Alan T. Mulgrew, MB; Nurit Fox, MSc, CCRP; Najib T. Ayas, MD, MPH; C. Frank Ryan, MB
ClinicalTrials.gov identifier: NCT00254059.
Acknowledgments: The authors thank their colleagues, staff, and patients of the University of British Columbia Hospital Sleep Disorders Program for their help in the conduct of this study. They also thank Drs. Penny Brasher and Michael Schulzer for their help with the statistical analysis.
Grant Support: By way of a Grant-in-Aid from ResMed Corp., Poway, California, and Vitalaire Canada Inc., Mississauga, Ontario, Canada; and a Michael Smith Foundation for Health Research Infrastructure Grant (Sleep-Disordered Breathing). One Remmers Sleep Recorder (formerly SnoreSat, Sagatech Electronics Inc., Calgary, Alberta, Canada) was provided on loan for the duration of the study. Dr. Mulgrew is supported by a BC Lung Fellowship and by the CIHR/HSFC IMPACT training program. Dr. Ayas is supported by a Michael Smith Foundation for Health Research Scholar Award, a CIHR/BC Lung Association New Investigator Award, and a Departmental Scholar Award from the University of British Columbia.
Potential Financial Conflicts of Interest: Grants received: N.T. Ayas (Respironics Inc.), C.F. Ryan (ResMed Corp., Vitalaire Canada, Inc.).
Requests for Single Reprints: Frank Ryan, MB, The Lung Centre, 7th Floor, Diamond Health Care Centre, 2775 Laurel Street, Vancouver, British Columbia, V5Z 1M9, Canada; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Mulgrew, Fox, Ayas, and Ryan: The Lung Centre, 7th Floor, Diamond Health Care Centre, 2775 Laurel Street, Vancouver, British Columbia V5Z 1M9, Canada.
Author Contributions: Conception and design: C.F. Ryan.
Analysis and interpretation of the data: A.T. Mulgrew, C.F. Ryan.
Drafting of the article: A.T. Mulgrew, C.F. Ryan.
Critical revision of the article for important intellectual content: A.T. Mulgrew, N.T. Ayas.
Final approval of the article: A.T. Mulgrew, N. Fox, N.T. Ayas, C.F. Ryan.
Provision of study materials or patients: N.T. Ayas, C.F. Ryan.
Statistical expertise: A.T. Mulgrew, N.T. Ayas.
Obtaining of funding: C.F. Ryan.
Administrative, technical, or logistic support: A.T. Mulgrew, N. Fox.
Collection and assembly of data: N. Fox.
Mulgrew A., Fox N., Ayas N., Ryan C.; Diagnosis and Initial Management of Obstructive Sleep Apnea without Polysomnography: A Randomized Validation Study. Ann Intern Med. 2007;146:157-166. doi: 10.7326/0003-4819-146-3-200702060-00004
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Published: Ann Intern Med. 2007;146(3):157-166.
Symptomatic obstructive sleep apnea is a common, underdiagnosed condition that occurs in 4% of men and in 2% of women (1). Patients with obstructive sleep apnea have considerable comorbid conditions, including excessive daytime sleepiness; concentration difficulties; and an increased risk for motor vehicle accidents, hypertension (2), coronary artery disease, and strokes. Obstructive sleep apnea may result in a systemic inflammatory state that predisposes the patient to cardiac and cerebrovascular conditions (3). Continuous positive airway pressure (CPAP) is an effective treatment that is commonly prescribed for symptomatic patients with obstructive sleep apnea: It is cost-effective (4) and reduces daytime sleepiness, rates of motor vehicle accidents, and blood pressure.
Konrad E. Bloch
Pulmonary Division, University Hospital of Zurich
March 4, 2007
Ambulatory management of sleep apnea syndrome
Mulgrew et al (1) propose an ambulatory diagnostic/therapeutic algorithm for the obstructive sleep apnea syndrome (OSAS). Patients with a very high likelihood of OSAS based on a questionnaire and an ambulatory polygraphic sleep study were treated with autoadjusted continuous positive airway pressure (autoCPAP) without confirming the diagnosis by polysomnography. Compared to a control group undergoing diagnostic in- laboratory polysomnography the group managed according to the ambulatory algorithm had a similar outcome after 3 months, i.e., a median apnea/hypopnea index on CPAP of 2.5/h vs. 3.2/h. Given the high prevalence of OSAS and the limited availability of polysomnography simplified diagnostic and treatment procedures are needed. Whether the algorithm proposed by Mulgrew et al significantly contributes to solve this problem is debatable. Very conservative criteria required for applying ambulatory care and other reasons resulted in randomization of only 68 out of 2216 patients (3%) referred for evaluation of sleep-disordered breathing. Moreover, these highly selected patients had to return multiple times to the clinic: for the ambulatory sleep study, for pulse oximetry on day 6 and 13, and for interrogation of the CPAP device on day 7 and 14. Additional visits were required in some cases. Contrary to the claim of Mulgrew et al., studies on ambulatory diagnostic/therapeutic algorithms for OSAS have been performed before (2;3). We have evaluated a novel ambulatory approach to the diagnosis and treatment of OSAS based on the response to empiric autoCPAP therapy during 2 weeks in sleepy snorers with clinically suspected OSAS (2). The trial result suggested OSAS if the patient had used CPAP for >2 h per night and wished to continue therapy. The CPAP trial predicted OSAS (apnea/hypopnea index >10/h) with positive and negative predictive values of 97% and 78%, respectively. Furthermore, it identified patients using CPAP for >4months who experienced persistent symptomatic improvement with positive and negative predictive values of 92% and 100%, respectively. Therefore, a CPAP trial may help to diagnose OSAS, to identify patients who benefit from CPAP, and to reduce the need for polysomnography. We believe that simple ambulatory diagnostic/therapeutic strategies for OSAS should not only be considered in sleep clinics with inadequate access to polysomnography as concluded by Mulgrev et al. but they should be applied in all patients with a high likelihood of OSAS if an equivalent or even superior clinical outcome compared to the conventional laboratory-based approach has been demonstrated.
(1) Mulgrew AT, Fox N, Ayas NT, Ryan CF. Diagnosis and initial management of obstructive sleep apnea without polysomnography: a randomized validation study. Ann Intern Med. 2007;146:157-66.
(2) Senn O, Brack T, Russi EW, Bloch KE. A continuous positive airway pressure trial as a novel approach to the diagnosis of the obstructive sleep apnea syndrome. Chest. 2006;129:67-75.
(3) Whitelaw WA, Brant RF, Flemons WW. Clinical usefulness of home oximetry compared with polysomnography for assessment of sleep apnea. Am J Respir Crit Care Med. 2005;171:188-93.
Dominic A. Munafo
Med. Director, Sleep Data, Inc., Assist. Clinical Prof. (voluntary), Univ. of California, San Diego
March 19, 2007
Ambulatory Sleep Apnea Testing
TO THE EDITOR:
Mulgrew and colleagues (1) have significantly advanced the dialogue on the appropriate use of ambulatory sleep testing protocols for the diagnosis and therapy of patients with a high pre-test probability of sleep apnea. It is however, important to note that the first such report was published quite a number of years ago by Coppola and Lawee (2). These authors identified eleven patients with severe apnea (mean apnea-hypopnea index (AHI) = 41) on the basis of four channel unattended studies. Continuous positive airway pressure (CPAP) therapy was begun empirically with 5 to 7.5 cm H2O pressure and then adjusted based on reported symptoms and snoring. All of the patients had documented return of their AHI to normal levels and long-term follow-up (mean 18 months) found all patients wearing their CPAP. Thus, these patients were successfully diagnosed and managed on an exclusively outpatient basis.
With regard to the current study I would like to make two points. First, it would be interesting to know whether Mulgrew and colleagues found that the addition of two follow-up oximetry studies added significantly to the already available clinical information when deciding whether to adjust a patient's CPAP pressure. Clearly this represents a significant added expense and inconvenience and thus impacts the attractiveness of this particular approach.
Second, it would seem reasonable to draw a more powerful conclusion based on the outcome data reported. The adherence to CPAP therapy was statistically significantly better by more than one hour in the ambulatory group. After three months of therapy there was no difference in AHIs between the two groups. And, fully 62% of the PSG patients would have preferred an ambulatory approach as opposed to only 6% of the ambulatory group preferring in-lab management. Given these findings why should the ambulatory approach be relegated only to instances when access to PSG is inadequate?
It seems a shame that it has taken over a decade for the works of Mulgrew, Masa (3), and Fitzpatrick (4), among others, to continue to move the ambulatory paradigm forward. Some of the delay has resulted from the fact that so much of the ambulatory testing literature has had as it's focus the comparison of the AHIs obtained from polysomnograms (PSG) and a variety of ambulatory monitors. This body of literature often makes the assumption that all in-lab PSGs yield the same results on any given patient. This assumption has not been substantiated. More importantly, it fails to focus on the more important endpoint of patient outcomes. As a result, the finding of statistically significant differences in the AHIs obtained between the techniques has been used to limit the acceptance of ambulatory monitors. The differences seen in AHI between the different techniques may reach statistical significance while having virtually no clinical significance. Hopefully, continued work such as that of Mulgrew and colleagues will continue to stress clinically significant outcome variables and allow an intelligent discussion of the role of ambulatory testing in the overall approach to patients with obstructive sleep apnea.
1. Mulgrew AT, Fox N, Ayas NT, Ryan CF. Diagnosis and Initial Management of Obstructive Sleep Apnea without Polysomnography. Ann Intern Med. 2007;146:157-166.
2. Coppola MP, Lawee M. Management of Obstructive Sleep Apnea Syndrome in the Home. Chest 1993;104:19-25.
3. Masa JF, Jimenez A, Duran J, et al. Alternative Methods of Titrating Continuous Positive Airway Pressure. A Large Multicenter Study. Am J Respir Crit Care Med. 2004;170:1218-1224.
4. Fitzpatrick MF, Alloway CED, Wakeford TM, MacLean AW, Munt PW. Can Patients with Obstructive Sleep Apnea Titrate Their Own Continuous Positive Airway Pressure? Am J Respir Crit Care Me
Medical Director, Sleep Data, Inc.
C. Frank Ryan
University of British Columbia
March 28, 2007
Ambulatory Management of Obstructive Sleep Apnea Without Polysomnography
We are grateful to Bloch and colleagues for drawing attention to some important points for discussion regarding our article1.We focused exclusively on high probability patients in order to test our strategy first in patients most in need, while minimizing the risk of misdiagnosis. Bloch and colleagues infer that our selection criteria excluded 97% of our patients from the trial (figure 2). Many patients could not participate in the trial due to time or distance constraints, rather than our stringent inclusion criteria. The proportion of eligible patients based only on the characteristics of their disease would be closer to 15%. Our trial protocol was rigorous to ensure patient safety, and we do not suggest replicating those conditions in clinical practice. Our suggested approach to patients in the clinic is included in the much-simplified clinical algorithm (figure 5) that requires an initial consultation, a follow-up visit for initiation of CPAP after ambulatory diagnosis, and a follow-up after 2 weeks on CPAP to confirm efficacy.
Bloch and colleagues point to previous studies that tested diagnostic/therapeutic algorithms2,3.In Whitelaw's study all patients were placed on auto-CPAP, and in Senn's study there was no randomized component. An earlier study by Coppola and associates was a small retrospective case series4. The recommended approach to diagnosis and treatment of OSA involves 2 nights in the sleep lab "“ 1 diagnostic study and 1 CPAP titration. We tested both components against an ambulatory strategy and we believe that this is the first study to do so in a randomized manner. Furthermore our results allow for the separation of the components of our algorithm "“ the diagnostic and treatment strategies can be used independently. In many countries a diagnosis of OSA is required before reimbursement for CPAP equipment; therefore we felt it important to achieve a diagnosis prior to treatment. Our experience in this study supports the use of a 2-week CPAP trial as confirmation of the diagnosis of OSA, and we include that in our algorithm (figure 5).
Finally, we agree with Bloch and colleagues that ambulatory approaches should be adopted as a first-line strategy for high probability patients, with the caveat that patients who do not meet the criteria of the diagnostic algorithm or who fail to respond favorably to CPAP should have polysomnography. It is estimated that 82% of patients with OSA are undiagnosed5. Increasing awareness of OSA and increasing prevalence of obesity will likely make ambulatory strategies a necessity.
1. Mulgrew A FN, Ayas N, Ryan CF. Diagnosis and Initial Management of Obstructive Sleep Apnea without Polysomnography: A Validation Study. Annals of Internal Medicine 2007:In Press.
2. Senn O, Brack T, Russi EW, Bloch KE. A continuous positive airway pressure trial as a novel approach to the diagnosis of the obstructive sleep apnea syndrome. Chest 2006;129(1):67-75.
3. Whitelaw WA, Brant RF, Flemons WW. Clinical usefulness of home oximetry compared with polysomnography for assessment of sleep apnea. Am J Respir Crit Care Med 2005;171(2):188-93.
4. Coppola MP, Lawee M. Management of obstructive sleep apnea syndrome in the home. The role of portable sleep apnea recording. Chest 1993;104(1):19 -25.
5. Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep 1997;20(9):705-6.
N.T. Ayas (Respironics Inc.), C.F. Ryan (ResMed Corp., Vitalaire Canada, Inc.).
April 2, 2007
We thank Dr. Munafo for his comments and for making 2 excellent points about our study which merit further discussion. Regarding our use of oximetry, we agree that 2 follow-up studies are neither necessary nor practical in the clinical setting. We would point out, however, that in our study we did adjust CPAP pressure upwards in close to 50% of patients in the ambulatory group as a result of oximetry or CPAP download data. Despite these adjustments, 20% of patients had a residual apnea-hypopnea index of > 10/h at the end of the study. Persistent OSA is common in patients treated with CPAP, even following titration using polysomnography, as our results attest. Downloaded information from CPAP machines at the end of our study had a sensitivity of only 46% and a specificity of 91% for the prediction of residual sleep disordered breathing in our patients. Although we cannot provide similar data for oximetry, our impression is that it is a more sensitive predictor of residual sleep-disordered breathing. The consequences of residual OSA are largely unknown(1).Given the potential adverse cardiac consequences(2) of partial treatment of OSA, however, we consider it wise to use an objective assessment of treatment efficacy in our ambulatory patients, and thus recommend the use of a single oximetry follow-up in our clinical algorithm (fig 5).Fitzpatrick(3) and others(4) have suggested alternative methods of ambulatory CPAP titration which have also proven successful.
Munafo suggests that our conclusions are a little cautious given the outcomes of our trial, and feels that an ambulatory approach should be recommended more robustly. We would point to Reilly and Evans5 recent adaptation of the Evidence-Based Medicine Working Groups recommendations on how to use articles about clinical prediction rules(5). We have performed a narrow validation of a prediction rule(evidence level 2 of 5). Although we fully anticipate the widespread adoption of decision rules based on ambulatory techniques in the diagnosis and treatment of OSA, this should follow broad validation studies and impact analysis in a wider setting. Significant progress can be anticipated in this regard in that the American Academy of Sleep Medicine plans to conduct a multi-center trial of ambulatory techniques in the management of OSA using an algorithm similar to our own. The results of that trial will likely prove critical to the everyday practice of sleep medicine.
1. Baltzan MA, Kassissia I, Elkholi O, Palayew M, Dabrusin R, Wolkove N. Prevalence of persistent sleep apnea in patients treated with continuous positive airway pressure. Sleep 2006;29(4):557-63.
2. Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet 2002;359(9302):204-10.
3. Fitzpatrick MF, Alloway CE, Wakeford TM, MacLean AW, Munt PW, Day AG. Can patients with obstructive sleep apnea titrate their own continuous positive airway pressure? Am J Respir Crit Care Med 2003;167(5):716-22.
4. West SD, Jones DR, Stradling JR. Comparison of three ways to determine and deliver pressure during nasal CPAP therapy for obstructive sleep apnoea. Thorax 2006;61(3):226-31.
5. Reilly BM, Evans AT. Translating clinical research into clinical practice: impact of using prediction rules to make decisions. Ann Intern Med 2006;144(3):201-9.
C.F.Ryan (ResMed Corp, Vitalaire Canada Inc.) N.T.Ayas (Respironics Inc.)
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