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A 28-year-old neuromuscular patient chronically treated with nocturnal noninvasive ventilation developed pulmonary lobar atelectasis and daytime hypoxemia. Twenty four-hour 5 L/min oxygen was begun, while mechanical cough assist aids were applied for seven days. In the following three days, treatment with nebulized Dornase alpha (rhDNase) b.i.d. was tested, without any significant improvement. On 11 and 13th days rhDNase was instilled by flexible bronchoscopy. A rapid resolution of the atelectasis was observed with relief of hypoxemia, without significant side effects. On day 16 the patient was discharged without oxygen requirements. In non-intubated neuromuscular patients with atelectasis who do not respond successfully to non-invasive treatments intrabronchial instillation of rhDNase may safely help to improve airway clearance. Resumo: Um doente neuromuscular crónico de 28 anos de idade, tratado com ventilação noturna não invasiva, desenvolveu atelectasia lobar pulmonar e hipoxemia diurna. Foi iniciado suporte de oxigénio durante 24 horas, enquanto uma ajuda mecânica para a tosse era aplicada por 7 dias. Nos 3 dias seguintes o tratamento com Dornase alfa nebulizado (rgDNase) b.i.d. foi testado, sem qualquer melhoria significativa. No 11.° e 13.° dias rhDNase foi introduzido por broncoscopia flexível. Um restabelecimento rápido da atelectasia foi observado com alívio da hipoxemia, sem efeitos secundários significativos. No 16.° dia o doente teve alta sem necessidade de oxigénio. Em doentes neuromusculares não intubados, com atelectasia, que não respondam positivamente a tratamentos não invasivos, a introdução intrabronquial de rhDNase pode com segurança ajudar a melhorar a abertura das vias respiratórias. Keywords: Dornase alpha, Neuromuscular diseases, Atelectasis, Palavras-chave: Dornase alfa, Doenças neuromusculares, Atelectasia

Background and Aim. The short, repetitive hypoxaemic episodes observed in obstructive sleep apnoea (OSA) may determine small augmentations in mature red blood cells. It is unknown whether they affect reticulocyte release. This study explored whether the number and degree of maturation of circulating reticulocytes may be altered in OSA, possibly through the effect of erythropoietin. Methods. Fifty male adult patients with suspected OSA, normoxic during wakefulness, were studied. After nocturnal polysomnography, a blood sample was withdrawn for blood cells count, erythropoietin, iron and transferrin determination. Reticulocyte concentration and degree of immaturity [high (H), medium (M), or low (L)] were also determined. Immature reticulocyte fraction (IRF) was calculated as (M+H) percentage of reticulocytes. Results. A wide range of OSA severity was found [apnoea/ hypopnoea index (AHI): 44.3±30.4, range 0.3-105; sleep time spent at oxyhaemoglobin saturation 2% had higher EPO levels (p

Two young boys with Duchenne muscular dystrophy, who had contracted 2009 pandemic influenza A/H1N1 (pH1N1), had been treated with antibiotics and steroids without significant improvement. One of them showed severe scoliosis. After hospitalization chest CT scan revealed extensive pulmonary bilateral segmental atelectasis. Their clinical and radiological findings rapidly improved when a sequential respiratory physiotherapy protocol was adopted that consisted of the application of multiple sessions of high-frequency chest wall oscillations, each one followed by mechanically assisted coughing manoeuvres. The protocol was well tolerated, effective, easy to apply and special positioning was not required. Fifteen days after treatment initiation both patients clinically recovered. This treatment can be very helpful for neuromuscular patients, particularly when scoliosis prevents conventional respiratory physiotherapy. Resumo: Duas crianças do sexo masculino com distrofia muscular de Duchenne que contraíram o vírus da gripe pandémica A/H1N1(pH1N1) de 2009 foram tratados com antibióticos e esteróides sem melhoria significativa.Um deles revelou escoliose severa. Depois da hospitalização, um TAC ao peito revelou uma atelectasia pulmonar segmentar bilateral extensa. Os seus resultados clínicos e radiológicos melhoraram rapidamente quando foi adoptado um tratamento de fisioterapia respiratória sequencial, consistente na aplicação de múltiplas sessões de oscilações torácicas de alta frequência, cada uma seguida por exercícios de tosse mecanicamente assistidos. O tratamento foi bem tolerado, eficaz e fácil de aplicar, sendo que não foi necessário um posicionamento especial. Quinze dias depois do início do tratamento, ambos os pacientes se encontravam clinicamente recuperados. Este tratamento pode ser muito útil em pacientes com doenças neuromusculares, particularmente quando a escoliose impede a fisioterapia respiratória convencional. KEYWORDS: Duchenne muscular dystrophy, High frequency chest wall oscillation, Pandemic H1N1 influenza, Atelectasis, : PALAVRAS-CHAVE, Distrofia muscular de Duchenne, Oscilação torácica de alta frequência, Pandemia de gripe H1N1, Atelectasia

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 patient's 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.

Background: Automatic CPAP has been developed to improve CPAP efficiency and compliance. Continually matching the effective pressure may be associated to more frequent arousals that could disturb sleep. The aim of the present study was to compare sleep architecture after one month’s home therapy with CPAP or with an AutoCPAP device. Methods: Twenty OSAS patients (18 M / 2 F) after polysomnographic study with CPAP titration received either an automatic (AutoSet T, ResMed, Sydney, Australia) or a fixed level CPAP machine in a random, single blind fashion for one month. At the end of the home treatment period polysomnography was repeated while CPAP was administered by the same machine used at home. Results: There was no significant difference between groups in terms of age (50.0 vs 45.5, NS), sex, BMI (38.3 vs 35.1, NS), RDI (45.4 vs 48.0, NS), and CPAP effective level (9.8 vs 10.8, NS). After one month of therapy the correction of sleep respiratory disturbances and of sleep structure was satisfactory in both groups. No difference in any polysomnographic variable or in subjective sleepiness was found at re-evaluation. Conclusions: The results of this study demonstrate that on average CPAP administered by a fixed CPAP machine and by the AutoSet T autoCPAP device has similar effects in improving respiratory function during sleep, nocturnal sleep architecture, and subjective daytime sleepiness after a one-month therapy. As autoCPAP devices are more expensive than fixed CPAP machines, their prescription should be considered only after a clear demonstration of an increase in compliance to treatment by these devices.

Sleep-disordered breathing is common among children with spinal muscular atrophy, but has been hardly studied among adult subjects. Little is known about sleep quality in spinal muscular atrophy. The aims of this study were to evaluate occurrence and characteristics of sleep-disordered breathing and subjective sleep quality among adolescent and adult patients with spinal muscular atrophy type 2 or 3. Twenty patients aged 33.9 ± 15.2 years were studied. They underwent nocturnal cardiorespiratory monitoring, lung and muscular function evaluation, and were administered the Pittsburgh Sleep Quality Index questionnaire. Nineteen patients showed sleep-disordered breathing, with obstructive events in seven subjects and non-obstructive events in the remaining 12. In the latter group, 10 patients showed pseudo-obstructive hypopneas. Patients with non-obstructive sleep-disordered breathing were younger (p = 0.042), had a lower body mass index (p = 0.0001), were more often affected by spinal muscular atrophy type 2 (p = 0.001), and showed worse impairment of respiratory function than patients with obstructive sleep-disordered breathing. Ten patients were classified as poor sleepers and 10 patients good sleepers. In the whole sample, sniff nasal inspiratory pressure proved to be the only independent predictor of sleep quality (p = 0.009). In conclusion, sleep-disordered breathing is common even among adult patients with spinal muscular atrophy type 2 and 3, and may show either obstructive or different types on non-obstructive features. A worse respiratory muscle function is associated to non-obstructive sleep-disordered breathing and poorer sleep quality. Sleep quality should receive greater attention especially in patients with spinal muscular atrophy type 2, who have a poorer respiratory muscle function, as it could affect their quality of life., (© 2024 European Sleep Research Society.)

Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Grazia Crescimanno reports was provided by Italian Union for the Fight against Muscular Dystrophy.

Background: In Duchenne muscular dystrophy (DMD), dysphagia is a common but often overlooked symptom, which may affect quality of life (QoL). Its possible causes are progressive deterioration of muscle groups involved in swallowing function (oropharyngeal, inspiratory muscles) or impairment of autonomic function., Objectives: In adult patients with DMD, we aimed to identify predictors of swallowing-related QoL and to compare swallowing-related QoL at different ages., Methods: Forty-eight patients aged 30.0±6.6 years were enrolled. Questionnaires were administered: the Swallowing Quality of Life questionnaire (SWAL-QOL) for swallowing-related QoL assessment, and the Compass 31 for autonomic symptoms assessment. The Brooke Upper Extremity Scale was used for upper limbs muscular function assessment. Respiratory and muscle function tests were performed, including spirometry, arterial blood gases, polysomnography, maximal inspiratory pressure (MIP), maximal expiratory pressure and sniff nasal inspiratory pressure., Results: An abnormal composite SWAL-QOL score (≤86) was found in 33 patients. Autonomic symptoms were mild, while a severe impairment was shown by the Brooke Upper Extremity Scale. Spirometry and muscle strength tests demonstrated severe alterations, while diurnal and nocturnal blood gases were normal, due to effective use of noninvasive ventilation. Independent predictors of the composite SWAL-QOL score were age, MIP and Compass 31. A MIP < 22 had an accuracy of 92% in predicting altered swallowing-related QoL. The composite SWAL-QOL score was worse in subjects > 30 years old than in younger patients (64.5±19.2 vs 76.6±16.3, p < 0.02), due to worse scores in items pertinent to mental and social functioning; scores in domains pertinent to the physical function were similar in both groups., Conclusions: In adult DMD, swallowing-related QoL, which is altered in most patients, can be predicted by age, inspiratory muscles strength and autonomic dysfunction symptoms. While swallowing function is already altered in young patients, swallowing-related QoL can progressively worsen with advancing age due to psychological and social factors.

Background: Cardiovascular events commonly cause death in amyotrophic lateral sclerosis (ALS) even in patients treated by noninvasive ventilation (NIV)., Objectives: to evaluate autonomic function with the assessment of heart rate variability (HRV) in ALS patients treated by assist pressure control ventilation (APCV) and assist control ventilation (ACV) during sleep., Methods: Consecutive ALS patients underwent one polysomnography during APCV and one during ACV. HRV was analyzed both in the total sleep period (from first stage N1 to last awakening) and in a 5-minute period of stable stage N2. Time domain, frequency domain and nonlinear indexes of HRV were measured., Results: Nineteen patients (age 62.0 ± 8.7, 9F/10 M) were studied. The analysis did not reveal differences in blood gasses between NIV modalities, but a longer expiratory time (3.01±0.6 vs 2.8 ± 0.6 s, respectively APCV vs ACV, p = 0.001) and a lower arousal index (17.5 ± 9.1 vs 23.1 ± 13.9, p = 0.02) during APCV. HRV was indicative of higher vagal activity during APCV, especially in the 5-minute periods. In the total sleep periods, the HRV time domain indexes reflecting parasympathetic activity were positively correlated with the expiratory time and negatively with the inspiratory/expiratory time ratio. Low frequencies were positively, and high frequencies negatively, correlated with inspiratory time. HRV and sleep structure parameters were not correlated, except very low frequencies that were correlated to the arousal index., Conclusions: Respiratory influences on autonomic control can be preserved in ALS. The slower breathing pattern during APCV may help to maintain a higher vagal activity. Through this mechanism, in the long-term APCV could more beneficial to ALS patients than ACV., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time., Methods: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice., Results: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%)., Conclusion: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Treatment of obstructive sleep apnoea (OSA) in adults is evolving, as new therapies have been explored and introduced in clinical practice, while other approaches have been refined or reconsidered. In this European Respiratory Society (ERS) guideline on non-continuous positive airway pressure (CPAP) therapies for OSA, we present recommendations determined by a systematic review of the literature. It is an update of the 2011 ERS statement on non-CPAP therapies, advanced into a clinical guideline. A multidisciplinary group of experts, including pulmonary, surgical, dentistry and ear-nose-throat specialists, methodologists and patient representatives considered the most relevant clinical questions (for both clinicians and patients) relating to the management of OSA. Eight key clinical questions were generated and a systematic review was conducted to identify published randomised clinical trials that answered these questions. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the quality of the evidence and the strength of recommendations. The resulting guideline addresses gastric bypass surgery, custom-made dual-block mandibular advancement devices, hypoglossal nerve stimulation, myofunctional therapy, maxillo-mandibular osteotomy, carbonic anhydrase inhibitors and positional therapy. These recommendations can be used to benchmark quality of care for people with OSA across Europe and to improve outcomes., Competing Interests: Conflicts of Interest: W. Randerath reports personal fees received from Weinmann, Heinen & Löwenstein, Resmed, Inspire, Philips Respironics, and Bioprojet, outside the submitted work. Conflicts of interest: J. Verbraecken reports receiving payments to institution for lectures, presentations, speakers bureaus, manuscript writing or educational events from SomnoMed and Inspire Medical Systems, outside the submitted work. Participation on a Data Safety Monitoring Board or Advisory Board for ResMed Narval, payments to institution, outside the submitted work. Conflicts of interest: C.A.L. de Raaff has nothing to disclose. Conflicts of interest: J. Heder reports grants received from ResMed, outside the submitted work. Lecture fees from Bayer Pharma and Jazz Pharmaceuticals outside the submitted work. Patent filed and granted for Pharmacological therapy in OSA. Participation on a data safety monitoring board or advisory board for DSMB. Conflicts of interest: S. Herkenrath has nothing to disclose. Conflicts of interest: W. Hohenhorst has nothing to disclose. Conflicts of interest: T. Jakob has nothing to disclose. Conflicts of interest: O. Marrone has nothing to disclose. Conflicts of interest: M. Marklund has nothing to disclose. Conflicts of interest: W.T. McNicholas has nothing to disclose. Conflicts of interest: R.L. Morgan has nothing to disclose. Conflicts of interest: J-L. Pépin reports grants and research funds from (payments made to the institutions) Air Liquide Foundation, Agiradom, AstraZeneca, Fisher and Paykel, Mutualia, Philips, Resmed and Vitalaire, outside the submitted work. Consulting fees from: Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz pharmaceutical, Night Balance, Philips, Resmed, and Sefam, outside the submitted work. Conflicts of interest: S. Schiza has nothing to disclose. Conflicts of interest: N. Skoetz reports support for the present manuscript from the European Respiratory Society. Personal payments received from Cochrane outside the submitted work. Conflicts of interest: D. Smyth has nothing to disclose. Conflicts of interest: J. Steier reports receiving grants from the British Lung Foundation, outside the submitted work. Payments of honoraria received from Jazz Pharmaceuticals and Sanofi. Named inventor on pending patent WO2016124739A1. President of the British Sleep Society. Conflicts of interest: T. Tonia acts as an ERS methodologist. Conflicts of interest: W. Trzepizur has nothing to disclose. Conflicts of interest: P-H. van Mechelen has nothing to disclose. Conflicts of interest: P. Wijkstra has nothing to disclose., (Copyright ©The authors 2021.)

Patients with obstructive sleep apnea (OSA) are at increased risk of developing metabolic disease such as diabetes. The effects of positive airway pressure on glycemic control are contradictory. We therefore evaluated the change in glycated hemoglobin (HbA1c) in a large cohort of OSA patients after long-term treatment with positive airway pressure. HbA1c levels were assessed in a subsample of the European Sleep Apnea Database [n=1608] at baseline and at long-term follow up with positive airway pressure therapy (mean 378.9±423.0 days). In a regression analysis, treatment response was controlled for important confounders. Overall, HbA1c decreased from 5.98±1.01% to 5.93±0.98% (p=0.001). Patient subgroups with a more pronounced HbA1c response included patients with diabetes (-0.15±1.02, p=0.019), those with severe OSA baseline (-0.10±0.68, p=0.005), those with morbid obesity (-0.20±0.81, p<0.001). The strongest HbA1c reduction was observed in patients with a concomitant weight reduction >5 kilos (-0.38±0.99, p<0.001). In robust regression analysis, severe OSA (p=0.038) and morbid obesity (p=0.005) at baseline, and weight reduction >5 kilos (p<0.001) during follow up were independently associated with a reduction of HbA1c following PAP treatment. In contrast, PAP treatment alone without weight reduction was not associated with significant Hb1Ac reduction. In conclusion, positive airway pressure therapy is associated with HbA1c reduction in patients with severe OSA, in morbidly obese patients. and most obviously in those with significant weight lost during the follow-up. Our study underlines the importance to combine positive airway pressure use with adjustments in lifestyle to substantially modify metabolic complications in OSA., (© 2021 European Sleep Research Society.)

The bidirectional relationship between sleep disordered breathing and chronic kidney disease (CKD) has recently gained a lot of interest. Several lines of evidence suggest the high prevalence of coexistent obstructive sleep apnea (OSA) in patients with CKD and end-stage renal disease (ESRD). In addition, OSA seems to result in loss of kidney function in some patients, especially in those with cardio-metabolic comorbidities. Treatment of CKD/ESRD and OSA can alter the natural history of each other; still better phenotyping with selection of appropriate treatment approaches is urgently needed. The aim of this narrative review is to provide an update of recent studies on epidemiological associations, pathophysiological interactions, and management of patients with OSA and CKD or ESRD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Comparison of the effects of pressure controlled and volume controlled noninvasive ventilations (NIV) has usually been limited to the degree of improvement in blood gases. We compared sleep quality, abnormal respiratory events, and patient-ventilator asynchronies during administration of pressure controlled continuous mandatory ventilation (PC-CMV) and volume controlled continuous mandatory ventilation (VC-CMV) in subjects with amyotrophic lateral sclerosis naive to NIV after titration aimed at maximally improving nocturnal arterial blood gases., Methods: A crossover evaluation of PC-CMV and VC-CMV was performed in 27 subjects with amyotrophic lateral sclerosis. After baseline polysomnography, ventilators were set in random order so as to warrant similar and satisfactory oxygen saturation and transcutaneous [Formula: see text] in both NIV modalities during day and night. Soon after titration, polysomnography was repeated during administration of each type of NIV., Results: With respect to the baseline night, non-rapid eye movement 3, and rapid eye movement sleep stages increased, and the arousal index decreased during PC-CMV ( P = .005, P = .02, and P = .01, PC-CMV vs VC-CMV, respectively) but not during VC-CMV. The arousal index during NIV was correlated to the peak pressure delivered by the ventilators (ρ = 0.47, P < .001). Few abnormal respiratory events were observed in both NIV modes. Patient-ventilator asynchronies were more frequent during VC-CMV (median [IQR] 20.8 [0.0 - 22.0] vs 31.8 [30.1 - 34.0] no./h, PC-CMV vs VC-CMV; P = .002). Twenty-one subjects declared that they preferred PC-CMV therapy., Conclusions: In the short term, PC-CMV may be a preferred NIV modality to VC-CMV for patients with amyotrophic lateral sclerosis, even when both NIV modes are similarly effective in the correction of hypoventilation. Evaluation of the effectiveness of NIV should not be limited to the assessment of blood gas correction., (Copyright © 2021 by Daedalus Enterprises.)

Excessive daytime sleepiness (EDS) is a symptom of obstructive sleep apnea (OSA) that resolves under treatment with continuous positive airway pressure (CPAP). In some patients, sleepiness persists despite CPAP treatment. We retrospectively analyzed data on subjective residual EDS, assessed as an Epworth Sleepiness Scale score (ESS) >10, in patients from the European Sleep Apnea Database ( n = 4,853, mean age ± SD 54.8 ± 11.8 years, 26.1% females), at baseline and at the first visit (median follow-up: 5 months, interquartile range 3-13). An ESS > 10 occurred in 56% of patients at baseline and in 28.2% of patients at follow-up. Residual EDS was analyzed in 2,190 patients (age: 55.1 ± 12.0 years, 26.1% females) with sleep monitoring data (median follow-up: 3 months, interquartile range 1-15). Sleep studies during CPAP use were obtained in 58% of these patients; EDS was reported by 47.2% of patients at baseline and by 30.3% at follow-up. Residual OSA, defined as an apnea-hypopnea index >10/h, and insufficient CPAP adherence, defined as nightly use <4 h, occurred with similar frequency in patients with and without EDS at follow-up. Prevalence of residual EDS was highest (40%) in patients with a first follow-up visit at 0-3 months, then it was 13-19% in patients with a first follow-up visit after 4 months to 2 years. The change in ESS ( n = 2,190) was weakly correlated with CPAP use (R 2 = 0.023, p < 0.0001). Logistic regression showed that an ESS score >10 at the first follow-up visit was associated directly with ESS at baseline and inversely with duration of follow-up, and CPAP use (R 2 of the model: 0.417). EDS showed heterogeneity in different European countries both at baseline and at the first follow-up visit, suggesting modulation by cultural and lifestyle factors. In conclusion, residual EDS in CPAP-treated OSA occurred in approximately one in four patients at follow-up; its prevalence was highest (40%) in the first 3 months of treatment and subsequently decreased. The finding of residual EDS in a significant percentage of optimally treated OSA patients suggests that wake-promoting agents may be useful, but their indication should be evaluated after at least 3 months of treatment., Competing Interests: MB has no conflict of interest with regard to the submitted work. Outside the work he has the following COI: Honoraria or consultation fees: Bioprojet and Eisai. JV has no conflict of interest with regard to the submitted work. Outside the work he has the following COI: Honoraria or consultation fees: Bioprojet. LG has no conflict of interest with regard to the submitted work. Outside the work he has the following COI: Honoraria or consultation fees: Philips, Resmed, Itamar, Fisher & Paykel, and Astra Zeneca. Research collaboration with Resmed, Desitin, Weinmann, Itamar, and Breas. LG is a co-owner of patents related to pharmacological treatment of OSA. WM has no conflict of interest with regard to the submitted work. Outside the work he has the following COI: Honoraria or consultation fees: Jazz Pharmaceuticals. JP has no conflict of interest with regard to the submitted work. Outside the work he has the following COI: Grants/research support: Resmed, Philips, Fisher and Paykel, Agiradom, Astra Zeneca, Mutualia (research support), Vitalaire Air Liquide Foundation (research support), SEFAM; Honoraria or consultation fees: Resmed, Philips, Agiradom, Astra Zeneca, JAZZ, ITAMAR, SEFAM, Bioprojet. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bonsignore, Pepin, Cibella, Barbera, Marrone, Verbraecken, Saaresranta, Basoglu, Trakada, Bouloukaki, McNicholas, Bailly, Pataka, Kvamme, Hein, Mihaicuta, Grote, Fanfulla and ESADA Study Group.)

Study Objectives: Motor-vehicle crashes are frequent in untreated OSA patients but there is still uncertainty on prevalence as well as physiological or clinical determinants of sleepiness at the wheel (SW) in OSA patients. We assessed determinants of SW or sleepiness related near-miss car accident (NMA) in a group of non-professional drivers with OSA., Methods: A 237 consecutive, treatment-naïve PSG-diagnosed OSA patients (161 males, 53.1 ± 12.6 years) were enrolled. Self-reported SW was assessed by positive answer to the question, "Have you had episodes of falling asleep while driving or episodes of drowsiness at wheel that could interfere with your driving skill in the last year?" Occurrence of NMA in the last 3 years was also individually recorded. Habitual self-reported average sleep time was collected., Results: SW was found in 41.3% of patients but one-quarter of patients with SW did not report excessive daytime sleepiness. Predictors of SW were the following subjective factors: Epworth sleepiness scale score (ESS-OR 1.26; IC 1.1-1.4; p < 0.0001), depressive symptoms (BDI-OR 1.2; IC 1.06-1.18; p < 0.0001) and level of risk exposure (annual mileage-OR 1.9; IC 1.15-3.1; p = 0.007). NMAs were reported by 9.7% of patients, but more frequently by SW + than SW - (22.4% vs. 0.7%; χ 2 31, p < 0.0001). The occurrence of NMAs was significantly associated to ESS, BDI, habitual sleep duration and ODI ( R 2 = 0.41)., Conclusion: SW is not predicted by severity of OSA. Evaluation of risk exposure, assessment of depressive symptoms, and reported NMA should be included in the clinical evaluation, particularly in patients with reduced habitual sleep time and severe nocturnal hypoxia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fanfulla, Pinna, Marrone, D’Artavilla Lupo, Arcovio, Bonsignore and Morrone.)

Obstructive sleep apnoea (OSA) is highly prevalent and is a recognised risk factor for motor vehicle accidents (MVA). Effective treatment with continuous positive airway pressure has been associated with a normalisation of this increased accident risk. Thus, many jurisdictions have introduced regulations restricting the ability of OSA patients from driving until effectively treated. However, uncertainty prevails regarding the relative importance of OSA severity determined by the apnoea-hypopnoea frequency per hour and the degree of sleepiness in determining accident risk. Furthermore, the identification of subjects at risk of OSA and/or accident risk remains elusive. The introduction of official European regulations regarding fitness to drive prompted the European Respiratory Society to establish a task force to address the topic of sleep apnoea, sleepiness and driving with a view to providing an overview to clinicians involved in treating patients with the disorder. The present report evaluates the epidemiology of MVA in patients with OSA; the mechanisms involved in this association; the role of screening questionnaires, driving simulators and other techniques to evaluate sleepiness and/or impaired vigilance; the impact of treatment on MVA risk in affected drivers; and highlights the evidence gaps regarding the identification of OSA patients at risk of MVA., Competing Interests: Conflict of interest: M.R. Bonsignore has nothing to disclose. Conflict of interest: W. Randerath reports grants and personal fees for lectures from Philipps Respironics, Heinen & Löwenstein and Resmed, outside the submitted work. Conflict of interest: S. Schiza has nothing to disclose. Conflict of interest: J. Verbraecken reports grants and personal fees for advisory board work from ResMed and Bioprojet, personal fees for consultancy from Philips, personal fees for lectures from Sanofi, Agfa-Gevaert, Springer and AstraZeneca, grants and personal fees for study participation from Jazz Pharmaceutics, grants and personal fees for lectures from SomnoMed, grants from AirLiquide, Westfalen Medical, Vivisol, Total Care, Medidis, Fisher & Paykel, Wave Medical, OSG, Mediq Tefa, NightBalance, Heinen & Löwenstein, Accuramed, Bekaert Deslee Academy and UCB Pharma, outside the submitted work. Conflict of interest: M.W. Elliott has nothing to disclose. Conflict of interest: R. Riha has nothing to disclose. Conflict of interest: F. Barbe has nothing to disclose. Conflict of interest: I. Bouloukaki has nothing to disclose. Conflict of interest: A. Castrogiovanni has nothing to disclose. Conflict of interest: O. Deleanu has nothing to disclose. Conflict of interest: M. Goncalves has nothing to disclose. Conflict of interest: D. Leger reports grants from grants from Philips (Netherlands), Vanda (USA), Sanofi, Vitalaire International, Merck, Jannsen, Jazz and RYTHM outside the submitted work. Conflict of interest: O. Marrone has nothing to disclose. Conflict of interest: T. Penzel reports grants from Cidelec and Philips, personal fees for consultancy from Heel Pharmaceuticals, personal fees for advisory board work from Bayer, outside the submitted work; and is a shareholder of Advanced Sleep Research, Somnico, Nukute, and The Siestagroup GmbH. Conflict of interest: S. Ryan has nothing to disclose. Conflict of interest: D. Smyth has nothing to disclose. Conflict of interest: C. Turino has nothing to disclose. Conflict of interest: W.T. McNicholas has nothing to disclose., (Copyright ©ERS 2021.)

Objective: In amyotrophic lateral sclerosis (ALS), early recognition of nocturnal hypoventilation (NH) is essential to start noninvasive ventilation (NIV), but nocturnal transcutaneous PCO 2 (PtcCO 2 ) is difficult to monitor. Usefulness of respiratory and muscular function test in the prediction of NH has been explored without distinguishing among ALS phenotypes. We evaluated cross-sectional relationships between functional tests and nocturnal PCO 2 , and the best predictors of NH, separately in patients with spinal and bulbar onset of ALS. Methods : ALS patients candidate to NIV were recruited. Diurnal respiratory and muscular function tests and nocturnal polysomnography with PtcCO 2 monitoring were performed. NH was defined as peak PtcCO 2 >49 mm Hg. Results : Thirty-six patients with spinal and 11 with bulbar onset ALS were included. Nocturnal oxygen saturation and PtcCO 2 , and proportion of subjects with NH were similar in each group (spinal: 50%; bulbar: 45.5%). Significant differences between groups were found in forced vital capacity ( p  = 0.03), maximal inspiratory pressure ( p  = 0.01) and sniff nasal inspiratory pressure (SNIP) ( p  = 0.007), but not in diurnal arterial blood gases. In the spinal group, SNIP and Base Excess (BE) independently predicted nocturnal PtcCO 2 (R 2 0.59, p  < 0.0001). In the bulbar group only SNIP was correlated to PtcCO 2 , but it varied little in relationship to PtcCO 2 changes. Conclusions : Respiratory and muscle function parameters are differently related to NH in ALS patients with spinal and bulbar presentation. SNIP and BE may be helpful to reveal NH in spinal patients, while in bulbar patients no respiratory or muscle function tests may reliably predict NH.

Aims: Arterial hypertension is highly prevalent and difficult to control in patients with obstructive sleep apnea (OSA). High sympathoadrenergic activity is a hallmark physiological phenomenon in OSA. We hypothesized that an antihypertensive drug with inhibitory properties on this activity, such as beta blockers (BBs), may be particularly efficacious in OSA patients., Methods: Hypertensive OSA patients receiving blood pressure-lowing treatment in the European Sleep Apnea Database (ESADA) (n = 5818, 69% men, age 58 ± 11 years, body mass index 33 ± 7 kg/m2, apnea hypopnea index 34 ± 26 events/h) were analyzed. Reported medications [BB, diuretic, renin-angiotensin blocker (RAB), calcium channel blocker (CCB), and centrally acting antihypertensive (CAH)] were classified according to ATC code. Office blood pressure was compared in patients with monotherapy or combination therapy controlling for confounders., Results: Poorly controlled SBP according to the ESC/ESH guidelines was found in 66% of patients. Patients receiving monotherapy with RAB, CCB or CAH had 2.2 (95% CI 1.4-3.0), 3.0 (1.9-4.1) and 3.0 (1.7-4.7) mmHg higher SBP compared with those on BB (adjusted model, P = 0.007, 0.008 and 0.017, respectively). In those with a combination of two antihypertensive drugs, SBP was 5.5 (4.0-7.1), 5.1 (3.7-6.6), 4.3 (2.5-6.1) and 3.1 (1.6-4.6) mmHg higher in those on CCB/RAB, BB/RAB, BB/CCB or diuretic/RAB compared with those on BB/diuretic (adjusted model, P < 0.001, <0.001, 0.018 and 0.036, respectively)., Conclusion: Poorly controlled blood pressure was common in OSA patients with antihypertensive medication. Treatment with BB alone or BB in combination with a diuretic was associated with the lowest systolic pressure in this large clinical cohort., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Obstructive sleep apnea (OSA) has been recognized as a risk factor for cancer mainly through hypoxia, based on studies that did not distinguish among cancer types. The purpose of this review is to discuss the most recent data on epidemiology and pathophysiology of the OSA-cancer association., Recent Findings: According to epidemiological studies, OSA may have different influences on each type of cancer, either increasing or decreasing its incidence and aggressiveness. Time spent with oxygen saturation below 90% appears the polysomnographic variable most strongly associated with unfavorable effects on cancer. Experimental studies support the role of hypoxia as an important risk factor for cancer growth and aggressiveness, especially when it shows an intermittent pattern. These effects are largely mediated by the hypoxia-inducible factor, which controls the synthesis of molecules with effects on inflammation, immune surveillance and cell proliferation. Sleep fragmentation participates in increasing cancer risk. Modulating effects of age remain controversial., Summary: Effects of OSA on cancer may largely vary among neoplastic diseases, both in their magnitude and direction. The worse risk associated with intermittent rather than persistent hypoxia, and the effects of OSA therapy on cancer natural history are still poorly known, and deserve new careful studies.

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/m 2 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Study Objectives: Patients with chronic kidney disease (CKD) often report poor sleep quality, but they commonly exhibit OSA. The aim of this study was to evaluate the influence of OSA severity and of estimated glomerular filtration rate impairment on objective sleep quality in nondialyzed patients with CKD, defined as an estimated glomerular filtration rate <60 mL/min/1.73m²., Methods: Polysomnographic sleep characteristics were compared between patients with (n = 430) and without CKD (n = 6,639) in the European Sleep Apnea Database cohort. Comparisons were repeated in 375 patients with CKD and 375 control patients without CKD matched for sleep center, age, sex, and AHI, and in 310 matched CKD and non-CKD patients without psychiatric disturbances., Results: Among all patients with and without CKD, total sleep time was similar but sleep stage N1 (median 8.7% [IQR 4.8-18.0] vs 6.7% [3.6-12.7], respectively) and sleep stage R (12.6% [6.8-17.7] vs 14.2% [8.8-19.8], respectively) significantly differed (P < .0001). No difference in sleep characteristics was observed between matched patients either with or without psychiatric disturbances. After subdividing the matched patients according to AHI tertile (<25, ≥25 to <49, and ≥49 events/h) and estimated glomerular filtration rate (≥60, 45 to <60, <45 mL/min/1.73m²), we found a significant effect of AHI on sleep stages N2, N3, and R (P < .001), but there was no effect of CKD., Conclusions: In nondialyzed patients with CKD, objective sleep quality is influenced similarly by AHI as in patients without CKD but is not affected by CKD severity. Previously reported poor sleep quality in CKD may partly result from the high prevalence of OSA in CKD., (© 2020 American Academy of Sleep Medicine.)

Study Objectives: The association of mild obstructive sleep apnea (OSA) with important clinical outcomes remains unclear. We aimed to investigate the association between mild OSA and systemic arterial hypertension (SAH) in the European Sleep Apnea Database cohort., Methods: In a multicenter sample of 4,732 participants, we analyzed the risk of mild OSA (subclassified into 2 groups: mild AHI 5-<11/h (apnea-hypopnea index [AHI], 5 to <11 events/h) and mild AHI 11-<15/h (AHI, ≥11 to <15 events/h) compared with nonapneic snorers for prevalent SAH after adjustment for relevant confounding factors including sex, age, smoking, obesity, daytime sleepiness, dyslipidemia, chronic obstructive pulmonary disease, type 2 diabetes, and sleep test methodology (polygraphy or polysomnography)., Results: SAH prevalence was higher in the mild AHI 11-<15/h OSA group compared with the mild AHI 5-<11/h group and nonapneic snorers (52% vs 45% vs 30%; P < .001). Corresponding adjusted odds ratios for SAH were 1.789 (mild AHI 11-<15/h ; 95% confidence interval [CI], 1.49-2.15) and 1.558 (mild AHI 5-<11/h ; 95%, CI, 1.34-1.82), respectively (P < .001). In sensitivity analysis, mild AHI 11-<15/h OSA remained a significant predictor for SAH both in the polygraphy (odds ratio, 1.779; 95% CI, 1.403-2.256; P < .001) and polysomnography groups (odds ratio, 1.424; 95% CI, 1.047-1.939; P = .025)., Conclusions: Our data suggest a dose-response relationship between mild OSA and SAH risk, starting from 5 events/h in polygraphy recordings and continuing with a further risk increase in the 11- to <150-events/h range. These findings potentially introduce a challenge to traditional thresholds of OSA severity and may help to stratify participants with OSA according to cardiovascular risk., (© 2020 American Academy of Sleep Medicine.)

Objective: In stable neuromuscular patients under long-term non-invasive ventilation (NIV), subjective sleep quality may be predicted by chronic hypoventilation, as assessed by base excess (BE), and %N3 sleep stage duration. In this study, we explored how other variables, closely associated with self-reported health complaints, contributed to subjective sleep quality in adult patients with Duchenne muscular dystrophy (DMD)., Methods: This is a secondary analysis of a quality of life study in 48 adult DMD patients under NIV therapy, with little evidence of residual hypoventilation. Subjective sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI). A PSQI score >5 was considered indicative of poor sleep quality. Several other symptoms were evaluated: sleepiness, by the Epworth Sleepiness Scale (ESS); depression and anxiety, by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale (HADS-A and HADS-D); autonomic symptoms, by the Composite Autonomic Symptom Score 31; pain, by the Numeric Pain Rating Scale (NPRS); and fatigue, by the Fatigue Severity Scale (FSS)., Results: Mean PSQI was 6.1 ± 2.9. Abnormal scores were found for NPRS in 40, for HADS-A in 10 and for FSS in 24 subjects. The NPRS, HADS-A and FSS scores and the N3 sleep stage, independently predicted PSQI (R 2  = 0.47, p < 0.0001)., Conclusions: In adult DMD patients, pain, fatigue and anxiety may have a prominent influence on subjective sleep quality. Improvement of sleep quality may be of utmost importance in DMD, as it may ameliorate quality of life and extend its benefits to cardiovascular morbidity and life expectancy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In obstructive sleep apnea, patients' sleep is fragmented leading to excessive daytime sleepiness and co-morbidities like arterial hypertension. However, traditional metrics are not always directly correlated with daytime sleepiness, and the association between traditional sleep quality metrics like sleep duration and arterial hypertension is still ambiguous. In a development cohort, we analysed hypnograms from mild (n = 209), moderate (n = 222) and severe (n = 272) obstructive sleep apnea patients as well as healthy controls (n = 105) from the European Sleep Apnea Database. We assessed sleep by the analysis of two-step transitions depending on obstructive sleep apnea severity and anthropometric factors. Two-step transition patterns were examined for an association to arterial hypertension or daytime sleepiness. We also tested cumulative distributions of wake as well as sleep-states for power-laws (exponent α) and exponential distributions (decay time τ) in dependency on obstructive sleep apnea severity and potential confounders. Independent of obstructive sleep apnea severity and potential confounders, wake-state durations followed a power-law distribution, while sleep-state durations were characterized by an exponential distribution. Sleep-stage transitions are influenced by obstructive sleep apnea severity, age and gender. N2 → N3 → wake transitions were associated with high diastolic blood pressure. We observed higher frequencies of alternating (symmetric) patterns (e.g. N2 → N1 → N2, N2 → wake → N2) in sleepy patients both in the development cohort and in a validation cohort (n = 425). In conclusion, effects of obstructive sleep apnea severity and potential confounders on sleep architecture are small, but transition patterns still link sleep fragmentation directly to obstructive sleep apnea-related clinical outcomes like arterial hypertension and daytime sleepiness., (© 2019 European Sleep Research Society.)

Obstructive sleep apnea is associated with excessive daytime sleepiness in about 50% of cases, and with increased risk of driving accidents. Treatment with continuous positive airway pressure effectively decreases such risk, but compliance with continuous positive airway pressure treatment is often suboptimal. According to the European Union Directive on driving risk, retention of a driving license in patients with obstructive sleep apnea requires assessment of sleepiness and adherence to continuous positive airway pressure treatment, but there remains uncertainty on the optimal methods to assess sleepiness on a large scale., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Prevalence of both chronic kidney disease (CKD) and obstructive sleep apnea (OSA) is continuously increasing. Moreover, the prevalence of OSA increases as kidney function declines and is higher among patients with end-stage renal disease (ESRD). In addition, OSA is recognized as a potential nontraditional risk factor for development and progression of CKD. Continuous positive airway pressure (CPAP) plays a pivotal role in the management of OSA, eliminating patients' symptoms and improving their quality of life. Recent studies suggested that CPAP treatment may have beneficial effects on kidney function among patients with OSA. This narrative review summarizes the existing knowledge on the association between CKD and OSA, with emphasis on the epidemiology, the pathophysiology of the development of CKD in OSA and vice versa, as well as the effect of CPAP on renal function., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The aim of this study was to evaluate quality of life (QoL) and its possible determinants in patients affected by Duchenne muscular dystrophy (DMD) in late stages of their disease, when non-invasive ventilation (NIV) is already established. Forty-eight DMD patients who were treated by NIV were enrolled. QoL was assessed by the Individualized Neuromuscular Quality of Life (INQoL) questionnaire. By this questionnaire, different aspects of QoL were assessed on a scale from 0 (best) to 100 (worst). In addition, motor and respiratory function tests were performed. Dysautonomia symptoms, sleep quality, sleepiness, anxiety, and depression were evaluated by validated questionnaires. The global INQoL score was 42.8 ± 19, reflecting a moderately altered QoL. The physical health domain was heavily impaired while the psychosocial domain was only mildly affected. Independence had the highest scores (81.1 ± 21.2), proving to be the most affected item. On multivariate analysis, maximal inspiratory pressure and Pittsburgh Sleep Quality Index, but not daily duration of NIV therapy, predicted global INQoL score. Respiratory impairment and sleep quality were independent predictors of poor QoL in DMD patients under NIV. Sleep quality in DMD is often disregarded, while it should be carefully addressed to ensure a better QoL., (Copyright © 2019 Elsevier B.V. All rights reserved.)