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Study objectives: Fluid overload shifting from the legs to the upper airway during sleep promotes obstructive sleep apnea (OSA) and interventions targeting fluid attenuate OSA. Fluid shift has been previously measured by bioelectrical impedance, a complex and time-consuming technique not applicable in the daily clinical settings. The aim of this study is to evaluate the presence of clinically detectable fluid overload and shift and its association with OSA. Methods: Patients undergoing sleep study for suspected OSA were asked to report the presence of 11 signs/symptoms associated to excessive accumulation of fluid in different parts of the body at different times of the day. Results: Among 392 patients (male: 53%, median [interquartile range] age: 56years [1], body mass index, BMI: 29kg/m2 [2]) included in the study, 135 (34%) had moderate-to-severe OSA (apnea hypopnea index, AHI ≥ 15). Daytime fluid accumulation and nocturnal fluid shift, clinically detectable by patient-reported “evening sock marks,” “heavy legs during the day,” and “morning stuffed nose,” were prevalent in the entire population (46%, 43%, and 33%, respectively). In multivariate analysis, evening sock marks was an independent correlate of having an AHI ≥ 15, together with male sex, older age, and self-reported snoring and apneas. Conclusions: Clinically detectable fluid overload and shift are prevalent in patients addressed for suspected OSA, and evening sock marks, a marker for leg swelling, is an independent correlate of moderate-to-severe OSA. This sign might contribute to OSA diagnosis and identification of patients likely to be treated by interventions targeting fluid overload and shift.

Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a collapse of the upper airways leading to a decrease (hypopneas) or interruption of air flow (apneas). Since its identification, only forty years ago, definitions, diagnostic techniques have evolved, the consequences of this syndrome have been widely studied but establishing it as an independent cardiovascular (CV) risk factor has come up against the existence of many confounding factors, such as obesity, high blood pressure (hypertension)… Paraclinical diagnosis is based on the results of poly(somno)graphy. Recommendations on measurement techniques and scoring are regularly published, evolving in parallel with technological progress, with the aim of standardizing and ensuring the reliability of the diagnosis. At the same time, large cohort studies were set up in the 1990s, allowing for transversal and longitudinal follow-up of thousands of patients. Finally, the pathophysiological mechanisms of the consequences of SAHOS were explored. OSA has been shown to be responsible for a particularly high accidental risk due to sleep fragmentation induced by abnormal respiratory events. It has been possible to establish an independent statistical relationship between SAHOS and CV diseases, metabolic disorders and more recently cancer, mainly explained by intermittent hypoxia. OSAHOS is a frequent disease, diagnosed on the basis of clinical signs and poly(somno)graphy, now established as an independent risk factor for morbidity and mortality (accidental and CV).

Introduction : Le traitement du syndrome d’apnées-hypopnées obstructives du sommeil (SAHOS) doit permettre la suppression des symptômes et pouvoir également prévenir ses conséquences immédiates et à long terme. Matériels et méthodes : L’évaluation de l’efficacité des traitements repose, aujourd’hui, sur la normalisation de l’index d’apnées-hypopnées (IAH), de la saturation en oxygène et sur la disparition de la fragmentation du sommeil. Le suivi clinique et biologique des comorbidités doit être assuré. L’observance au traitement, élément majeur de réussite, doit être surveillée. Résultats : La ventilation par pression positive continue (PPC) est toujours le traitement le plus efficace et le plus utilisé. Mais l’orthèse d’avancée mandibulaire (OAM) est désormais recommandée en première intention dans les formes modérées en l’absence de comorbidités cardiovasculaires (CV) sévères et reste une alternative thérapeutique en cas de refus ou d’intolérance à la PPC. Une prise en charge nutritionnelle en cas d’obésité et un programme d’activité physique doivent être systématiquement proposés. Une réduction des troubles respiratoires nocturnes peut également être obtenue grâce à un dispositif anti-décubitus dorsal en cas de SAHOS positionnel, ou en limitant les mouvements de fluides. L’apport de la thérapie myofonctionnelle est en cours d’évaluation. Très récemment, une étude a testé l’efficacité d’un traitement pharmacologique sur la sévérité du SAHOS et la réactivité du génioglosse, qui semble être prometteur. Conclusion : L’évaluation de ces différents traitements et de leur combinaison devrait permettre d’évoluer vers une prise en charge personnalisée adaptée à chaque patient.

Introduction : Le syndrome d’apnées-hypopnées obstructives du sommeil (SAHOS) est un collapsus des voies aérifères supérieures (VAS) conduisant à une diminution (hypopnées) ou une interruption du débit aérien (apnées). Depuis son identification il y a seulement une quarantaine d’années, les définitions et les techniques diagnostiques ont évolué, les conséquences de ce syndrome ont été largement étudiées, mais l’établir comme facteur de risque cardiovasculaire (CV) indépendant s’est heurté à l’existence de nombreux facteurs confondants ayant pignon sur rue, telles l’obésité, l’hypertension artérielle (HTA)… Matériels et méthodes : Le diagnostic paraclinique repose sur les résultats de la poly(somno)graphie. Des recommandations sur les techniques de mesures et le codage sont régulièrement éditées, évoluant parallèlement avec les progrès technologiques, dans le but de standardiser et d’assurer la fiabilité du diagnostic. Parallèlement, des études de larges cohortes ont été mises en place à partir des années 1990, permettant un suivi transversal puis longitudinal de milliers de patients. Enfin, les mécanismes physiopathologiques des conséquences du SAHOS ont été explorés. Résultats : Il a été démontré que le SAHOS était responsable d’un risque accidentel particulièrement élevé, imputable à la fragmentation du sommeil induite par les événements respiratoires anormaux. Il a pu être établi une relation statistique indépendante entre SAHOS et pathologies CV, troubles métaboliques et plus récemment le cancer, expliquée majoritairement par l’hypoxie intermittente. Conclusions : Le SAHOS est une maladie fréquente, dont le diagnostic repose sur des signes cliniques et la poly(somno) graphie, établi aujourd’hui comme facteur de risque indépendant de morbi-mortalité (accidentelle et CV).

International audience; Identification of sleep stages is a fundamental step in clinical sleep analysis. Existing automatic sleep staging systems ignore two major issues: 1) Most of existing automatic sleep staging systems are using numerical classification methods without involving medical knowledge. These kinds of systems are not yet understood and accepted by physicians. 2) Individual variability sources are ignored. However, individual variability is observed in many aspects of sleep research (such as polysomnography recordings, sleep patterns, and sleep architecture). In this paper, a hybrid expert system is proposed to mimic the decision-making process of clinical sleep staging in accordance with the medical knowledge by using symbolic fusion. To formalize the medical guideline and knowledge, thresholds are used for translating the sleep events into symbols and the sleep event’s threshold dependencies are analyzed for fully understanding the thresholds dependencies among different sleep stages and subjects. Meanwhile, the differential evolution algorithm is adopted to automate the setting-up of thresholds that are used in the symbolic fusion model and to provide personalized thresholds, which allows taking the individual variability into consideration. The robustness and clinical applicability of the proposed system are evaluated and demonstrated on a clinical dataset. The dataset is composed of 16 patients (nine males and seven females) and scored by physicians. Only 5% of the dataset is used for the training process to obtain the personalized thresholds. Then, these personalized thresholds are passed to the classification process, and the overall accuracy on the identification of five sleep stages reaches 80.09%. Using a small dataset for the training process, the proposed system not only drastically reduces the training set but also achieves favorable results compared with most of the existing works.

Interest in sleep has been growing in the last decades, considering its benefits for well-being, but also to diagnose sleep troubles. The gold standard to monitor sleep consists of recording the course of many physiological parameters during a whole night. The human interpretation of resulting curves is time consuming. We propose an automatic knowledge-based decision system to support sleep staging. This system handles temporal data, such as events, to combine and aggregate atomic data, so as to obtain high-abstraction-levels contextual decisions. The proposed system relies on a semantic reprentation of observations, and on contextual knowledge base obtained by formalizing clinical practice guidelines. Evaluated on a dataset composed of 131 full night polysomnographies, results are encouraging, but point out that further knowledge need to be integrated.

Backgrounds As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged. The aim of this study was to describe the clinical characteristics of ASV-treated patients in real-life conditions. Methods The OTRLASV-study is a prospective, 5-centre study including patients who underwent ASV-treatment for at least 1 year. Patients were consecutively included in the study during the annual visit imposed for ASV-reimbursement renewal. Results 177/214 patients were analysed (87.57% male) with a median (IQ25–75) age of 71 (65–77) years, an ASV-treatment duration of 2.88 (1.76–4.96) years, an ASV-usage of 6.52 (5.13–7.65) hours/day, and 54.8% were previously treated via continuous positive airway pressure (CPAP). The median Epworth Scale Score decreased from 10 (6–13.5) to 6 (3–9) (p p 45% in 92.7% of patients. Associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (neurological for 12.4%, renal for 4.5%, opioid-treatment for 3.4%). 9.6% had idiopathic central-sleep-apnea. 6.2% of the patients were hospitalized the year preceding the study for cardiological reasons. In the 6 months preceding inclusion, night monitoring (i.e. polygraphy or oximetry during ASV usage) was performed in 34.4% of patients, 25.9% of whom required a subsequent setting change. According to multivariable, logistic regression, the variables that were independently associated with poor adherence (ASV-usage ≤4 h in duration) were TECSA group versus CSA group (p = 0.010), a higher Epworth score (p = 0.019) and lack of a night monitoring in the last 6 months (p Conclusions In real-life conditions, ASV-treatment is often associated with high cardiac comorbidities and high compliance. Future research should assess how regular night monitoring may optimize devices settings and patient management. Trial registration The OTRLASV study is registered on ClinicalTrials.gov (Identifier: NCT02429986) on 1 April 2015.

Objectif Pour expliquer la surmortalite cardiovasculaire associee a la Ventilation Auto-Asservie (VAA) de l’etude SERVE-HF, il a ete evoque que les reglages de la VAA auraient induit une hyperventilation. Les objectifs de cette etude sont de decrire: – les reglages de la VAA et, – la ventilation minute (VM) en fonction de l’algorithme de la VAA (VAA-volume ResMed® et VAA-debit Philips®). Methodes Etude « vie reelle » transversale multicentrique incluant des patients traites par VAA depuis plus de 1 an, aucune consigne de reglage n’etant donnee aux 8 experts investigateurs. L’analyse des donnees est realisee: – en fonction du diagnostic initial du SAS (central, obstructif, emergent sous traitement), – en fonction de 5 clusters non supervises (partitionnement en K moyennes). Resultats 177 patients sont analyses avec une mediane (IQ25–75) d’IAH initial de 50 (38-62)/h, une duree de VAA de 2.88 (1.76–4,96) ans, 61,58 % traites par VAA-volume. Seule l’analyse basee sur les 5 clusters permet de mettre en evidence des differences entre clusters et/ou type de machine: – reglage d’une pression expiratoire (EPAP) fixe plus faible dans le groupe des patients obstructifs et a fraction d’ejection ventriculaire gauche reduite, – l’usage plus frequent de l’auto-EPAP chez les patients non cardiopathes, – des VM differents entre clusters, ces differences variant en fonction du type de VAA, – un risque d’hyperventilation quel que soit le cluster et le type de VAA. Conclusion Dans l’attente des etudes en cours, il serait prudent de telesuivre les donnees de VM des patients sous VAA.

Respiratory inflammation has been described in patients with obstructive sleep apnea syndrome, but it is unknown whether the increased neutrophil and interleukin (IL)-8 levels observed in induced sputum reflect systemic or local airway inflammation. We assessed the potential role of resident cells in intermittent hypoxia-induced airway inflammation. Airway epithelial cells (AEC) and bronchial smooth muscle cells (BSMC) were exposed to intermittent hypoxia (IH) in vitro. Cell supernatants were assessed for matrix metalloproteinase, growth factor, and cytokine expression. The role of IH on neutrophil and BSMC migration capacities was evaluated, and the effect of supernatants from IH-exposed or control AEC was tested. Compared to normoxic conditions, 24 h of exposure to IH induced a significant increase of MMP-9 and MMP-2 expression and pro-MMP-9 activation (p

Scoring sleep stages can be considered as a classification problem. Once the whole recording segmented into 30-seconds epochs, features, extracted from raw signals, are typically injected into machine learning algorithms in order to build a model able to assign a sleep stage, trying to mimic what experts have done on the training set. Such approaches ignore the advances in sleep medicine, in which guidelines have been published by the AASM, providing definitions and rules that should be followed to score sleep stages. In addition, these approaches are not able to solve conflict situations, in which criteria of different sleep stages are met. This work proposes a novel approach based on AASM guidelines. Rules are formalized integrating, for some of them, preferences allowing to support decision in conflict situations. Applied to a doubtful epoch, our approach has taken the appropriate decision.

International audience; La reconnaissance des stades de sommeil est une étape indispensable au diagnostic des troubles du sommeil. L'approche habituelle est d'utiliser un classifieur avec des méthodes d'apprentissage automatique. Nous proposons une approche innovante conçue à partir de la connaissance et de l'observation de la pratique des experts. Notre approche permet de mieux prendre en compte les aspects dynamiques du sommeil, mais aussi les raisonnements à des niveaux d'abstraction différents, ainsi qu'à des échelles de temps différentes. Après avoir extrait, à partir des signaux acquis, les grapho-éléments nécessaires à la décision en appliquant la fusion symbolique, un système expert incluant des règles d'inférence, intégrant si nécessaire des préférences, est ap-pliqué. Mise en oeuvre sur trois époques généralement mal scorées avec les classifieurs habituels, la méthode s'est avérée efficace.

Polysomnography is the gold standard test for sleep disorders among which the Sleep Apnea Syndrome (SAS) is considered a public health issue because of the increase of the cardio-and cerebro-vascular risk it is associated with. However, the reliability of this test is questioned since sleep scoring is a time-consuming task performed by medical experts with a high inter- and intra-scorers variability, and because data are collected from 15 sensors distributed over a patient's body surface area, using a wired connection which may be a source of artefacts for the patient's sleep. We have used symbolic fusion to support the automated diagnosis of SAS on the basis of the international guidelines of the AASM for the scoring of sleep events. On a sample of 70 patients, and for the Apnea-Hypopnea Index, symbolic fusion performed at the level of sleep experts (97.1% of agreement). The next step is to confirm these preliminary results and move forward to a smart wireless polysomnograph.

Sleep stage identification is the first step in modern sleep disorder diagnostics process. K-complex is an indicator for the sleep stage 2. However, due to the ambiguity of the translation of the medical standards into a computer-based procedure, reliability of automated K-complex detection from the EEG wave is still far from expectation. More specifically, there are some significant barriers to the research of automatic K-complex detection. First, there is no adequate description of K-complex that makes it difficult to develop automatic detection algorithm. Second, human experts only provided the label for whether a whole EEG segment contains K-complex or not, rather than individual labels for each subsegment. These barriers render most pattern recognition algorithms inapplicable in detecting K-complex. In this paper, we attempt to address these two challenges, by designing a new feature extraction method that can transform visual features of the EEG wave with any length into mathematical representation and proposing a hybrid-synergic machine learning method to build a K-complex classifier. The tenfold cross-validation results indicate that both the accuracy and the precision of this proposed model are at least as good as a human expert in K-complex detection. © 1998-2012 IEEE.

Introduction Le deplacement rostral nocturne de fluide favorise le syndrome d’apnees obstructives du sommeil (SAOS). Les interventions capables de l’attenuer reduisent la gravite du SAOS. Actuellement, ce deplacement est mesure par bio-impedancemetrie, technique complexe et chronophage. Reperer cliniquement ce deplacement pourrait orienter vers des traitements alternatifs a la pression positive continue (PPC). L’objectif de l’etude est d’evaluer la presence des manifestations cliniques du deplacement rostral nocturne de fluide dans le SAOS. Methodes Nous avons developpe un questionnaire pour tester la presence de 11 signes/symptomes causes par l’accumulation de liquide dans le bas du corps a la fin de la journee et dans la partie superieure du corps pendant la nuit et le matin. Tous les patients enregistres dans notre service pour suspicion de SAOS entre mai 2015 et janvier 2016 ont complete ce questionnaire « fluide ». Nous avons inclus dans cette etude les patients non obeses avec SAOS leger a severe. Resultats Parmi les 109 patients, 63 avec SAOS leger (index d’apnees-hypopnees entre 5 et 15) et 46 patients avec SAOS modere ou severe (index d’apnees-hypopnees > 30) apparies sur l’âge, le sexe et l’indice de masse corporel (59 ans, 56 % d’hommes, 26 kg/m2 respectivement) ont repondu au questionnaire. Nous avons retrouve chez 30 % ou plus de l’ensemble des patients, 3 des 11 signes/symptomes du questionnaire « fluide » : « marque des chaussettes le soir », « sensation de jambes lourdes » et « nez obstrue le matin ». Deux symptomes ou signes etaient plus frequents dans le groupe SAOS modere/severe par rapport au groupe SAOS leger : « necessite de dormir avec 2 coussins » et « nez obstrue le matin » (16 % vs. 2 %, p = 0,007 et 46 % vs. 24 %, p = 0,019). Conclusion Nous retrouvons des signes ou symptomes compatibles avec un deplacement rostral nocturne de fluide chez les patients SAOS non obeses. La frequence de certains de ces symptomes augmente avec la gravite du SAOS. La recherche de ces signes/symptomes evocateurs d’un deplacement rostral nocturne de fluide dans la prise en charge du SAOS pourrait conduire a la mise en route de traitement alternatif a la ventilation par PPC chez les patients SAOS non obeses.

Polysomnography (PSG) is the current standard for diagnosing sleep apnea syndrome (SAS). A reliable test would be useful to reduce the considerable resources required for PSG.We developed a new mathematical analysis, which quantifies amplitude variations of pulse oximetry (SpO(2)) and heart rate (HR) throughout the night, allowing measurement of the total time in which ΔSpO(2)4% and presented as a new oximetric index ventilatory hypoxemic index (VHI). VHI was compared prospectively with standard PSG parameters apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) in 106 patients (aged, 57 ± 14 years; BMI, 29 ± 5 kg/m(2)) suspected of having SAS. The criterion for diagnosis of SAS was AHI15/h of sleep during PSG. The relationship between ΔSpO(2) and ΔΗR was also investigated.We observed a significant correlation between the AHI and VHI (R = 0.87, p 0.0001). Using VHI15 as the criterion for SpO(2), oximetry had a sensitivity of 81%, specificity of 98%, positive predictive value (PPV) of 98%, and negative predictive value (NPV) of 84% as a screening test for SAS. We also observed a clear linear relationship between ΔSpO(2) and ΔΗR, and concomitant use of VHI and the ΔSpO(2)/ΔHR slope improved the NPV to 90%.The present findings from wavelet-aggregate processing of oximeter data and the relationship between ΔSpO(2) and ΔΗR show promise as a useful summary prediction of screening SAS.

Objectif Les troubles respiratoires du sommeil (TRS) sont frequents dans l’obesite morbide (indice de masse corporelle, IMC ≥ 40 kg/m2), notamment le syndrome d’apnees obstructives du sommeil (SAOS) qui en presence d’hypoventilation diurne rentre dans le cadre du syndrome d’obesite-hypoventilation (SOH). Ces TRS et le SOH en particulier sont associes a une morbi-mortalite augmentee. Une prise en charge precoce et optimale est donc necessaire. L’objective de l’etude est d’identifier la meilleure approche diagnostique. Methodes Les patients hospitalises pour plus de 24 h dans le service de nutrition de notre hopital pour la prise en charge de leur obesite ont une polygraphie ventilatoire (PV) et des gaz du sang. Les patients avec obesite morbide presentant un index de desaturation > 30/h sans hypoventilation diurne ont ete enregistres dans le service du SOMMEIL par polysomnographie avec mesure du dioxyde de carbone transcutanee (PtcCO2). Resultats Entre mai et septembre 2017, nous avons inclus 14 patients (3 hommes, âge m ± SD 49 ± 15 ans, IMC 45 ± 4 kg/m2, index des apnees/hypopnees, IAH a la PV 43 ± 17/h). La PSG avec PtcCO2 n’a confirme la presence d’un SAOS severe (IAH > 30) que chez 7 patients (50 %) et a en revanche identifie une hypoventilation nocturne chez 3 (21 %). Conclusion Au cours de l’obesite morbide une simple evaluation par PV ne semble pas etre appropriee pour un diagnostic correct des TRS. Une etude diagnostique plus approfondie semble donc etre utile pour une prise en charge optimale. L’etude merite d’etre poursuivie pour etre confirmee sur un plus grand nombre de patients.

Background and purpose Despite correct treatment with positive airway pressure (PAP), obstructive sleep apnea (OSA) patients sometimes remain subjectively somnolent. The reliability of the Epworth Sleepiness Scale (ESS) has been established for healthy subjects and patients under stable conditions; the ESS may eventually vary among treated OSA patients, biasing the results of a cross-sectional analysis of persisting sleepiness. The objective of this study was to depict the evolution of subjective vigilance under treatment using an index of ESS variability (ΔESS). Methods In 80 OSA patients (apnea–hypopnea index [AHI]=54±26/h), initially somnolent (ESS=15±3) and treated with auto-titrating PAP (APAP) (oxyhaemoglobin desaturation index 3% [ODIapap]=3.4±2.2/h; daily APAP use=5.3±1.5h) during 434±73 days, ESS scores were regularly collected four times every 109±36 days. DESS was calculated and data mining methods (Segmentation and Decision Tree) were used to determine homogeneous groups according to the evolution of ESS scores. Results When assessed cross-sectionally, 14–25% of the subjects were recognized as somnolent, depending on the moment when ESS was administered. Using data mining methods, three groups were clearly identifiable: two without residual somnolence – group 1, n =38 (47%), with high ΔESS=−2.9±0.8, baseline ESS=16.3±3.3, AHI=58.5±26.1/h, mean ESSapap=5.1±2.4 and group 2, n =31 (39%), with low ΔESS=−1.1±0.5, baseline ESS=13.2±1.4, AHI=53±27.3/h, mean ESSapap=8.8±1.9; and one with persisting sleepiness; group 3, n =11 (14%), with low ΔESS=−0.3±0.8, baseline ESS=16.3±3, AHI=38.7±10.8/h, mean ESSapap=14.1±1.9. Compliance to PAP was high and comparable in the three groups. Age and body mass index (BMI) did not differ. Conclusion Data mining methods helped to identify 14% of subjects with persisting sleepiness. Validation needs to be done on a larger population in order to determine predictive rules.

International audience; With the rapid extension of clinical data and knowledge, decision making becomes a complex task for manual sleep staging. In this process, there is a need for integrating and analyzing information from heterogeneous data sources with high accuracy. This paper proposes a novel decision support algorithm—Symbolic Fusion for sleep staging application. The proposed algorithm provides high accuracy by combining data from heterogeneous sources, like EEG, EOG and EMG. This algorithm is developed for implementation in portable embedded systems for automatic sleep staging at low complexity and cost. The proposed algorithm proved to be an efficient design support method and achieved up to 76% overall agreement rate on our database of 12 patients.

The presence of increased numbers of tumor-infiltrating neutrophils is associated with poorer outcome in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype. We evaluated the role of inflammatory environment on C-X-C chemokine tumor production.Bronchoalveolar lavage from 31 consecutive patients with adenocarcinoma of the BAC subtype as well as tumor and normal pulmonary tissue samples. A549 BAC cell line. Peripheral blood mononuclear cells (PBMC), polymorphonuclear neutrophils (PMN) and alveolar macrophages (AM).Elisa measurements and immunohistochemical studies of ENA-78, IL-8, IL-1beta and TNF-alpha. RNA isolation, reverse transcription, and PCR amplification of ENA-78 and IL-8.C-X-C peptides were expressed by tumor cells of all the tumor specimens tested. ENA-78 and IL-8 were also expressed by AM. To better understand the regulation of the C-X-C production, BAC cell line was cultured alone or with inflammatory cells. PBMC upregulated both tumor ENA-78 and IL-8 mRNA expression and protein release whereas AM only upregulated ENA-78 mRNA expression and protein release; PMN had no effect. Anti-human IL-1beta antibodies (ab) inhibited the A549 ENA-78 and IL-8 production stimulated by PBMC-CM. Anti-human TNF-alpha ab inhibited A549 ENA-78 production stimulated by AM-CM. IL-1beta and TNF-alpha were expressed in vivo by inflammatory cells, although TNF-alpha was also expressed by tumor cells.This work emphasizes the role of the host inflammatory response in promoting tumor growth in vivo.

Study objective To compare home unattended polysomnography (H-PSG) with polysomnography performed in a local hospital and telemonitored by a sleep laboratory (T-PSG) in the diagnosis of obstructive sleep apnea syndrome (OSAS). Design Randomized crossover trial. Patients Ninety-nine patients with suspected OSAS who underwent H-PSG and T-PSG on 2 consecutive nights, according to a randomized order. Measurements H-PSG and T-PSG were compared in terms of (1) effectiveness, only recordings providing interpretable signals from at least one EEG, the electro-oculograph, the electromyograph, air flow, thoracic or abdominal movements, and arterial oxygen saturation for 180 min of sleep were considered to be effective; (2) patient preference assessed by a questionnaire; and (3) polysomnographic indexes and final interpretative results in patients for whom both recordings were legible. Results Recordings were considered to be ineffective in 11.2% of T-PSG (95% confidence interval [CI], 4.9 to 17.4%) and in 23.4% of H-PSG (95% CI, 19.12 to 27.68%). Thermistor problems were the main cause of failure of H-PSG. Forty-one percent of patients preferred H-PSG, and 55% preferred T-PSG. H-PSG and T-PSG did not differ in terms of sleep and respiratory indexes in the 65 patients in whom both recordings were legible. H-PSG and T-PSG were concordant in 58 of 65 patients using a 10-event-per-hour apnea-hypopnea index cutoff value for the diagnosis of OSAS. Conclusions T-PSG is clearly superior to H-PSG from a technical point of view and tends to be preferred by patients. The site of recording (home vs hospital) has no influence on polysomnographic indexes.

Objectif Developper une nouvelle technique d’analyse automatique des polysomnographies par approche symbolique avec integration de preferences, pour une meilleure concordance avec la lecture manuelle. Methodes A partir de traces de sujets normaux enregistres plusieurs nuits consecutives, et de traces de patients, deux experts ont code les traces selon les regles de l’AASM. Puis les donnees brutes anonymisees ont ete exportees, pour en extraire les grapho-elements individuels par fusion symbolique. Resultats Cent trente polysomnographies de10 temoins enregistres sur 3 nuits consecutives, et 100 patients avec suspicion de syndrome d’apnees du sommeil ont ete doublement scorees. Les grapho-elements ont ete extraits par fusion symbolique (concept semantique et non numerique). Les regles d’inference de l’AASM ont ete traduites en langage mathematique avec integration de preferences en fonction de ce que chaque expert interprete. Puis le programme informatique pour traduire la formalisation en langage JAVA a ete elabore. Dans un premier temps, nous nous sommes focalises sur l’analyse des stades. Testee sur 8 patients, l’analyse donne les taux de concordance avec l’analyse manuelle suivants : N2 : 70,1 % ± 10,9 % N3 : 79,5 % ± 9,1 %. Conclusion Ces premiers resultats montrent la necessite de continuer a enrichir les regles formalisees en collaboration avec les experts. Cette nouvelle technique vise a reproduire la demarche analytique des experts, par opposition a celle reposant sur une analyse purement numerique du signal. Ceci devrait en ameliorer ses performances.

Objectives: In a context where sleep laboratories are overwhelmed by a growing demand to diagnose obstructive sleep apnea syndrome (OSAS), efficient substitutive solutions to in-laboratory polysomnography should be found. To compare the effectiveness and costs of home unattended polysomnography (Hpsg) and telemonitored polysomnography (TMpsg), a cost minimization study was performed.Methods: In a crossover trial, 99 patients underwent on two consecutive nights TMpsg and Hpsg according to a randomized order. A legibility recording criterion was retained to measure effectiveness. A microcosting study of TMpsg and Hpsg was performed. The risks to adopt home strategy or telemonitored strategy, according to different scenario chosen to reach the diagnosis in case of failure of Hpsg or TMpsg, were analyzed.Results: The recording was considered to be ineffective in 11.2% of TMpsg (95% CI, 4.9–17.4) and in 23.4% (95% CI, 19.12–27.68) of Hpsg. The effectiveness differential was 12.2% (95% CI, 1.8–22.6) (p = .02). Assuming that in case of failure PSGs would be re-realized in the same condition to reach the diagnosis, then TMpsg could be selected if Hc/TMc (cost of Hpsg/cost of TMpsg) > 0.97; Hpsg could be selected if Hc/TMc < 0.76. If 0.76 ≤ Hc/TMc ≤ 0.97, the choice of TMpsg would be ambiguous. TMc was estimated to be $244, while Hc was $153 (Hc/TMc = 0.63).Conclusion: Unless some specific geographical situations generate significant transport costs, the implementation of a strategy based on unattended polysomnography at home is cost-saving compared to a telemonitoring strategy.

Stimulation of macrophages with endotoxin and/or cytokines is responsible for the expression of the inducible isoform of nitric oxide synthase (iNOS). Because macrophages are exposed to low pH within the microenvironment of inflammatory lesions, the potential role of acidic pH as an additional regulator of iNOS was investigated. Substitution of the culture medium of rat peritoneal macrophages at pH 7.4 with medium at pH 7.0 up-regulated iNOS activity, as reflected by a 2.5-fold increase in nitrite accumulation. The increase in iNOS activity was associated with a similar increase in iNOS mRNA expression that reflected an increase in iNOS mRNA synthesis rather than stability. Low environmental pH-induced iNOS gene transcription involved the activation of nuclear factor-κB (NF-κB) transcription factor since exposure of macrophages to low environmental pH both increased NF-κB binding activity in the nucleus and enhanced NF-κB-driven reporter gene expression. In addition, treatment of macrophages with pyrrolidine dithiocarbamate orn-acetyl-leucinyl-leucinyl-norleucinal, two drugs preventing NF-κB translocation to the nucleus, canceled low pH-induced nitrite accumulation. The overall mechanism required the synthesis of tumor necrosis factor α (TNFα). Indeed, 1) elevated TNFα bioactivity was observed in the medium of macrophages exposed to pH 7.0, and 2) incubation of macrophages with a neutralizing anti-TNFα antibody impaired both NF-κB activation and nitrite accumulation in response to acid challenge. In summary, exposure of macrophages to acidic microenvironment in inflammatory lesions leads to the up-regulation of iNOS activity through the activation of NF-κB.

We examined the effect of insulin on nuclear factor kappa B (NF-kappa B) activity in Chinese ovary (CHO) cells overexpressing wild-type (CHO-R cells) or -defective insulin receptors mutated at Tyr1162 and Tyr1163 autophosphorylation sites (CHO-Y2 cells). In CHO-R cells, insulin caused a specific, time-, and concentration-dependent activation of NF-kappa B. The insulin-induced DNA-binding complex was identified as the p50/p65 heterodimer. Insulin activation of NF-kappa B: 1) was related to insulin receptor number and tyrosine kinase activity since it was markedly reduced in parental CHO cells which proved to respond to insulin growth factor-1 and phorbol 12-myristate 13-acetate (PMA) activation, and was dramatically decreased in CHO-Y2 cells; 2) persisted in the presence of cycloheximide and was blocked by pyrrolidine dithiocarbamate, aspirin and sodium salicylate, three compounds interfering with I kappa B degradation and/or NF-kappa B.I kappa B complex dissociation; 3) was independent of both PMA-sensitive and atypical (zeta) protein kinases C; and 4) was dependent on Raf-1 kinase activity since insulin-stimulated NF-kappa B DNA binding activity was inhibited by 8-bromo-cAMP, a Raf-1 kinase inhibitor. Moreover, insulin activation of NF-kappa B-driven luciferase reporter gene expression was blocked in CHO-R cells expressing a Raf-1 dominant negative mutant. This is the first evidence that insulin activates NF-kappa B in mammalian cells through a post-translational mechanism requiring both insulin receptor tyrosine kinase and Raf-1 kinase activities.

Fish oil supplementation and essential fatty acid deficiency reduce nitric oxide synthesis by rat macrophages. Both fish oil-derived ω-3 polyunsaturated fatty acid (ω3 PUFA) supplementation and essential fatty acid (EFA) deficiency have been shown to exert anti-inflammatory effects and, hence, to ameliorate immune-mediated glomerulonephritis. The mechanisms underlying these effects include alterations in the production of eicosanoids, cytokines (that is, tumor necrosis factor, TNF-α) and reactive oxygen species by blood borne cells. Because, in addition to these mediators nitric oxide (NO) is also implicated in glomerular injury, we have examined if both diets affected macrophage NO production as well. Rats were fed a standard chow, an ω3 PUFA-supplemented diet, or an EFA-deficient diet for six weeks before resident peritoneal macrophages were isolated. These cells were exposed to lipopolysaccharide (LPS) and the NO metabolite, nitrite (NO2-), was measured in the medium using the Griess reagent. Release of NO2- was enhanced by LPS in a dosedependent manner. With 10 ng/ml LPS challenge, NO2- release was reduced by 37% and 57% by ω3 PUFA supplementation and EFA deficiency, respectively. NO2- returned to control levels two weeks after the end of diet. Macrophage production of TNF-α responded in a similar manner. Diet-induced reduction of NO2- release was neither attributable to a reduction of inducible NO synthase mRNA levels as shown by Northern blot analysis, nor to an increased competition of NO synthase and arginase for the substrate (L-arginine). Indeed, arginase activity of macrophages was even slightly reduced by both ω3 PUFA-supplemented diet and EFA-deficient diet. Diet-induced reduction of NO synthase activity was specific for the inducible form since constitutive NO synthase activity in vascular wall was unaffected by EFA deficiency, and even significantly increased by ω3 PUFA supplementation. These data demonstrate that NO synthesis by rat macrophages is down-regulated by both ω3-PUFA supplemented diet and EFA-deficient diet. This may contribute to the explanation of the anti-inflammatory effects of such dietary treatments.

Increasing evidence supports a role of cytokines, tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and IL-6 in the development of endotoxin-induced acute renal failure. Several activities of these cytokines require a local rather than a systemic production and function. Thus, this study investigates the chronology of cytokine expression in glomeruli isolated from normal rats or rats given iv lipopolysaccharide injections. Detectable levels of TNF alpha could be found in glomeruli isolated from normal rats as assessed by L-929 fibroblast lytic assay and ELISA. Glomeruli isolated from rats given lipopolysaccharide transiently released increased amounts of TNF alpha in relation to the dose of lipopolysaccharide (10 to 500 micrograms/kg body wt) and the lag period between lipopolysaccharide injection and glomerular isolation (20 to 120 min). TNF alpha was released in similar amounts by glomeruli from normal rats that were exposed in vitro to lipopolysaccharide challenge (0.01 to 10 micrograms/mL), indicating that lipopolysaccharide had direct effects on the release of TNF alpha from glomerular cells. These cells consisted mainly of resident cells because reduction of glomerular infiltration by bone marrow-derived cells after the irradiation of normal rats did not affect TNF alpha release. Glomerular IL-1 and IL-6 production was evaluated by specific bioassays under identical conditions. No IL-1 activity could be detected in the medium or within the glomerular cells at any time within 120 min after lipopolysaccharide injection. By contrast, glomerular IL-6 production was induced after lipopolysaccharide challenge both in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

SUMMARYThe effect of endogenously generated reactive oxygen metabolites on the interaction of human blood monocytes with tumour necrosis factor-alpha (TNF-α) was investigated. Pre-exposure of unactivated human blood monocytes to dimethylthiourea, a scavenger of hydroxyl radical (OH˙) or to desferrioxamine (DFX), an iron chelator preventing the synthesis of OH˙, enhanced the specific binding of 125I-TNF-α to its receptors. Scavengers of superoxide anion or hydrogen peroxide were without effect. DFX-induced up-regulation of 125I-TNF-α binding depended on the concentration of the drug (1–5 mm) and on the duration of the treatment (1–18 h). It was not due to a reduction of receptor occupancy by endogenously generated TNF-α. Scatchard analysis of binding data revealed that DFX caused an approximately two-fold increase in the number of type II TNF-α receptors, with no change in their affinity. This up-regulation, that did not require synthesis of new proteins, was associated with a decrease in the internalization rate of TNF-α receptors, the half-life of which was doubled. Conversely, these findings suggest that OH˙ generation by monocytes may have a physiological role in reducing the activity of membrane-associated TNF-α receptors.

Bacterial infections promote important alterations in immune, hemodynamic, and metabolic function which can result in irreversible shock. These changes are mediated by host-secreted cytokines rather than by direct action of the endotoxin lipopolysaccharide (LPS) derived from the cell wall of bacteria. One cytokine that has been extensively studied for its role in infection is macrophage-derived tumor necrosis factor alpha (TNFα) [1]. Three observations suggest that TNFα has a central involvement in endotoxic shock: (i) High levels of TNFα can be found in blood of animals and humans with endotoxic shock; (ii) When injected to animals, TNFα causes a syndrome similar to endotoxic shock, with hypotension, decreased tissue perfusion, organ failure, and lactic acidosis; (iii) The effects of LPS can be prevented by prior passive immunization of animals with polyclonal or monoclonal antibody directed against TNFα. During severe bacterial infections, acute renal insufficiency occurs frequently and contributes significantly to the morbidity and mortality of the shock. In vivo studies indicate that LPS induces an increase in renal vascular resistance and a decrease in glomerular filtration rate [2]. A variety of mediators could contribute to these hemodynamic changes. They include: arachidonic acid metabolites (thromboxane A 2 , TXA 2 ; leukotrienes, LT), platelet activating factor (PAF), adenosine, catecholamines, angiotensin II and cytokines. Their synthesis is probably initiated by the release of TNFα [3]. The present paper discusses the cellular origin of TNFα within the kidney, and reviews the mechanisms whereby factors released in response to TNFα participate in controlling the secretion of this cytokine.

Tumor necrosis factor is generated in inflammatory lesions of the glomerulus. Its release and binding are regulated by simultaneously generated reactive oxygen metabolites. The main consequence is a limitation of autocrine and paracrine action of tumor necrosis factor without any reduction of its systemic activity.

International audience; The sleep apnea syndrome is a real public health problem. Improving its diagnosis using the polysomnography is of huge importance. Optisas was a visual method allowing translating the polysomnographic data into a meaningful image. In a previous paper, it was shown to bring extra information in 62% of cases. Here its capacity for displaying information of the same relevance as the one got using the classical report of the polysomnography is studied. The main result is that this capacity is weak and seems to be present only to identify the obstructive sleep apnea syndrome. Moreover this study suggests to improve the standardization of the classical report in the framework of a quality insurance process.