Editorial 3, Issue 2.1
Combination Therapy for Obstructive Sleep Apnea in Order to Achieve Complete Disease Alleviation: from Taboo to New Standard of Care?
http://dx.doi.org/10.15331/jdsm.4428
Olivier M. Vanderveken, MD, PhD1,2
1 University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium; 2 Antwerp University Hospital, Otolaryngology and Head and Neck Surgery, Edegem, Antwerp, Belgium
Obstructive sleep apnea (OSA) is a highly prevalent disease with a complex pathophysiology.1,2 When undiagnosed or untreated OSA leads to subsequent morbidity and significant long-term mortality, also in patients with mild to moderate disease.3 Treatment with continuous positive airway pressure (CPAP) and oral appliance therapy with mandibular advancement devices (OAm) are the two treatments for OSA whose effects on cardiovascular endpoints have been assessed in randomized controlled trials (RCT).4–7 However, both therapeutic options have their possible limitations as CPAP treatment often comes with low patients’ acceptance, poor tolerance and suboptimal compliance, whereas OAm therapy generally has an inferior efficacy as compared to CPAP.4,8–10 Indeed, according to the mean disease alleviation (MDA) concept, the risk that the greater efficacy of CPAP is being offset by its inferior compliance relative to OAm therapy is not imaginary, resulting in a similar overall effectiveness for both therapeutic modalities.4,9 In other words, treatment of OSA with CPAP, OAm or other non-CPAP modalities, as a single treatment, will commonly be associated with an incomplete elimination of the disease with mean values of the MDA index, as a marker of real clinical effectiveness, ranging from 40 to 59 %.8,11,12
Supporting data from the literature on the role and impact of adjunct therapy that can be used as needed in order to improve the MDA index of the primary treatment options are scarce.13 Case series have been published on the combination of CPAP with OAm therapy for the treatment of OSA.14,15 It has been demonstrated that when mandibular protrusion is limited in case of OAm therapy, a combined approach utilizing both mandibular protrusion and tongue retention is able to provide an effective treatment for moderate-to-severe OSA as the addition of a tongue bulb to the OAm provides further therapeutic effectiveness.16 Furthermore, adjunct OAm therapy has been shown to be an effective mode of combination therapy to control OSA after failure of upper airway surgery.2,17 Multilevel surgery, being the combination of more than one surgical technique, can also be considered as combination therapy for OSA.18–23 In obese patients with severe OSA, CPAP requirements might be decreased after bariatric surgery and these lower CPAP pressures may yet lead to an increased CPAP tolerance and an improved overall compliance with CPAP.23 The effectiveness of other conceivable and convenient combinations in specific patients needs to be put into perspective and requires further investigation in ongoing studies or future trials.
Interestingly, in addition, at least half of OSA patients are reported to suffer from supine-dependent or positional OSA (POSA), commonly defined as an apnea/hypopnea-index (AHI) being at least twice as high in the supine sleeping position as compared to the AHI in the non-supine positions.24,25 While newer methods to treat POSA with higher compliance rates are emerging, the relevance of this finding of POSA being that common is highly relevant.26–28 Recently, it has been reported that about 1 out of 3 patients still suffer from residual POSA while undergoing OAm therapy.29 The results of a recently published RCT indicate that in these patients with residual POSA under OAm therapy the combination of OAm and a sleep position trainer leads to a significant improvement of the therapeutic effectiveness with an increase of the MDA index changing from 42% with OAm alone to 70% with the combination treatment of OAm and sleep position trainer, respectively.30 Similarly, positional treatment might also be an adjunct treatment in patients on CPAP who require higher pressure levels in the supine sleeping position than in the non-supine positions in order to improve CPAP compliance.31 From a theoretical and conceptual perspective, the combination of positional therapy and surgical upper airway modifications could also result in a significant decrease in OSA severity in patients with POSA.32,33 In summary, the combination of different treatment options for the alleviation of OSA is clearly underestimated, undervalued and underinvestigated in the field of sleep medicine. In order to reach the target, preferably an alleviation of the disease, it might indeed be necessary to prescribe two or more therapies with adjunctive therapies used as needed to supplement the primary treatment options.13 In order to avoid incomplete alleviation of OSA, our field needs to think out of the box and try to get rid of the taboo of combining different treatment options in the individual patients in order to reach a well-defined target correlating with long-term elimination of disease. Further research on the clinical effectiveness of the possible combinations to completely eliminate the patient’s OSA is highly needed.
CITATION
Vanderveken OM. Combination therapy for obstructive sleep apnea in order to achieve complete disease alleviation: from taboo to new standard of care. Journal of Dental Sleep Medicine 2015;2(1):7–8.
REFERENCES
1. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 2013;177:1006–14.
2. Malhotra A, White DP. Obstructive sleep apnoea. Lancet 2002;360:237– 45.
3. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005;365:1046–53.
4. Phillips CL, Grunstein RR, Darendeliler MA, et al. Health outcomes of continuous positive airway pressure versus oral appliance treatment for obstructive sleep apnea: a randomized controlled trial. Am J Respir Crit Care Med 2013;187:879–87.
5. Vanderveken OM, Boudewyns A, Ni Q, et al. Cardiovascular implications in the treatment of obstructive sleep apnea. J Cardiovasc Transl Res 2011;4:53–60.
6. Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet 2009;373:82–93.
7. Randerath WJ, Heise M, Hinz R, Ruehle KH. An individually adjustable oral appliance vs continuous positive airway pressure in mild-tomoderate obstructive sleep apnea syndrome. Chest 2002;122:569–75.
8. Grote L, Hedner J, Grunstein R, Kraiczi H. Therapy with nCPAP: incomplete elimination of Sleep Related Breathing Disorder. Eur Respir J 2000;16:921–7.
9. Vanderveken OM, Dieltjens M, Wouters K, De Backer WA, Van de Heyning PH, Braem MJ. Objective measurement of compliance during oral appliance therapy for sleep-disordered breathing. Thorax 2013;68:91–6.
10. Kribbs NB, Pack AI, Kline LR, et al. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. Am Rev Respir Dis 1993;147:887–95.
11. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep 1996;19:156–77.
12. Strollo PJ, Jr., Soose RJ, Maurer JT, et al. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med 2014; 370:139–49.
13. Epstein LJ, Kristo D, Strollo PJ, Jr., et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med 2009;5:263–76.
14. Denbar MA. A case study involving the combination treatment of an oral appliance and auto-titrating CPAP unit. Sleep Breath 2002;6:125–8.
15. El-Solh AA, Moitheennazima B, Akinnusi ME, Churder PM, Lafornara AM. Combined oral appliance and positive airway pressure therapy for obstructive sleep apnea: a pilot study. Sleep Breath 2011;15:203–8.
16. Dort L, Remmers J. A combination appliance for obstructive sleep apnea: the effectiveness of mandibular advancement and tongue retention. J Clin Sleep Med 2012;8:265–9.
17. Millman RP, Rosenberg CL, Carlisle CC, Kramer NR, Kahn DM, Bonitati AE. The efficacy of oral appliances in the treatment of persistent sleep apnea after uvulopalatopharyngoplasty. Chest 1998;113:992–6.
18. Vicini C, Montevecchi F, Pang K, et al. Combined transoral robotic tongue base surgery and palate surgery in obstructive sleep apneahypopnea syndrome: expansion sphincter pharyngoplasty versus uvulopalatopharyngoplasty. Head Neck 2014;36:77–83.
19. Kezirian EJ, Malhotra A, Goldberg AN, White DP. Changes in obstructive sleep apnea severity, biomarkers, and quality of life after multilevel surgery. Laryngoscope 2010;120:1481–8.
20. Handler E, Hamans E, Goldberg AN, Mickelson S. Tongue suspension: an evidence-based review and comparison to hypopharyngeal surgery for OSA. Laryngoscope 2014;124:329–36.
21. Lee JM, Weinstein GS, O’Malley BW, Jr., Thaler ER. Transoral robotassisted lingual tonsillectomy and uvulopalatopharyngoplasty for obstructive sleep apnea. Ann Otol Rhinol Laryngol 2012;121:635–9.
22. Vicini C, Dallan I, Canzi P, et al. Transoral robotic surgery of the tongue base in obstructive sleep apnea-hypopnea syndrome: anatomic considerations and clinical experience. Head Neck 2012;34:15–22.
23. Kotecha BT, Hall AC. Role of surgery in adult obstructive sleep apnoea. Sleep Med Rev 2014;18:405–13.
24. Cartwright RD. Effect of sleep position on sleep apnea severity. Sleep 1984; 7:110–4.
25. Ravesloot MJ, van Maanen JP, Dun L, de Vries N. The undervalued potential of positional therapy in position-dependent snoring and obstructive sleep apnea-a review of the literature. Sleep Breath 2013;17:39–49.
26. Eijsvogel M, Ubbink R, Dekker J, et al. Sleep position trainer versus tennis ball technique in positional obstructive sleep apnea syndrome. J Clin Sleep Med 2014 Nov 11. [Epub ahead of print].
27. van Maanen JP, de Vries N. Long-term effectiveness and compliance of positional therapy with the sleep position trainer in the treatment of positional obstructive sleep apnea syndrome. Sleep 2014;37:1209–15.
28. van Maanen JP, Meester KA, Dun LN, et al. The sleep position trainer: a new treatment for positional obstructive sleep apnoea. Sleep Breath 2013;17:771–9.
29. Dieltjens M, Braem MJ, Van de Heyning PH, Wouters K, Vanderveken OM. Prevalence and clinical significance of supine-dependent obstructive sleep apnea in patients using oral appliance therapy. J Clin Sleep Med 2014;10:959–64.
30. Dieltjens M, Vroegop AV, Verbruggen AE, et al. A promising concept of combination therapy for positional obstructive sleep apnea. Sleep Breath 2014 Oct 22. [Epub ahead of print].
31. Pevernagie D, Sastry M, Vanderveken OM. Treatment of respiratory sleep disorders. In: Bassetti CL, Dogas Z, Peigneux P, eds. ESRS European Sleep Medicine Textbook. Regensburg, Germany: European Sleep Research Society, 2014.
32. van Maanen JP, Witte BI, de Vries N. Theoretical approach towards increasing effectiveness of palatal surgery in obstructive sleep apnea: role for concomitant positional therapy? Sleep Breath 2014;18:341–9.
33. van Maanen JP, Ravesloot MJ, Witte BI, Grijseels M, de Vries N. Exploration of the relationship between sleep position and isolated tongue base or multilevel surgery in obstructive sleep apnea. Eur Arch Otorhinolaryngol 2012;269:2129–36.
SUBMISSION & CORRESPONDENCE INFORMATION
Submitted for publication December, 2014
Accepted for publication December, 2014
Address correspondence to: Olivier M. Vanderveken, MD, PhD, Deputy Editor JDSM, Assistant Professor, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium: Tel: +32 3 821 33 84; Email: olivier.vanderveken@uantwerp.be or olivier.vanderveken@uza.be