Ventilatory Burden as a Measure of Obstructive Sleep Apnea Severity Is Predictive of Cardiovascular and All-Cause Mortality.

Rationale: The apnea-hypopnea index (AHI), used for the diagnosis of obstructive sleep apnea, captures only the frequency of respiratory events and has demonstrable limitations. Objectives: We propose a novel automated measure, termed "ventilatory burden" (VB), that represents the proportion of overnight breaths with less than 50% normalized amplitude, and we show its ability to overcome limitations of AHI. Methods: Data from two epidemiological cohorts (EPISONO [Sao Paolo Epidemiological Study] and SHHS [Sleep Heart Health Study]) and two retrospective clinical cohorts (DAYFUN; New York University Center for Brain Health) were used in this study to 1) derive the normative range of VB, 2) assess the relationship between degree of upper airway obstruction and VB, and 3) assess the relationship between VB and all-cause and cardiovascular disease (CVD) mortality with and without hypoxic burden that was derived using an in-house automated algorithm. Measurements and Main Results: The 95th percentiles of VB in asymptomatic healthy subjects across the EPISONO and the DAYFUN cohorts were 25.2% and 26.7%, respectively (median [interquartile range], VBEPISONO, 5.5 [3.5-9.7]%; VBDAYFUN, 9.8 [6.4-15.6]%). VB was associated with the degree of upper airway obstruction in a dose-response manner (VBuntreated, 31.6 [27.1]%; VBtreated, 7.2 [4.7]%; VBsuboptimally treated, 17.6 [18.7]%; VBoff-treatment, 41.6 [18.1]%) and exhibited low night-to-night variability (intraclass correlation coefficient [2,1], 0.89). VB was predictive of all-cause and CVD mortality in the SHHS cohort before and after adjusting for covariates including hypoxic burden. Although AHI was predictive of all-cause mortality, it was not associated with CVD mortality in the SHHS cohort. Conclusions: Automated VB can effectively assess obstructive sleep apnea severity, is predictive of all-cause and CVD mortality, and may be a viable alternative to the AHI.

Brazilian Thoracic Association Consensus on Sleep-disordered Breathing.

Sleep is essential for the proper functioning of all individuals. Sleep-disordered breathing can occur at any age and is a common reason for medical visits. The objective of this consensus is to update knowledge about the main causes of sleep-disordered breathing in adult and pediatric populations, with an emphasis on obstructive sleep apnea. Obstructive sleep apnea is an extremely prevalent but often underdiagnosed disease. It is often accompanied by comorbidities, notably cardiovascular, metabolic, and neurocognitive disorders, which have a significant impact on quality of life and mortality rates. Therefore, to create this consensus, the Sleep-Disordered Breathing Department of the Brazilian Thoracic Association brought together 14 experts with recognized, proven experience in sleep-disordered breathing.

Prevalence of upper airway resistance syndrome in the São Paulo Epidemiologic Sleep Study.

OBJECTIVE: To establish the prevalence of upper airway resistance syndrome (UARS) according to different diagnostic criteria and evaluate its epidemiological characteristics in a representative sample of a large urban center. METHODS: This was a single-center evaluation involving volunteers from EPISONO, an epidemiological study focused on sleep disturbances and related factors in adults from São Paulo, Brazil in 2007. RESULTS: Considering the diagnostic criteria for UARS to be an apnea-hypopnea index of <5 events/h, minimum SpO2 ≥ 92%, the presence of airflow limitation during sleep for ≥5% of total sleep time, and daytime symptoms (sleepiness and/or fatigue), we observed a prevalence of the condition of 3.1% (4.4% in women and 1.5% in men). CONCLUSIONS: Although the diagnostic criteria for UARS, or even its existence as a syndrome, are still a subject of debate in the literature, the findings from this epidemiological study highlights UARS as a non-hypoxic sleep-disordered breathing condition with a significant prevalence in the general population, being more frequent among female young adults.

Brazilian Thoracic Association Consensus on Sleep-disordered Breathing / Consenso em Distúrbios Respiratórios do Sono da Sociedade Brasileira de Pneumologia e Tisiologia

ABSTRACT Sleep is essential for the proper functioning of all individuals. Sleep-disordered breathing can occur at any age and is a common reason for medical visits. The objective of this consensus is to update knowledge about the main causes of sleep-disordered breathing in adult and pediatric populations, with an emphasis on obstructive sleep apnea. Obstructive sleep apnea is an extremely prevalent but often underdiagnosed disease. It is often accompanied by comorbidities, notably cardiovascular, metabolic, and neurocognitive disorders, which have a significant impact on quality of life and mortality rates. Therefore, to create this consensus, the Sleep-Disordered Breathing Department of the Brazilian Thoracic Association brought together 14 experts with recognized, proven experience in sleep-disordered breathing.

RESUMO O sono é essencial para o adequado funcionamento de todos os indivíduos. Os distúrbios respiratórios do sono ocorrem em todas as faixas etárias, constituindo motivo frequente de consulta médica. O objetivo deste consenso foi atualizar os conhecimentos sobre os principais distúrbios respiratórios do sono tanto na população adulta quanto na pediátrica, com ênfase na apneia obstrutiva do sono. A apneia obstrutiva do sono é uma doença extremamente prevalente, porém frequentemente subdiagnosticada. Associa-se frequentemente a uma série de comorbidades, notadamente cardiovasculares, metabólicas e neurocognitivas, que impactam significativamente na qualidade de vida e na mortalidade. Por conta disso, o Departamento de Distúrbios Respiratórios do Sono da Sociedade Brasileira de Pneumologia e Tisiologia reuniu 14 especialistas com reconhecida e comprovada experiência em distúrbios respiratórios do sono para a elaboração deste documento.

Comorbid Insomnia and Sleep Apnea: mechanisms and implications of an underrecognized and misinterpreted sleep disorder.

Sleep-disordered breathing (SDB) and insomnia have long been recognized as important sleep disrupters often associated with increased morbidity and mortality. Although they are often seen as divergent conditions, mainly because their cardinal symptoms (excessive daytime sleepiness, and sleep loss) differ, these two sleep disorders present with many common symptoms, which may hinder diagnosis and treatment. In addition to possible bidirectional pathways between SDB and insomnia, other factors such as circadian timing may play a role. In this paper, we review the mechanisms, differential clinical aspects, and implications of Comorbid Insomnia and Sleep Apnea, sometimes termed COMISA.

Long term oral appliance therapy decreases stress symptoms in patients with upper airway resistance syndrome.

STUDY OBJECTIVES: To evaluate the long-term effects of a mandibular advancement device (MAD) on stress symptoms and cognitive function in patients with upper airway resistance syndrome (UARS) compared with placebo. METHODS: This study was a randomized placebo-controlled clinical trial. Thirty UARS patients were randomized into 2 groups: placebo and MAD groups. UARS criteria were the presence of sleepiness (Epworth Sleepiness Scale ≥ 10) and/or fatigue (Modified Fatigue Impact Scale ≥ 38) associated with an apnea-hypopnea index ≤ 5 events/h and a respiratory disturbance index > 5 events/h of sleep, and/or flow limitation in more than 30% of total sleep time. All patients completed the Rey Auditory-Verbal Learning Test, the Logical Memory test, the Stroop Color Test, the Trail Making Test, the Digit Symbol Substitution Test, and Inventory of Stress Symptoms. Cognition protocol was defined based on the most used neuropsychological tests in the literature. Evaluations were performed before and after 1.5 years of treatment. RESULTS: Mean adherence to placebo and to MAD was 6.6 ± 2.6 and 6.1 ± 2.4 h/night, respectively. Side effects reported by MAD group were minor and short-term. There was no statistically significant difference in Rey Auditory-Verbal Learning Test, Logical Memory test, Stroop Color Test, Trail Making Test, and Digit Symbol Substitution Test before and after 1.5 years of treatment in both groups. Inventory of Stress Symptoms score decreased at the alert phase and the resistance phase after 1.5 years of MAD treatment compared to the placebo. CONCLUSIONS: Mandibular advancement devices were effective in decreasing stress symptoms in UARS patients after 1.5 years of treatment. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Efficacy of Oral Appliance for Upper Airway Resistance Syndrome; URL: https://clinicaltrials.gov/ct2/show/record/NCT02636621; Identifier: NTC02636621.

Long-Term Oral Appliance Therapy Improves Daytime Function and Mood in Upper Airway Resistance Syndrome Patients.

Objectives: To evaluate the long-term effects of an oral appliance on clinical symptoms, respiratory sleep parameters, sleep quality, and sustained attention in patients with upper airway resistance syndrome (UARS) were compared with placebo. Methods: This study was a randomized placebo-controlled clinical trial. Thirty UARS patients were randomized in two groups: placebo and mandibular advancement device (MAD) groups. UARS criteria were presence of sleepiness (Epworth Sleepiness Scale ≥ 10) and/or fatigue (Modified Fatigue Impact Scale ≥ 38) associated with an apnea/hypopnea index ≤ 5 and a respiratory disturbance index (RDI) > 5 events/hour of sleep, and/or flow limitation in more than 30% of total sleep time. All patients completed the Pittsburgh Sleep Quality Index (PSQI), the Functional Outcomes of Sleep Questionnaire, the Beck Anxiety and Depression Inventories, underwent full-night polysomnography, multiple sleep latency test, and Psychomotor Vigilance Test (PVT). Evaluations were performed before and after 1.5 years of treatment. Results: RDI, number of respiratory effort-related arousal, percentage of total sleep time with flow limitation, and arousal index significantly decreased after 1.5 years of MAD treatment. PSQI total score improved, severity of depression symptoms decreased, and mean reaction time in the PVT, based on the first measurement taken at 8:00 am, significantly decreased (p = .03) at the end of the protocol. Conclusions: The MAD was effective in decreasing respiratory events in UARS patients. For UARS, 1.5 years of oral appliance therapy also improved sleep quality and sustained attention, and decreased the severity of depression symptoms. Clinical Trial: Efficacy of Oral Appliance for Upper Airway Resistance Syndrome: Randomized, Parallel, Placebo-Controlled Study, NCT02636621.

An Official American Thoracic Society Workshop Report: Noninvasive Identification of Inspiratory Flow Limitation in Sleep Studies.

This report summarizes the proceedings of the American Thoracic Society Workshop on the Noninvasive Identification of Inspiratory Flow Limitation in Sleep Studies held on May 16, 2015, in Denver, Colorado. The goal of the workshop was to discuss methods for standardizing the scoring of flow limitation from nasal cannula pressure tracings. The workshop began with presentations on the physiology underlying flow limitation, existing methods of scoring flow limitation, the effects of signal acquisition and filtering on flow shapes, and a review of the literature examining the adverse outcomes related to flow limitation. After these presentations, the results from online scoring exercises, which were crowdsourced to workshop participants in advance of the workshop, were reviewed and discussed. Break-out sessions were then held to discuss potential algorithms for scoring flow limitation. Based on these discussions, subsequent online scoring exercises, and webinars after the workshop, a consensus-based set of recommendations for a scoring algorithm for flow limitation was developed. Key conclusions from the workshop were: (1) a standardized and automated approach to scoring flow limitation is needed to provide a metric of nonepisodic elevated upper airway resistance, which can then be related to clinical outcomes in large cohorts and patient groups; (2) at this time, the most feasible method for standardization is by proposing a consensus-based framework, which includes scoring rules, developed by experts (3) hardware and software settings of acquisition devices, including filter settings, affect the shape of the flow curve, and should be clearly specified; and (4) a priority for future research is the generation of an open-source, expert-derived training set to encourage and support validation of automated flow limitation scoring algorithms.

Sleep continuity is positively correlated with sleep duration in laboratory nighttime sleep recordings.

Sleep duration varies widely across individuals and appears to be trait-like. Differences in the stability of underlying sleep processes may underlie this phenomenon. To investigate underlying mechanisms, we examined the relationship between sleep duration and sleep continuity in baseline polysomnography (PSG) recordings from three independently collected datasets: 1) 134 healthy controls (ages 37 ± 13 years) from the São Paulo Epidemiologic Sleep Study, who spent one night in a sleep laboratory, 2) 21 obstructive sleep apnea (OSA) patients who were treated with continuous positive airway pressure for at least 2 months (45 ± 12 years, respiratory disturbance index <15), who spent one night in a sleep laboratory with previous experience of multiple PSG studies, and 3) 62 healthy controls (28 ± 6 years) who, as part of larger experiments, spent 2 consecutive nights in a sleep laboratory. For each dataset, we used total sleep time (TST) to separate subjects into those with shorter sleep (S-TST) and those with longer sleep (L-TST). In all three datasets, survival curves of continuous sleep segments showed greater sleep continuity in L-TST than in S-TST. Correlation analyses with TST as a continuous variable corroborated the results; and the results also held true after controlling for age. There were no significant differences in baseline waking performance and sleepiness between S-TST and L-TST. In conclusion, in both healthy controls and treated OSA patients, sleep continuity was positively correlated with sleep duration. These findings suggest that S-TST may differ from L-TST in processes underlying sleep continuity, shedding new light on mechanisms underlying individual differences in sleep duration.

Upper Airway Resistance Syndrome Patients Have Worse Sleep Quality Compared to Mild Obstructive Sleep Apnea.

PURPOSE: To compare sleep quality and sustained attention of patients with Upper Airway Resistance Syndrome (UARS), mild Obstructive Sleep Apnea (OSA) and normal individuals. METHODS: UARS criteria were presence of excessive daytime sleepiness (Epworth Sleepiness Scale-ESS-≥ 10) and/or fatigue (Modified Fatigue Impact Scale-MFIS-≥ 38) associated to Apnea/hypopnea index (AHI) ≤ 5 and Respiratory Disturbance Index (RDI) > 5 events/hour of sleep or more than 30% of total sleep time with flow limitation. Mild OSA was considered if the presence of excessive daytime sleepiness (ESS ≥ 10) and/or fatigue (MFIS ≥ 38) associated to AHI ≥ 5 and ≤ 15 events/hour. "Control group" criteria were AHI < 5 events/hour and RDI ≤ 5 events/hour and ESS ≤ 9, without any sleep, clinical, neurological or psychiatric disorder. 115 individuals (34 UARS and 47 mild OSA patients and 34 individuals in "control group"), adjusted for age, gender, body mass index (BMI) and schooling years, performed sleep questionnaires and sustained attention evaluation. Psychomotor Vigilance Task (PVT) was performed five times (each two hours) from 8 a.m. to 4 p.m. RESULTS: UARS patients had worse sleep quality (Functional Outcomes of Sleep Questionnaire-FOSQ-and Pittsburgh Sleep Quality Index-PSQI: p < 0.05) and more fatigue than mild OSA patients (p = 0.003) and scored significantly higher in both Beck inventories than "control group" (p < 0.02). UARS patients had more lapses early in the morning (in time 1) compared to the results in the afternoon (time 5) than mild OSA (p = 0.02). Mild OSA patients had more lapses in times 2 than in time 5 compared to "control group" (p = 0.04). CONCLUSIONS: UARS patients have a worse sleep quality, more fatigue and a worse early morning sustained attention compared to mild OSA. These last had a worse sustained attention than controls.

Musculoskeletal Pain as a Marker of Health Quality. Findings from the Epidemiological Sleep Study among the Adult Population of São Paulo City.

BACKGROUND: We are witnessing the growth of urban populations, particularly in the developing world. São Paulo, the largest city in South America, continues to grow, and this growth is dramatically effecting the environment and human health. The aim of this study was to estimate the point prevalence of chronic pain in São Paulo city dwellers and to explore the influence of aspects related to urbanicity. METHODS: A two-stage cluster randomized sample included 1100 individuals of the city of Sao Paulo, representing the population proportionally in terms of gender, age and social classes in 2007. For this observational cross-sectional study, the household sample was interviewed using validated questionnaires for sociodemographic aspects, the Beck inventories for anxiety and depression, the WHOQoL-REF for quality of life, the Chalder Fatigue Scale. Musculoskeletal pain was defined as diffuse pain or pain located in the back, joints or limbs. Data regarding sleep complaints and polysomnography were obtained from the Epidemiologic Sleep Study conducted in São Paulo city in 2007. RESULTS: The prevalence estimate of chronic musculoskeletal pain was approximately 27%, with a female/male ratio of approximately 2.6/1. The predictors were being in the age-range of 30-39 years, low socioeconomic and schooling levels, obesity, sedentarism, fatigue, non-restorative sleep, daytime sleepiness, poor sleep quality, poor life quality, anxiety and depression symptoms. Psychological wellbeing was the main discriminator between responders with chronic musculoskeletal pain and the controls, followed by depression for the participants with poor psychological wellbeing, and fatigue, for the remaining ones. Insomnia syndrome was the third-level discriminator for those with fatigue, whereas sleep quality for those without fatigue. CONCLUSIONS: Musculoskeletal pain was frequently reported by São Paulo city dwellers and its correlates with psychological and sleep aspects are suggestive of a response to urbanicity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00596713.

Treatment of upper airway resistance syndrome in adults: Where do we stand?

OBJECTIVE: To evaluate the available literature regarding Upper Airway Resistance Syndrome (UARS) treatment. METHODS: Keywords "Upper Airway Resistance Syndrome," "Sleep-related Breathing Disorder treatment," "Obstructive Sleep Apnea treatment" and "flow limitation and sleep" were used in main databases. RESULTS: We found 27 articles describing UARS treatment. Nasal continuous positive airway pressure (CPAP) has been the mainstay therapy prescribed but with limited effectiveness. Studies about surgical treatments had methodological limitations. Oral appliances seem to be effective but their efficacy is not yet established. CONCLUSION: Randomized controlled trials with larger numbers of patients and long-term follow-up are important to establish UARS treatment options.

Treatment of obstructive sleep apnea syndrome associated with stroke.

The association between sleep-disordered breathing and stroke has been a subject of increased interest and research. Obstructive sleep apnea (OSA) is an important risk factor for stroke incidence and mortality. Moreover, OSA is a common clinical outcome after stroke, directly influencing the patient's recovery. The treatment of choice for OSA is positive airway pressure (PAP) support and the PAP appliance is considered the most recommended clinical management for the treatment of patients with cardiovascular complications. However, the implementation of PAP in stroke patients remains a challenge, considering the increased frequency of motor and language impairments associated with the cerebrovascular event. In the present study, we reviewed the main findings describing the association between stroke and OSA treatment with continuous positive airway pressure. We also discussed the types of OSA treatment, the different options and indications of PAP treatment, PAP adherence and the clinical outcomes after treatment.

New insights on the pathophysiology of inspiratory flow limitation during sleep.

INTRODUCTION: Inspiratory flow limitation (IFL) is defined as a "flattened shape" of inspiratory airflow contour detected by nasal cannula pressure during sleep and can indicate increased upper airway resistance especially in mild sleep-related breathing disorders (SRBD). The objective of this study was to investigate the association between upper airway abnormalities and IFL in patients with mild SRBD. METHODS: This study was derived from a general population study consisting of selected individuals with apnea-hypopnea index (AHI) below 5 events/h of sleep, ("no obstructive sleep apnea" group) and individuals with AHI between 5 and 15 events/h ("mild obstructive sleep apnea" group). A total of 754 individuals were divided into four groups: group 1: AHI <5/h and <30 % of total sleep time (TST) with IFL (515 individuals), group 2: AHI <5/h and >30 % of TST with IFL (46 individuals), group 3: AHI: 5-15/h and <30 % of TST with IFL (168 individuals), and group 4: AHI: 5-15/h and >30 % of TST with IFL (25 individuals). RESULTS: Individuals with complains of oral breathing demonstrated a risk 2.7-fold larger of being group 4 compared with group 3. Abnormal nasal structure increased the chances of being in group 4 3.2-fold in comparison to group 1. Individuals with voluminous lateral wall demonstrated a risk 4.2-fold larger of being group 4 compared with group 3. CONCLUSION: More than 30 % of TST with IFL detected in sleep studies was associated with nasal and palatal anatomical abnormalities in mild SRBD patients.

Inspiratory flow limitation in a normal population of adults in São Paulo, Brazil.

STUDY OBJECTIVES: Inspiratory flow limitation (IFL) during sleep occurs when airflow remains constant despite an increase in respiratory effort. This respiratory event has been recognized as an important parameter for identifying sleep breathing disorders. The purpose of this study was to investigate how much IFL normal individuals can present during sleep. DESIGN: Cross-sectional study derived from a general population sample. SETTING: A "normal" asymptomatic sample derived from the epidemiological cohort of São Paulo. PATIENTS AND PARTICIPANTS: This study was derived from a general population study involving questionnaires and nocturnal polysomnography of 1,042 individuals. A subgroup defined as a nonsymptomatic healthy group was used as the normal group. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All participants answered several questionnaires and underwent full nocturnal polysomnography. IFL was manually scored, and the percentage of IFL of total sleep time was considered for final analysis. The distribution of the percentage of IFL was analyzed, and associated factors (age, sex, and body mass index) were calculated. There were 95% of normal individuals who exhibited IFL during less than 30% of the total sleep time. Body mass index was positively associated with IFL. CONCLUSIONS: Inspiratory flow limitation can be observed in the polysomnography of normal individuals, with an influence of body weight on percentage of inspiratory flow limitation. However, only 5% of asymptomatic individuals will have more than 30% of total sleep time with inspiratory flow limitation. This suggests that only levels of inspiratory flow limitation > 30% be considered in the process of diagnosing obstructive sleep apnea in the absence of an apnea-hypopnea index > 5 and that < 30% of inspiratory flow limitation may be a normal finding in many patients.

The human leucocyte antigen DQB1*0602 allele is associated with electroencephelograph differences in individuals with obstructive sleep apnoea syndrome.

Human leucocyte antigen (HLA) DQB1*0602 allele, a well-known genetic risk factor for narcolepsy, has been associated with sleep parameters in healthy subjects. We aimed to assess the association of this allele with daytime sleepiness and altered sleep electroencephalogram characteristics in the general population and in patients with obstructive sleep apnoea syndrome (OSAS). Eight hundred and ninety-four individuals from the Epidemiologic Study of Sleep were genotyped for the HLA DQB1*0602 allele. Full-night polysomnography was performed, and daytime sleepiness was analysed according to the Epworth Sleepiness Scale. HLA-DQB1*0602 allele-positive and -negative subjects in the general population, as well as in patients with OSAS, exhibited similar sleep parameters and levels of daytime sleepiness. However, spectral analysis showed that allele-positive individuals with OSAS exhibited higher theta power during sleep Stage 1 (P < 0.05) in occipital derivations, and lower delta power during sleep Stages 1 and 2 (P < 0.01) compared with individuals negative for the allele, even after correction for potential confounders as age, sex, body mass index and European ancestry. No significant differences in the electroencephalogram variables were found in individuals without OSAS. The data highlight the HLA-DQB1*0602 as a potential genetic factor influencing sleep physiology in individuals diagnosed with OSAS.