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.

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.

Using craniofacial characteristics to predict optimum airway pressure in obstructive sleep apnea treatment / Uso de características craniofaciais para predizer a pressão ideal nas vias aéreas notratamento da apneia obstrutiva do sono

Abstract Introduction: Manual titration is the gold standard to determinate optimal continuous positive airway pressure, and the prediction of the optimal pressure is important to avoid delays in prescribing a continuous positive airway pressure treatment. Objective: To verify whether anthropometric, polysomnographic, cephalometric, and upper airway clinical assessments can predict the optimal continuous positive airway pressure setting for obstructive sleep apnea patients. Methods: Fifty men between 25 and 65 years, with body mass indexes of less than or equal to 35 kg/m2 were selected. All patients had baseline polysomnography followed by cephalometric and otolaryngological clinical assessments. On a second night, titration polysomnography was carried out to establish the optimal pressure. Results: The average age of the patients was 43 ± 12.3 years, with a mean body mass index of 27.1 ± 3.4 kg/m2 and an apnea-hypopnea index of 17.8 ± 10.5 events per hour. Smaller mandibular length (p = 0.03), smaller atlas-jaw distance (p = 0.03), and the presence of a Mallampati III and IV (p = 0.02) were predictors for higher continuous positive airway pressure. The formula for the optimal continuous positive airway pressure was: 17.244 − (0.133 × jaw length) + (0.969 × Mallampati III and IV classification) − (0.926 × atlas-jaw distance). Conclusion: In a sample of male patients with mild-to-moderate obstructive sleep apnea, the optimal continuous positive airway pressure was predicted using the mandibular length, atlas-jaw distance and Mallampati classification.

Resumo Introdução: A titulação manual é o padrão-ouro para determinar a pressão ideal para o tratamento com a pressão positiva contínua nas vias aéreas; e a predição da pressão ideal é importante para evitar retardos na sua prescrição. Objetivo: Verificar se as avaliações clínicas antropométricas, polissonográficas, cefalométricas e das vias aéreas superiores podem predizer a configuração ideal da pressão do aparelho de pressão positiva contínua nas vias aéreas para pacientes com apneia obstrutiva do sono. Método: Foram selecionados 50 homens entre 25 e 65 anos, com índice de massa corporal menor ou igual a 35 kg/m2. Todos os pacientes fizeram polissonografia basal, seguida de avaliações clínicas cefalométricas e otorrinolaringológicas. Na segunda noite, foi feita polissonografia de titulação para estabelecer a pressão ideal. Resultados: A média de idade dos pacientes foi de 43 ± 12,3 anos, com índice de massa corporal médio de 27,1 ± 3,4 kg/m2 e índice de apneia-hipopneia de 17,8 ± 10,5 eventos por hora. Menor comprimento mandibular (p = 0,03), menor distância atlas-maxila (p = 0,03) e a presença de Mallampati III e IV (p = 0,02) foram preditores de pressão mais elevada. A fórmula para a pressão positiva contínua nas vias aéreas foi: 17,24 - (0,133 × comprimento da mandíbula) + (0,969 × classificação de Mallampati III e IV) - (0,926 × distância atlas-mandíbula). Conclusão: Em uma amostra de homens com apneia obstrutiva do sono leve a moderada, a pressão positiva contínua nas vias aéreas foi predita com o comprimento mandibular, a distância atlas-mandíbula e a classificação de Mallampati.

Using craniofacial characteristics to predict optimum airway pressure in obstructive sleep apnea treatment.

INTRODUCTION: Manual titration is the gold standard to determinate optimal continuous positive airway pressure, and the prediction of the optimal pressure is important to avoid delays in prescribing a continuous positive airway pressure treatment. OBJECTIVE: To verify whether anthropometric, polysomnographic, cephalometric, and upper airway clinical assessments can predict the optimal continuous positive airway pressure setting for obstructive sleep apnea patients. METHODS: Fifty men between 25 and 65 years, with body mass indexes of less than or equal to 35kg/m2 were selected. All patients had baseline polysomnography followed by cephalometric and otolaryngological clinical assessments. On a second night, titration polysomnography was carried out to establish the optimal pressure. RESULTS: The average age of the patients was 43±12.3 years, with a mean body mass index of 27.1±3.4kg/m2 and an apnea-hypopnea index of 17.8±10.5 events per hour. Smaller mandibular length (p=0.03), smaller atlas-jaw distance (p=0.03), and the presence of a Mallampati III and IV (p=0.02) were predictors for higher continuous positive airway pressure. The formula for the optimal continuous positive airway pressure was: 17.244-(0.133×jaw length)+(0.969×Mallampati III and IV classification)-(0.926×atlas-jaw distance). CONCLUSION: In a sample of male patients with mild-to-moderate obstructive sleep apnea, the optimal continuous positive airway pressure was predicted using the mandibular length, atlas-jaw distance and Mallampati classification.

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.

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.

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.