen systems, which deliver gaseous oxygen stored as liquid in a tank; and 3) oxygen cylinders, which contain compressed gaseous oxygen. All are available in portable versions. Oxygen is breathed in through a nasal cannula or through a mask covering the mouth and nose. The treating clinician determines the flow rate, duration of use, method of administration, and oxygen source according to individual patient needs. Two landmark randomized controlled trials (RCTs) of patients with COPD established the role of LTOT in COPD. Questions regarding the use of LTOT, however, still remain.

Research Question: What is the effectiveness, cost-effectiveness, and safety of LTOT compared with no LTOT in patients with COPD, who are stratified by severity of hypoxemia?

Search Strategy: A literature search was performed on September 8, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, CINAHL, the Cochrane Library, and INAHTA for studies published from January 1, 2007 to September 8, 2010.

A single clinical epidemiologist reviewed the abstracts, obtained full-text articles for studies meeting the eligibility criteria, and examined reference lists for additional relevant studies not identified through the literature search. A second clinical epidemiologist and then a group of epidemiologists reviewed articles with an unknown eligibility until consensus was established.

Inclusion Criteria:

1. patients with mild, moderate, or severe hypoxemia;

2. English-language articles published between January 1, 2007 and September 8, 2010;

3. journal articles reporting on effectiveness, cost-effectiveness, or safety for the comparison of interest;

4. clearly described study design and methods;

5. health technology assessments, systematic reviews, RCTs, or prospective cohort observational studies;

6. any type of observational study for the evaluation of safety.

Exclusion Criteria:

1. no hypoxemia

2. non-English papers

3. animal or in vitro studies

4. case reports, case series, or case-case studies

5. studies comparing different oxygen therapy regimens

6. studies on nocturnal oxygen therapy

7. studies on short-burst, palliative, or ambulatory oxygen (supplemental oxygen during exercise or activities of daily living)

Outcomes of Interest:

1. mortality/survival

2. hospitalizations

3. readmissions

4. forced expiratory volume in 1 second (FEV₁)

5. forced vital capacity (FVC)

6. FEV₁/FVC

7. pulmonary hypertension

8. arterial partial pressure of oxygen (PaO₂)

9. arterial partial pressure of carbon dioxide (PaCO₂)

10. end-exercise dyspnea score

11. endurance time

12. health-related quality of life

Note: Outcomes of interest were formulated according to existing studies, with arterial pressure of oxygen and carbon dioxide as surrogate outcomes.

Conclusions:

1. Based on low quality of evidence, LTOT (~ 15 hours/day) decreases all-cause mortality in patients with COPD who have severe hypoxemia (PaO₂ ~ 50 mm Hg) and heart failure.

2. The effect for all-cause mortality had borderline statistical significance when the control group was no LTOT: one study.

3. Based on low quality of evidence, there is no beneficial effect of LTOT on all-cause mortality at 3 and 7 years in patients with COPD who have mild-to-moderate hypoxemia (PaO₂ ~ 59-65 mm Hg)

4. Based on very low quality of evidence, there is some suggestion that LTOT may have a beneficial effect over time on FEV₁ and PaCO₂ in patients with COPD who have severe hypoxemia and heart failure: improved methods are needed.

5. Based on very low quality of evidence, there is no beneficial effect of LTOT on lung function or exercise factors in patients with COPD who have mild-to-moderate hypoxemia, whether survivors or nonsurvivors are assessed.

6. Based on low to very low quality of evidence, LTOT does not prevent readmissions in patients with COPD who have severe hypoxemia. Limited data suggest LTOT increases the risk of hospitalizations.

7. Limited work has been performed evaluating the safety of LTOT by severity of hypoxemia.

8. Based on low to very low quality of evidence, LTOT may have a beneficial effect over time on health-related quality of life in patients with COPD who have severe hypoxemia. Limited work using disease-specific instruments has been performed.

9. Ethical constraints of not providing LTOT to eligible patients with COPD prohibit future studies from examining LTOT outcomes in an ideal way.

Figure 1:. Citation Flow Chart*

Figure 2:. Mortality (Number of Events)

Figure 3:. Forced Expiratory Volume in One Second (Litres)

Figure 4:. Forced Expiratory Volume in One Second (% Predicted)

Figure 5:. Forced Expiratory Volume in One Second by Forced Vital Capacity (%)

Figure 6:. Forced Vital Capacity (Litres)

Figure 7:. Forced Vital Capacity (% Predicted)

Figure 8:. Arterial Pressure of Oxygen (mm Hg),

Figure 9:. Arterial Pressure of Carbon Dioxide (mm Hg)

Figure 10:. Dyspnea (Borg Scale)

Figure 11:. Endurance Time (Minutes),