0
Editorials: Point and Counterpoint |

COUNTERPOINT: Does Low-Dose Oxygen Expose Patients With COPD to More Radiation-Like Risks Than Patients Without COPD? No FREE TO VIEW

Kent L. Christopher, MD, RRT, FCCP; John E. Repine, MD
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST the following: K. L. C. has licensed patents to Transtracheal Systems, Inc, and might receive financial gain in the future. None declared (J. E. R.).

CORRESPONDENCE TO: Kent L. Christopher, MD, RRT, FCCP, 9086 East Colorado Circle, Denver, CO 80231


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(2):306-308. doi:10.1016/j.chest.2015.10.074
Text Size: A A A
Published online

We interpret “radiation-like” risk to represent the potential for cellular toxicity caused by low-dose oxygen (LDO) exposure to result in a deleterious clinical outcome. The question asks whether or not patients with COPD exposed to LDO are at higher risk of cellular toxicity (oxygen toxicity) than patients without COPD who are receiving LDO. Because sufficient evidence of the benefit of LDO in normoxemic patients with COPD is lacking,, discussion will focus on hypoxemic patients with COPD.

Lung tissue, particularly at the alveolar level where gas exchange occurs, is exposed to the highest concentration of oxygen in the body, thus has exposure to the greatest risk of oxygen toxicity (OT). OT has been shown to be dependent on the relationship between oxygen concentration (dose) and time (duration) of administration. This discussion pertains to oxygen administration in low concentration to self-breathing patients at atmospheric pressure. A nasal cannula (NC) is generally used to administer LDO with low flows from 1 to 4 L/min, but most commonly at approximately 2 L/min. A 24% or 28% venturi mask may be used for LDO in patients with chronic hypercapnia who have blunted CO2 ventilatory responsiveness, but face masks are more cumbersome than the NC. Schacter et al measured Fio2 in the trachea of patients with NC at rest with the mouth closed. The Fio2 was 24.3% ± 0.6% and 26.3% ± 1.2% with flows of 1 and 4 L/min, respectively. Poulton et al reported peak tracheal Fio2 with NC in a resting normal subject during nasal breathing with 2 L/min (32%) and 4 L/min (47%). At the same flow rates, peak flows with more clinically realistic mouth breathing were 22% and 24%, respectively. The Fio2 delivered to the lungs by LDO with NC has variability, essentially based on air dilution.

The recently published evidence-based British Thoracic Society Guidelines for Home Oxygen in Adults (BTS Home Oxygen Guidelines) are heavily supported by two randomized control trials. With regard to LDO with NC use in chronically hypoxemic (CH) patients with COPD, the Nocturnal Oxygen Therapy Trial (NOTT) evaluated nocturnal (12 ± 2.5 h/d) vs continuous (17 ± 4.8 h/d) use; the Medical Research Council (MRC) study compared 15 h/d with no supplemental oxygen in CH control patients with COPD. The two investigations collectively support BTS Home Oxygen Guidelines’ evidence that stable CH patients with COPD (resting Pao2< 55 mm Hg) have improved life expectancy when treated with long-term oxygen therapy (LTOT) for > 15 h/d (evidence level 1+). Use in this group was also recommended because of improved pulmonary hemodynamics (grade A). Stable patients with COPD who have a resting Pao2< 60 mm Hg with cor pulmonale, polycythemia, or pulmonary hypertension have improved outcomes with LTOT (evidence level 1+). Use of 24 h of oxygen therapy offers additional survival benefit compared with shorter durations (12-15 h) but can contribute to higher Paco2 levels (evidence level 1-). LTOT in hypercapnic patients with COPD does not lead to increased morbidity, mortality, or healthcare utilization (evidence level 1+). For CH patients with COPD it was recommended that LTOT be initiated at a flow rate of 1 L/min and titrated up in 1-L/min increments until an oxygen saturation by pulse oximetry (Spo2) > 90% and an arterial blood gas confirming a target Pao2> 60 mm Hg at rest are achieved (grade B). An upper limit for Pao2 was not identified in the MRC study nor recommended in the BTS Home Oxygen Guidelines. However, arterial blood gas assessment was periodically done throughout the NOTT study, and LDO was adjusted to maintain a Pao2 of 60 to 80 mm Hg. With regard to OT, the BTS Home Oxygen Guidelines acknowledge the MRC findings. The MRC authors concluded that “[t]here was no evidence of oxygen toxicity resulting from treatment, either in the few post mortem examinations available or in physiological evidence of widening of the alveolar to arterial oxygen tension gradient.” Furthermore, the MRC results showed that compared with CH control patients with COPD, there was no increase in hospital days or days spent away from work, and no increased mortality before 500 days in the LTOT group. These findings do not support OT as a result of LDO. After comprehensive review and grading of the medical literature, the BTS Home Oxygen Guidelines presented neither evidence nor recommendations regarding the risk of OT with the use of LDO in CH patients with COPD. Furthermore, as evidence was low (evidence level 4) for LTOT in patients without COPD (cystic fibrosis, interstitial lung disease, pulmonary hypertension, advanced cardiac failure, and neuromuscular or chest wall disorders), recommendations for LTOT were extrapolated from CH COPD evidence. Of interest, in the MRC study 52% of patients in the combined groups were cigarette smokers (reduced to only 44% at study’s end). Although cigarette smoking produces reactive oxygen species and plays a major role in the pathogenesis of COPD, the BTS Home Oxygen Guidelines reported that evidence was insufficient to determine adverse clinical outcomes related to the effect of continued smoking in patients undergoing LTOT who were receiving LDO compared with never smokers (evidence level 2+).

Hypoxemic patients with COPD without LDO may have increased radiation-like risk. Compared with nonhypoxemic patients with COPD with similar disease severity, hypoxemic patients with COPD breathing room air had lower quadriceps endurance time and worse muscle oxidative stress at rest and after exercise. Additionally, pulmonary rehabilitation in patients with COPD with submaximal intensity and increased exercise duration (73%) resulted in a decrease in reactive oxygen species–induced DNA damage. The BTS Home Oxygen Guidelines confirm that ambulatory oxygen therapy (AOT) acutely increases exercise capacity in laboratory-based exercise tests in patients not eligible for LTOT, but who demonstrate oxygen desaturation during exercise (evidence level 1+). AOT in a pulmonary rehabilitation program leads to improvement in those with > 10% increase in walking capacity (evidence level 1-). Finally, AOT should be offered during exercise in a pulmonary rehabilitation program or exercise program when improvement in exercise endurance has been demonstrated (grade B).

The evidence-based British Thoracic Guideline for Emergency Oxygen Use in Adult Patients emphasizes maintaining the Spo2 > 90% for the majority of acutely ill patients, and suggests a target normoxemic Spo2 range of 94% to 98%. However, for patients with COPD or other diseases who are at risk for hypercapnic respiratory failure, an Spo2 of 88% to 92% is recommended pending arterial blood gases, and that specific Spo2 level should be maintained with hypercapnia or hypercapnic respiratory failure history. LDO with NC or with 24% or 28% venturi mask was recommended. The British Thoracic Guideline for Emergency Oxygen Use in Adult Patients states that “[h]igh oxygen concentrations lead to an increase in reactive oxygen species which may cause tissue damage and may be responsible for detrimental effects observed with high-flow oxygen in myocardial infarction and stroke.” However, after comprehensive review and grading of the medical literature, that guideline did not present evidence of risk of OT with LDO in acutely ill hypoxemic patients with COPD.

There is compelling evidence that LDO in hypoxemic COPD is both safe and effective, and improves survival and pulmonary hemodynamics when used long-term in CH patients with COPD. Indications for treatment in both acutely ill patients with COPD and CH patients with COPD as well as recommendations for achieving a clinically safe, objectively targeted LDO delivery have been reasonably established. Does low-dose oxygen expose patients with COPD to more radiation-like risks than patients without COPD? No. Particularly with regard to CH patients with COPD, it is an increasing challenge from a US regulatory and clinical care perspective to ensure that qualified patients have access to LDO for LTOT. Generating a concern for a theoretical and speculative risk could unintentionally add to the list of impediments to access to evidence-based care.

References

O’Driscoll B.R. .Howard L.S. .Davison A.G. . British Thoracic Society BTS guideline for emergency oxygen use in adult patients. Thorax. 2008;63:vi1-vi68 [PubMed]journal. [PubMed]
 
Hardinge M. .Annandale J. .Bourne S. . British Thoracic Society Home Oxygen Guideline Development Group; British Thoracic Society Standards of Care Committeeet al British Thoracic Society guidelines for home oxygen use in adults. Thorax. 2015;70:i1-i43 [PubMed]journal. [CrossRef] [PubMed]
 
Kallet R.H. .Matthay M.A. . Hyperoxic acute lung injury. Respir Care. 2013;58:123-141 [PubMed]journal. [CrossRef] [PubMed]
 
Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med. 1980;93:391-398 [PubMed]journal. [CrossRef] [PubMed]
 
Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet. 1981;1:681-686 [PubMed]journal. [PubMed]
 
Schacter E.N. .Littner M.R. .Luddy P. .Beck G.J. . Monitoring of oxygen delivery systems in clinical practice. Crit Care Med. 1980;8:405-409 [PubMed]journal. [CrossRef] [PubMed]
 
Poulton T.J. .Comer P.B. .Gibson R.L. . Tracheal oxygen concentrations with a nasal cannula during oral and nasal breathing. Respir Care. 1980;25:739-741 [PubMed]journal
 
Casaburi R. . Assessing the dose of supplemental oxygen: let us compare methodologies [editorial]. Respir Care. 2005;50:594-595 [PubMed]journal. [PubMed]
 
Kirkham P.A. .Barnes P.J. . Oxidative stress in COPD. Chest. 2013;144:266-273 [PubMed]journal. [CrossRef] [PubMed]
 
Koechlin C. .Maltais F. .Saey D. .et al Hypoxaemia enhances peripheral muscle oxidative stress in chronic obstructive pulmonary disease. Thorax. 2005;60:834-841 [PubMed]journal. [CrossRef] [PubMed]
 
Mercken E.M. .Hageman G.J. .Schols A.M. .Akkermans M.A. .Bast A. .Wouters E.F. . Rehabilitation decreases exercise-induced oxidative stress in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;172:994-1001 [PubMed]journal. [CrossRef] [PubMed]
 
Christopher K.L. .Porte P. . Long-term oxygen therapy. Chest. 2011;139:430-434 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

O’Driscoll B.R. .Howard L.S. .Davison A.G. . British Thoracic Society BTS guideline for emergency oxygen use in adult patients. Thorax. 2008;63:vi1-vi68 [PubMed]journal. [PubMed]
 
Hardinge M. .Annandale J. .Bourne S. . British Thoracic Society Home Oxygen Guideline Development Group; British Thoracic Society Standards of Care Committeeet al British Thoracic Society guidelines for home oxygen use in adults. Thorax. 2015;70:i1-i43 [PubMed]journal. [CrossRef] [PubMed]
 
Kallet R.H. .Matthay M.A. . Hyperoxic acute lung injury. Respir Care. 2013;58:123-141 [PubMed]journal. [CrossRef] [PubMed]
 
Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med. 1980;93:391-398 [PubMed]journal. [CrossRef] [PubMed]
 
Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet. 1981;1:681-686 [PubMed]journal. [PubMed]
 
Schacter E.N. .Littner M.R. .Luddy P. .Beck G.J. . Monitoring of oxygen delivery systems in clinical practice. Crit Care Med. 1980;8:405-409 [PubMed]journal. [CrossRef] [PubMed]
 
Poulton T.J. .Comer P.B. .Gibson R.L. . Tracheal oxygen concentrations with a nasal cannula during oral and nasal breathing. Respir Care. 1980;25:739-741 [PubMed]journal
 
Casaburi R. . Assessing the dose of supplemental oxygen: let us compare methodologies [editorial]. Respir Care. 2005;50:594-595 [PubMed]journal. [PubMed]
 
Kirkham P.A. .Barnes P.J. . Oxidative stress in COPD. Chest. 2013;144:266-273 [PubMed]journal. [CrossRef] [PubMed]
 
Koechlin C. .Maltais F. .Saey D. .et al Hypoxaemia enhances peripheral muscle oxidative stress in chronic obstructive pulmonary disease. Thorax. 2005;60:834-841 [PubMed]journal. [CrossRef] [PubMed]
 
Mercken E.M. .Hageman G.J. .Schols A.M. .Akkermans M.A. .Bast A. .Wouters E.F. . Rehabilitation decreases exercise-induced oxidative stress in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;172:994-1001 [PubMed]journal. [CrossRef] [PubMed]
 
Christopher K.L. .Porte P. . Long-term oxygen therapy. Chest. 2011;139:430-434 [PubMed]journal. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
Evaluation of Wet Cupping Therapy: Systematic Review of Randomized Clinical Trials. J Altern Complement Med Published online Aug 24, 2016;
Nano-based rescue of dysfunctional autophagy in chronic obstructive lung diseases. Expert Opin Drug Deliv Published online Aug 26, 2016;
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543