Taking Control: Combination Therapy and Adjunctive Treatments for Obstructive Sleep Apnea 
Liana Groza, DDS
May 23, 2015



In addition to CPAP, Oral Appliance Therapy (OAT) and surgical interventions (the most effective and well researched solutions for OSA) there are a number of adjunctive approaches and FDA-approved therapies that patients can consider adding to their treatment strategy once they are faced with this diagnosis. The reasons for looking "outside the box" may vary from incomplete response to OAT in a patient with CPAP intolerance to patients wanting to actively reduce their risk factors. Either way, becoming aware of these adjunctive approaches is an important part of patients' self-education, providing additional tools as they begin to regain control over this life-threatening condition.



1. Weight loss. Perhaps the most significant modifiable risk factor for sleep apnea, excess weight has been shown to increase airway collapsibility and reduce neuromuscular activity, especially during sleep. The prevalence of OSA in overweight patients is much higher than in the general population, ranging from 50% to as high as 98% in patients who are morbidly obese (Cowan and Livingston 2012). A frequently cited longitudinal study of 690 adults followed over a period of 4 years ( Peppard et al. 2000) demonstrated that a 10% weight gain predicted a 32% increase in AHI and a 6-fold increase in the odds of developing moderate-to-severe sleep-disordered breathing. Fortunately, the reverse is also true: the same study showed that a 10% weight loss resulted in a 26% decrease in AHI. Another study (Smith et al 1985) showed that as patients decreased their body weight from an average of 106.2 kg to an average of 96.6 kg, apnea frequency fell from a mean of 55.0 to 29.2 episodes per hour. These significant positive changes can be achieved through a variety of interventions, from dietary counseling and a prescribed exercise regimen to bariatric surgery in the severely obese, when nonsurgical measures have failed. In addition to improving airway function, such measures would go a long way toward reducing the risk of weight-associated comorbidities such as diabetes, hypertension and heart disease, so that in patients with obesity-associated apnea, a weight loss program should be at the top of the list as patients begin to consider additional treatment options.



2. Positional Therapy. One of the oldest interventions for snoring and sleep apnea, positional therapy (which involves a variety of devices which promote sleeping on one's side as opposed to one's back) has received renewed attention over the past few years as a number of inconspicuous electronic gadgets have begun to replace the bulkier belts and other mechanical devices. While older devices consisted of various protruding objects which made it uncomfortable for the patient to sleep on his/her back, newer gadgets worn on the chest or neck detect body orientation and begin to vibrate when the patient moves on the back. For patients with position-dependent apnea (defined as an AHI that is at least twice as high when sleeping on one's back when compared to a side-sleeping position), studies have shown that positional therapies could decrease the AHI index from the moderate-severe range to mild apnea: an AHI change from 26.7 to 6.9 was reported by Heinzer et al.(2012); Lee at al. (2012) demonstrated a mean AHI change from 32.1 to 8.6 in a group of 80 position-dependent patients and from 56.4 to 15.7 in position non-dependent patients; and Lewendowski et al. (2014) found a mean AHI reduction of 69% in position-dependent apnea patients.

Although current positional therapy interventions do not appear capable of fully eliminating apnea events, the fact that approximately 1 in 3 patients undergoing oral appliance therapy continue to suffer from residual obstructive episodes while on their back (Vanderveken 2015) is a strong argument in favor of considering some type of positional intervention (such as Night Shift by Advanced Brain Monitoring, or the Sleep Position Trainer by NightBalance, or even mechanical belt devices) as part of the overall strategy for patients who are CPAP intolerant and do not fully respond to oral appliance therapy. Indeed, a recent study (Dieltjens et al. 2014) showed that the clinical effectiveness (MDA index) changed from 42% with oral appliances alone to 70% when a sleep position trainer was added. In addition, Vanderveken has argued that in patients struggling with high pressure levels on CPAP therapy, positional devices may allow for a reduction in the overall pressure, as supine sleeping is eliminated (Vanderveken 2015). Patients with cardiac arrhythmias corrected by a pacemaker, or who have acute neck, shoulder or back pain, should not use such positional training devices, unless approved by their physician.



3. Resolving nasal obstruction

Numerous studies have demonstrated that there is a high occurrence of nasal alterations in patients with obstructive apnea syndrome (de Aguiar et al. 2013; Biao Zeng 2008; Morris et al. 2005) . These nasal abnormalities, which may include septal deviations, turbinate hypertrophy, chronic allergies and other conditions resulting in increased nasal airway resistance, have been shown to induce or exacerbate obstructive apnea (Zeng 2008) and may play a significant role in the development of sleep-disordered breathing (SDB), especially in patients who are not overweight. In patients with a body mass index below 25, Morris has shown that the size of the nasal airway correlated significantly with CPAP titration pressure as well as the respiratory distress index. Another observation of clinical significance is that baseline nasal airway resistance is typically lower in patients who respond to oral appliance therapy, compared to nonresponders (Zeng et al 2008). Breathing through one's mouth as a result of chronic nasal obstruction contributes to obstructive apnea by reducing the nasal ventilatory reflex, creating an unstable breathing pattern, promoting central apnea events and allowing the lower jaw and tongue to fall backward, which results in partial blockage of the airway (Michels et al. 2014). This may in turn compromise the outcome of OSA therapy, reducing the efficacy of oral appliances and requiring higher pressure settings on the CPAP, which frequently translates into loss of compliance Therefore it is important that a nasal resistance evaluation be performed in sleep disordered breathing patients (ideally by an ENT specialist), and that the root causes of the obstruction be eliminated, either surgically or medically.



4. Oropharyngeal exercises

The collapsibility of the upper airway is strongly influenced by muscle function. In a 2009 study of 31 patients with moderate OSA , Guimaraes et al. have shown that oropharyngeal exercises derived from speech therapy and involving the tongue, soft palate and oropharyngeal wall, when performed for aproximately 30 minutes daily over a 3 month period, were able to reduce the AHI from an average of 22.4 to 13.7, in addition to improving snoring frequency, day time sleepiness and sleep quality score (Guimaraes et al 2009). A similar study conducted on patients with mild apnea and primary snoring found that such exercises decreased the snore index by approximately half (Ieto et al 2015). Although more research needs to be conducted in this area, these results are encouraging and provide a conservative, readily available supporting intervention that may prove effective in some patients trying to lower their AHI.



5. Combination Oral Appliance/CPAP Therapy

In a 2014 review of oral appliance therapy, Sutherland et al. concluded that nearly double the number of patients were successfully treated on CPAP compared to oral appliance therapy, where a complete response (AHI below 5) was the chosen success criterion (Sutherland et al. 2014). However, the same review found that most patients preferred oral appliance therapy over CPAP and that adherence (based on a definition of 4 hrs of use/night for effective treatment) was only 43% in patients on CPAP, compared to 76% in OA patients. As a result, health outcomes and the overall therapeutic effectiveness of OAT tend to be similar to CPAP in the general population (Vanderveken 2012, Phillips et al 2013, Roy 2014).

Nevertheless, for the individual patient who is unable to tolerate CPAP for a variety of reasons (irritation from headgear and straps, claustrophobia, poor mask fit and air leakage, aerophagia or uncomfortably high air pressure) and in whom oral appliance therapy produces less than an optimal response, these statistics offer little consolation. Is there a viable, non-surgical alternative?

One option that has received increasingly more attention in recent years is Combination Therapy (CT) - the simultaneous use of a mandibular repositioning splint, which mechanically increases airway size, lowering velopharyngeal resistance, and CPAP (typically auto-PAP) which as a consequence requires significantly less pressure to deliver an effective treatment. In fact, a 2015 study pooling together data from 4 individual sleep practices offering Combination Therapy to their CPAP-intolerant patients found that the treatment was able to reduce the mean AHI to less than 5, comparable to CPAP, while the compliance (wear) rate at 14 months exceeded 70% (Sanders et al 2015). In another study Borel et al. showed that Combination Therapy was at least as effective as nasal PAP alone (Borel et al 2012), while El-Sohl and his team demonstrated that a 29% reduction in the effective CPAP pressure could be achieved with this approach, significantly reducing CPAP complaints (El Sohl et al 2011) . Because the effective pressure is typically lower, nasal pillows or a nasal mask can be used in most cases. This reduces air leakage, claustrophobia, pressure sores and mouth dryness, since the mouth is kept closed with the appliance in place. Moreover, the rigid attachment securing the nasal pillows to the mandibular advancement splint produced a rigid, stable connection that lowered the number of arousals. Side effects were minimal, with fewer complaints than conventional PAP, as air leakage and mouth breathing were reduced with this type of interface.

Although Combination Therapy has similar contraindications to oral appliance therapy (primarily related to poor dentition and TMJ dysfunction), the ability to integrate two mechanisms of action into OSA treatment and achieve significantly higher compliance and efficacy suggests that this may be a valuable option that should be discussed with patients struggling to tolerate CPAP long before they drop out of the system.



Finding an effective, long-term solution to obstructive sleep apnea is not always a one-step process. Although a significant proportion of people initially struggle with the idea or the implementation of CPAP therapy, it is important to keep in mind that for some patients positive airway pressure is truly the optimal treatment - and that a well-informed, creative approach combining multiple interventions can often transform OSA treatment failures into treatment successes.





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