Introduction
Patient exercises have been shown in two randomized controlled studies to be effective for reducing both the symptoms and severity in patients with moderate obstructive sleep apnea syndrome. A study by Puhan,1 et. al. involved lessons to practice and play the didgeridoo, a wind instrument that involves voice control as well as breath control. Regularly playing the didgeridoo, 5.9 days per week for an average playing time of 25.3 minutes per day, for a four month period of time reduced the average Apnea/Hypopnea Index (a measure of severity) by almost 50% (22.3 to 11.6) and lowered the sleepiness (symptom) from an average Epworth Sleepiness Scale score of 11.8 to 7.4. Guimares,2 et al, showed in a randomized controlled trial that oropharyngeal exercises developed for the treatment of OSAS significantly reduced the AHI (severity) and subjective symptoms as well. The exercises, derived from speech therapy, consisted of isometric and isotonic involvement of muscles of the tongue, soft palate, and lateral pharyngeal wall. The exercise set consisted of activities simulating suction, swallowing, chewing, breathing and speech. The target effects are soft palate elevation, tongue protrusion and mandibular elevation to keep the lips together. This study was not designed to explore the exact mechanism by which the signs and symptoms were improved. It does demonstrate that daytime exercises alter muscle tone during sleep.

Reflex Activity
The oral cavity, the tongue and the pharynx are functionally integrated to perform such vital and complex life functions as breathing, drinking, masticating, swallowing, and speaking. The sensory receptors that innervate these parts are constituents of reflex systems that reflect a huge range of complexity. These oropharyngeal reflexes are in fact critical to maintaining life. Reflexes in the upper airway are protective by preventing aspiration, facilitating vocalization, transporting boluses of food and water and protective of breathing by maintaining a patent airway.

Genioglossus, the main tongue muscle, is a protruder. It has an important role in airway protection and maintenance of airway patency, especially in patients with obstructive sleep apnea. Styloglossus and hyoglossus are tongue retruders. Activation of genioglossus under hypoxic and hypercapnic conditions brings about tongue protrusion and pharyngeal air- way dilation.3,4 In a study by Mateika,5 et. al. the styloglossus and hyoglossus were also coactivated in response to hypoxia and hypercapnia. This coactivation is the response of complex reflex activity between tongue protruders, tongue retruders and chemical sensors in the central nervous system. A reflex is defined as the sum total of any particular involuntary activity.6 Specific sensory inputs can subconsciously induce motor responses that have reciprocal effects on different motoneuron pools. Reflexes provide relatively hard wired circuits through the central nervous system to control a set of often antagonistic muscles for co-ordination of a given response, such as a swallow. The motor neurons and the Golgi tendon system are part of a neurologic feed- back loop for maintaining muscle tone.

A reflex reaction is conditioned not by one reflex arc but many. Coordination is part of the reflex. According to Sherrington,7 “the main secret of nervous coordination lies in the compounding of reflexes”. Learning is involved in establishing many reflexes. Reflexes elicited from stimulating the oral region alter recruitment of lip, tongue and jaw muscles. The type of sensory stimulus determines the type of reflex elicited – from simple reflexes to complex behavior affecting oral and pharyngeal regions. Motor neurons responsible for the reflex activity of the head and neck are located in the brainstem – medulla, pons and midbrain.

The tongue is a complex muscular organ. Extrinsic tongue muscles attach to at least one bone and function to alter the shape of the tongue. Intrinsic tongue muscles have both their origin and insertion in muscle. They protrude, retrude and move the tongue laterally. The chief tongue protruder, the genioglossus muscle is extrinsic. The electromyographic activity of genioglossus has been shown to be in phase with respiration when awake or in a resting state.8 Changes in mandibular posture have a direct effect on tongue activity and may relate to the role of the tongue in airway maintenance.9 Reflexes elicited from stimu- lating the oral region alter recruitment of lip, tongue and jaw muscles. The type of sensory stimulus determines the type of reflex elicited – from simple reflexes to complex behavior affecting oral and pharyngeal regions.

An important part of the research of A. J. Miller10 has been description and study of reflexes controlling orofacial func- tion. Relative to tongue protrusion Miller has identified five tongue reflexes. Tongue reflexes are activated from motoneurons from three cranial nerves: hypoglossal, trigeminal and glossopharyngeal.

Jaw-Hypoglossal Reflex7
The hypoglossal nerve (XII) is the only motor nerve to the genioglossus muscle. Stimulation of the medial branch of the hypoglossal nerve causes genioglossus protrusion. The jaw-hypoglossal reflex is that stimulation of the inferior alveolar nerve (VIII) causes firing of hypoglossal motoneurons, a phe- nomenon that could not be activated by direct stimulation of the hypoglossal nerve. The hypoglossal motoneurons in this reflex protrude the tongue. Passive opening of the mandible by a sleep appliance increases the activity of genioglossus muscle. The position of the mandible in a sleep appliance affects tongue posture and the amount of protrusion. Forward protrusion of the tongue helps maintain a patent airway. Oral appliances for sleep apnea should be conceived to facilitate this reflex by a non-restrictive, open anterior design.

Masseter-Hypoglossal Reflex7
Direct stimulation of the masseteric nerve (V ) contracts the III masseter muscle. The masseter-hypoglossal reflex is that masseteric nerve stimulation also inhibits polysynaptic firing of hypoglossal motoneurons to retrusive tongue muscles. A passive jaw opening beyond rest position stimulates the masseter to shorten, eliciting reproducible inhibition of tongue muscle retrusion that lasts as long as the jaw is open. Stimulation of this reflex can be easily incorporated into oral sleep appliances to inhibit tongue retrusion while the appliance is worn in the mouth.

Lingual-Hypoglossal Reflex7
The lingual nerve is a branch of the third and largest division of the trigeminal nerve (V) with a mostly sensory function. Mechanical stimulation of the surface of the tongue by light probing or scraping can induce multiple reflexes involving such functions as opening the jaws, closure of the glottis, elevation of the palate and some degree of tongue retru- sion, but mostly tongue protrusion. The lingual-hypoglossal reflex, triggered by tongue stimulation, depends on the site of the sensory input. Stimulation of the medial branch of the hypoglossal nerve innervates intrinsic tongue muscles and brings about protrusion. The lingual-hypoglossal reflex can be facilitated by a prior conditioning reflex and thus trained by exercise. Stimulation of this reflex can also be incorporated into oral appliance design.

Glossopharyngeal-Hypoglossal Reflex7
The glossopharyngeal nerve contains sensory fibers that innervate the lateral border of the posterior 1⁄3 of the tongue. Stimulation of the lateral border of the posterior 1⁄3 of the tongue induces reflex discharges in hypoglossal motoneurons that cause the tongue to protrude and that also inhibit retrusive hypoglossal motoneurons.

Tongue–Tongue Reflex7
The lingual nerve provides sensory innervations to the tip of the tongue. The tongue-tongue reflex is that touch or stroking on the tip of the tongue stimulates hypoglossal motoneurons that cause the tongue to orient toward the stimulus.11 The more intense the stimulation, the higher the probability of tongue movement toward the source. Mechanical stimulation of the dorsal surface of the tongue will induce the same reflex as direct stimulation of the lingual sensory nerve. Coordination of the tongue-tongue relies heavily on exteroceptors on the tongue surface. Stimulation of this reflex can be incorporated into the design of oral sleep apnea appliances.

Fig. 1. The Moses, an open anterior, adjustable, FDA cleared oral airway dilator.

It would seem to be a reasonable assumption based on the Moses study and the cited studies on exercises that the operative mechanism by which airway dilation works in both cases is stimulation of hypoglossal reflexes. Reflex training during the day by exercises has a carryover effect during sleep. The reflex effect of oral appliances works as long as the appliance remains in the mouth. Hypoglossal reflexes operate at a site apart from the origin of the stimulus.

The effectiveness of oral appliances at treating OSA is well documented in the scientific literature.19,20,21,22,23 The effectiveness of exercise training is well demonstrated in the two articles cited.1,2 Neither methodology alone appears to be better than CPAP when using PSG measures; however, in a recent paper, Chan & Cistulli24 presented data that patient compliance, acceptance and comfort is better with oral appliances than CPAP .

Fig. 2. Left image above is a posterior view of a three dimensional volumetric reconstruction of the patient’s airway without MAD. Right image is a posterior view of a three dimensional reconstruction of the patient’s airway with MAD properly positioned in the mouth. The increase in size of the airway is substantial and obvious. The appliance used in the figure on the right is The MosesTM.

Evolution
The old idea that oral appliances are merely mandibular advancement devices, moving the tongue forward to pre- vent its collapse on the airway is an oversimplification. It does not account for the dilation of the sides and back of the pharynx visible on the 3-D computerized cone beam image with The MosesTM in place. The multidimensional airway dilation cannot be accounted for solely by active anterior movement of the mandible and the attendant passive pull- forward of the tongue base. Consideration and testing of oral appliance therapy in terms of their effect on airway dilation by reflex stimulation is warranted. It would seem that there is no downside or risk to a clinical strategy of a treatment protocol combining the two methodologies of oropharyngeal exercises and oral appliance therapy. It would also seem that future controlled trials to objectively evaluate the combined effects of oral appliances and exercises is warranted.

References
1. Puhan MA, Suarez A, Lo Cascio C, Zahn A, Heitz M, Braendli O, Didgeridoo playing as alternative treatment for obstructive sleep apnoea syndrome: randomized controlled study. BMJ, doi:1136/ bmj.38705.470590.55 (23 Dec. 2005).
2. Guimares KC, Drager LF, Genta PR, Marcondes BF, Lorenzo- Filho G, Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome. 179: 962–966, 2009.
3. McEvoyRD,PopovicRM,SaundersNA,WhiteDP,Effectsofsustain ed and repetitive isotonic hypoxia on on ventilation and geniogloos- sal and diaphragmatic EMGs. J APPL Physiol, 81:866–875, 1996.
4. Strohl KP, Hensley MJ, Hallet M, Saunders NA, Ingram RH, Activation of upper airway muscles before onset of inspiration in normal humans. J Appl Physiol. 49:638–642, 1980.
5. Mateika JH, Millrood DL, Kim J, Rodriguez HP, Samara GJ, Response of human tongue protrudor and retractors to hypoxia and hypercapnia. Am J Crit Care Med 160: 1976–1982, 1999.
6. Dictionary 7. Sherrington C, “The Integrative Action of the Nervous System” Yale University Press, 1906. 8. Sabolsky JP, Butler JE, Fogel RB, Taylor JL, Trinder JA, White DP, Gandevia SC, Tonic and phasic respiratory drives to human genioglossus motoneurons during breathing. J Neurophysiol, 95:2213–2231, 2006.
9. Blom S, Afferent influences on tongue muscle activity. Acta Physiol Scand. Vol 49 (Suppl 170) 1–97, 1960.
10. Miller AJ, Oral and pharyngeal reflexes in the mammalian nervous system: Their diverse range in complexity and the pivotal role of the tongue. Crit Rev Oral Biol Med, 13(5):409–425, 2002.
11. Weiffenbach JM, Discrete elicited motions of the newborn’s tongue. In: “Oral sensation and Perception” ed. Bosma JF, US Govt Printing Ofc , p232–243, 1972.
12. Isono S, Tanaka A, Nishino T, Effects of tongue electrical stimu- lation on pharyngeal mechanics in anesthetized patients with obstructive sleep apnea. Eur Respir J, 14:1258–1265, 1999.
13. Miki H, Hida W, Chonan T, Kikuchi Y, Takishima T, Effects of submental electrical stimulation during sleep on upper airway patency in patients with obstructive sleep apnea. Am Rev Respir Dis, 140: 1285–1289, 1989.
14. Edmonds LC, Daniels BK, Stanson AW, Sheedy PF, Shepard JW, The effects of transcutaneous electrical stimulation during wake- fulness and sleep in patients with obstructive sleep apnoea. 146: 1030–1036 , 1992.
15. Decker MJ, Haaga J, Arnold JL, Atzberger D, Strohl KP, Functional electrical stimulation and respiration during sleep. J Appl Physiol, 75:1053–1061, 1993.
16. Guilleminault C, Powell N, Bowman B, Stoohs R, the effect of electrical stimulation on obstructive sleep apnoea syn- drome. Chest, 107:67–73, 1995.
17. Schwartz AR, Eisele DW, Hari A, Testerman R, Erickson D, Smith PL, Electrical stimulation of the lingual mus- culature in obstrudctive sleep apnoea. J Appl Physiol, 81:643–652, 1996.
18. Moses AJ, Bedoya JA, Learreta JA, Case study of the ana- tomic changes effected by a mandibular advancement device in a sleep apnea patient. Sleep Diagnosis and Therapy 5:1, 30–34, 2010.
19. Schmidt-Nowara WW, Mead TE, Hayes MB, Treatment of snoring and obstructive sleep apnea with a dental orthosis. Chest, 99:1378–1385, 1991.
20. IchiokaM, Tojo N, Yoshizawa M, et.al. A dental device for the treatment of sleep apnea: a preliminary study. Otolaryngol head Neck Surg, 104: 555–558, 1991.
21. Eveloff SE, Rosenberg CL, Carlisle CC, Millman RP, Efficacy of a Herbst mandibular advancement device in obstructive sleep apnea. Am J Resp Crit Care Med 149: 905–909, 1994.
22. Clark GT, Arand D Chung E, Tong D, Effect of anterior mandibular positioning on obstructive sleep apnea. Am Rev Resp Dis 147: 624–629, 1993.
23. Bonham PE, Currier GF, Orr WC, Othman J, Nanda RS, The effect of a modified functional appliance on obstruc- tive sleep apnea. Am J Orthod Dentofacial Orthop, 94: 384–392, 1988.
24. Chan ASL, Cistulli PA, Oral appliance treatment of obstructive sleep apnea: an update. Current Opinion in Pulmon Med, 2009, 15: 591–595.

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Getting the Message

Braebon’s Don C. Bradley has seen a lot in his years in the sleep industry, but a subtle shift at the 2010 APSS signaled a new awareness that surprised the 20-year sleep veteran.

Previously, inquiries at Braebon’s APSS booth were noticeably more reserved in their enthusiasm about portable sleep monitoring. Don C. Bradley, the co-founder of Braebon Medical Corp, sensed the apprehension and compared it to dipping toes in the water. At the 24th annual APSS in San Antonio, attendees clearly knew the temperature of the water—and many decided to dive in. The subtle shift in sophistication and acceptance mirrors the industry’s continuing validation of ambulatory sleep monitoring. The shallow questions of the past have been replaced by serious inquiries. “The level of acceptance is noticeably greater than previous years,” says Bradley. “People want to get accurate data and results. They want to know how the software works and what is actually happening within the algorithms—as well as how easy is the device to use for patient and clinicians.”  
Separate measuring of oral and nasal pressure was a hot topic, as was the possibility of expanding capabilities to monitor the performance of the CPAP while it is attached to the patient within the patient’s own bedroom.

Better Sensors, Better Data
Braebon’s titration sensor accomplishes a further expansion of a sleep lab’s capabilities by allowing technicians to see flows, volumes, leaks, and actual pressures from any PAP device. Bradley educates attendees about this equipment, while also teaching technicians the finer points. “Knowing the tricks of using a sensor effectively is another important point,” explains Bradley. “At a recent event, we had several groups of technicians who were using our cannulae. They were concerned about occlusions inside the nose. One tip is to ask patients to blow their noses and clean out nostrils before they come to the lab. Maybe have them trim nose hairs so you don’t occlude. You can also trim the nasal prongs so they are actually perpendicular to the flow of air, and you get much more accurate signals.”

Focus on Snoring
As portable monitoring becomes ever more refined, Bradley maintains that focusing on overlooked details such as snoring can make a difference. Merely paying attention to these differences is often a foreign concept, but determining snores per hour is a good start.If you have the number of snores per hour, asks Bradley, then what about the effect in magnitude and volume/power? Knowing the actual change in volume when a patient undergoes therapy has merit, and it is one reason Braebon developed the Q-Snor, as well as placing this technology within the MediByte™ portable sleep screener (invented by Bradley and Richard A. Bonato, PhD, RPSGT, co-founder and CEO of Braebon Medical Corp, Ontario, Canada, to monitor the efficacy of oral appliance therapy).

Within the three main types of technologies used to determine snoring, technicians can access sensors that qualitatively measure vibrations on the neck—qualitative auditory signals or quantitative auditory signals. “The vibratory signal may contain artifacts such as cardiac pulses or head/body movements,” explains Bradley. “The qualitative or quantitative audio sensor may contain external artifacts such as talking. It is the quantitative audio sensor that can give us the most valuable information related to snoring in the patient. The quantitative audio sensor (Braebon Q-Snor) allows you to do a proper pre- and post-comparison of both snoring indices and change in overall volume in patients. This is paramount if one is to assess the effectiveness of certain types of therapies.”

Accurate Signals
Understanding sensor technology is paramount in ensuring the collection of accurate signals. As an example, piezo technology cannot measure events with low frequency content. At 10 HZ or higher, a piezo sensor responds acceptably well to what is going on. “If, however, you are looking to measure respiratory effort in patients with breathing rates of between 6 to 30 breaths per minute, and look for relative amplitude changes for each breath, a piezo sensor cannot give you what you need.” explains Bradley. “An accurate signal refers to not only the sensor’s ability to react quickly enough to the physiological event being measured, but to also output a signal that should be linearly proportional to the physiological event being measured.
“If I inhale and then exhale quickly, you won’t see the proper signal with a piezo based pressure sensor,” continues Bradley. “There will be a slow decay because of the filtering that has been added by the manufacturer to generate signals in the low frequency band that do not really exist. Properly developed sensors ensure that the sensor technology used generates an accurate signal. Some technologies are better than others. One must also consider the fact that just because a manufacturer states a type of technology is being used, it is not a guarantee that the sensor will accurately reproduce the physiological signal being measured. There are other factors that must be considered such as internal filtering of the raw signal before it even reaches the PSG amplifier system.”

Can You Trust Your Equipment?
Respected organizations such as the American Academy of Sleep Medicine (AASM) are always concerned with accuracy standards for things such as hypopneas. Bradley points out that the AASM did in fact come out with guidelines on nasal hypopneas. Calling them “a great first stab,” he laments that the guidelines could only go so far since there has not yet been enough research to substantiate measuring oral pressure for indications of oral only events.

At the base of all sleep units, the question is essentially the same: Is what you see on the screen an accurate reflection of what is physiologically going on with patient? The recorded and displayed signals have meaning to the trained eye, but are they reliable? If you can’t trust your equipment, or know how to effectively use it, says Bradley, you have a fundamental problem. Sensors are the primary piece of equipment for obtaining signals and they must accurately reflect the physiological event being measured.
All sensors have limitations, and those limitations must be understood. Without proper understanding, you cannot expect to obtain accurate signals. The same type of sensor can use different technologies to give you a signal.
Accurately assessing the chest and abdominal effort of breathing is a basic function. When sensors are plugged into a PSG system, some technicians are simply hoping the filters and sampling rates are set right and that the sensor is working according to what they need. “The information comes up on the screen and you take that as gospel,” says Bradley, who in addition to his role as founder also serves as chief technology officer at Braebon. “But is that really what is happening? Is there effort happening on the chest and abdomen? One cannot answer that question without having a basic understanding of the technology involved.”
There are many technologies and methods for measuring airflow: pressure sensors; thermal sensors; and esophageal balloons to name three. Whatever method is used, Bradley contends that quality matters. “I could go out and buy the cheapest pressure sensor, and then I could buy a more expensive one,” says Bradley. “If you put a cannula on the patient and feed it simultaneously to both pressure sensors, you will see two totally different signals—yet people think if it is a pressure sensor, they are measuring accurately.”

Problems with Pressure
There are several different types of cannulae used to measure airflow to gauge the nasal and/or oral breathing component. “You’ve got the thermal side, so you can measure nasal and oral apneas because you’ve got a thermal sensor,” says Bradley. “However, you don’t have the oral component on the cannula, and that is something Braebon looked at and worked out. We have the PureFlow and PureFlow Duo cannulae. These cannulae have a big scoop designed to give you an accurate, almost 1:1 relationship between the nasal breathing and the oral breathing—as well as give you a reliable signal.

The PureFlow combines both the nasal and oral component into one signal whereas the PureFlow Duo, when working with the Braebon PT2 Dual Pressure Transducer, gives separate oral and nasal signals. This family of cannula allows users to look into oral breathing and be able to determine oral hypopneas or other phenomena that may be present in the oral signal and not in the nasal signal.

There are a lot of technical issues in trying to grab oral pressure and accurately represent it, because engineers are not dealing with an enclosed system. “You’ve got leaks everywhere as well as the changing shape of the oral orifice,” laments Bradley. “The nasal one is a little easier because you design prongs that go in and they act like pitot tubes so you can measure the pressures and infer airflow fairly accurately. Even though people have different diameters on their nose, there is not that much of a change. But the mouth really changes shape throughout the night plus, it has been shown, people change their breathing patterns throughout the night between nasal and oral. They have even had studies showing that the person will actually change their breathing between left and right nostrils throughout the night. It is almost like we are just getting into the science of these types of things and it is all coming down to how can we easily and accurately measure the amount of air moving in and out of the patient.”

The Future
If 2010 feels like a new awareness, what will the next decade bring? For Braebon, the long-term goals are part of a day-to-day strategy that builds on the fundamentals of meeting customers at trade shows and sleep laboratories. Spreading the message about MediByte and the MediByte Jr. is a top priority since the unit takes the company’s best sensor technology and essentially puts it in a compact device to record and store data. Deemed too far ahead of the curve in 2003, the locking connectors, simple software, and explanatory videos are all poised to properly outline the product for patients and clinicians.

For Bradley, optimism is easy to come by thanks to growing recognition that sleep is nothing less than an enormous part of overall health. “We spend a third of our life sleeping, and you need to know what is going on while in this state of slumber. I enjoy helping people and improving their quality of life. The industry has really grown and the best companies are lean, mean, and responsive—and have attributes that I have boiled down to the four Fs— Focused, Flexible, Friendly, and Fast.”

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Don Bradley is founder and chief technology officer for Braebon. He has worked in the sleep diagnostic industry for more than 19 years. He has designed and developed many medical devices including PSG systems and sleep sensors, authored several articles in technical and research publications, and given talks on technology in sleep.

For more information, visit www.braebon.com

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