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Background: Previous studies have shown that changes in lung volume influence upper airway size and resistance, particularly in patients with obstructive sleep apnoea (OSA), and that continuous positive airway pressure (CPAP) requirements decrease when the lung volume is increased. We sought to determine the effect of a constant lung volume increase on sleep disordered breathing during non-REM sleep. Methods: Twelve subjects with OSA were studied during non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. The increase in lung volume due to CPAP (at a therapeutic level) was determined with four magnetometer coils placed on the chest wall and abdomen. CPAP was then stopped and the subjects were studied for 1 hour in three conditions (in random order): (1) no treatment (baseline); (2) at “CPAP lung volume”, with the increased lung volume being reproduced by negative extrathoracic pressure alone (lung volume 1, LV1); and (3) 500 ml above the CPAP lung volume(lung volume 2, LV2). Results: The mean (SE) apnoea/hypopnoea index (AHI) for baseline, LV1, and LV2, respectively, was 62.3 (10.2), 37.2 (5.0), and 31.2 (6.7) events per hour (p = 0.009); the 3% oxygen desaturation index was 43.0 (10.1), 16.1 (5.4), and 12.3 (5.3) events per hour (p = 0.002); and the mean oxygen saturation was 95.4 (0.3)%, 96.0 (0.2)%, 96.3 (0.3)%, respectively (p = 0.001). Conclusion: An increase in lung volume causes a substantial decrease in sleep disordered breathing in patients with OSA during non-REM sleep.

Kleine-Levin syndrome (KLS) is a disorder characterized by recurrent episodes of hypersomnia associated with perception, cognitive, and behavioral disturbances, such as hyperphagia and hypersexuality.1 Episodes are separated by intervals of normal alertness, cognition, and behavior. Primary KLS predominantly affects adolescent males, with a prevalence of 2–10 …

Objectif Le trouble du comportement en sommeil paradoxal (TCSP) est une parasomnie caracterisee par des reves agites et une perte de l’atonie musculaire en sommeil paradoxal (SP). Le suivi prospectif de ces patients montre que la plupart d’entre eux risquent de developper une maladie neurodegenerative. Le but de notre etude a ete d’estimer la prevalence du TCSP sur un echantillon representatif de la population generale. Methodes Les donnees cliniques et demographiques de 1999 sujets (51,2 % de femmes, âge moyen 58,9 ± 11,1) participant a l’etude de cohorte hypnoLaus (Lausanne, Suisse) ont ete recoltees. Ils ont rempli des questionnaires concernant leur sommeil dont le questionnaire Munich Parasomnia Screening (MUPS), et ont eu une polysomnographie (PSG) complete a domicile. La presence d’une activite musculaire excessive en SP a ete evaluee visuellement sur les muscles tibiaux anterieurs et du menton. Resultats Un total de 110 (6 %) participants ont repondu « oui » aux deux questions du MUPS relatives a un possible TCSP (« Est ce que vous avez deja donne des coups durant votre sommeil ? », « Est-ce que vous avez deja eu l’impression de vivre votre reve, p.e. gesticulations ? »). Parmi ces 110 participants, 60 (3 %) avaient en plus un tonus musculaire excessif objective par la PSG en SP. Conclusion En combinant le depistage par questionnaire valide et l’objectivation d’une perte d’atonie musculaire en SP a la PSG, nous trouvons une prevalence du TCSP de 3 % dans un echantillon representatif de la population generale adulte.

BACKGROUND: Sleep-disordered breathing is associated with major morbidity and mortality. However, its prevalence has mainly been selectively studied in populations at risk for sleep-disordered breathing or cardiovascular diseases. Taking into account improvements in recording techniques and new criteria used to define respiratory events, we aimed to assess the prevalence of sleep-disordered breathing and associated clinical features in a large population-based sample. METHODS: Between Sept 1, 2009, and June 30, 2013, we did a population-based study (HypnoLaus) in Lausanne, Switzerland. We invited a cohort of 3043 consecutive participants of the CoLaus/PsyCoLaus study to take part. Polysomnography data from 2121 people were included in the final analysis. 1024 (48%) participants were men, with a median age of 57 years (IQR 49-68, range 40-85) and mean body-mass index (BMI) of 25·6 kg/m(2) (SD 4·1). Participants underwent complete polysomnographic recordings at home and had extensive phenotyping for diabetes, hypertension, metabolic syndrome, and depression. The primary outcome was prevalence of sleep-disordered breathing, assessed by the apnoea-hypopnoea index. FINDINGS: The median apnoea-hypopnoea index was 6·9 events per h (IQR 2·7-14·1) in women and 14·9 per h (7·2-27·1) in men. The prevalence of moderate-to-severe sleep-disordered breathing (≥15 events per h) was 23·4% (95% CI 20·9-26·0) in women and 49·7% (46·6-52·8) in men. After multivariable adjustment, the upper quartile for the apnoea-hypopnoea index (>20·6 events per h) was associated independently with the presence of hypertension (odds ratio 1·60, 95% CI 1·14-2·26; p=0·0292 for trend across severity quartiles), diabetes (2·00, 1·05-3·99; p=0·0467), metabolic syndrome (2·80, 1·86-4·29; p

Objective To examine the association of socioeconomic status (SES) with subjective and objective sleep disturbances and the role of socio-demographic, behavioural and psychological factors in explaining this association. Methods Analyses are based on 3391 participants (53% female, aged 40–81 years) of the follow-up of the CoLaus study (2009–2012), a population-based sample of the city of Lausanne, Switzerland. All participants completed a sleep questionnaire and a sub-sample ( N = 1569) underwent polysomnography. Results Compared with men with a high SES, men with a low SES were more likely to suffer from poor sleep quality [prevalence ratio (PR) for occupational position = 1.68, 95% Confidence Interval (CI): 1.30–2.17], and to have long sleep latency (PR = 4.90, 95%CI: 2.14–11.17), insomnia (PR = 1.47, 95% CI: 1.12–1.93) and short sleep duration (PR = 3.03, 95% CI: 1.78–5.18). The same pattern was observed among women (PR = 1.29 for sleep quality, 2.34 for sleep latency, 2.01 for daytime sleepiness, 3.16 for sleep duration, 95%CIs ranging from 1.00 to 7.51). Use of sleep medications was not patterned by SES. SES differences in sleep disturbances were only marginally attenuated by adjustment for other socio-demographic, behavioural and psychological factors. Results from polysomnography confirmed poorer sleep patterns among participants with low SES ( p 0.05 for sleep efficiency/stage shifts), but no SES differences were found for sleep duration. Conclusions In this population-based sample, low SES was strongly associated with sleep disturbances, independently of socio-demographic, behavioural, and psychological factors. Further research should establish the extent to which social differences in sleep contribute to socioeconomic differences in health outcomes.

Rationale Limited-channel portable monitors (PMs) are increasingly used as an alternative to polysomnography (PSG) for the diagnosis of obstructive sleep apnoea (OSA). However, recommendations for the scoring of PM recordings are still lacking. Pulse-wave amplitude (PWA) drops, considered as surrogates for EEG arousals, may increase the detection sensitivity for respiratory events in PM recordings. Objectives To investigate the performance of four different hypopnoea scoring criteria, using 3% or 4% oxygen desaturation levels, including or not PWA drops as surrogates for EEG arousals, and to determine the impact of measured versus reported sleep time on OSA diagnosis. Methods Subjects drawn from a population-based cohort underwent a complete home PSG. The PSG recordings were scored using the 2012 American Academy of Sleep Medicine criteria to determine the apnoea–hypopnoea index (AHI). Recordings were then rescored using only parameters available on type 3 PM devices according to different hypopnoea criteria and patients-reported sleep duration to determine the ‘portable monitor AHIs’ (PM-AHIs). Main results 312 subjects were included. Overall, PM-AHIs showed a good concordance with the PSG-based AHI although it tended to slightly underestimate it. The PM-AHI using 3% desaturation without PWA drops showed the best diagnostic accuracy for AHI thresholds of ≥5/h and ≥15/h (correctly classifying 94.55% and 93.27% of subjects, respectively, vs 80.13% and 87.50% with PWA drops). There was a significant but modest correlation between PWA drops and EEG arousals (r=0.20, p=0.0004). Conclusion Interpretation of PM recordings using hypopnoea criteria which include 3% desaturation without PWA drops as EEG arousal surrogate showed the best diagnosis accuracy compared with full PSG.

STUDY OBJECTIVES: To evaluate the association between objective sleep measures and metabolic syndrome (MS), hypertension, diabetes, and obesity. DESIGN: Cross-sectional study. SETTING: General population sample. PARTICIPANTS: There were 2,162 patients (51.2% women, mean age 58.4 ± 11.1). INTERVENTIONS: Patients were evaluated for hypertension, diabetes, overweight/obesity, and MS, and underwent a full polysomnography (PSG). MEASUREMENTS AND RESULTS: PSG measured variables included: total sleep time (TST), percentage and time spent in slow wave sleep (SWS) and in rapid eye movement (REM) sleep, sleep efficiency and arousal index (ArI). In univariate analyses, MS was associated with decreased TST, SWS, REM sleep, and sleep efficiency, and increased ArI. After adjustment for age, sex, smoking, alcohol, physical activity, drugs that affect sleep and depression, the ArI remained significantly higher, but the difference disappeared in patients without significant sleep disordered breathing (SDB). Differences in sleep structure were also found according to the presence or absence of hypertension, diabetes, and overweight/obesity in univariate analysis. However, these differences were attenuated after multivariate adjustment and after excluding subjects with significant SDB. CONCLUSIONS: In this population-based sample we found significant associations between sleep structure and MS, hypertension, diabetes, and obesity. However, these associations were cancelled after multivariate adjustment. We conclude that normal variations in sleep contribute little if any to MS and associated disorders.

Contains fulltext : 137735.pdf (Publisher’s version ) (Closed access) STUDY OBJECTIVE: Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. DESIGN: Retrospective case-control study. SETTING: A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. PATIENTS AND PARTICIPANTS: For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. MEASUREMENTS AND RESULTS: None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified. CONCLUSION: An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.

Objectif Investiguer la frequence des mouvements periodiques des jambes au cours du sommeil (MPJS) et leurs determinants dans la population generale. Methodes Nous avons analyse les donnees de 2162 sujets issus de la population generale (âge moyen 58 ± 11 ; 51,2 % des femmes) participant a l’etude Hypnolaus, une cohorte communautaire basee sur un echantillon representatif de la population de la ville de Lausanne (Suisse). Tous les participants ont eu une evaluation clinique, ont rempli une serie de questionnaires sur le sommeil et ont eu un enregistrement polysomnographique a domicile. L’index de MPJS (MPJSI) a ete determine en fonction des criteres de l’AASM 2007 avec un seuil pathologique de MPJSI fixe a > 15/h. Resultats Pour l’ensemble de la population, le MPJSI etait de (mediane [P05–P95]) 14 [1–75]/heure de sommeil et 618 sujets (28,6 %) avaient un MPJSI > 15/h (34 [17–97]). Compares aux sujets avec un MPJSI ≤ 15/h, ils etaient plus âges (63,7 ± 10,7 vs 56,4 ± 10,5 ans, p 15/h. Conclusion La presence de MPJS est frequente dans la population generale adulte. L’âge, le sexe masculin et la presence d’impatiences a l’eveil sont des facteurs predictifs independants d’un MPJSI superieur a 15/h.

The airway binary fluid layer and the structural characteristics of the upper airways have significant influence on the activity of the airway muscles by changing airway compliance and collapsibility during obstructive sleep apnea trauma. The uvula plays an important role in the collapse process. Using MRI scans, this paper develops a structural model for the uvula and determines its dynamic characteristics in terms of natural frequencies and mode shapes as a preliminary process to determine optimum conditions to therapeutically relieve upper airway obstruction. The effect of the variation of tissue elasticity due to water content is elaborated on.Copyright © 2013 by ASME

Background and Objective Restless legs syndrome (RLS) is a frequent conditionwith a prevalence of 5–15% in the general population. Clinical and geneticobservations have shown that iron deficiency, highly prevalent among blooddonors, can be related to RLS. The objective of this study was to assess the prev-alence of RLS in female blood donors 1 week after blood donation.Methods One week after blood donation, 291 female blood donors, aged

Contains fulltext : 149650.pdf (Publisher’s version ) (Closed access) The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 +/- 12.43 versus 21.49 +/- 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 +/- 13.79 versus 15.62 +/- 14.94, P = 0.044). The mean diagnostic delay was 14.63 +/- 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.

Objectif Explorer l’association entre sommeil et deficits cognitifs dans un echantillon de la population generale. Methodes Nous avons analyse les donnees de 580 sujets participant a l’etude HypnoLaus (Lausanne, Suisse) qui ont eu un enregistrement polysomnographique et une evaluation cognitive (Clinical Dementia Rating Scale, CDR). Les participants avec un score CDR global > 0 ont ete consideres comme ayant des troubles cognitifs. Resultats Nous avons identifie 291 sujets (72,4 ± 4,6 ans, 43,3 % femmes) avec des troubles cognitifs. Compares a 289 controles (72,1 ± 4,6 ans, 65,7 % femmes), ils presentaient moins de stade 3 (61,0 ± 33,4 vs 67,5 ± 32,5 min, p = 0,017), moins de sommeil paradoxal (73,6 ± 31,7 vs 79,9 ± 30,9 min, p = 0,016), ainsi que des index d’apnees/hypopnees (IAH : 16,0 ± 17,6 vs 10,7 ± 12,8/h, p p p = 0,043), l’IDO4 % (1,0162 [1,0013–1,0313], p = 0,033) et le IDO6 % (1,0289 [1,0028–1,0557], p = 0,029) restaient independamment associes a la presence de troubles cognitifs. Conclusion Dans le modele multivarie, l’IAH, l’IDO4 % et l’IDO6 % etaient independamment associes a la presence de deficits cognitifs. Les troubles respiratoires au cours du sommeil pourraient jouer un role dans leur developpement.

The physiological impacts of continuous positive airway pressure (CPAP) are not yet fully understood. In this study we developed an MRI protocol to assess the impact of CPAP on cerebral hemodynamics and cerebrospinal fluid (CSF) hydrodynamics in the upper cervical spine. MRI measurements were obtained on 14 healthy male subjects. The preliminary results indicated that the CSF pulsation decreased and venous outflow was altered with CPAP usage in comparison to the baseline values. Cerebral arterial flow was not impacted by CPAP usage. These findings support the hypothesis that the CSF system can act to dampen cerebral blood flow (CBF) pulsations.

BACKGROUND AND PURPOSE: Sleep disordered breathing (SDB) is frequent in acute stroke patients and is associated with early neurologic worsening and poor outcome. Although continuous positive airway pressure (CPAP) effectively treats SDB, compliance is low. The objective of the present study was to assess the tolerance and the efficacy of a continuous high-flow-rate air administered through an open nasal cannula (transnasal insufflation, TNI), a less-intrusive method, to treat SDB in acute stroke patients. METHODS: Ten patients (age, 56.8 ± 10.7 years), with SDB ranging from moderate to severe (apnea-hypopnea index, AHI, >15/h of sleep) and on a standard sleep study at a mean of 4.8 ± 3.7 days after ischemic stroke (range, 1-15 days), were selected. The night after, they underwent a second sleep study while receiving TNI (18 L/min). RESULTS: TNI was well tolerated by all patients. For the entire group, TNI decreased the AHI from 40.4 ± 25.7 to 30.8 ± 25.7/h (p = 0.001) and the oxygen desaturation index >3% from 40.7 ± 28.4 to 31 ± 22.5/h (p = 0.02). All participants except one showed a decrease in AHI. The percentage of slow-wave sleep significantly increased with TNI from 16.7 ± 8.2% to 22.3 ± 7.4% (p = 0.01). There was also a trend toward a reduction in markers of sleep disruption (number of awakenings, arousal index). CONCLUSIONS: TNI improves SDB indices, and possibly sleep parameters, in stroke patients. Although these changes are modest, our findings suggest that TNI is a viable treatment alternative to CPAP in patients with SDB in the acute phase of ischemic stroke.

Continuous Positive Airway Pressure (CPAP) is used as the gold standard treatment for sleep disordered breathing, acting as a pneumatic splint to prevent collapse of the pharyngeal airway. However, the influence that CPAP has on Cerebral Blood Flow (CBF) dynamics is not well understood. This preliminary study investigates the influence of CPAP on total CBF in 23 healthy awake subjects by measuring flow velocity and lumen diameter of the left and right proximal Internal Carotid Arteries (ICA), Vertebral Arteries (VA), and Middle Cerebral Arteries (MCA) using Duplex Color Doppler Ultrasound (US) with and without CPAP at a level of 15 cm H2O. Transcutaneous Carbon Dioxide (PtcCO2) level, heart rate, Blood Pressure (BP), and oxygen saturation (SaO2) were monitored before and after each test. The preliminary measurements indicate that CPAP results in a decrease of CBF by 17% (p-value < 0.05). The theoretically predicted decrease in CBF from PtcCO2 variation was 6%. The study should be further explored in patients with sleep apnea and various types of cerebrovascular and craniospinal disorders.Copyright © 2011 by ASME

Sleep disordered breathing with central apnea or hypopnea frequently occurs at high altitude and is thought to be caused by a decrease in blood CO(2) level. The aim of this study was to assess the effects of added respiratory dead space on sleep disordered breathing.Full polysomnographies were performed on 12 unacclimatized swiss mountaineers (11 males, 1 female, mean age 39 ± 12 y.o.) in Leh, Ladakh (3500 m). In random order, half of the night was spent with a 500 ml increase in dead space through a custom designed full face mask and the other half without it.Baseline data revealed two clearly distinct groups: one with severe sleep disordered breathing (n=5, AHI30) and the other with moderate to no disordered breathing (n=7, AHI30). DS markedly improved breathing in the first group (baseline vs DS): apnea hypopnea index (AHI) 70.3 ± 25.8 vs 29.4 ± 6.9 (p=0.013), oxygen desaturation index (ODI): 72.9 ± 24.1/h vs 42.5 ± 14.4 (p=0.031), whereas it had no significant effect in the second group or in the total population. Respiratory events were almost exclusively central apnea or hypopnea. Microarousal index, sleep efficiency, and sleep architecture remained unchanged with DS. A minor increase in mean PtcCO(2) (n=3) was observed with DS.A 500 ml increase in dead space through a fitted mask may improve nocturnal breathing in mountaineers with severe altitude-induced sleep disordered breathing.

Sleep disorders are common in patients with chronic renal failure (CRF), especially in those receiving hemodialysis. Sleep-related complaints in this patient population may include insomnia, daytime sleepiness or fatigue and depression. In addition to causing impairment of daytime function and quality of life, sleep apnea may also increase the cardiovascular morbidity and mortality, especially in dialysis patients. In CRF patients, an increased prevalence of sleep apnea, restless legs syndrome and periodic limb movement during sleep has been reported. Epidemiology, pathophysiology and treatment of sleep disorders in CRF and dialysis patients are still unclear and require further research.

OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS) IS A SLEEP BREATHING DISORDER CHARACTERIZED BY INTERMITTENT UPPER AIRWAY NARROWING OR collapse during sleep that occurs in 2% to 5% of adults.1–4 Most OSAS patients complain of excess daytime sleepiness, cognitive impairment, and decreased psychological well-being.5–11 These daytime effects lead to an increased risk of motor vehicle accidents, work inefficiency, and have a negative social impact.12–15 Altered sleep architecture and decreased sleep efficiency are believed to result from sleep fragmentation caused by brief repeated arousals from sleep.16–18 Arousals have been found to be associated with central autonomic activation,19 which leads to increased sympathetic activity and resulting peripheral vasoconstriction. Repeated exposure to autonomic and hemodynamic stressors may be responsible for the significant association of OSAS with cardiovascular and cerebrovascular disorders.20–22 Autonomic activation concomitant with arousals from sleep induces acute measurable hemodynamic changes such as elevated arterial pressure and heart rate, and altered pulse transit time (PTT) and skin blood flow.23–31 Changes in PWA measured by finger plethysmography or photoplethysmography have been shown to be a reliable method of determining sympathetic activation.32–34 Finger plethysmography measures pulsatile blood volume in the fingertip using a peripheral arterial tonometry (PAT) device. Photoplethysmography is a noninvasive technique that measures the relative absorption of red light and infrared light across the finger. Arterial blood flow pulsation passing through finger arteries modulates light absorption and generates a pulse wave signal. This signal can be easily derived from conventional pulse oximeters and, unlike PAT, does not require a variable pressure at the fingertip. Photoplethysmographic pulse waves have also been used as markers of finger vasoconstriction.35 The gold standard diagnostic tool for OSAS is polysomnography (PSG), but for practical reasons limited-channel sleep recordings without EEG (type III portable monitors) are increasingly used as an alternative.36 While apneas are easily scored in the latter setting, hypopneas, which require, according to the 2007 AASM manual either a concomitant drop in oxygen saturation of 3% or an arousal (alternative definition),37 are more difficult to detect, because no electroencephalography (EEG) channels are available in these recordings. Moreover arousals are required to score respiratory effort related arousals (RERA). The aim of this study was to determine whether PWA drops were associated with changes in cortical activity as measured by EEG spectral analysis, and whether these events could be considered as surrogates for arousals on limited-channel sleep recordings.

SummaryPatent foramen ovale and obstructive sleep apnoea are frequently encountered in the general population. Owing to their prevalence, they may coexist fortuitously; however, the prevalence of patent foramen ovale seems to be higher in patients with obstructive sleep apnoea. We have reviewed the epidemiological data, pathophysiology, and the diagnostic and therapeutic options for both patent foramen ovale and obstructive sleep apnoea. We focus on the interesting pathophysiological links that could explain a potential association between both pathologies and their implications, especially on the risk of stroke.

Contains fulltext : 88508.pdf (Publisher’s version ) (Closed access) Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing narcolepsy. To further define the genetic basis of narcolepsy risk, we performed a genome-wide association study (GWAS) in 562 European individuals with narcolepsy (cases) and 702 ethnically matched controls, with independent replication in 370 cases and 495 controls, all heterozygous for DRB1*1501-DQB1*0602. We found association with a protective variant near HLA-DQA2 (rs2858884; P < 3 x 10(-8)). Further analysis revealed that rs2858884 is strongly linked to DRB1*03-DQB1*02 (P < 4 x 10(-43)) and DRB1*1301-DQB1*0603 (P < 3 x 10(-7)). Cases almost never carried a trans DRB1*1301-DQB1*0603 haplotype (odds ratio = 0.02; P < 6 x 10(-14)). This unexpected protective HLA haplotype suggests a virtually causal involvement of the HLA region in narcolepsy susceptibility. 01 september 2010

STUDY OBJECTIVES We sought to determine the effect of expiratory positive airway pressure on end expiratory lung volume (EELV) and sleep disordered breathing in obstructive sleep apnea patients. DESIGN Observational physiology study PARTICIPANTS We studied 10 OSA patients during sleep wearing a facial mask. We recorded 1 hour of NREM sleep without treatment (baseline) and 1 hour with 10 cm H2O EPAP in random order, while measuring EELV and breathing pattern. RESULTS The mean EELV change between baseline and EPAP was only 13.3 mL (range 2-25 mL). Expiratory time was significantly increased with EPAP compared to baseline 2.64 +/- 0.54 vs 2.16 +/- 0.64 sec (P = 0.002). Total respiratory time was longer with EPAP than at baseline 4.44 +/- 1.47 sec vs 3.73 +/- 0.88 sec (P = 0.3), and minute ventilation was lower with EPAP vs baseline 7.9 +/- 4.17 L/min vs 9.05 +/- 2.85 L/min (P = 0.3). For baseline (no treatment) and EPAP respectively, the mean apnea+hypopnea index (AHI) was 62.6 +/- 28.7 and 56.8 +/- 30.3 events per hour (P = 0.4). CONCLUSION In OSA patients during sleep, the application of 10 cm H2O EPAP led to prolongation of expiratory time with only marginal increases in FRC. These findings suggest important mechanisms exist to avoid hyperinflation during sleep.

A low arousal threshold is believed to predispose to breathing instability during sleep. The present authors hypothesised that trazodone, a nonmyorelaxant sleep-promoting agent, would increase the effort-related arousal threshold in obstructive sleep apnoea (OSA) patients. In total, nine OSA patients, mean+/-sd age 49+/-9 yrs, apnoea/hypopnoea index 52+/-32 events.h(-1), were studied on 2 nights, one with trazodone at 100 mg and one with a placebo, in a double blind randomised fashion. While receiving continuous positive airway pressure (CPAP), repeated arousals were induced: 1) by increasing inspired CO(2) and 2) by stepwise decreases in CPAP level. Respiratory effort was measured with an oesophageal balloon. End-tidal CO(2 )tension (P(ET,CO(2))) was monitored with a nasal catheter. During trazodone nights, compared with placebo nights, the arousals occurred at a higher P(ET,CO(2)) level (mean+/-sd 7.30+/-0.57 versus 6.62+/-0.64 kPa (54.9+/-4.3 versus 49.8+/-4.8 mmHg), respectively). When arousals were triggered by increasing inspired CO(2) level, the maximal oesophageal pressure swing was greater (19.4+/-4.0 versus 13.1+/-4.9 cm H(2)O) and the oesophageal pressure nadir before the arousals was lower (-5.1+/-4.7 versus -0.38+/-4.2 cm H(2)O) with trazodone. When arousals were induced by stepwise CPAP drops, the maximal oesophageal pressure swings before the arousals did not differ. Trazodone at 100 mg increased the effort-related arousal threshold in response to hypercapnia in obstructive sleep apnoea patients and allowed them to tolerate higher CO(2) levels.

Summary Obstructive sleep apnoea syndrome Obstructive sleep apnoea syndrome (OSAS) is a common disorder affecting about 4% of middle-aged men and 2% of middle-age women (~120000 persons in Switzerland), many of them remaining undiagnosed and untreated. OSAS is characterised by repetitive pharyngeal collapses during sleep. These collapses are mainly due to anatomical conditions such as obesity or retrognathism. Recent data suggest that respiratory control (loop gain) instability can also be a cause. Sleep apnoea and hypopnoea induce repetitive micro-arousals leading to decreased quality of sleep and daytime sleepiness associated with an increased risk of traffic accidents. Recent epidemiological studies show that patients with OSAS are also at higher risk of developing cardiovascular disease such as stroke, high blood pressure and congestive heart failure.

Background: Most patients with obstructive sleep apnoea (OSA) can restore airflow after an obstructive respiratory event without arousal at least some of the time. The mechanisms that enable this ventilatory recovery are unclear but probably include increased upper airway dilator muscle activity and/or changes in respiratory timing. The aims of this study were to compare the ability to recover ventilation and the mechanisms of compensation following a sudden reduction of continuous positive airway pressure (CPAP) in subjects with and without OSA. Methods: Ten obese patients with OSA (mean (SD) apnoea-hypopnoea index 62.6 (12.4) events/h) and 15 healthy non-obese non-snorers were instrumented with intramuscular genioglossus electrodes and a mask/pneumotachograph which was connected to a modified CPAP device that could deliver either continuous positive or negative pressure. During stable non-rapid eye movement sleep the CPAP was repeatedly reduced 2–10 cm H 2 O below the level required to eliminate flow limitation and was held at this level for 5 min or until arousal from sleep occurred. Results: During reduced CPAP the increases in genioglossus activity (311.5 (49.4)% of baseline in subjects with OSA and 315.4 (76.2)% of baseline in non-snorers, p = 0.9) and duty cycle (123.8 (3.9)% of baseline in subjects with OSA and 118.2 (2.8)% of baseline in non-snorers, p = 0.4) were similar in both groups, yet patients with OSA could restore ventilation without cortical arousal less often than non-snorers (54.1% vs 65.7% of pressure drops, p = 0.04). When ventilatory recovery did not occur, genioglossus muscle and respiratory timing changes still occurred but these did not yield adequate pharyngeal patency/ventilation. Conclusions: Compensatory mechanisms (increased genioglossus muscle activity and/or duty cycle) often restore ventilation during sleep but may be less effective in obese patients with OSA than in non-snorers.

Objectif Le but de cette etude etait de comparer les caracteristiques du sommeil chez les patients migraineux et chez des temoins apparies sur l’âge et le sexe. Methodes Les donnees de 2162 participants a l’etude Hypnolaus/Psycholaus, une cohorte basee sur un echantillon representatif de la population de Lausanne (Suisse), ont ete analysees. Nous avons identifie les sujets migraineux sur la base des criteres de l’International Headache Society. Les plaintes et les habitudes du sommeil ont ete evaluees a l’aide de l’index de qualite du sommeil de Pittsburgh, l’echelle d’Epworth, les criteres diagnostiques du syndrome des jambes sans repos, le questionnaire de Berlin pour les troubles respiratoires et du questionnaire de typologie circadienne de Horne/Ostberg. Tous les sujets ont eu une polysomnographie (PSG) complete a domicile. Resultats Cent quinze sujets migraineux (âge moyen : 54,3 ± 10,7 annees, 69,5 % de femmes) ont ete identifies. Par rapport a 230 temoins apparies, les migraineux ont rapporte une moins bonne qualite de sommeil (score PSQI : 6,1 ± 3,3 vs 5 ± 2,8, p = 0,006), une latence d’endormissement subjective plus longue (20,2 ± 18,8 vs 16,2 ± 14,5 min, p = 0,009), plus de jambes sans repos (22,6 % vs 13,9 %, p = 0,039) et plus d’apnees constatees par l’entourage (11,3 % vs 5,2 %, p = 0,014). Nous n’avons pas observe de differences majeures entre les deux groupes en ce qui concerne les parametres PSG, sauf une tendance a un allongement du temps total de sommeil (415,7 ± 58,2 vs 403,1 ± 73 min, p = 0,10) et a une diminution du sommeil lent profond (20,4 ± 7,3 % vs 21,9 ± 8,2 %, p = 0,10). Aucune difference significative n’a ete observee concernant la prise de medicaments pouvant influencer le sommeil. Conclusion Compares a des sujets temoins, les migraineux rapportent plus de plaintes liees au sommeil, malgre l’absence de differences significatives concernant les variables objectives du sommeil mesurees par PSG.

Study objectives The objective was to evaluate the responsiveness of upper airway muscles to hypercapnia with and without intrapharyngeal negative pressure during non-rapid eye movement (NREM) sleep and wakefulness. Design We assessed the genioglossal muscle response to CO2 off and on continuous positive airway pressure (CPAP) (to attenuate negative pressure) during stable NREM sleep and wakefulness in the supine position. Setting Laboratory of the Sleep Medicine Division, Brigham and Women's Hospital. Patients or participants Eleven normal healthy subjects. Interventions During wakefulness and NREM sleep, we measured genioglossal electromyography (EMG) on and off CPAP at the normal eupneic level and at levels 5 and 10 mm Hg above the awake eupneic level. Measurements and results We observed that CO2 could increase upper-airway muscle activity during NREM sleep and wakefulness in the supine position with and without intrapharyngeal negative pressure. The application of nasal CPAP significantly decreased genioglossal EMG at all 3 levels of PETCO2 during NREM sleep (13.0 +/- 4.9% vs. 4.6 +/- 1.6% of maximal EMG, 14.6 +/- 5.6% vs. 7.1 +/- 2.3% of maximal EMG, and 17.3 +/- 6.3% vs. 10.2 +/- 3.1% of maximal EMG, respectively). However, the absence of negative pressure in the upper airway did not significantly affect the slope of the pharyngeal airway dilator muscle response to hypercapnia during NREM sleep (0.72 +/- 0.30% vs. 0.79 +/- 0.27% of maximal EMG per mm Hg PCO2, respectively, off and on CPAP). Conclusions We conclude that both chemoreceptive and negative pressure reflex inputs to this upper airway dilator muscle are still active during stable NREM sleep.

Diseases affecting the respiratory system are usually present during the day and the night; however, sleep apnea/hypopnea syndrome is a disease manifesting only during sleep. It is defined as a cessation (apnea) or a reduction of breathing (hypopnea) of 10 seconds or more during sleep. Each of these apneas or hypopneas is usually terminated when the person awakens for a few seconds. Typically, patients do not remember these transient awakenings. There are two general categories of apnea: central and obstructive. These categories are classified according to the presence or the absence of respiratory effort. Central sleep apnea is a result of the absence of nerve impulses from the brain to the respiratory muscles and therefore occurs in absence of respiratory effort. Obstructive sleep apnea is much more common. This condition is caused by repetitive obstruction of the upper airway (pharynx) during sleep. Therefore, respiratory efforts are still present during apnea and usually increase throughout the apnea. The individual makes larger and larger respiratory efforts until they arouse from sleep apnea and reopen their upper airway so breathing can resume. As will be discussed, some overlap exists between obstructive and central apnea in both disease presentation (so-called mixed apnea) and in pathogenesis. Keywords: apnea; hypopnea; pneumotachography; inductance plethysmography; impedance pneumography

ContextPatients with venous thromboembolism (VTE) are susceptible to recurrent events, but whether prolonging anticoagulation is warranted in patients with VTE remains controversial.ObjectiveTo review the available evidence and quantify the risks and benefits of extending the duration of anticoagulation in patients with VTE.Data SourcesPubMed, EMBase Pharmacology, the Cochrane database, clinical trial Web sites, and a hand search of reference lists.Study SelectionIncluded studies were randomized controlled trials with results published from 1969 through 2004 and evaluating the duration of anticoagulation in patients with VTE that measured recurrent VTE. Excluded studies were those enrolling only pure populations of high-risk patients. Two independent reviewers assessed each article for inclusion and exclusion criteria, with adjudication by a third reviewer in cases of disagreement. Fifteen of 67 studies were included in the analysis.Data ExtractionTwo independent reviewers performed data extraction using a standardized form, with adjudication by the remainder of the investigators in cases of disagreement. Data regarding recurrent VTE, major bleeding, person-time at risk, and study quality were extracted.Data SynthesisIf patients in the long-term therapy group remained receiving anticoagulation, the risk of recurrent VTE with long- vs short-term therapy was reduced (weighted incidence rate, 0.020 vs 0.126 events/person-year; rate difference, −0.106 [95% confidence interval {CI}, −0.145 to −0.067]; P

Previous studies have demonstrated that lung volume during wakefulness influences upper airway size and resistance, particularly in patients with sleep apnea. We sought to determine the influence of lung volume on the level of continuous positive airway pressure (CPAP) required to prevent flow limitation during non-REM sleep in subjects with sleep apnea. Seventeen subjects (apnea-hypopnea index, 42.6 +/- 6.2 [SEM]) were studied during stable non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. An epiglottic pressure catheter plus a mask/pneumotachometer were used to assess flow limitation. When lung volume was increased by 1,035 +/- 22 ml, the CPAP level could be decreased from 11.9 +/- 0.7 to 4.8 +/- 0.7 cm H(2)O (p0.001) without flow limitation. The decreased CPAP at the same negative extrathoracic pressure yielded a final lung volume increase of 421 +/- 36 ml above the initial value. Conversely, when lung volume was reduced by 732 +/- 74 ml (n = 8), the CPAP level had to be increased from 11.9 +/- 0.7 to 17.1 +/- 1.0 cm H(2)O (p0.001) to prevent flow limitation, with a final lung volume decrease of 567 +/- 78 ml. These results demonstrate that relatively small changes in lung volume have an important effect on the upper airway in subjects with sleep apnea during non-REM sleep.

Introduction Sleep disordered breathing (SDB) is a common finding in chronic hemodialysis (CHD) patients. Two recent American studies investigated the prevalence of SDB in patients with different degree of chronic kidney disease and reported a prevalence of 26–57%. The purpose of this study is to evaluate the prevalence of SDB and to evaluate the predictive value of Berlin questionnaire, hemodialysis frequency and duration, and biometric parameters in a large group of European patients undergoing CHD. Materials and methods All the patients attending six CHD centers in the western part of Switzerland were screened. Eligible patients completed the Berlin questionnaire, a validated 11 items form used to evaluate the risk of obstructive sleep apnea and the Epworth Sleepiness Scale (ESS). All patients underwent a home nocturnal polygraphy (PG) using Apnea Link Plus system recording nasal pressure, oxygen saturation, thoracic movements and heart rate. Respiratory events were scored according to the AASM 99 criteria. Apnea-hypopnea index (AHI) was calculated by dividing the total number of apnea and hypopnea during the night by the recording time. Results Among 166 screening patients, 98 were included and 71 completed the study (50 men, mean age 61.8 ± 15.4, neck circumference 40.6 ± 4.6 cm, BMI 25.7 ± 4.8 kg/m2). Mean AHI was 23.9 ± 20.4/h (18% obstructive apnea, 8.5% central apnea, 2.4% mixed apnea). Among these 71 patients, 31% had severe SDB (AHI ⩾ 30/h), 23.9% had moderate SDB (AHI 15–30/h), 31% had mild SDB (AHI 5–15/h) and 14.1% were normal (AHI 5/h). Berlin’s questionnaire showed a high risk of SDB in 62.5% of the patients with a sensitivity of 65%, a specificity of 39%, a positive predictive value of 58% and a negative predictive value of 47%. According to ESS, 18.5% of the patients had significant sleepiness ( > 10/24). Using a logistic regression model including age, sex, BMI, neck circumference, Berlin questionnaire, ESS, smoking, alcohol, number/week and duration of CHD session, the only independent predictor was neck circumference with odds ratio of 1.59 (p = 0.023). Conclusion The prevalence of SDB in the CHD population is higher than expected. Berlin questionnaire is not useful to screen for SDB in CHD patients but neck circumference seems to be an independant predictor of SDB in this population. Acknowledgements Supported by the Leenaards Foundation, Ligue Pulmonaire Vaudoise, Swiss National Foundation for Research, GSK.

Introduction Background: Upper airway resistance syndrome (UARS) shares common clinical features with obstructive sleep apnea and hypopnea (OSAH). It is characterized by repetitive respiratory effort-related arousal (RERA), which may lead to daytime sleepiness and functional impairment. Little is known about the prevalence of UARS in the general population. Objectives: To determine the prevalence of UARS in the general population and to compare its characteristics to matched control subjects without UARS. Materials and methods 2020 subjects (50.0% women, 57.3 ± 10.7 years old, BMI 25.5 ± 4.3 kg/m2) participating in an ongoing population-based sleep cohort study (HypnoLaus, Lausanne, Switzerland) underwent complete polysomnographic recordings at home. Respiratory events were scored according to the AASM Chicago criteria. UARS was present if the RERA index was ⩾5/h and accounted for more than 50% of the respiratory disturbance index (RDI), which is defined by the sum of the apnea–hypopnea index (AHI) and RERA index. Characteristics of each subject with confirmed UARS were compared with 5 age and sex matched control subjects with similar AHI but no RERA. Results The prevalence of UARS was 0.84% of this general population sample. Median AHI and RDI were respectively 4.4/h (IQ range 3.5–6.8/h) and 10.7/h (IQ range 9.1–15.6/h). Mean Epworth Sleepiness Score was 6.6 ± 3.2; male-to-female ratio was 0.7. There were no significant differences between UARS subjects and the control subjects regarding BMI (24.7 ± 3.1 vs. 24.0 ± 3.3, p = 0.46) and the Epworth Sleepiness Score (6.6 ± 3.2 vs. 7.4 ± 2.5, p = 0.15). Also, the same prevalence of hypertension (29.4 ± 47.0% vs. 25.9 ± 19.7%, p = 0.77), diabetes (5.9 ± 24.2% vs. 5.9 ± 11.8%, p = 1.0) and metabolic syndrome (29.4 ± 47.0% vs. 12.9 ± 12.1%, p = 0.16) were found in UARS and control subjects. Conclusion In our middle-aged population-based cohort, the prevalence of UARS is lower than previously reported. There was no significant difference between UARS and control subjects in terms of BMI, daytime sleepiness, hypertension, diabetes and metabolic syndrome. Acknowledgement Funding: Ligue pulmonaire vaudoise, Fondation Leenaards, Fond national Suisse and GSK.

Introduction Historical studies suggest that there is an increased male/female ratio in the prevalence of sleep disordered breathing (SBD). Moreover, SDB was reported to increase in postmenopausal women. The aim of this study was to assess the prevalence and the characteristics of SDB in pre-menopausal and post-menopausal women. Materials and methods 2114 subjects (50.4% women, 58.5 ± 10.7 y.o, BMI 26.2 ± 4.4 kg/m2) participating in an ongoing population-based sleep cohort study (HypnoLaus, Lausanne, Switzerland) underwent full polysomnographic recordings at home. They also had a complete clinical workup including metabolic, cardiovascular, genetic and morphometric evaluation. Hormonal status was recorded in 981 women (30.6% pre-menopausal and 69.4% post-menopausal). Respiratory events were scored according to the AASM 2013 criteria. Results The prevalence of SDB in women with AHI thresholds of 5/h, 15/h and 30/h was 60.9%, 22.8% and 7.5%. Prevalence of an Epworth score > 10 and SDB with the same thresholds was 18.9% (AHI > 5/h), 11.5% (AHI > 15/h) and 5% (AHI > 30/h) with a male/female ratio of 1.75, 2.4 and 2.8 respectively. Male vs female prevalence was significantly different in each severity group (p 0.0001). Compared to men, women with an AHI > 15/h were older (p 0.0001), had a lower neck circumference (p = 0.0001), a lower Mallampati score (p = 0.0001), a lower waist/hip ratio (p 0.0001) but the BMI was not significantly different: 28.2 kg/m2 in women vs 28.1 kg/m2 in men (p = 0.711). Women also reported less sleepiness at the wheel (p 0.0002), less witnessed sleep apnea (p = 0.0006) but more morning fatigue (p = 0.034), more sleeping pill intake (p = 0.0003) but the same rate of snoring (p = 0.55). Compared to post-menopausal, pre-menopausal women had a lower SDB prevalence. AHI > 5/h: 26.6% vs 42.5% (p 0.0001), AHI > 15/h: 7.2% vs 18.6% (p 0.0001), AHI > 30/h: 1.3% vs 10.2% (p 0.0001). Post-menopausal women had a larger neck (p = 0.006) a higher waist-hip ratio (p = 0.0001) and a higher Mallampati score (p = 0.009) but the BMI was not significantly different(p = 0.5). Conclusion The prevalence of SDB is lower in women than in men with a male/female ratio increasing with SDB severity. Women with SDB tend to report more morning fatigue but less sleepiness at the wheel and less witnessed sleep apnea than men. Post-menopausal compared to premenopausal women have a higher SDB prevalence not due to an increased BMI but mainly because differences in fat distribution. Acknowledgements Funding: Fondation Leenaards, FNS, GSK, Ligue Pulmonnaire Vaudoise and CIRS.

Introduction Il y a peu de donnees sur la prevalence du syndrome d’apnees du sommeil (SAS) chez les patients en hemodialyse chronique intermittente (HD), et la plupart des etudes ont utilise des questionnaires comme outil de depistage. Nos objectifs etaient d’evaluer la prevalence des apnees du sommeil dans une population europeenne en HD avec des enregistrements nocturnes, d’evaluer la valeur predictive des outils de depistage classiques et de developper un nouvel algorithme de depistage specifique. Patients et methodes Etude observationnelle transversale. Les patients de 6 centres de HD en Suisse francophone ont ete depistes. Deux questionnaires utilises pour le depistage du SAS ont ete soumis a chaque patient. L’index d’Apnee-Hypopnee (AHI) a ete evalue par polygraphie nocturne a domicile. La population a ete divisee en 2 sous-groupes pour developper et valider un nouvel outil de depistage. Resultats Cent quatre patients ont termine l’etude. Au total, 86 % avaient un SAS (AHI > 5/h), dont 56 % un SAS modere-severe (AHI > 15/h). Dix-neuf pour cent des sujets avec un SAS modere-severe avaient un diagnostic prealable et 10 % d’entre eux etaient deja traites. Les questionnaires de depistage classiques ont donne des resultats mediocres, avec une sensibilite/specificite de 52/54 % pour le questionnaire de Berlin et de 85/54 % pour le STOP-BANG. L’âge > 70 ans, la circonference cervicale > 40 cm et un temps en therapie de substitution renale > 10 ans ont ete identifies comme les meilleurs facteurs de prediction d’un SAS modere-severe et ont ete utilises pour developper un nouveau algorithme de depistage. Le nouveau score a montre une sensibilite/specificite de 91 %/71 %. Discussion et conclusion Dans la population de HD, nous avons observe une haute prevalence du SAS, sous-diagnostique et sous-traite. Les outils de depistage et les facteurs de risque classiques de la population generale ne permettent pas un depistage fiable du SAS en HD. Nous avons developpe et valide un algorithme de depistage simple pour identifier les patients necessitant des investigations supplementaires.

Introduction Les apnees obstructives du sommeil (AOS) sont frequentes chez les patients en hemodialyse (HD). L’augmentation des resistances des voies aeriennes superieures causant des AOS est d’origine multifactorielle, mais le deplacement volemique nocturne des membres inferieurs vers la region cervicale joue un role important dans ce phenomene. L’objectif de cette etude etait d’evaluer l’impact de la soustraction liquidienne sur la severite des AOS chez les patients en HD. Patients et methodes Etude interventionnelle, randomisee, non controlee. Dix-sept patients atteints d’AOS moderees-severes ont ete investigues par 2 polysomnographies nocturnes (PSG) consecutives, avant et apres HD. L’etat hydrique global, l’etat d’hyperhydratation, le volume d’eau des jambes ont ete evalues par bioimpedance pre- et post-PSG. La circonference cervicale a ete mesuree pre- et post-PSG. Resultats L’index moyen (SD) des apnees-hypopnees obstructives par heure (OAIH) etait de 46,8 (± 22,0)/h. Le volume d’eau des jambes diminuait de 10,3 (± 1,9) L le soir a 9,3 (± 1,8) L le matin, avec un deplacement volemique nocturne de 1,0 (± 0,5) L (p Discussion et conclusion La surcharge liquidienne et le deplacement volemique nocturne des membres inferieurs vers la region cervicale influencent la severite des AOS chez les patients hemodialyses en surcharge hydrique. Le bilan hydrique negatif obtenu par hemodialyse permet de reduire le volume d’eau deplace et d’ameliorer la severite des AOS chez les patients en surcharge volemique.