Rehabilitation Program as an Alternative Therapy for Moderate to Severe Obstructive Sleep Apnea Syndrome
Rehabilitation Program as an Alternative Therapy for Moderate to Severe Obstructive Sleep Apnea Syndrome
The obstructive sleep apnea/hypopnea syndrome (OSAS) is a common disease (2-4% of the general
 population) that generates intermittent hypoxemia and sleep fragmentation. OSAS is associated
 with various metabolic disorders such as metabolic syndrome, type 2 diabetes. OSAS is a risk
 factor for cardio-vascular diseases by increasing morbidity/mortality. OSAS patients suffer
 from excessive daytime sleepiness (EDS), a symptom also responsible for at least 30% of
 traffic accidents but also other cognitive disorders with significant impact on quality of
 life. OSAS generates oxidative stress, inflammation and resistance to insulin and other
 systemic metabolic dysregulation of many whose levels are correlated with the severity of the
 disease.

 Treatment with Continuous Positive Airway Pressure (CPAP) has clearly demonstrated its
 effectiveness to eliminate apneas and improve EDS but it is sometimes difficult to accept
 and/or poorly tolerated, limiting its effectiveness.

 Weight loss and regular physical activity are clearly recommended but rarely done in clinical
 practice. A few studies have applied to study the effects of rehabilitation training (REE) on
 the sleep apnea patients and have shown an improvement in sleep quality, reduction of
 awakenings and arousals from sleep and the Index of Apnea/Hypopnea (AHI), but their
 methodology was questionable, and the number of patients included was too low.

 The investigators hypothesis is that an in-patient multidisciplinary rehabilitation program
 comprising educational activities, dietary management and individualized exercise training
 (IET) will decrease OSAS severity, improve sleep quality and symptoms (EDS, fatigue, QoL).
 This IET program (24 sessions during 4 weeks) could also help to improve many metabolic
 dysregulation, inflammation and oxidative stress (also markers of cardiovascular risk).
 Leptin, a hormone involved in regulating appetite, energy expenditure and ventilatory control
 is increased in OSA (mechanism of leptin resistance). The improved sensitivity to leptin may
 play a role in enabling a better control of ventilation in these patients.
The obstructive sleep apnea/hypopnea syndrome (OSAS), with an estimated prevalence of between
 2 and 4% (1) is characterized by repetitive obstructions of the upper airway that generate
 intermittent hypoxemia and sleep fragmentation. The typical clinical profile of the apneic
 patient is an middle aged (50-55 years) obese male, snoring and drowsy. Moreover, OSAS is a
 risk factor for hypertension independent of obesity (2, 3) and it is now clear evidence that
 untreated apnea patients have high cardiovascular morbidity / mortality (CVM) higher than
 subjects treated with CPAP (4-6).

 Clinically, excessive daytime sleepiness (EDS) is the main symptom (7) but the attentional
 and cognitive disorders (8.9), depression or simply a state of fatigue are other possible
 manifestations of OSAS. The impact on quality of life (QoL) (10-12) are significant and
 underestimated. The origins of this drowsiness are multiple: one finds the fragmentation of
 sleep (13,14), intermittent hypoxia, respiratory effort, obesity (15) and certain cytokines
 such as TNF-alpha and IL-6 involved in sleep regulation (16-19).

 On the pathophysiology, the investigators find in the obstructive apneic oxidative stress
 (20-24) and systemic inflammation (25-27). CRP and levels of some cytokines (IL-1 beta, IL-6,
 IL-8 and TNF-alpha) are increased and their levels are correlated with the severity of
 disease as the increase of CVD (28-30 ). Intermittent hypoxia appears to play an essential
 role in the genesis of these abnormalities (31).

 On the metabolic dysregulation of many coexist. Found abnormal fasting blood glucose, a state
 of insulin resistance, dyslipidemia, and hyperleptinemia. Insulin resistance increases with
 body weight independent of the index of apnea / hypopnea (AHI) (18, 32-34). Intermittent
 hypoxia appears to be the cause. Leptin secreted by adipocytes, regulates weight by
 controlling appetite and energy expenditure. The hyperleptinemia found in OSA is
 controversial. Obesity appears to be primarily responsible for some (36) while others suggest
 the role of nocturnal hypoxemia (37). In fact, it is more the state of leptin resistance that
 hyperleptinemia alone that seems to be involved.

 Treatment with continuous positive airway pressure (CPAP) has clearly demonstrated its
 effectiveness to suppress apneas and sleep fragmentation associated. A meta-analysis (38) has
 confirmed the improvement of IDS by the PPC. However, in less severe forms, improving the SDE
 is less clear (39) and the PPC is sometimes not easily accepted, not tolerated and limiting
 its effectiveness is its poor compliance (40,41). From a pathophysiological point of view,
 CSF improves systemic inflammation (26,27) and diminishes the CVD (5.6). For cons, the
 metabolic dysregulation (insulin resistance, hyperleptinemia, dyslipidemia) are improving
 somewhat CPAP except in patients without obesity (42-44).

 The dietary guidelines are essential for the management of this disease is the result for a
 large part of a healthy lifestyle deleterious. Weight loss, regular physical activity is also
 clearly recommended but unfortunately rarely performed and / or supported by our healthcare
 system. Few studies have focused on studying the effects of such treatment on sleep apneic
 patients. In normal subjects, the effects of exercise on sleep are described in a
 meta-analysis (45). The practice of regular physical activity endurance improves quality of
 sleep (45-47). Sleep latency is shorter, there is less change in stages and fewer awakenings
 and arousals from sleep. Unlike other studies show that in situations where physical activity
 is reduced (physical inactivity, obesity, or prolonged bed rest, for example) sleep
 deteriorates, breaks and daytime alertness decreases. The effect of exercise in OSAS (48,49)
 and especially the training in physical exercise (48) shows an improvement in sleep quality
 and reduction of awakenings and arousals from sleep and fewer respiratory events (IAH).
 Pathophysiological point of view, there is a decrease in concentrations of leptin (50-53) and
 inflammatory cytokines (54-55) in different populations of subjects (healthy, older, obese,
 or with heart failure). And the investigators know the effects of exercise on carbohydrate
 metabolism in particular (decreased insulin resistance).

 And physical activity improves sleep quality in normal subjects while in parallel it would
 have an anti-inflammatory. For patients with severe OSAS, our hypothesis is to improve the
 quality of sleep (SLP rate) and a decrease in AHI and EDS through rehabilitation training
 (REE) associated with a comprehensive care (patient education, dietary, psychological, ...).
 On the pathophysiology, this improvement would be through a reduction of biological
 abnormalities associated with OSA are also markers of cardiovascular risk. Mainly metabolic
 disorders, oxidative stress and systemic inflammation.
Inclusion Criteria:

 -  Moderate to severe Obstructive Sleep Apnea Hypopnea Syndrome (AHI > 15/h)

 -  Sedentary patient (Activity Voorrips Questionnary score < 9,4)

 Exclusion Criteria:

 -  OSAS already treated by CPAP or other therapy (OAM,...)

 -  BMI > 40/m²

 -  Hypnotic and sedative medications

 -  Cranio-facial malformation

 -  Obstructive respiratory disease (COPD, asthma,...)

 -  Instable heart ischemic disease and all