Abstract
Background
Retrospective survival data have suggested poor effectiveness of oxygen therapy in patients with interstitial lung disease (ILD).
Objectives
To determine the effect of domiciliary oxygen therapy on survival and quality of life in patients with a diagnosis of ILD and hypoxaemia.
Search methods
Randomized Controlled Trials (RCTs) were identified from searches of the Airways Group Specialised Register, CENTRAL, MEDLINE and EMBASE. Searches were current as of October 2010. No language restrictions were applied.
Selection criteria
Any randomized controlled trial (RCT) in adult patients with hypoxaemia and ILD that compared long term domiciliary or home oxygen therapy with a control group.
Data collection and analysis
Studies were assessed by two authors. Data were entered into Review Manager 5 and analysed.
Main results
Only one trial met the eligibility criteria of the review. Mortality for both the oxygen treated and control groups was approximately 91% after three years (Peto odds ratio 0.99, 95% confidence intervals 0.16 to 6.26). The effect of oxygen therapy on quality of life and physiological parameters was not reported.
Authors' conclusions
The assumption that home oxygen therapy has a beneficial survival effect in patients with ILD has not been demonstrated in the single RCT identified.
Plain language summary
Domiciliary oxygen for interstitial lung disease
Oxygen therapy is used to treat patients with interstitial lung disease (ILD) with low arterial blood oxygen levels. This review evaluated the effect of domiciliary long‐term oxygen therapy on survival and quality of life in patients with ILD. Only one randomized controlled trial was identified. This unpublished study reported that long‐term oxygen therapy did not improve survival compared with no oxygen therapy in patients with ILD. No data on quality of life was available.
Background
Diffuse interstitial lung disease (ILD) refers to a heterogeneous group of acute or chronic progressive lung disorders with varying degrees of pulmonary inflammation and fibrosis. The aetiology of ILD is often unknown. The spectrum of patient diagnoses includes idiopathic pulmonary fibrosis, ILD with collagen vascular disease, granulomatous ILD, ILD caused through drug reaction or particle deposition, lymphangioleiomyomatosis, bronchocentric granulomatosis, and bronchiolitis obliterans with organizing pneumonia (Reynolds 1998). Patients with ILD often develop chronic hypoxaemia which is related to the progression of their underlying condition and has been treated with long‐term home oxygen supplementation. Retrospective survival data have suggested poor effectiveness of oxygen therapy in ILD patients (Crockett 1991).
Objectives
The aim of this review was to determine the effect of long‐term domiciliary oxygen therapy on survival and quality of life in patients with a diagnosis of ILD and hypoxaemia.
Methods
Criteria for considering studies for this review
Types of studies
Any randomized controlled trial (RCT) in adult patients with hypoxaemia and ILD that compared long‐term domiciliary or home oxygen therapy with a control group.
Types of participants
Adults with ILD, who received home oxygen therapy in the community.
Types of interventions
The intervention in the active treatment group covered all forms of long‐term domiciliary oxygen therapy including provision of home oxygen by cylinders, concentrators or liquid oxygen therapy. In the control group, the intervention was to be either placebo air by the same method of delivery or no specific intervention.
Types of outcome measures
The outcomes determined in advance for this review were:
Survival
Health related quality of life as measured by a validated instrument
Improvement in physiological parameters
Search methods for identification of studies
Electronic searches
Trials were identified from the following sources:
Airways Group Specialised Register (all years to October 2010)
Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 4, 2010)
MEDLINE (1950‐October 2010)
EMBASE (1980‐October 2010)
No language restrictions were applied. The search strategies for each database were amended in 2007 and both sets of search strategies are detailed in Appendix 1.
Searching other resources
The bibliographies of each trial were searched for additional reports of RCTs. Authors of identified RCTs were contacted for additional data. In addition, companies who supplied the oxygen delivery devices and members of the International Respiratory Care Association were contacted for unpublished studies.
Data collection and analysis
All studies that appeared potentially relevant were assessed by two reviewers, who independently selected the trials for inclusion in this review. Disagreement was resolved by consensus.
The selected trial was scored for blinding as double blind, single blind or not blinded/not known.
The quality of concealment of allocation was rated according to the method proposed by Schulz 1995. Data for the trials was extracted by two reviewers (AC and JC).
Statistical considerations
Subgroup analysis, determined in advance, was to include where possible:
A comparison of male with female patients
A comparison of oxygen therapy treatment versus no oxygen therapy
Results
Description of studies
The original literature search was conducted in 2000 and has been updated on an annual basis. A total of 758 references have been identified and screened for inclusion. One unpublished RCT (Braghiroli 2000) was identified from the bibliographies of three review papers identified in the original search (Braghiroli 1993; Donner 1990; Zielinski 2000). The latest search was in 2010.
Only one study was identified which met the inclusion criteria for this review (Braghiroli 2000). This study has not yet been published. The controlled multi‐centre study was commenced in 1988 and compared long‐term oxygen therapy to a control, no oxygen therapy group. Patients of either gender and under 79 years of age with a diagnosis on X‐ray examination of interstitial pulmonary fibrosis were considered for inclusion into the study. The patients were clinically stable and without other major causes of morbidity and mortality such as malignancy, unstable angina, or recent myocardial infarction, congestive cardiac failure, alcoholism, recent pulmonary embolism, diabetes or pregnancy. The included patients were hypoxic, arterial oxygen tension (PaO2) between 45‐60 mm Hg (6.0‐8.0 kPa). Total lung capacity (TLC) was < 80% predicted. Pharmacological treatment was kept steady for as long as possible during the study. The patients were followed over a four year period. The outcome variables were survival, total lung capacity, dyspnoea trends and blood gases.
Risk of bias in included studies
The method of randomisation for the study was not stated. The method of blinding was not described. However, random sampling was set up by blocks, each with six cases allocated to the treatment group and five cases to the control group.
Effects of interventions
Sixty two patients were randomized into the study, 37 to treatment with long‐term domiciliary oxygen therapy (17 males and 20 females) and 25 (14 males and 11 females) to control group (no oxygen therapy). Forty nine of the patients (28 treated and 21 controls) had a diagnosis of idiopathic pulmonary fibrosis, and 13 (9 treated and 4 controls) had pulmonary fibrosis secondary to other diseases. Only mortality data with both disease groups combined was provided for the included patients (personal communication only). There was no difference in mortality at 12, 24 or 36 months between the treated and control groups. Mortality for both the oxygen treated and control groups was 91% after three years (Peto OR 0.99; 95% CI 0.16 to 6.26). The effect of oxygen therapy on physiological parameters was not indicated. Data on quality of life was not reported.
Discussion
There has been only one RCT of domiciliary long‐term oxygen therapy in ILD. The results of this study have not been published due to difficulties in collecting data on quality of life from some of the participating centres (verbal communication). This study showed that home oxygen therapy did not improve survival in patients with ILD when respiratory insufficiency had developed, compared to no oxygen therapy. At the present time long‐term oxygen therapy is prescribed if clinically indicated to treat hypoxaemia and relieve symptoms rather than on the basis of scientific evidence from RCTs. A non‐randomized study of long term oxygen therapy in patients with idiopathic pulmonary fibrosis (Polonski 1995) concluded that chronic home oxygen therapy attenuated cardiac dysfunction in the treated patients. However, the number of patients included in this study was small (n=18). The effect of long‐term oxygen therapy on quality of life and physiological parameters in ILD remains unknown.
Authors' conclusions
Implications for practice.
The assumption that home oxygen therapy has a beneficial effect on survival in patients with ILD has not been demonstrated in this review. The only relevant trial showed that long‐term oxygen therapy did not improve survival in patients with ILD. The effect of oxygen therapy on quality of life and physiological parameters was not reported.
Implications for research.
Multicentre studies are required to assess the use of adjunctive measures such as oxygen therapy in ILD. However, randomized controlled trials are difficult to perform if a patient is hypoxic. Ethical concerns have been raised about the randomization of patients to placebo and this may be a bar to obtaining more appropriate health status data about the effects of oxygen in more severely hypoxaemic subjects with ILD.
What's new
| Date | Event | Description |
|---|---|---|
| 28 October 2010 | New search has been performed | Literature search run; no new studies found. Minor copy edits made. |
History
Protocol first published: Issue 1, 1999 Review first published: Issue 3, 2001
| Date | Event | Description |
|---|---|---|
| 28 October 2009 | New search has been performed | Literature search re‐run; no new studies found |
| 24 October 2008 | New search has been performed | Literature search re‐run; no new studies were identified. |
| 23 July 2008 | Amended | Converted to new review format. |
| 22 May 2001 | New citation required and conclusions have changed | Substantive amendment |
Acknowledgements
We wish to acknowledge the assistance provided by the Cochrane Airways Review Group staff (Steve Milan, Toby Lasserson, Karen Blackhall and Liz Arnold) in identifying the trials from the register and obtaining copies of the papers and the three translators (Charlotta Pisinger, Anna Amstead and Derek Scoins) who translated the papers for us.
Appendices
Appendix 1. Search strategies
| Database searched | Search (up to 2006) | Search (from 2007 onwards) |
| CENTRAL | #1. LUNG DISEASES INTERSTITIAL explode tree 1 (MeSH); #2. (interstitial* near lung* near disease*); #3. alveolitis*; #4. (interstitial near pneumo*); #5. (lung* near purpura); #6. (goodpasture* near syndrome*); #7. granulomatosis; #8. bagassosis; #9. (berylliosis or beryllium); #10. hemosiderosis; #11. (hamman‐rich next syndrome*); #12. (pulmonary near fibros*); #13. (histiocytosis near langerhans); #14. (pulmonary near sarcoidosis); #15. (wegener* near granuloma*); #16. ((bird* near lung*) or (bird* near disease*)); #17. ((pigeon* near lung*) or (pigeon* near disease*)); #18. ((farmer* near lung*) or (farmer* near disease*)); #19. (asbestosis or byssinosis or silicosis or anthracosis or anthracosilicosis); #20. pneumoconiosis; #21. (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20) 949; #22. OXYGEN INHALATION THERAPY explode tree 1 (MeSH); #23. OXYGEN single term (MeSH); #24. HOME CARE SERVICES explode tree 1 (MeSH); #25. ((oxygen next therap*) or ((home* or domicil*) and oxygen) or (long next term next oxygen next therapy) or ltot); #26. (#22 or #23 or #24 or #25); #27 (#26 and #21) | #1 MeSH descriptor Lung Diseases, Interstitial explode all trees #2 pulmonary near fibros* #3 interstitial* near lung* #4 (#1 OR #2 OR #3) #5 MeSH descriptor Oxygen Inhalation Therapy explode all trees #6 MeSH descriptor Home Care Services explode all trees #7 MeSH descriptor Oxygen, this term only #8 ((oxygen next therap*) or ((home* or domicil*) and oxygen) or (long next term next oxygen next therapy) or ltot) #9 (#5 OR #6 OR #7 OR #8) #10 (#4 AND #9) |
| MEDLINE (combined with an RCT filter as described in the Airways Group Module) |
1. exp Lung Diseases, Interstitial/ 2. alveolitis.mp. 3. (interstitial adj3 lung$ adj3 disease$).mp. 4. (interstitial adj3 (pneumonia or pneumonitis)).mp. 5. (lung adj3 purpura).mp. 6. (goodpasture$ adj3 syndrome$).mp. 7. granulomatosis.mp. 8. bagassosis.mp. 9. (beryllium adj3 disease).mp. 10. hemosiderosis.mp. 11. hamman‐rich syndrome.mp. 12. (pulmonary adj3 (fibrosis or fibroses)).mp. 13. histiocytosis langerhans‐cell.mp. 14. pneumoconiosis.mp. 15. (asbestosis or berylliosis or byssinosis or siderosis or silicosis or anthracosis or anthracosilicosis or silicotuberculosis).mp. 16. (pulmonary adj3 sarcoidosis).mp. 17. (wegener$ adj3 granuloma$).mp. 18. ((bird$ or pigeon$ or hen$ or farmer$) adj3 (lung$ or disease$)).mp. 19. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 20. exp OXYGEN INHALATION THERAPY/ 21. exp OXYGEN/ 22. exp HOME CARE SERVICES/ 23. ((oxygen adj3 therap$) or ((home$ or domicil$) adj5 oxygen) or long term oxygen therap$ or LTOT).mp. 24. 20 or 21 or 22 or 23 25. 19 and 24 | 1. exp Lung Diseases, Interstitial/ 2. (interstitial adj3 lung$ adj3 disease$).mp. 3. (interstitial adj3 (pneumonia or pneumonitis)).mp. 4. (pulmonary adj3 (fibrosis or fibroses)).mp. 5. exp OXYGEN INHALATION THERAPY/ 6. exp OXYGEN/ 7. exp HOME CARE SERVICES/ 8. ((oxygen adj3 therap$) or ((home$ or domicil$) adj5 oxygen) or long term oxygen therap$ or LTOT).mp. 9. 5 or 6 or 7 or 8 10. or/1‐4 11. 9 and 10 |
| EMBASE (combined with an RCT filter as described in the Airways Group Module) |
1. exp Interstitial Lung Disease/ 2. (interstitial adj3 (lung$ or disease$ or fibros$ or pneumonitis or pneumonia or pneumopathy)).mp. 3. (Berylliosis or Beryllium).mp. 4. (Alveolitis or Pulmonary Fibrosis).mp. 5. (Hamman Rich adj3 (Disease$ or Syndrome$)).mp. 6. (Fibroid adj3 Phthisis).mp. 7. (Caplan$ adj3 (Syndrome$ or Disease$)).mp. 8. (Pneumoconiosis or Pneumokoniosis or Pneumonoconiosis or Pneumonokoniosis).mp. 9. (Lung adj3 Coniosis).mp. 10. ((Wegener$ or Pneumogenic or respiratory) adj3 (granulomatosis or disease$ or syndrome$)).mp. 11. (lung$ adj3 (coniosis or alveolitis or emphysema$ or fibrosis or infec$ or occupational)).mp. 12. (lung adj3 purpura).mp. 13. (pulmonary adj3 (fibrosis or fibroses)).mp. 14. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13; 15. exp Oxygen Therapy/ 16. exp OXYGEN/ 17. exp Home Care/ 18. ((oxygen adj3 therap$) or ((home$ or domicil$) adj5 oxygen) or long term oxygen therap$ or LTOT).mp. 19. 15 or 16 or 17 or 18 20. 14 and 19 | 1. exp Interstitial Lung Disease/ 2. (interstitial adj3 (lung$ or disease$ or fibros$ or pneumonitis or pneumonia or pneumopathy)).mp. 3. (pulmonary adj3 (fibrosis or fibroses)).mp. 4. exp Oxygen Therapy/ 5. exp OXYGEN/ 6. exp Home Care/ 7. ((oxygen adj3 therap$) or ((home$ or domicil$) adj5 oxygen) or long term oxygen therap$ or LTOT).mp. 8. 4 or 5 or 6 or 7 9. or/1‐3 10. 8 and 9 |
| Airways Group Specialised Register (restricted to records coded as 'interstitial lung disease) | (home OR domiciliary) AND oxygen | oxygen* or home* or domicil* or LTOT |
Data and analyses
Comparison 1. Oxygen therapy versus no oxygen therapy.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Mortality | 1 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 1.1 Mortality at 12 months | 1 | 62 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.50 [0.15, 1.61] |
| 1.2 Mortality at 24 months | 1 | 62 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.76 [0.64, 4.86] |
| 1.3 Mortality at 3 years | 1 | 62 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.99 [0.16, 6.26] |
1.1. Analysis.
Comparison 1 Oxygen therapy versus no oxygen therapy, Outcome 1 Mortality.
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Braghiroli 2000.
| Methods | Block randomization, with six cases allocated to the treatment group and five to the control group. | |
| Participants | Patients less than 79 years of age with interstitial pulmonary fibrosis. Inclusion criteria included a total lung capacity (TLC) <80% predicted and an arterial oxygen tension (PaO2) of 45‐60 mm Hg. | |
| Interventions | Long‐term oxygen therapy versus a control group. | |
| Outcomes | Survival over 4‐years. Physiological parameters of total lung capacity, arterial blood gases and dyspnea. | |
| Notes | Unpublished study ‐ data from Donner CF. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | Block randomisation; concealment of randomisation not described. |
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Polonski 1995 | This study was not randomised. |
Contributions of authors
AC and JC initiated the study. AC and JC reviewed the trials. JC was responsible for data entry and analysis. All reviewers participated in the discussion and interpretation of the results. AC and JC wrote the paper. AC is guarantor for the study.
Sources of support
Internal sources
NHS Research and Development, UK.
External sources
No sources of support supplied
Declarations of interest
None known
New search for studies and content updated (no change to conclusions)
References
References to studies included in this review
Braghiroli 2000 {unpublished data only}
- Braghiroli A, Donner CF. A multicentre randomized controlled trial on long term oxygen therapy in pulmonary fibrosis. Personal communication 2000.
References to studies excluded from this review
Polonski 1995 {published data only}
- Polonski L, Krzywiecki A, Polonska A, Tendera M, Cwiertka P, Oklek K, et al. Effects of long term oxygen therapy in patients with idiopathic pulmonary fibrosis. I. Effect on the course of the primary disease and on pulmonary circulation. Polskie Archiwum Medycyny Wewnetrznej 1995;94(4):331‐6. [PubMed] [Google Scholar]
- Polonski L, Kusnierz B, Krzywiecki A, Polonska A, Tendera M, Oklek K, et al. Effects of long term oxygen therapy in patients with idiopathic pulmonary fibrosis. II. Effect of oxygen therapy on function of heart ventricles. Polskie Archiwum Medycyny Wewnetrznej 1995;94(4):337‐41. [PubMed] [Google Scholar]
Additional references
Braghiroli 1993
- Braghiroli A, Ioli F, Spada EL, Vecchio C, Donner CF, Braghiroli A, et al. LTOT in pulmonary fibrosis. Monaldi Archives for Chest Disease 1993;48(5):437‐40. [PubMed] [Google Scholar]
Crockett 1991
- Crockett AJ, Alpers JH, Moss JR. Home oxygen therapy: an audit of survival. Australian and New Zealand Journal of Medicine 1991;21(2):217‐21. [DOI] [PubMed] [Google Scholar]
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Reynolds 1998
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Schulz 1995
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