Frédéric Sériès

Physiologic, metabolic, and muscle fiber type characteristics of musculus uvulae in sleep apnea hypopnea syndrome and in snorers.

Upper airway dilator muscles play an important role in the pathophysiology of sleep apnea hypopnea syndrome (SAHS). The mechanical and structural characteristics of these muscles remain unknown. The aim of this study was to compare the physiologic, metabolic, and fiber type characteristics of one upper airway dilator muscle (musculus uvulae, MU) in 11 SAHS and in seven nonapneic snorers. The different analyses were done on MU obtained during uvulo-palato-pharyngoplasty. Snorers and SAHS differed only in their apnea + hypopnea indices (11.5 +/- 5.9 and 34.2 +/- 14.6/h, respectively, mean +/- SD). Absolute twitch and tetanic tension production of MU was significantly greater in SAHS than in snorers while the fatigability index was similar in the two groups. Protein content and anaerobic enzyme activities of MU were significantly greater in SAHS than in snorers; no difference was observed for aerobic enzyme activities. The total muscle fiber cross-sectional area of MU was significantly higher in SAHS (2.2 +/- 0.9 mm2) than in snorers (1.1 +/- 0.7 mm2). The surface occupied by type IIA muscle fibers of MU was larger in SAHS (2.00 +/- 0.96) than in snorers (0.84 +/- 0.63 mm2). We conclude that the capacity for tension production and the anaerobic metabolic activity of MU are greater in SAHS than in snorers.

Surgical correction of nasal obstruction in the treatment of mild sleep apnoea: importance of cephalometry in predicting outcome.

BACKGROUND--A study was undertaken to determine if cephalometric radiographs could identify those who will benefit from nasal surgery in patients with a sleep apnoea hypopnoea syndrome (SAHS) and chronic nasal obstruction. METHODS--Fourteen patients with SAHS were enrolled. Those with normal posterior airway space and mandibular plane to hyoid bone distances on preoperative cephalometric radiographs were matched with those with abnormal cephalometry for the frequency of sleep disordered breathing and body mass index. Polysomnographic studies (all subjects) and nasal resistance measurements (n = 10) were performed one to three months before and two to three months after surgery (septoplasty, turbinectomy, and polypectomy). RESULTS--There was no difference in the baseline results of the polysomnographic studies between the two groups of patients. Nasal resistance decreased from a mean (SE) value of 2.9 (0.3) cm H2O/l/s before surgery to 1.4 (0.1) cm H2O/l/s after surgery in the normal cephalometry group and from 2.7 (0.3) cm H2O/l/s to 1.3 (0.3) cm H2O/l/s in the other group. The apnoea + hypopnoea index returned to normal (< 10 breathing abnormalities/hour) in all but one subject with normal cephalometric measurements, and sleep fragmentation improved with a decrease in the arousal index from 23.9 (3.3)/hour at baseline to 10.6 (2.5)/hour after surgery. Both of these parameters remained unchanged after surgery in the patients with abnormal cephalometry. CONCLUSIONS--Normal cephalometry is helpful in identifying patients with mild SAHS and nasal obstruction who will benefit from nasal surgery. The presence of craniomandibular abnormalities makes it unlikely that nasal surgery will improve sleep related breathing abnormalities.

Efficacy of Automatic Continuous positive airway pressure therapy that uses an estimated required pressure in the treatment of the obstructive sleep apnea syndrome

The obstructive sleep apnea syndrome (OSAS) is highly prevalent; it is found in 4% of middle-aged men and 2% of middle-aged women [1]. The increase in the rate of illness and death associated with this disease emphasizes the need for effective treatment [2-5]. Approaches to therapy include weight loss [6], upper airway surgery [7], oral appliances [8], and nasal continuous positive airway pressure (CPAP) [9]. Therapy with CPAP decreases the rate of illness and death associated with sleep apnea [5, 10, 11]. Before CPAP therapy is started at home, a polysomnographic study must be done to determine the pressure needed to resolve apnea, hypopnea, snoring, and respiratory-related arousals in all sleep stages and body positions. The CPAP device is then set to this level. Effective pressure can also be estimated by using a regression model that takes into account anthropometric characteristics, neck circumference, and the frequency of nocturnal breathing abnormalities [12]. However, the regression model often underestimates the positive pressure requirements. A recent report [13] suggested that effective pressure can be reliably estimated during unattended sleep studies by using automatic adjustments of the positive pressure made on the basis of a record of respiratory variables. Because the optimal CPAP comprises several factors, the effective pressure can change within one night and from one night to another depending on changes in body position [14, 15], sleep stage [14], neck and mandibular position [16, 17], nasal patency, upper airway edema [18], and other factors. This variability has led to the development of automatic CPAP devices that continuously adapt the positive pressure in response to varying needs. We compared the efficacy of conventional CPAP therapy with that of automatic CPAP therapy administered by an automatic CPAP machine (Morphee Plus, Pierre Medical, Verrieres-Le-Buisson, France) for OSAS [19]. With this machine, the user must establish a reference pressure that usually corresponds to the effective pressure determined by a conventional titration sleep study. However, the effective pressure can be estimated by the users characteristics; we hypothesized that the ability of the automatic CPAP machine to automatically adjust the positive pressure should compensate for the uncertainty in effective pressure determination obtained by the regression model. This procedure may provide effective treatment of OSAS without doing a CPAP titration sleep study. We compared the efficacy of automatic CPAP given at an estimated reference pressure, automatic CPAP given at a measured reference pressure, and conventional CPAP therapy. Methods Patients The study was conducted between 30 May 1995 and 16 May 1996. Thirty-nine patients were asked to participate, but 3 refused to participate because of their work schedules. Therefore, 36 patients (age range, 36 to 65 years; mean body mass index SD, 36.4 7.6 kg/m2) with previously untreated OSAS were included. All patients were seen at the sleep clinic at Hopital Laval. A diagnosis was made on the basis of clinical features and was confirmed by a polysomnographic study (mean apnea + hypopnea index [events per hour] SD, 43.6 19.8). After this diagnostic study, all patients who chose to be treated with nasal CPAP and had no exclusion criteria were asked to participate in the study. Patients were excluded if they had life-threatening forms of OSAS (such as severe hypersomnolence) that required immediate treatment, OSAS associated with nonobstructive sleep-related breathing disorders (such as periodic breathing and hypoventilation) or with nonrespiratory sleep disorders (such as narcolepsy and periodic leg movements), or an estimated pressure above 15 cm H2O. Treatment with Continuous Positive Airway Pressure A titration sleep study was conducted within 1 week after the diagnostic sleep study to determine the effective pressure in all patients. Patients were then randomly assigned to one of three treatment groups in a single-blind fashion. The Morphee Plus automatic CPAP device will soon be distributed in North America by Nellcor Puritan-Bennett (Eden Prairie, Minneapolis, Minnesota) under the name of Cloudnine. The device has not yet been approved by the U.S. Food and Drug Administration. Because the Morphee Plus device can be set to a constant or an automatic CPAP mode, we used this machine to treat the three groups. In the automatic CPAP mode, the positive pressure is allowed to change within a determined range around the reference pressure. The reference pressure and the upper and lower pressure thresholds are chosen separately by the physician. Group 1 was treated with conventional CPAP; that is, a constant pressure was set at the effective pressure. For groups 2 and 3, the machine was used in the automatic CPAP mode; the reference pressure was set at the measured effective pressure for group 2 and at the estimated effective pressure for group 3. The estimated effective pressure was calculated by using the following formula [12]: (Equation 1) We set the range of pressure at 3 cm H2O above the reference pressure to 4 cm H2O below the reference pressure in accordance with our previous experience with this machine [19] and the level of underestimation reported with the estimated pressure formula [12]. Patients were blinded to treatment assignment. For each block of three patients, the treatment regimen was determined by using a randomization table. To compare patients with similar severity of disease, patients were paired for the estimated pressure value. In each block of three patients, the estimated pressure could not differ by more than 1 cm H2O from the value of the first patient included in that block. If a candidate did not meet this criterion, he or she was assigned to the first randomized position in the next block of three patients. Characteristics of Automatic Continuous Positive Airway Pressure In the automatic CPAP mode, the positive pressure is maintained as long as ventilation remains stable; however, any respiratory disorder results in a progressive increase in the pressure. If a breathing disturbance has not occurred for more than 4 minutes, the positive pressure decreases again. Changes in pressure are regulated by a constant feedback analysis of the patients ventilation by the nasal CPAP device. The breath-by-breath difference between maximal inspiratory and expiratory flow is estimated by the changes in compressor speed required to maintain a constant positive pressure throughout the respiratory cycle. Apneic and hypopneic events are associated with a decrease in the difference between the inspiratory and expiratory flow; this leads to an increase in the pressure until the flow regimen of the compressor has become stable or the fixed upper limit of pressure has been reached. Outcome Measures Sleep and breathing characteristics were measured during polysomnographic studies that consisted of continuous electroencephalography [C4/A1, C3/A2, O2/A1, and O1/A2], submental electromyography, electrooculography, and electrocardiography and measurement of 1) nasobuccal airflow by thermistors, 2) thoracoabdominal movements by inductive plethysmography [Respitrace, Ambulatory Monitoring, Inc., Arsdley, New York], 3) arterial oxyhemoglobin saturation (Sao 2) level with an ear oximeter [504 Pulse oximeter, Criticare Systems, Inc., Waukesha, Wisconsin], and 4) breathing noises by two microphones placed at the bedside. All variables were recorded on a computer (Sandman, Melleville Diagnostics, Ottawa, Ontario, Canada). Polysomnographic recordings were manually interpreted in 30-second periods according to established criteria [20]. Arousals were scored according to the definition established by the American Sleep Disorders Association [21]. Apnea was defined as the cessation of nasal-oral airflow for at least 10 seconds. Hypopnea was defined as a decrease of more than 50% in total thoracoabdominal movements for at least 10 seconds and was associated with a 2% decrease in Sao 2 level or an arousal. Diurnal somnolence was assessed by using the Epworth Sleepiness Scale [22] and maintenance-of-wakefulness tests [23]. For the latter, patients were seated in a comfortable armchair every 2 hours and asked to remain awake as long as possible during four consecutive 40-minute periods in darkness. Each maintenance-of-wakefulness test was stopped after 10 minutes of sleep or after 40 minutes if no sleep was recorded; sleep onset was defined as three continuous periods of stage I sleep, any period of stage II to IV or rapid eye movement sleep. Sleep latency was defined as the mean value of the four tests. The mean positive pressure, the proportion of time spent at different pressures, and the time at which positive pressure was applied were automatically recorded each night by the CPAP device for 3 weeks. Changes in positive pressure were analyzed during the control sleep study by continuous recording of mask pressure. Compliance with CPAP therapy was assessed by measuring the amount of CPAP used during the study period and was quantified by measuring the percentage of time during which the machine was turned on and positive pressure was applied (effective pressure-time index) and the number of nights during which positive pressure was applied for more than 4 hours and more than 7 hours [24]. After 3 weeks of treatment with CPAP, a control sleep study was done by using the CPAP device on the setting that patients had used for the past 3 weeks. The Epworth Sleepiness Scale and maintenance-of-wakefulness tests were completed at baseline and on the day after the third polysomnographic recording. Time and pressure readings were printed from the machine at the end of the study period. Changes in the apnea + hypopnea index and diurnal hypersomnolence after CPAP therapy and differences in compliance with CPAP therapy among the three treatment groups were the main study end points. The

Sleep apnoea attenuates the effects of a lifestyle intervention programme in men with visceral obesity

Background Excess visceral adiposity and sleep apnoea are two conditions independently associated with cardiovascular diseases. The two conditions are often combined and are believed to interact in a vicious circle. Objectives To compare the response of men with visceral obesity with or without sleep apnoea syndrome to a 1-year healthy eating, physical activity/exercise intervention programme. Methods 77 men, selected on the basis of increased waist circumference (≥90u2005cm) and dyslipidaemia (triglycerides ≥1.69 and/or high-density lipoprotein (HDL) cholesterol <1.03u2005mmol/litre), participated in this study. Body composition and fat distribution were assessed by dual-emission X-ray absorptiometry or CT and sleep breathing disorders by home-based polygraphic recording. Cardiorespiratory fitness, plasma adipokines, plasma inflammatory markers, fasting lipoprotein–lipid profile and oral glucose tolerance test were assessed. Results After the 1-year lifestyle intervention, the mean oxygen desaturation index (ODI) of the whole sample decreased (−3±13 events/h, p<0.05). Men with sleep apnoea syndrome at baseline (ODI ≥10 events/h, n=28) showed smaller reductions in body mass index, waist circumference, triglycerides and smaller increases in HDL cholesterol and adiponectin than men without sleep apnoea (ODI <10 events/h, n=49), despite similar compliance to the programme. The higher the baseline ODI and the time spent under 90% saturation, the lower the reductions in fat mass and visceral adiposity, and the smaller the improvement in glucose/insulin homeostasis indices after 1u2005year. Conclusions Men with sleep apnoea syndrome at baseline had smaller reduction in body weight and less metabolic improvements associated with the lifestyle intervention programme than men without sleep apnoea syndrome.

Upper airway collapsibility, and contractile and metabolic characteristics of musculus uvulae.

Physiologic, metabolic, and histochemi‐ cal characteristics of one upper airway (UA) dilator muscle (musculus uvulae; MU) differ between sleep apnea hypopnea syndrome (SAHS) and nonapneic snorers. We hypothesized that these differences in MU characteristics could result from the cumulative effects of the diurnal and nocturnal intermittent contractions of UA muscles in order to compensate for a permanent increase in UA collapsibility. The aim of this study was to determine the influence of UA collapsibility on MU characteristics. Seventeen SAHS and three nonapneic snorers, who underwent an uvulo‐palato‐pharyngoplasty as a treatment for snoring or SAHS, participated in the study. Awake and sleeping UA critical pressure (Pcrit) was measured during continuous positive or negative airway pressure trials by analysis of the relationship between maximal inspiratory flow and the upstream pressure of flow‐limited breathing cycles. Maximum isometric twitch (P1) and tetanic tension (P0), fatigability measurements, activities of marker enzymes for anaerobic and aerobic‐oxidative profile, and fiber type proportions and areas of MU were determined. There was a significant positive relationship between Pt, P0, and Pcrit measured during wakefulness and sleep. The fatigability index was negatively correlated with awake Pcrit values (r = ‐0.79). Activity level of the anaerobic enzymes as well as the percentage of surface occupied by type I and type IIA muscle fibers as correlated with awake Pcrit. We conclude that the differences in awake UA collapsibility help to determine the contractile properties and metabolic and histochemical characteristics of MU.—Sériès, F., Côté, C., Simoneau, J‐A., St. Pierre, S., Marc, I. Upper airway collapsibility, and contractile and metabolic characteristics of musculus uvulae. FASEB J. 897‐904 (1996)

Muscle fiber area distribution of musculus uvulae in obstructive sleep apnea and non-apneic snorers.

OBJECTIVE: To determine whether differences exist in the morphology of upper airway muscles between apneic and non-apneic snorersDESIGN: Muscle characteristic analysis in patients undergoing upper airway surgery in a tertiary sleep center.SUBJECTS: 10 non-apneic snorers and 10 sleep apnea hypopnea syndrome (SAHS).MEASUREMENTS: Frequency distribution of musculus uvulae (MU) muscle fiber area determined from 475±207 (mean±s.d.) and 697±165 type IIA fibers and 92±32 and 68±45 type I fibers in snorers and SAHS, respectively.RESULTS: Histochemical analyses of MU revealed as expected that type IIA fibers occupied a significantly larger area within that muscle in SAHS compared to Snorers (89.4±5.8% and 76.1±15.1% respectively, P=0.01). No difference was found in the frequency distribution of type I and type IIA fiber areas between the two groups comparing the between-groups and within-group variance of individual area distributions found in snorers and SAHS.CONCLUSION: There is no difference in muscle fiber area frequency distribution between non-apneic snorers and SAHS patients. This suggests that musculus uvulae of these groups of patients does not have a specific prevalence of atrophic or hypertrophic muscle fibers.

Relationship between severity of nocturnal desaturation and adaptive thermogenesis : preliminary data of apneic patients tested in a whole-body indirect calorimetry chamber

The purpose of this study was to investigate the possibility of a relationship between the severity of obstructive sleep apnea syndrome (OSAS) and adaptive thermogenesis. Daily energy expenditure (DEE) and sleeping metabolic rate (SMR) were measured in apneic and a priori nonapneic subjects who were tested in a whole-body indirect calorimetry chamber for 24u2009h. The apneic patients were diagnosed by nocturnal home oximetry to determine the percentage of total recording time spent below 90% arterial oxygen saturation (% TRT <90% SaO2). Reference equations established from body weight and age in nonapneic subjects were used to predict DEE and SMR in apneic patients. The predicted values of the apneic patients were then compared to their measured values. No significant difference was found between predicted and measured values in SMR nor in DEE. We observed a significant relationship between the severity of nocturnal desaturation and the difference between predicted and measured DEE in apneic patients (r=−0.74, P<0.05) and a similar negative trend with SMR (r=−0.65, P=0.08). These preliminary data suggest that a nocturnal hypoxia may influence adaptive thermogenesis in apneic patients and complicate their body weight regulation.

Corticomotor control of the genioglossus in awake OSAS patients: a transcranial magnetic stimulation study

BackgroundUpper airway collapse does not occur during wake in obstructive sleep apnea patients. This points to wake-related compensatory mechanisms, and possibly to a modified corticomotor control of upper airway dilator muscles. The objectives of the study were to characterize the responsiveness of the genioglossus to transcranial magnetic stimulation during respiratory and non-respiratory facilitatory maneuvers in obstructive sleep apnea patients, and to compare it to the responsiveness of the diaphragm, with reference to normal controls.MethodsMotor evoked potentials of the genioglossus and of the diaphragm, with the corresponding motor thresholds, were recorded in response to transcranial magnetic stimulation applied during expiration, inspiration and during maximal tongue protraction in 13 sleep apnea patients and 8 normal controls.Main ResultsIn the sleep apnea patients: 1) combined genioglossus and diaphragm responses occurred more frequently than in controls (P < 0.0001); 2) the amplitude of the genioglossus response increased during inspiratory maneuvers (not observed in controls); 3) the latency of the genioglossus response decreased during tongue protraction (not observed in controls). A significant negative correlation was found between the latency of the genioglossus response and the apnea-hypopnea index; 4) the difference in diaphragm and genioglossus cortico-motor responses during tongue protraction and inspiratory loading differed between sleep apnea and controls.ConclusionSleep apnea patients and control subjects differ in the response pattern of the genioglossus and of the diaphragm to facilitatory maneuvers, some of the differences being related to the frequency of sleep-related events.

Tumor Necrosis Factor-α Expression in Uvular Tissues Differs Between Snorers and Apneic Patients

BACKGROUNDnInflammatory changes such as subepithelial edema and excessive inflammatory cell infiltration have been observed in uvular tissues of obstructive sleep apnea (OSA) subjects. The levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin-6 are elevated in the serum of apneic patients and have been proposed as mediators of muscle weakness. TNF-alpha has been shown to affect diaphragm contractility in mice and rabbit in vivo.nnnOBJECTIVESnTo assess total and compartmental TNF-alpha expression in uvular tissues of apneic and nonapneic patients.nnnMETHODSnUvular tissues were collected from 14 snorers without sleep disorders breathing, 14 subjects with OSA (OSA 1 group) whose body mass index (BMI) was similar to that of snorers, and 12 additional obese OSA subjects (OSA 2 group) who underwent an uvulopalatopharyngoplasty. Sections were examined using immunohistochemistry and Western blot analysis. TNF-alpha expression was evaluated in the musculus uvulae (MU), epithelial layer, and perimuscular tissues from proximal uvular sections.nnnRESULTSnTNF-alpha was more highly expressed in whole uvular protein extracts of apneic groups than in snorers ([mean +/- SEM] snorers, 100.5 +/- 3.0%; OSA 1 group, 127.1 +/- 6.9%; OSA 2 group, 140.7 +/- 11.0%; p = 0.01). In the muscular area, TNF-alpha levels were higher in the more obese OSA subjects than in the other two groups (snorers, 100.3 +/- 3%; OSA 1 group, 107.4 +/- 0.7%; OSA 2 group, 124.1 +/- 4.2%; p = 0.007). In the muscular area, TNF-alpha was correlated with BMI, but no relationship was found with the apnea-hypopnea index.nnnCONCLUSIONSnWe conclude that MU is the major TNF-alpha source in uvular tissue and that TNF-alpha is more highly expressed in the heaviest OSA patients compared to less obese OSA patients and nonapneic snorers.

Obstructive sleep apnea and driving: A Canadian Thoracic Society and Canadian Sleep Society position paper

Untreated patients with obstructive sleep apnea (OSA) are at increased risk for motor vehicle collisions; however, it is unclear how this should be translated into fitness-to-drive recommendations. Accordingly, the Canadian Thoracic Society (CTS) Sleep Disordered Breathing Clinical Assembly and the Canadian Sleep Society (CSS) assembled a CTS-CSS working group to propose recommendations with regard to driving in patients with OSA. Recommendations for assessing fitness to drive in noncommercial drivers: 1. Severity of OSA alone is not a reliable predictor of collision risk and, therefore, should not be used in isolation to assess fitness to drive; 2. The severity of sleep apnea should be considered in the context of other factors to assess fitness to drive; 3. The decision to restrict driving is ultimately made by the motor vehicle licensing authority; however, they should take into account the information and recommendations provided by the sleep medicine physician and should follow provincial guidelines; 4. For patients prescribed continuous positive airway pressure (CPAP) therapy, objective CPAP compliance should be documented. Efficacy should also be documented in terms of reversing the symptoms and improvement in sleep apnea based on physiological monitoring; 5. For patients treated with surgery or an oral appliance, verification of adequate sleep apnea treatment should be obtained; and 6. A driver diagnosed with OSA may be recertified as fit to drive based on assessment of symptoms and demonstrating compliance with treatment. The assessment should be aligned with the provincial drivers license renewal period. Commercial vehicles: Assessment of fitness to drive should be more stringent for patients operating commercial vehicles. In general, the CTS-CSS working group was in agreement with the Medical Expert Panel recommendations to the Federal Motor Carrier Safety Administration in the United States; these recommendations were adapted for Canadian practitioners.