Tongue Protrusion Force: A Pilot Study

Obstructive sleep apnea (OSA) is a condition characterized by temporary diminutions or
cessations of breathing caused by repetitive collapse of the upper airway (UA) during sleep
(1). OSA is a common disorder associated with abnormalities in pharyngeal anatomy and
physiology in which the muscles of the airway, which normally relax during sleep, fail to
provide sufficient dilatory force to balance the contractive force from inspiratory activity
(2). This force imbalance serves to either partially or completely collapse the UA, thereby
preventing sufficient air from reaching the lungs. These pauses in breathing lead to blood
oxygen desaturation and induce neurological arousal resulting in sleep disruption and
fragmentation. The cycle of airway collapse and arousal can repeat hundreds of times per
night (1). According to the National Sleep Foundation, OSA affects 18-22 million Americans,
80% of whom are undiagnosed. OSA is more prevalent among overweight and older individuals and
those with reduced muscle tone, skeletal anomalies such as micrognathia or retrognathia, and
airways crowded by redundant or enlarged soft tissue structures.

OSA is associated with significant physiological and psychological problems. OSA results in
excessive daytime sleepiness, fatigue, memory impairment, and reduced reaction time,
increasing the risk for motor vehicle (3) and workplace (4) accidents. In addition, OSA
sufferers face increased cardiovascular risk including hypertension, heart disease, and
stroke (5). OSA has even recently been linked to increased cancer incidence (6) and mortality
(7), presumably through hypoxia-induced angiogenesis.

On the morning of December 1, 2013, a Metro-North passenger train derailed in the Bronx. The
accident killed 4 passengers, injured 61, and caused $9 million worth of damage.
Investigators determined human error was to blame: the train engineer admitted that before
reaching the curve he had "gone into a daze," allowing the train to travel at three times the
posted speed limit (8). A medical examination conducted after the accident diagnosed the
train engineer with OSA, which hampered his ability to fully adjust his sleep patterns to the
morning shift he had begun working just two weeks prior to the accident (9).

The Harvard Medical School released a report in 2010 entitled, "The Price of Fatigue: The
Surprising Economic Costs of Unmanaged Sleep Apnea," in which it estimated the annual
economic cost of moderate to severe OSA in the United States to be $65-165B (compared to $60B
for drunk driving and $150B for not wearing seatbelts), including $10-40B in OSA-related
traffic accidents and $5-20B in OSA-related workplace accidents (10).

Existing treatments for OSA include lifestyle modifications (11) such as weight loss,
position restriction, and avoidance of muscle relaxants such as alcohol and benzodiazepine
drugs. Oral appliances including mandibular advancement devices and tongue retaining devices
have been increasingly employed. OSA is also treated through surgery, including tonsillectomy
and uvulopalatopharyngeoplasty (UPPP) to reduce tissue crowding of the UA lumen, genioglossal
advancement, and maxillomandibular advancement. The most widespread and generally effective
treatment for OSA, however, remains the use of various devices for maintaining positive
airway pressure (PAP) such as Continuous Positive Airway Pressure (CPAP), BiLevel Positive
Airway Pressure (BiPAP), and Autotitrating (AutoPAP) devices.

CPAP and related treatments are both costly and cumbersome. 40-60% of patients prescribed
CPAP fail to adhere to the treatment (12; 13; 14). Patients cite comfort and lifestyle
factors (sensation of claustrophobia, dry mouth, ill-fitting mask, and lack of portability of
the system precluding use during travel) as reasons for abandoning treatment (15; 16). Benign
Prostatic Hypertrophy (BPH), with accompanying nocturia, has also been associated with
noncompliance with CPAP among older men (17). Poor compliance with CPAP is prompting the
search for alternative forms of treatment for OSA.

The Genioglossus (GG), which makes up most of the body of the tongue, is the major muscle
responsible for protruding the tongue and is the major UA dilator that opposes collapsing
force in the pharynx upon inspiration. Reduced UA dilator force in sleep is posited to
contribute to the collapse of the pharynx in OSA (Schwartz 2001). A number of controlled
studies have demonstrated that strengthening the GG can result in clinically significant
reductions of OSA severity.

In a randomized controlled trial (RCT) of OSA patients (18), a group that performed
oropharyngeal exercises for 30 minutes a day for three months reduced the average apnea
hypopnea index (AHI, the number of apnea and hypopnea events per hour of sleep) by almost 35%
(22.4 to 14.7, P < 0.05). The exercises consisted of isometric and isotonic exercises
involving the tongue. Another RCT (19) designed to increase UA dilator muscle strength
demonstrated that playing the didgeridoo (an aboriginal wind instrument) six times per week
for an average of 25 minutes per day over four months decreased average AHI by almost 50%
(22.3 to 11.6, P < 0.01). Electrical stimulation of the hypoglossal nerve (which innervates
the GG) also promotes UA patency during sleep. Hypoglossal stimulation reduced UA resistance
in both healthy persons and subjects with OSA and reduced AHI in OSA subjects by over 50%
(20).

II. Aims

The investigators assert that training the GG muscle while awake will serve to dilate the
pharyngeal pathway - restriction of which results in obstructive apnea - during sleep. If
confirmed, the investigators will have developed an effective behavioral treatment for OSA.
The investigators anticipate it being an attractive alternative for OSA patients who are
unable to acclimate to CPAP or adhere to its use for comfort or lifestyle reasons.

This IRB approved clinical study is designed to determine both an effective training regimen
to increase GG muscle strength as well as obtain preliminary data on the effect of tongue
protrusive force training (TPFT) on OSA. In this study, the investigators will use subjects
with moderate to severe OSA. OSA severity will be assessed with a sleep study conducted prior
to beginning the training regimen. After six weeks of daily training, OSA severity will be
measured again with a follow-up sleep study.

Inclusion Criteria:

1. Age: 21 to 70

2. At home confirmation of moderate to severe OSA (AHI 15-60)

3. BMI less than or equal to 35

4. Not currently on a weight loss plan and no intention of beginning a weight loss
regimen during the duration of the study

5. If not currently treated for OSA (AHI 15-20), not planning on starting treatment for
OSA during the duration of the study

6. Willing to have a diagnostic sleep study before the training

7. Willing to have a diagnostic sleep study after the training

8. Willing to perform tongue training exercises twice daily for 6 weeks

9. Willing to keep a sleep diary

Exclusion Criteria:

1. Dental problems, e.g., less than a full complement of front teeth, loose front teeth,
brittle teeth, by history

2. Temporomandibular joint (TMJ) disorder by history

3. Jaw, neck, or facial muscle pain or discomfort by history

4. Consumes more than one alcoholic beverage per day and unwilling to reduce alcohol
consumption to no more than one alcoholic beverage per day (muscle relaxant)

5. On benzodiazepine medication (or specific muscle relaxant)

6. Sleeps less than 5 hours per night on average (sleep deprivation can weaken UA)

7. Pregnant

8. Has had an upper airway surgical procedure for sleep apnea below the level of the
nasopharynx

9. Non-English speaker or illiterate