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COPD overlap: in which direction one may look
Accepted Manuscript Predictors of CPAP failure in OSA/ COPD overlap: In which direction one may look A.S. Sandhya, DTCD, DNB, Antonio M. Esquinas, MD, Brijesh Prajapat, MD, DM PII:
S1389-9457(17)30273-3
DOI:
10.1016/j.sleep.2017.06.020
Reference:
SLEEP 3437
To appear in:
Sleep Medicine
Received Date: 19 June 2017 Revised Date:
1389-9457 1389-9457
Accepted Date: 28 June 2017
Please cite this article as: Sandhya A, Esquinas AM, Prajapat B, Predictors of CPAP failure in OSA/ COPD overlap: In which direction one may look, Sleep Medicine (2017), doi: 10.1016/ j.sleep.2017.06.020. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Elsevier Editorial System(tm) for Sleep Medicine Manuscript Draft
Manuscript Number: SLEEP-D-17-00441
Article Type: Letter to the Editor Corresponding Author: Dr. Sandhya A S, DTCD, DNB Corresponding Author's Institution:
SC
First Author: Sandhya A S, DTCD, DNB
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Title: Predictors of CPAP failure in OSA/ COPD overlap: In which direction one may look
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Order of Authors: Sandhya A S, DTCD, DNB; Antonio M Esquinas, MD; Brijesh Prajapat, MD,DM
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The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author) Click here to download The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author): COI form Sandh ACCEPTED MANUSCRIPT
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The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author) Click here to download The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author): COI form-2-sign ACCEPTED MANUSCRIPT
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The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author) Click here to download The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author): COI form- Brijes ACCEPTED MANUSCRIPT
*Manuscript Click here to view linked References
ACCEPTED MANUSCRIPT
Title : Predictors of CPAP failure in OSA/ COPD overlap: In which direction one may look Daytime hypercapnia and nocturnal hypoxia are independent predictors of early CPAP failure in patients with the OSA-COPD overlap syndrome. Keywords: overlap syndrome; obstructive sleep apnea; chronic obstructive pulmonary disease;
hypercapnia, hypoxia Abbreviations BIPAP: Bilevel positive airway pressure BMI: Body mass index
CPAP: continuous positive airway pressure FEV1: forced expiratory volume in 1 s
To Editor
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OSA: Obstructive sleep apnea
M AN U
COPD chronic obstructive pulmonary disease
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RI PT
continuous positive airway pressure; nocturnal oxygen; bilevel positive airway pressure; daytime
EP
Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are independent risk factors for cardiovascular diseases; COPD acts as an additive risk factor in OSA patients for
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cardiovascular diseases[1]. Continuous positive airway pressure (CPAP) therapy is the recommended therapy for COPD-OSA overlap, as it/because it improves survival, nocturnal hypoxemia, quality of life[2], and reduces hospitalisations [3]. We have read with great interest this large study by Kuklisova Z et al, that evaluated risk factors for CPAP failure in COPD-OSA overlap patients[4]. This is a controversial topic with important clinical and practical implications. However, reasons for CPAP failure needs more precise analysis. First, authors retrospectively analysed the CPAP success and failure and those who failed were again titrated with BIPAP. Reasons cited for failure were intolerance, failure to reduce hypoxemia (ODI) and more CT90%. However, CPAP with nocturnal oxygen therapy was not tried. CPAP
ACCEPTED MANUSCRIPT
with oxygen therapy is used especially if patients have predominantly nocturnal hypoventilation.[5]. This has noteworthy methodological implications and needs to be evaluated.
Second, CPAP and Bilevel groups have high BMI 30 kg/m2 vs 33 kg/m2. Obesity itself can impair the ventilatory mechanics in COPD by protean effects. Level of Leptin and leptin resistance could
RI PT
be an important determinant in these groups [2]. The daytime hypoventilation mechanism in COPD overlap is largely unknown; however, concomitant obesity with leptin resistance can explain a part of it and thus, the failure of these treatment modalities.
Third, in this study patients were p a r t o f a mild to moderate COPD group (CPAP group –
SC
FEV1 around 80% while BIPAP group- moderate COPD group). Under typical circumstances, a COPD patient shows daytime hypercapnia when FEV1 decreases to around 30% predicted and
M AN U
hypoxemia when FEV1 decreases to 50% predicted [6]. However, COPD-OSA overlap shows hypercapnia if they are mostly moderate to severe COPD patients. It may be possible that the predominantly hypoventilators variety of OHS (around 10% of OHS) are contributing to the nocturnal hypoxemia and daytime hypercapnia and subsequent failure of CPAP therapy for which bilevel is the choice [7].
TE D
The use of CPAP has both short term and long term effects[8]; immediate effects are abolishment of apneas/hypopneas, removing upper airway obstruction, and increasing lung volumes at end expiration. A long term effect is the resetting of ventilatory drive, which needs weeks to months
EP
to occur as illustrated by Piper et al [8]. Patients were immediately put into bilevel group once the CPAP failed during titration. It may be possible that long term use of CPAP along with/without
AC C
oxygen therapy would have a beneficial role in patients who failed CPAP therapy on the first night, due to re- setting of ventilatory drive or improvement in blunting of chemosensitivity. We believe that further clinical trials are needed to confirm and delineate between real implications and differences in assessment, and how nocturnal hypoxia and daytime hypercapnia predicts CPAP failure in patients with COPD and OSA.
Authors declare no conflict of interest Editor’s note: Dr Kuklisova and colleagues were offered the opportunity to respond, but declined the invitation.
References
ACCEPTED MANUSCRIPT
1. Shiina K, Tomiyama H, Takata Y, et al.Overlap syndrome: additive effects of COPD on the cardiovascular damages in patients with OSA. Respir Med 2012;106(9):1335-41. 2. Owens RL, Malhotra A. Sleep disordered breathing in COPD. Respir Care. 2010 Oct; 55(10): 1333–1346.
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3. Marin JM, Soriano JB, Carrizo SJ et al. outcomes in patients with chronic obstructive pulmonary diseases and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med. 2010;182(3):325-31 4. Kuklisova Z, Tkacova R, Joppa P, Wouters E, Sastry M. Severity of nocturnal hypoxia and daytime hypercapnia predicts CPAP failure in patients with COPD and obstructive sleep apnea overlap syndrome. Sleep Med. 2017 Feb;30:139-145
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5. Jen R, Li Y, Owens RL, Malhotra A. Sleep in Chronic Obstructive Pulmonary Disease: Evidence Gaps and Challenges. Can Respir J. 2016;2016:7947198.
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6. Rodríguez DA, Jover L, Drakulovic MB, Gómez FP, Roca J, et al. Below what FEV1 should arterial blood be routinely taken to detect chronic respiratory failure in COPD? Arch Bronconeumol. 2011 Jul;47(7):325-9. 7. Mokhlesi B. Obesity hypoventilation syndrome: a state-of-the-art review. Respir Care. 2010;55:1347-1362. discussion 1363-65.
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8. Piper AJ, Wang D, Yee BJ, Barnes DJ, Grunstein RR. Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax 2008;63: 395–401.
S1389-9457(17)30273-3
DOI:
10.1016/j.sleep.2017.06.020
Reference:
SLEEP 3437
To appear in:
Sleep Medicine
Received Date: 19 June 2017 Revised Date:
1389-9457 1389-9457
Accepted Date: 28 June 2017
Please cite this article as: Sandhya A, Esquinas AM, Prajapat B, Predictors of CPAP failure in OSA/ COPD overlap: In which direction one may look, Sleep Medicine (2017), doi: 10.1016/ j.sleep.2017.06.020. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Elsevier Editorial System(tm) for Sleep Medicine Manuscript Draft
Manuscript Number: SLEEP-D-17-00441
Article Type: Letter to the Editor Corresponding Author: Dr. Sandhya A S, DTCD, DNB Corresponding Author's Institution:
SC
First Author: Sandhya A S, DTCD, DNB
RI PT
Title: Predictors of CPAP failure in OSA/ COPD overlap: In which direction one may look
AC C
EP
TE D
M AN U
Order of Authors: Sandhya A S, DTCD, DNB; Antonio M Esquinas, MD; Brijesh Prajapat, MD,DM
AC C
EP
TE D
M AN U
SC
RI PT
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author) Click here to download The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author): COI form Sandh ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author) Click here to download The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author): COI form-2-sign ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author) Click here to download The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest (for each author): COI form- Brijes ACCEPTED MANUSCRIPT
*Manuscript Click here to view linked References
ACCEPTED MANUSCRIPT
Title : Predictors of CPAP failure in OSA/ COPD overlap: In which direction one may look Daytime hypercapnia and nocturnal hypoxia are independent predictors of early CPAP failure in patients with the OSA-COPD overlap syndrome. Keywords: overlap syndrome; obstructive sleep apnea; chronic obstructive pulmonary disease;
hypercapnia, hypoxia Abbreviations BIPAP: Bilevel positive airway pressure BMI: Body mass index
CPAP: continuous positive airway pressure FEV1: forced expiratory volume in 1 s
To Editor
TE D
OSA: Obstructive sleep apnea
M AN U
COPD chronic obstructive pulmonary disease
SC
RI PT
continuous positive airway pressure; nocturnal oxygen; bilevel positive airway pressure; daytime
EP
Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are independent risk factors for cardiovascular diseases; COPD acts as an additive risk factor in OSA patients for
AC C
cardiovascular diseases[1]. Continuous positive airway pressure (CPAP) therapy is the recommended therapy for COPD-OSA overlap, as it/because it improves survival, nocturnal hypoxemia, quality of life[2], and reduces hospitalisations [3]. We have read with great interest this large study by Kuklisova Z et al, that evaluated risk factors for CPAP failure in COPD-OSA overlap patients[4]. This is a controversial topic with important clinical and practical implications. However, reasons for CPAP failure needs more precise analysis. First, authors retrospectively analysed the CPAP success and failure and those who failed were again titrated with BIPAP. Reasons cited for failure were intolerance, failure to reduce hypoxemia (ODI) and more CT90%. However, CPAP with nocturnal oxygen therapy was not tried. CPAP
ACCEPTED MANUSCRIPT
with oxygen therapy is used especially if patients have predominantly nocturnal hypoventilation.[5]. This has noteworthy methodological implications and needs to be evaluated.
Second, CPAP and Bilevel groups have high BMI 30 kg/m2 vs 33 kg/m2. Obesity itself can impair the ventilatory mechanics in COPD by protean effects. Level of Leptin and leptin resistance could
RI PT
be an important determinant in these groups [2]. The daytime hypoventilation mechanism in COPD overlap is largely unknown; however, concomitant obesity with leptin resistance can explain a part of it and thus, the failure of these treatment modalities.
Third, in this study patients were p a r t o f a mild to moderate COPD group (CPAP group –
SC
FEV1 around 80% while BIPAP group- moderate COPD group). Under typical circumstances, a COPD patient shows daytime hypercapnia when FEV1 decreases to around 30% predicted and
M AN U
hypoxemia when FEV1 decreases to 50% predicted [6]. However, COPD-OSA overlap shows hypercapnia if they are mostly moderate to severe COPD patients. It may be possible that the predominantly hypoventilators variety of OHS (around 10% of OHS) are contributing to the nocturnal hypoxemia and daytime hypercapnia and subsequent failure of CPAP therapy for which bilevel is the choice [7].
TE D
The use of CPAP has both short term and long term effects[8]; immediate effects are abolishment of apneas/hypopneas, removing upper airway obstruction, and increasing lung volumes at end expiration. A long term effect is the resetting of ventilatory drive, which needs weeks to months
EP
to occur as illustrated by Piper et al [8]. Patients were immediately put into bilevel group once the CPAP failed during titration. It may be possible that long term use of CPAP along with/without
AC C
oxygen therapy would have a beneficial role in patients who failed CPAP therapy on the first night, due to re- setting of ventilatory drive or improvement in blunting of chemosensitivity. We believe that further clinical trials are needed to confirm and delineate between real implications and differences in assessment, and how nocturnal hypoxia and daytime hypercapnia predicts CPAP failure in patients with COPD and OSA.
Authors declare no conflict of interest Editor’s note: Dr Kuklisova and colleagues were offered the opportunity to respond, but declined the invitation.
References
ACCEPTED MANUSCRIPT
1. Shiina K, Tomiyama H, Takata Y, et al.Overlap syndrome: additive effects of COPD on the cardiovascular damages in patients with OSA. Respir Med 2012;106(9):1335-41. 2. Owens RL, Malhotra A. Sleep disordered breathing in COPD. Respir Care. 2010 Oct; 55(10): 1333–1346.
RI PT
3. Marin JM, Soriano JB, Carrizo SJ et al. outcomes in patients with chronic obstructive pulmonary diseases and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med. 2010;182(3):325-31 4. Kuklisova Z, Tkacova R, Joppa P, Wouters E, Sastry M. Severity of nocturnal hypoxia and daytime hypercapnia predicts CPAP failure in patients with COPD and obstructive sleep apnea overlap syndrome. Sleep Med. 2017 Feb;30:139-145
SC
5. Jen R, Li Y, Owens RL, Malhotra A. Sleep in Chronic Obstructive Pulmonary Disease: Evidence Gaps and Challenges. Can Respir J. 2016;2016:7947198.
M AN U
6. Rodríguez DA, Jover L, Drakulovic MB, Gómez FP, Roca J, et al. Below what FEV1 should arterial blood be routinely taken to detect chronic respiratory failure in COPD? Arch Bronconeumol. 2011 Jul;47(7):325-9. 7. Mokhlesi B. Obesity hypoventilation syndrome: a state-of-the-art review. Respir Care. 2010;55:1347-1362. discussion 1363-65.
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8. Piper AJ, Wang D, Yee BJ, Barnes DJ, Grunstein RR. Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax 2008;63: 395–401.