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International audience; Background: Excessive daytime sleepiness (EDS) in individuals with OSA syndrome persisting despite good adherence to CPAP is a disabling condition. Pitolisant is a selective histamine H3-receptor antagonist with wake-promoting effects.Research question: Is pitolisant effective and safe for reducing daytime sleepiness in individuals with moderate to severe OSA adhering to CPAP treatment but experiencing residual EDS?Study design and methods: In a multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was titrated individually at up to 20 mg/day and taken over 12 weeks. The primary end point was change in the Epworth Sleepiness Scale (ESS) score in the intention-to-treat population. Key secondary end points were maintenance of wakefulness assessed by the Oxford Sleep Resistance Test, Clinical Global Impressions scale of severity, the patient's global opinion, EuroQoL quality-of-life questionnaire score, Pichot fatigue questionnaire score, and safety.Results: Two hundred forty-four OSA participants (82.8% men; mean age, 53.1 years; mean Apnea Hypopnea Index with CPAP, 4.2/h; baseline ESS score, 14.7) were randomized to pitolisant (n = 183) or placebo (n = 61). ESS significantly decreased with pitolisant compared with placebo (-2.6; 95% CI, -3.9 to -1.4; P < .001), and the rate of responders to therapy (ESS ≤ 10 or change in ESS ≥ 3) was significantly higher with pitolisant (71.0% vs 54.1%; P = .013). Adverse event occurrence (mainly headache and insomnia) was higher in the pitolisant group compared with the placebo group (47.0% and 32.8%, respectively; P = .03). No cardiovascular or other significant safety concerns were reported.Interpretation: Pitolisant used as adjunct to CPAP therapy for OSA with residual sleepiness despite good CPAP adherence significantly reduced subjective and objective sleepiness and improved participant-reported outcomes and physician-reported disease severity.

Background SARS-CoV-2 virus which targets the pulmonary vasculature is supposed to induce an intrapulmonary right to left shunt with an increased pulmonary blood flow. Such vascular injury is difficult to observe because it is hidden by the concomitant lung injury. We report here what may be, to the best of our knowledge, the first case of a pure Covid-19 related Acute Vascular Distress Syndrome (AVDS). Case presentation A 43-year-old physician, tested positive for Covid-19, was addressed to the emergency unit for severe dyspnoea and dizziness. Explorations were non informative with only a doubt regarding a sub-segmental pulmonary embolism (no ground-glass lesions or consolidations related to Covid-19 disease). Dyspnoea persisted despite anticoagulation therapy and normal pulmonary function tests. Contrast-enhanced transthoracic echocardiography was performed which revealed a moderate late right-to-left shunt. Conclusions This case report highlights the crucial importance of the vascular component of the viral disease. The intrapulmonary shunt induced by Covid-19 which remains unrecognized because generally hidden by the concomitant lung injury, can persist for a long time. Contrast-enhanced transthoracic echocardiography is the most appropriate test to propose in case of persistent dyspnoea in Covid-19 patients.

It was recently described that COVID-19 pneumonia patients had an atypical form of the ARDS syndrome and required gentle ventilation. We report here on benefits of CPAP treatment in a patient with COVID-19 pneumonia. A 63-year-old patient of African origin presented to the emergency room with COVID-19 pneumonia. Fever had started 5 days before her admission. On day 4, rapid clinical deterioration associated to a high respiratory rate and increased oxygen requirements was noted. The patient was working in an intensive care unit and refused to be intubated. Oxygen was administered at a rate of 15 litres per minute via a Boussignac valve, which initially restored normal oxygen saturation, but this treatment was poorly tolerated and the patient withdrew it after 2 h. A CPAP set at a pressure of 8 cm of water (Goodknight®) was then introduced with better tolerance, allowing the patient to wear it almost continuously for more than 38 h. The patient also benefited from the administration of methypredinsolone 40 mg. Concerning tolerance, a substantial advantage was noted for CPAP machine compared to the Boussignac valve with in addition, a clear decrease in respiratory rate. We would like to encourage the use of CPAP, better tolerated for extended hours with lower oxygen flows, in patients with COVID-19 pneumonia, where acute respiratory distress all too often leads to patient intubation and the genesis of deleterious lung lesions.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which targets the pulmonary vasculature is supposed to induce an intrapulmonary right to left shunt with an increased pulmonary blood flow. We report here what may be, to the best of our knowledge, the first videoendoscopic descriptions of an hypervascularization of the bronchial mucosa in two patients hospitalized for coronavirus disease 2019 (COVID-19) pneumonia.Cases Presentation: Two patients, 27- and 37-year-old, were addressed to our Pneumology department for suspicion of COVID-19 pneumonia. Their symptoms (fever, dry cough, and dyspnoea), associated to pulmonary ground glass opacities on thoracic CT, were highly suggestive of a COVID-19 disease despite repeated negative pharyngeal swabs RT-PCR. In both patients, bronchoscopy examination using white light was unremarkable but NBI bronchoscopy revealed a diffuse hypervascularization of the mucosa from the trachea to the sub-segmental bronchi, associated with dilated submucosal vessels. RT-PCR performed in bronchoalveolar lavage (BAL) confirmed the presence of Sars-CoV-2.Conclusions: These two case reports highlight the crucial importance of the vascular component of the viral disease. We suggest that such bronchial hypervascularization with dilated vessels contributes, at least in part, to the intrapulmonary right to left shunt that characterizes the COVID-19 related Acute Vascular Distress Syndrome (AVDS). The presence of diffuse bronchial hypervascularization in the context of COVID-19 pandemic should prompt the search for Sars-CoV-2 in BAL samples.

Background: The impact of removing the upper airway lymphoid tissue and in particular, tonsillectomy, in adults with OSA has not been demonstrated in large populations. Aims: To compare the severity of OSA and the prevalence of cardiovascular, metabolic and respiratory co-morbidities between patients with OSA who had undergone previous tonsillectomy and those who had not. Methods: The 19,711 participants in this study came from the European sleep apnea database (ESADA) which comprises data from unselected adult patients aged 18–80 years with a history of symptoms suggestive of OSA referred to sleep centers throughout Europe. Results: There were no differences between the two groups in terms of sex ratio and age (146 patients with previous tonsillectomy vs. 19565 patients without). Patients who had undergone tonsillectomy had a lower body mass index (29.3 ± 5.2 kg/m2 vs 32.2 ± 6.6 kg/m2, p < 0.001), lower subjective sleep latency (17.1 ± 17.8 min vs 25.5 ± 30.4 min, p = 0.001), lower ODI (15.7 ± 18.3 events/hour vs 30.7 ± 26.1 events/hour, p < 0.001), and SpO2, European Respiratory Society, ERS, The ESADA network has previously received support from the European Union COST action B26 and the European Respiratory Society. We gratefully acknowledge unrestricted seeding grants from ResMed Inc and Philips Respironics Inc. for establishment of the organisation and the database. Excellent technical assistance in terms of centre monitoring and database maintenance was provided by Ann-Christin Lundquist, RN and Jeanette Norum, RN.

DEAR SIR, We read with great interest the recent letter to the Editor by Lavinia Monaco et al. [1] about the article by Jeeban P. Das et al. [2] that were both published in your European Journal of Nuclear Medicine and Molecular Imaging. In six patients with a laboratory-confirmed diagnosis of COVID-19 and a moderate or high pre-test probability of pulmonary embolism (PE), perfusion (Q)-single-photon emission computed tomography (SPECT)/CT was found positive in 4/6 of patients with bilateral and segmental PE in 3/4 of patients. [...]

Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V., ResMed Foundation European Respiratory Society, ERS European Respiratory Society, ERS European Respiratory Society, ERS, The ESADA network has received support from the European Union COST action B26 and the European Respiratory Society (ERS) funded Clinical Research Collaboration (CRC). Unrestricted seeding grants from the ResMed Foundation and the Philips Respironics Foundation for establishment of the database in 2007 and 2011 are gratefully acknowledged. The ESADA network has a scientific collaboration with Bayer AG., Nonfinancial support was provided by the European Sleep Research Society (ESRS) and the European Respiratory Society (ERS) in terms of logistics for communication, meetings and data presentations for the ESADA collaborators., Dr. Verbraecken reports grants and personal fees from ResMed, Bioprojet, Jazz Pharmaceutics; personal fees from Philips, Sanofi, Agfa-Gevaert, grants from AirLiquide; personal fees from Springer, Westfalen Medical, SomnoMed, Vivisol, Total Care, Medidis, Fisher & Paykel, Wave Medical, OSG, Mediq Tefa, NightBalance, Heinen & Löwenstein, AstraZen, Accuramed, Bekaert Deslee Academy and UCB Pharma, outside the submitted work. Dr. Hedner reports grants from ResMed, Philips Respironics, and the European Respiratory Society all related to maintenance of database on behalf of the ESADA group during the conduct of the study. Dr. Grote reports grants from Bayer, Resmed, Respironics/Philips, and from the European Respiratory Society during the conduct of the study; non-financial support and other from Itamar Medical, Resmed, Philips, and Astra Zeneca, outside the submitted work. In addition, Dr. Grote has a patent on sleep apnea therapy licensed. The remaining co-authors have no conflict of interest to declare.

Objective/Background: The Clinical Global Impression scale (CGI) reflects the clinician's assessment of the disease impact on patient's global functioning. We assessed predictors of CGI scale rating in patients with obstructive sleep apnea (OSA). Patients/Methods: Consecutive patients with suspected OSA (n = 7581) were identified in the European Sleep Apnea Database (ESADA). Anthropometrics, comorbidities, apnea severity obtained by polygraphy or polysomnography, and daytime sleepiness [Epworth Sleepiness Scale (ESS)] were assessed. The CGI 7-point scale was completed at the end of the diagnostic process (CGI-severity, ie, CGI-S) and, in a sub-population, at treatment follow-up (CGI-Improvement). Results: CGI-S was rated mild to moderate in 44% of patients. CGI rating at any given apnea intensity was worse in women than in men (p < 0.01). Patients undergoing polygraphy (n = 5075) were more frequently rated as severely ill compared to those studied with polysomnography (19.0% vs 13.0%, p < 0.001). In patients aged

Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent chronic respiratory disorder with prevalence among adult males of ≥10%. The most common daytime symptom associated with OSAS is excessive sleepiness, which in more severe manifestations can result in sleepiness at the wheel while driving and probably contributes to the substantial increase in accident risk among patients with OSAS. Fortunately, current evidence indicates that successful therapy of OSAS, particularly with continuous positive airway pressure, can bring the accident risk down to levels similar to an equivalent general population. The recognition of the increased driving accident risk in OSAS prompted the Transport and Mobility Directorate of the European Commission to establish a working group on this topic in 2012, which ultimately led to a revision of Annex III of the EU Driving Licence Directive, which is subject to mandatory implementation by European Union member states by December 2015. This directive specifies that patients with moderate or severe OSAS associated with significant daytime sleepiness should be prohibited from driving until effective therapy is established. These new regulations are designed to balance the legitimate objective of public safety with not penalising OSAS patients who are complying with effective therapy. Successful implementation of regulations on driving in OSAS patients must also include measures to educate relevant stakeholders including patients, medical personnel, traffic police and employers in the transport industry. The key objective is to encourage patients with possible OSAS to seek diagnosis and treatment and not to inhibit OSAS patients from coming forward.

Purpose of the study Periodic leg movements (PLMs) are found in 30% of patients suffering from OSA. Under CPAP, we observed that PLMs can increase, decrease, or remain unchanged. The predictors of these changes are not well established. Objective To determine the predictors of PLMs change under CPAP and its impact on long-term adherence. Materials and method The patients were referred to the sleep laboratory for snoring or sleepiness. A single PSG night has been performed before and after CPAP treatment. Data on medication used, comorbidities and ferritin level were collected. Results A total of 160 patients were recruited with a severe OSA. About 32.5% (52/160) patients had emerging PLM i.e. that appeared after the disappearance of respiratory events. By comparing patients with emerging-PLMs to others, we found that only the blood ferritin level was significantly different between groups. Moreover, after one-year follow-up, a significant difference in adherence and long-term compliance was observed between patients without PLM at both screening and CPAP polysomnographies or emerging PLM at the second study (56%) vs. patients with baseline PLM, whether PLM remained stable or decreased under CPAP treatment (75%) (p-value 0.028). Serum ferritin and presence of diabetes mellitus predicted the evolution of PLM observed. Patients with low ferritin levels demonstrated an increase of PLM after initiation of nasal CPAP treatment. Conclusion The emergence of PLM negatively impacts long-term adherence to nasal CPAP treatment in OSA. Blood ferritin level is a predictor of the evolution of PLM under CPAP therapy.

In Belgium, patients with moderate to severe OSA (AHI 20) who show less than 30 micro-arousals per hour slept (MAI) cannot benefit from CPAP refund by the social security (SS).To assess the influence of reimbursement on CPAP acceptance, and long-term adherence.OSA patients (AHI 20) were included regardless of MAI. All patients were offered a CPAP trial of 3-5 days for habituation. Two groups were defined and compared: «Out of pocket money» patients (OOP) with MAI 30 that were invited to purchase their device and «reimbursed group» that were offered a CPAP reimbursed by the social security.812 patients were found: 59 in the OOP group, mostly females, sleepier and using more hypnotics. Out of the reimbursed group, 183 patients were matched to the OOP patients on the grounds of age, AHI and BMI. 90% of OOP and 94% of reimbursed patients (p 0.379) accepted a CPAP trial; 74% of OOP and 90% of reimbursed patients acquired a CPAP device (p 0.005) thereafter, whereas 82% and, respectively, 84% of those (p 0.254) were still on CPAP after a mean follow-up of 711 and 604 days with a mean ± SD daily compliance of 5.3 ± 3 and 6.1 ± 2 h, respectively (p 0.159). Only fatigue scale seems to influence the purchase of CPAP by OOP patients.CPAP reimbursement influences the purchase of CPAP but once the device becomes available there is no difference with reimbursed patients in long-term adherence.

Compared with invasive ventilation, non-invasive ventilation (NIV) has two unique characteristics: its non-hermetic nature and the fact that the ventilator-lung assembly cannot be considered as a single-compartment model because of the presence of variable resistance represented by the upper airways. When NIV is initiated, the ventilator settings are determined empirically based on clinical evaluation and blood gas variations. However, NIV is predominantly applied during sleep. Consequently, to assess overnight patient-machine "agreement" and efficacy of ventilation, more specific and sophisticated monitoring is needed. The effectiveness of NIV might therefore be more correctly assessed by sleep studies than by daytime assessment. The simplest monitoring can be done from flow and pressure curves from the mask or the ventilator circuit. Examination of these tracings can give useful information to evaluate if the settings chosen by the operator were the right ones for that patient. However, as NIV allows a large range of ventilatory parameters and settings, it is mandatory to have information about this to better understand patient-ventilator interaction. Ventilatory modality, mode of triggering, pressurization slope, use or not of positive end expiratory pressure and type of exhalation as well as ventilator performances may all have physiological consequences. Leaks and upper airway resistance variations may, in turn, modify these patterns. This article discusses the equipment available for NIV, analyses the effect of different ventilator modes and settings and of exhalation and connecting circuits on ventilatory traces and gives the background necessary to understand their impact on nocturnal monitoring of NIV.

Sleepiness may account for up to 20% of crashes on monotonous roads, especially highways. Obstructive sleep apnea (OSA) is the most common medical disorder that causes excessive daytime sleepiness, increasing the risk for drowsy driving two to three times. The purpose of these guidelines is to update the 1994 American Thoracic Society Statement that described the relationships among sleepiness, sleep apnea, and driving risk.A multidisciplinary panel was convened to develop evidence-based clinical practice guidelines for the management of sleepy driving due to OSA. Pragmatic systematic reviews were performed, and the Grading of Recommendations, Assessment, Development, and Evaluation approach was used to formulate and grade the recommendations. Critical outcomes included crash-related mortality and real crashes, whereas important outcomes included near-miss crashes and driving performance.A strong recommendation was made for treatment of confirmed OSA with continuous positive airway pressure to reduce driving risk, rather than no treatment, which was supported by moderate-quality evidence. Weak recommendations were made for expeditious diagnostic evaluation and initiation of treatment and against the use of stimulant medications or empiric continuous positive airway pressure to reduce driving risk. The weak recommendations were supported by very low-quality evidence. Additional suggestions included routinely determining the driving risk, inquiring about additional causes of sleepiness, educating patients about the risks of excessive sleepiness, and encouraging clinicians to become familiar with relevant laws.The recommendations presented in this guideline are based on the current evidence, and will require an update as new evidence and/or technologies becomes available.

Background: Unintentional leaks, patient-ventilatory asynchrony, and obstructive or central events (either residual or induced by noninvasive positive pressure ventilation [NPPV]) occur in patients treated with NPPV, but the impact of ventilator settings on these disturbances has been little explored. The objective of this study was to investigate the impact of backup respiratory rate (BURR) settings on the efficacy of ventilation, sleep structure, subjective sleep quality, and respiratory events in a group of patients with obesity hypoventilation syndrome (OHS). Methods: Ten stable patients with OHS treated with long-term nocturnal NPPV underwent polysomnographic recordings and transcutaneous capnography on 3 consecutive nights with three different settings for BURR in random order: spontaneous (S) mode, low BURR, and high BURR. No other ventilator parameter was modified. Results: The S mode was associated with the occurrence of a highly significant increase in respiratory events, mainly of central and mixed origin, when compared with both spontaneous/timed (S/T) modes. Accordingly, the oxygen desaturation index was significantly higher in the S mode than in either of the S/T modes. The results of nocturnal transcutaneous PCO 2 (PtcCO 2 ) (mean value and time spent with PtcCO 2 >50 mm Hg) were similar over the three consecutive nocturnal recordings. The quality of sleep was perceived as slightly better, and the number of perceived arousals as lower with the low- vs high-BURR (S/T) mode. Conclusions: In a homogenous group of patients treated with long-term NPPV for obesity-hypoventilation, changing BURR from an S/T mode with a high or low BURR to an S mode was associated with the occurrence of a highly significant increase in respiratory events, of mainly central and mixed origin. Trial registry: ClinicalTrials.gov; No.: NCT01130090; URL: www.clinicaltrials.gov. © 2013 American College of Chest Physicians.

Since the early 1980s, when noninvasive ventilation (NIV) showed efficacy in the management of some forms of respiratory failure [1–3], the number of patients receiving this treatment both in the acute setting and at home has steadily increased. This is explained by a growing number of indications in which the effectiveness of NIV has been proven, and also by major technological advances that led to the availability of high-performance portable ventilators and the development of a technical support infrastructure [4]. In the particular case of chronic respiratory failure patients, NIV applications were extended from conventional indications in chest wall and neuromuscular diseases to other more frequent conditions such as obesity hypoventilation and chronic obstructive pulmonary disease (COPD), although, in the latter, the role of NIV is still controversial [5–7]

La prevalence du syndrome d’apnees hypopnees du sommeil augmente avec l’âge, sans qu’on ait une explication claire du pourquoi de cette evolution. Ce chapitre passe en revue les modifications liees a l’âge survenant dans l’anatomie et la physiologie des voies aeriennes superieures, ainsi que dans la physiologie du sommeil, la fonction de l’appareil musculaire ou l’exposition a des medicaments hypnotiques ou antalgiques qui peuvent rendre compte de la plus forte prevalence de ce syndrome chez le sujet âge.

The physiology of sleep is not completely understood but it is widely accepted that sleep is important to the human body in the recovery of metabolic and neurological processes. This paper summarizes the effects of sleep dysfunction on different systems and considers implications in the context of rehabilitation. When sleep is experimentally completely or partially curtailed important brain functions are impacted leading to psychological and neurological disturbances. Increased cortisol levels, reduction of glucose tolerance, and increased sympathetic nervous system activity have also been identified in healthy subjects under such conditions. Several studies show that 50-80% of patients with chronic pain suffer from sleep dysfunction. It has been suggested that on the one hand pain can cause sleep dysfunction and on the other hand that sleep dysfunction can aggravate pain. The physiologic mechanism behind this interaction is not completely clear; although most authors describe the relationship between pain and sleep dysfunction as aberrant processing of tactile-cutaneous sensory inputs at the meso-encephalic level and in the trigeminal nucleus both when asleep and awake. Decreased duration of sleep also increases heart rate, blood pressure and sympathetic activity magnifying the individual's response to stressful stimuli. Possible causal mechanisms for the established connection between short sleep cycles and coronary pathology include sympathetic nervous system hyperactivity, increased blood pressure increase or reduced glucose tolerance. Finally, sleep and fatigue have traditionally been linked. Fatigue can have a physical etiology but is also associated with depression. Sleep alterations are also considered an important risk factor for psychological dysfunction and also mental illness. However, despite the noted repercussions of sleep dysfunction, studies investigating interventions to improve sleep have been limited in number. Benefits of exercise programs on sleep habits have been controversial with some have finding positive effects, whereas others did not find any significant effect. It is possible that the dose or intensity of exercise programs may have an important influence in the outcomes. It is our opinion that based on the multi-system repercussions of different sleep dysfunctions, evaluation of sleep habits should be considered fundamental in the context of rehabilitation and should be included as part of the clinical history of each patient attending physical therapy.

We report the case of a patient with an endobronchial chondroma, a rare benign endobronchial tumor. A 37-year-old woman was evaluated for suspicion of asthma. Computed tomography of the chest and flexible bronchoscopy showed an endoluminal tumor occluding the culmen (B3 left). The tumor was extirpated almost completely by bronchoscopy. Histologically, the biopsy specimens were composed of chondromatous tissue located under the normal bronchial mucosa, according to the diagnosis of chondroma. The symptoms disappeared immediately after the procedure and did not reappear after 1 year. Chondromas are usually located on the skeleton. Endobronchial presentation is rare. We know of only 41 cases reported in the literature. Hamartoma or chondrosarcoma constitutes the main histologic differential diagnosis. The treatment consists of complete resection to avoid any risk of recurrence or sarcomatous transformation. There is no consensus regarding the method of treatment, but endoscopic resection seems to be the first choice.

We have shown that expiratory flows increase when expirations are rapidly interrupted in stable asthmatic patients. We hypothesized that a similar increase could be obtained in patients with acute exacerbation of bronchial asthma treated in the Emergency Room. A total of 30 asthmatic patients were randomly allocated into two groups, the study and the control groups. Patients in the study group were connected to a device with an inspiratory line designed to administer pressurized aerosols. The expiratory line passed through a valve completely interrupting flow at 4 Hz, with an open/closed time ratio of 10/3. The control group patients were also connected to the device, but with the valve kept open. Mean expiratory flow at tidal volume (MEFTV) was measured under basal conditions and at 4, 8 and 12 minutes after connecting the patients to the device. All patients received standard treatment throughout the procedure. At all time points MEFTV increased more in the study than in the control group (p < 0.003 by two-way ANOVA). There was no residual effect after disconnection from the device. We conclude that TEFI can rapidly improve expiratory flows in patients with acute exacerbations of asthma, while pharmacologic interventions proceed.Demostramos que el flujo espiratorio máximo, en pacientes asmáticos en estado estable, se incrementaba cuando se generaban rápidas y transitorias interrupciones del flujo. Formulamos la hipótesis de que un incremento similar podría ser observado en pacientes con exacerbación aguda de asma tratados en la sala de emergencias. Un total de 30 pacientes asmáticos fueron distribuidos al azar en dos grupos. Los pacientes del grupo en estudio fueron conectados a un aparato con una vía inspiratoria diseñada para la administración de aerosoles. La vía espiratoria pasaba por una válvula que interrumpía el flujo completamente a 4 hz, con una relación tiempo abierta/tiempo cerrada de 10/3. Los pacientes del grupo control también fueron conectados al aparato pero con la válvula siempre abierta. Se midió el flujo medio de la espiración a volumen circulante en condiciones basales y a los 4, 8 y 12 minutos después de conectado el paciente al equipo. Todos los pacientes recibieron el tratamiento farmacológico estándar a lo largo del ensayo. Se observó un incremento significativamente mayor del flujo espiratorio medio a volumen circulante en el grupo en estudio en comparación al grupo control (p < 0.003 ANOVA de dos vías) durante todo el ensayo. No hubo efecto residual después de la desconexión del equipo. Concluimos que las interrupciones transitorias del flujo espiratorio pueden incrementar rápidamente el flujo espiratorio en pacientes con exacerbaciones agudas de asma dando tiempo a que el tratamiento farmacológico comience a actuar.

Obstructive sleep apnea has been associated with a high risk for motor vehicle accidents, probably the highest of all risks due to medical conditions. Treatment of sleep apnea with nasal continuous positive airway pressure appears to reduce the risk of traffic accidents to the one of the general population. The risk for accidents may also be increased in untreated patients in the home and work environment. The increased risk seems unrelated to the symptom of daytime excessive sleepiness, and in many studies lacks a clear dose-response relationship with respect to the severity of apneas and hypopneas. The association of sleep apnea, chronic sleep deprivation and consumption of hypnotics or alcohol has not been thoroughly studied, although alcohol has been considered as a confounding variable in some studies. The cost of traffic accidents due to sleep apnea has been estimated to be so high that diagnosing and treating all drivers with sleep apnea in the USA would be cost saving and result in a decrease in society costs related to the disease. Driving licenses are delivered according to national legislations. These are all but uniform, especially concerning sleep apnea. Even within the European Union, where a minimum set of rules is mandatory for all countries, sleep apnea is not included in the minimum. Therefore, drivers are left in a very uncomfortable position, behaving according to the law in one country but being unlawful once the border with the neighbor country is crossed. Physicians are also in a very difficult position if they have to counsel their patients on the best attitude when travelling by car. The situation is even worse for commercial drivers, for whom the legislation is more severe but leaves sleep apnea uncovered in many countries. This is all the more disturbing if one considers that sleep apnea can be suspected, screened and diagnosed with relative ease, and that once diagnosed the adequate treatment allows for safe driving. The inclusion of sleep apnea in the European traffic license regulations would represent a step forward towards safe routes for patients and healthy people alike.

Positive airway pressure systems are widely used to treat patients with moderate-to-severe obstructive sleep-disordered breathing. The application of stable continuous positive airway pressure (CPAP) via the nose (nasal CPAP) has been the mainstay of treatment since the early 1980s. For treatment to be effective, the pressure level must be fine-tuned to restore patency of the individual patient9s upper airway. Currently, there is ongoing controversy concerning which outcomes to observe when adapting the pressure level, and which methods to use for pressure adaptation. Adjusting the pressure level to control apnoeas and hypopnoeas is one major objective, but may not be sufficient to restore normal sleep. Evidence is available that elimination of inspiratory flow limitation leads to better results. In recent years, it has become evident that the use of empirically set CPAP or automatic CPAP devices parallel the clinical results obtained with the classical approach of manual CPAP titration. A striking and still unexplained paradox lies in the fact that automatic CPAP devices perform very differently on the bench, but still yield satisfactory results on several clinical outcomes, e.g. control of sleep-related respiratory disturbances, restoration of good sleep quality and daytime alertness. Understanding the functioning of automatic CPAP devices can prove difficult, as the mode of operation is usually not disclosed by the manufacturers. At present, it is impossible to make any scientifically sound statement on the appropriateness of using automatic continuous positive airway pressure devices for the routine treatment of patients with obstructive sleep-disordered breathing. For this purpose, convincing results of phase I–III clinical trials are needed.

Obstructive sleep apnea (OSA) is a very frequent affliction that affects about 1-5% of the adult population in its severe form. Continuous positive airway pressure (CPAP) is the most commonly used treatment and is highly effective, but its use is limited by low long-term adherence rates and overall poor acceptance among the patients. Therefore, there is a need for developing alternative approaches to OSA treatment, including a more 'natural' concept of maintaining an open airway through neuromodulation. Here we review the concept, scientific rationale, and technical details of hypoglossal nerve stimulation. We also review results of published clinical studies with several hypoglossal stimulation devices that are being investigated today. Hypoglossal nerve stimulation appears to be a very promising treatment for patients with moderate-to-severe OSA. If its efficacy is confirmed, it will probably be complementary with CPAP therapy and initially aimed at patients unable or unwilling to use CPAP. Once it becomes a standard therapy, its advantages might prove sufficient to challenge CPAP as the first-line therapy.

Obstructive sleep apnea (OSA) is a very frequent affliction that affects about 1-5% of the adult population in its severe form. Continuous positive airway pressure (CPAP) is the most commonly used treatment and is highly effective, but its use is limited by low long-term adherence rates and overall poor acceptance among the patients. Therefore, there is a need for developing alternative approaches to OSA treatment, including a more 'natural' concept of maintaining an open airway through neuromodulation. Here we review the concept, scientific rationale, and technical details of hypoglossal nerve stimulation. We also review results of published clinical studies with several hypoglossal stimulation devices that are being investigated today. Hypoglossal nerve stimulation appears to be a very promising treatment for patients with moderate-to-severe OSA. If its efficacy is confirmed, it will probably be complementary with CPAP therapy and initially aimed at patients unable or unwilling to use CPAP. Once it becomes a standard therapy, its advantages might prove sufficient to challenge CPAP as the first-line therapy.

" Fig.3), under the mucosal flap. The patient successfully restarted oral food intake and was discharged. Upper endoscopy and bronchoscopy confirmed the closure of the orifice during the subse- quent 8 months. There are currently multiple endoscopic options available for the treatment of tracheoesophageal fistulas, with an over- all success rate of 84% (1). Only one case report has described the use of mucosal resection (2). Biosynthetic mesh is fre- quently used in the surgical repair of multiple defects. However, endoscopic placement of mesh for tracheoesophageal fistula has only been described once, where it was deployed from the respira- tory tract and achieved a complete closure of the orifice (3). The case reported here describes a new endoscopic approach to tracheoesophageal fistulas that should be considered as an alternative in the man- agement of these challenging cases. Endoscopy_UCTN_Code_TTT_1AO_2AI

The intrapulmonary percussive ventilation (IPV), frequently coupled with a nebulizer, is increasingly used as a physiotherapy technique; however, its physiologic and clinical values have been poorly studied. The aim of this study was to compare lung deposition of amikacin by the nebulizer of the IPV device (Percussionaire; Percussionaire Corporation; Sandpoint, ID) and that of standard jet nebulization (SST; SideStream; Medic-Aid; West Sussex, UK). Amikacin was nebulized with both devices in a group of five healthy subjects during spontaneous breathing. The deposition of amikacin was measured by urinary monitoring. Drug output of both devices was measured. Respiratory frequency (RF) was significantly lower when comparing the IPV device with SST (8.2 +/- 1.6 breaths/min vs. 12.6 +/- 2.5 breaths/min, p < 0.05). The total daily amount of amikacin excreted in the urine was significantly lower with IPV than with SST (0.8% initial dose vs. 5.6% initial dose, p < 0.001). Elimination halflife was identical with both devices. Drug output was lower with IPV than with SST. The amount of amikacin delivered to the lung is sixfold lower with IPV than with SST, although a lower respiratory frequency was adopted by the subjects with the IPV. Therefore, the IPV seems unfavorable for the nebulization of antibiotics.

Continuous positive airway pressure (CPAP) remains the best treatment for sleep apnoea syndrome (SAS). In the 1990s, many authors reported on daily compliance, but all of the studies utilised relatively short periods of follow-up that did not exceed a few years. The mean annual rate of CPAP use in patients with SAS was prospectively recorded. In the current study, the results are presented along with compliance data from patients who started CPAP between 1991 and 1998 and were still using it by the end of 2003. The cohort was chosen in order to obtain >or=5 yrs of follow-up for each patient. In total, there were 204 patients. For the whole group, mean+/-sd compliance reached 321+/-90 and 393+/-84 min after 1 and 10 yrs, respectively. There was no significant change in the first 2 yrs, with a significant increase from the third year onwards. Compliance, or its evolution over time, was not correlated either to the baseline polysomnographical data (except slightly for the CPAP pressure), to the difference of these data before and under CPAP therapy, to the age of retirement or to changes in the marital status. In conclusion, very long-term compliance with continuous positive airway pressure increases by a mean of 8 min.day-1 per year of follow-up in patients with sleep apnoea syndrome.

This paper reviews some concepts on health economics from the authors personal perspective. It then examines the few papers published on health economics analysis applied to the field of sleep apnea syndrome, as well as the literature on the indirect (cost) consequences of sleep apnea syndrome. It appears that undiagnosed sleep apnea leads to a roughly two-fold increase in medical expenses in the years preceding the diagnosis and that treating the disease (once it is diagnosed) results in a decrease in these excess costs. It seems clear that sleep apnea increases the actual number of road traffic accidents, which will carry a definite, but unmeasured up to now, economic cost consequence. From the health economic point of view, the best diagnostic strategy is the one with the greater utility (i.e. polysomnography), although it could appear at first sight to be the more expensive one. From the patient's perspective, sleep apnea results in a given decrease in the possibilities to enjoy life, and its treatment is worth considering, especially if one takes into account that the actual treatment costs are not great. The global image of the health costs related to sleep apnea is still blurred, and further work is required to get the complete and clear picture of the economic consequences of this disease and of its treatment.

Introduction Domiciliary assisted ventilation (DAV) may be undertaken invasively or non-invasively. Non-invasive DAV is used for patients suffering from alveolar hypoventilation due to restrictive pathology. Invasive DAV is reserved for "indications of necessity" that is when non-invasive ventilation is contraindicated due to the absence of adequate cough and for alveolar hypoventilation leading to hypercapnoea during spontaneous ventilation. State of the art The main pathophysiological limitation to noninvasive ventilation is the interference of the glottis. In this mode the glottis imposes a variable resistance to the ventilation delivered. Its behaviour is more predictable during volume controlled than during pressure controlled ventilation. The control parameters of a volume controlled ventilator are very different from those used in invasive ventilation during which the respiratory system may be regarded as a single compartment (provided a cuffed tube bypasses the upper airway). In non-invasive DAV: mode VCM, tidal volume 13 mls kg(-1), rate 20 cycles min(-1), insp/exp ratio 1/1.2. In invasive DAV: mode VCM, tidal volume 8-10 mls kg(-1), rate 12 cycles min(-1), insp/exp ratio depending on the pathology 1/2. Perspectives As non-invasive DAV is essentially delivered during sleep the parameters for each patient can be optimised during polysomnography because waking, leading to a partial glottic occlusion, interferes with the ventilation delivered. Conclusions Recent understanding of the way the glottis interferes with mechanical ventilation when delivered non-invasively should lead to a revision of earlier practices based on invasive ventilation.

Background: So-called intrapulmonary percussive ventilation (IPV), frequently coupled with a nebulizer, is increasingly used as a physiotherapy technique; however, its physiologic and clinical values have not been rigorously assessed. Study objective: To compare in vitro and in vivo characteristics of the nebulizer of the IPV device (Percussionaire; Percussionaire Corporation; Sandpoint, ID) with those of standard jet nebulization (SST) [SideStream; Medic-Aid; West Sussex, UK]. Design: Aerodynamic particle size was studied by an cascade impactor. The deposition of 99m Tc-diethylenetriaminepenta-acetic acid was measured in 10 healthy subjects by tomoscintigraphy during spontaneous breathing with both nebulizers. Measurements and results: The mass median aerodynamic diameter (0.2 m vs 1.89 m for IPV and SST, respectively) and the fine-particle fraction (16.2% vs 67.5%, respectively) were significantly smaller with IPV. In vivo, respiratory frequency (RF) was lower with the IPV device (10.1 3.4 breaths/min vs 14.6 3.4 breaths/min, p 0.002). Whole-body deposition was significantly higher with IPV (15.63% vs 9.31%), but it was due to a higher extrapulmonary deposition. Although intrapulmonary deposition (IPD) was not different with both devices (4.20% for SST vs 2.49% for IPV), it was much more variable with IPV, compared to SST. The penetration index into the lung was higher with IPV than SST when normalized for RF (0.045 0.018 breaths/min vs 0.026 0.013 breaths/min, p 0.007). Conclusion: The two techniques showed comparable lung deposition despite a large difference in particle size. However, IPV IPD was too variable and thus too unpredictable to recommend its use for drug delivery to the lung. (CHEST 2004; 125:502–508)

Resume La ventilation non invasive (VNI) est actuellement largement utilisee en cas de detresse respiratoire aigue afin d’eviter le recours a l’intubation endotracheale. Cependant, le comportement de la glotte lors des differents modes ventilatoires de VNI peut influencer la ventilation minute effective. La ventilation en pression positive intermittente par voie nasale (VPPIn) en mode volumetrique induit une adduction des cordes vocales responsable d’une diminution de la proportion de ventilation minute insufflee parvenant reellement a l’echangeur pulmonaire (VMe). En mode barometrique controle, la reponse glottique a la VPPIn et donc la VMe sont variables et moins predictibles. En mode barometrique spontane, la glotte n’interfere pas sur la VMe qui augmente avec les niveaux de pression inspiratoire, essentiellement au-dessus de 20 cmH 2 O. Lors de la ventilation en pression negative intermittente (VPNI), l’augmentation de la ventilation ne s’accompagne pas d’une fermeture des cordes vocales permettant d’obtenir des niveaux de VMe superieurs a ceux observes en VPPIn. Ainsi, les parametres ventilatoires optimaux sont les suivants : en mode controle barometrique, une frequence respiratoire (Fr) de 20 cycles par minute, un rapport I/E de 1/1, une pression inspiratoire positive a 15 cmH 2 O, et une pression expiratoire aussi faible que possible ; en mode volumetrique : un volume courant de 13 ml/kg , une Fr de 20 cycles par minute, un debit inspiratoire de 0,56–0,85 l par seconde ; en VPNI : une pression negative de –30 cmH 2 O et une Fr de 20 cycles par minute. Par ailleurs, durant le sommeil, la reponse glottique a la VNI est differente de celle observee chez le sujet eveille. Les parametres ventilatoires « adaptes a l’eveil » peuvent donc etre inadequats pendant le sommeil du fait de la reduction du calibre glottique en sommeil lent. Ces donnees rappellent donc que le systeme respiratoire ne peut etre considere comme un modele a un seul compartiment sous VNI, a l’inverse de la ventilation mecanique endotracheale.

Objectif Evaluer l’efficacite et l’adherence sur le long terme du traitement anti-positionnel « Pasuldo » dans le syndrome des apnees hypopnees obstructives du sommeil positionnel (SAOSP) chez des patients moderes a severes. Methodes Nous avons inclus, entre le 30/04/2013 et le 30/12/2014, les patients diagnostiques SAOSP par PSG. Nous n’avons pas enrole, les patients pouvant beneficier d’une intervention ORL ou d’une CPAP. Apres 7 a 15 jours d’habituation a domicile, une PSG de controle a ete effectuee afin de verifier l’efficacite. L’adherence a ete mesuree par un agenda du sommeil et un suivi telephonique. Resultats Parmi 46 patients, 37 (80 %) ont accepte d’utiliser le dispositif. Nous avons observe la co-morbidite des patients : 48 % d’entre eux souffrent d’hypertension arterielle, 74 % d’hypercholesterolemie, 45 % de diabete et 11 % de trouble du rythme. La PSG sous Pasuldo montre une reduction significative du AHI (20 ± 7,3 a 12,3 ± 12,1, p = 0,0012) et du temps passe sur le dos durant le sommeil (164,2 ± 87,8 a 26,1 ± 45,7, p Conclusion Le Pasuldo est efficace car il diminue significativement l’AHI et le temps passe sur le dos, meme chez les patients moderes a severes. Peu de patients adherent au traitement sur le long terme et abandonnent a cause des effets secondaires (mal de dos, inconfort,…) et car ils pensent apprendre a dormir sur le dos.

OBJECTIVES: We compared, in a prospective study, the side effects and the postoperative complications of three procedures commonly used for the treatment of primary snoring. METHOD: Forty-nine patients underwent velopharyngeal surgery for primary snoring (17 for uvulopalatopharyngoplasty [UPPP]; 15 for laser-assisted uvulopalatoplasty [LAUP], and 17 for radiofrequency tissue volume reduction [RFTVR]). Preoperative full polysomnographic studies ruled out obstructive sleep apnea syndrome. Each patient's evaluation encompassed postoperative pharyngeal pain (as measured by a 5-point visual analogue scale) and use of narcotic drugs in the early postoperative period as well as a subjective evaluation of late postoperative complaints. A surgeon's examination was performed to report postoperative complications in the oropharynx. RESULTS: Postoperative pharyngeal pain was less important in the RFTVR group than in the UPPP and LAUP groups. Mean scores at days 3, 7, 16 were as follows: 4.2, 4.0, and 2.4, respectively, for UPPP; 4.6, 3.8, and 1.6 for LAUP; and 2.4, 2.0, and 0.7 for RFTVR. Mean duration of pain with a score greater than 2 was calculated as follows: UPPP, 21.3 days; LAUP, 15.1 days; and RFTVR, 6.1 days. Mean duration of narcotic drug use for the patients who needed this medication was 10.1 days for UPPP, 7.2 days for LAUP, and 1.3 for RFTVR. Postoperative side effects (trouble with smell and taste, pharyngeal dryness, globus sensation, voice change, and pharyngonasal reflux) were more present in the UPPP and LAUP groups than in the RFTVR group. Surgeon's assessment for postoperative complications reported more wound infection, dehiscence, and posterior pillar narrowing in the UPPP and LAUP groups than in the RFTVR group. CONCLUSION: RFTVR is a safer and less painful procedure than UPPP and LAUP for the treatment of primary snoring. Postoperative discomfort after LAUP and after UPPP appears to be very similar.

⇓Severe chronic obstructive pulmonary disease (COPD) patients, especially those with chronic respiratory failure, may frequently require periods of intensive treatment, monitoring, nursing and, occasionally, ventilatory assistance in order to overcome acute exacerbations. Ventilatory assistance is only rarely provided in the conventional ward 1, therefore admission to an intensive care unit (ICU) is often needed 2. ICU, however, are very precious and expensive resources where nursing costs represent a major expense 3. Patients with acute on chronic respiratory failure may experience a prolonged stay in the ICU not only because of the severity of their illness which precipitates the underlying acute respiratory failure (ARF) 2, but also because of ICU-related complications 4. For these reasons the treatment of acute on chronically ill patients in these areas creates ethical 5 and economic concerns 6, 7. It has been reported that ∼40% of the patients admitted to ICUs never received active intensive care, including mechanical ventilation 8–10. Only ∼40% of patients with ARF due to pulmonary disease needed to be invasively ventilated 11, 12. However, in some countries, such as the UK, with a severe ICU bed shortage, the vast majority of ICU admissions require mechanical ventilation. A recent Italian survey carried out on 99 ICUs showed that COPD was the dominant underlying chronic disease in patients admitted to the Italian ICU, and the need for cardiorespiratory monitoring was the most frequent indication for admission (31.2%) 13. These studies clearly indicate that in some centres there is an “overutilisation” of ICU resources for monitoring purposes, and that acute on chronic respiratory failure could be managed in many patients without invasive ventilation. Patients with chronic respiratory failure, especially those with underlying COPD, very often suffer from a high frequency of …

Rationale: Previous studies have shown that an increase in inspiratory pressure during nasal intermittent positive pressure ventilation (IPPV) does not result in increased effective minute ventilation ((V) over doe E) due to glottic interference. Study objectives: To test the consequences of increases in negative pressure ventilation (NPV) on (V) over dot E. Material and methods: Eight healthy awake subjects underwent NPV delivered by an iron lung. First, NPV was started at a respirator frequency (f) of 15 cycles per minute with an inspiratory negative pressure (INP) of - 15 cm H2O (F15-P15). Then,f was increased to 20 cycles per minute and INP was kept at - 15 cm H2O. Next,f was kept at 20 cycles per minute and INP was reduced to - 30 cm H2O (F20-P30). Finally,f was decreased to 15 cycles per minute and INP was kept at - 30 em H2O. At each step and for each breath, effective tidal volume (VT), (V) over dot E, and end-tidal carbon dioxide pressure were measured. In three subjects, the glottis width was assessed using fiberoptic bronchoseopy. Results: From spontaneous breathing to the first step of NPV (F15-P15), we observed an inhibition of the phasic inspiratory diaphragmatic electromyogram concomitant to a significant increase in (V) over dot E (p < 0.0005). For the group as a whole, the increase in mechanical ventilation (from F15-P15 to F20-P30) resulted in significant increases in VT and (V) over dot E leading to hypocapnia (p < 0.0005). Moreover, the glottis width did not decrease with the increase in mechanical ventilation. Conclusions: We conclude that in normal awake subjects, NPV allowed a significant increase in (V) over dot E. These results differ from those previously obtained with nasal IPPV in which the glottic width interferes with the delivered mechanical ventilation.