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In-laboratory polysomnography, the gold-standard for diagnosing sleep disorders, is resource-demanding and not conducive to multiple night evaluations. Ambulatory polysomnography, especially when self-applied, could be a viable alternative. This study aimed to assess the feasibility and reliability of self-applied polysomnography over three consecutive nights in untrained participants, assessing: technical success rate; comparing sleep diagnostic variables from single and multiple nights; and evaluating participants' subjective experience. Data were collected from 78 participants (55.1% females) invited to test a self-applicable polysomnography device for three consecutive nights at home. The technical success rate for valid sleep recordings was 82.5% out of 234 planned study nights, with 87.2% of participants obtaining at least two valid nights. Misclassification of obstructive sleep apnea severity was higher in participants with mild OSA (21.4%) compared with those with moderate-to-severe obstructive sleep apnea or no obstructive sleep apnea. Sleep efficiency and wake after sleep onset showed improvement from Night 1 to Night 3 (p < 0.001), and the mean polysomnography set-up time decreased significantly over this period. Participants reported moderate-to-high satisfaction with the device (System Usability Scale score 71.2 ± 12.4). The findings suggest that self-applied polysomnography is a feasible diagnostic method for untrained individuals at risk for sleep disorders, and that multiple night assessments can improve diagnostic precision for mild obstructive sleep apnea cases.
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OBJECTIVE: Daridorexant is approved for the treatment of insomnia at two dose levels (25 and 50 mg). Dose-efficacy and -safety response relationships were evaluated using Phase 2 and 3 data. METHODS: Data (N = 2153) from one Phase 2 (daridorexant 5, 10, 25, 50 mg, placebo once daily for 1 month) and two Phase 3 studies (daridorexant 10 and 25 or 25 and 50 mg, placebo once daily for 3 months) were pooled. Dose-response analyses at 1 month of double-blind treatment were performed using a linear regression and a two-stage meta-analysis approach. Efficacy endpoints were polysomnography-derived wake after sleep onset, latency to persistent sleep (LPS), self-reported total sleep time and the Insomnia Daytime Symptoms and Impacts Questionnaire total score (only Phase 3 data for the latter). Safety endpoints were the incidence of total adverse events (AEs) and AEs corresponding to somnolence/fatigue. RESULTS: Dose-responses for all efficacy endpoints were significant in the observed dose range (both statistical approaches, p < 0.01). All dose-response relationships were linear except for LPS (two-stage meta-analysis) which showed a change in slope above 10 mg without reaching a plateau. No significant dose-response was observed for any AE (both approaches, p > 0.05). The incidence of AEs corresponding to somnolence/fatigue was low at all doses and, without linear assumption (two-stage meta-analysis) there was no dose-dependency (p = 0.369). CONCLUSIONS: The data support the use of 50 mg as the preferred daridorexant dose in patients with insomnia disorder to provide the greatest opportunity for efficacy with no increased risk for AEs, including somnolence/fatigue, compared to lower doses.
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Relação Dose-Resposta a Droga , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Masculino , Método Duplo-Cego , Feminino , Pessoa de Meia-Idade , Adulto , Pirrolidinas/efeitos adversos , Pirrolidinas/administração & dosagem , Pirrolidinas/uso terapêutico , Resultado do Tratamento , Polissonografia , Ensaios Clínicos Fase III como Assunto , ImidazóisRESUMO
Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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Aterosclerose , Doenças das Artérias Carótidas , Doença da Artéria Coronariana , Enfisema , Masculino , Humanos , Feminino , Fatores de Risco , Doenças das Artérias Carótidas/epidemiologia , Aterosclerose/epidemiologia , Doença da Artéria Coronariana/epidemiologia , PulmãoRESUMO
BACKGROUND: The carbonic anhydrase inhibitor sulthiame reduces OSA severity, increases overnight oxygenation, and improves sleep quality. Insights into how sulthiame modulates OSA pathophysiologic features (endotypic traits) adds to our understanding of the breathing disorder itself, as well as the effects of carbonic anhydrases in respiratory regulation. RESEARCH QUESTION: How does sulthiame treatment modify endotypic traits in OSA? STUDY DESIGN AND METHODS: Per-protocol tertiary analysis of a randomized controlled trial with the inclusion criteria as follow: BMI, ≥ 20 to ≤ 35 kg/m2; age, 18-75 years; apnea-hypopnea index (AHI) ≥ 15 events/h; Epworth sleepiness scale score, ≥ 6; as well as nonacceptance or nontolerance of positive airway pressure treatment. Patients were randomized to receive placebo (n = 22), sulthiame 200 mg (n = 12), or sulthiame 400 mg (n = 24) during 4 weeks of treatment. Polysomnography was applied twice at baseline and follow-up. Endotypic traits were determined from polysomnography tracings (PUPBeta). Sulthiame plasma concentration was analyzed. Differences from baseline to follow-up (Δs) were analyzed with the analysis of covariance or Kruskal-Wallis H test and Pearson (r) or Spearman correlations (rs). RESULTS: Sulthiame (200-mg and 400-mg groups) consistently reduced loop gain (response to a 1-cycle/min disturbance, LG1; mean, -0.16 [95% CI, -0.18 to -0.13]; P < .05) in addition to increased ventilation at lowest decile of ventilatory drive (Vmin; median, +12 [95% CI, 4-20]; P < .05) and median ventilation at eupneic ventilatory drive (Vpassive; median, +4 [95% CI, 0-5]; P < .05). ΔLG1 correlated with ΔAHI percentage (200 mg: r = 0.65; P < .05). Vmin and Vpassive correlated with ΔAHI (all sulthiame: rs = -0.59 and rs = -0.65; P < .05 for all). The reduction of LG1 was seen already in the lower sulthiame concentration range, whereas changes in Vmin peaked in the higher range. INTERPRETATION: The effect of sulthiame in OSA may be explained by a reduction of ventilatory instability (LG1) as well as upper airway collapsibility (Vmin and Vpassive). TRIAL REGISTRY: European Union Drug Regulating Authorities Clinical Trials Database; No.: EudraCT 2017-004767-13; URL: https://www.clinicaltrialsregister.eu.
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Benzenossulfonamidas , Apneia Obstrutiva do Sono , Tiazinas , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/uso terapêutico , Apneia Obstrutiva do Sono/terapia , Tiazinas/farmacologia , Tiazinas/uso terapêutico , Polissonografia , Pressão Positiva Contínua nas Vias Aéreas/métodosRESUMO
BACKGROUND: In people with OSA, excessive daytime sleepiness is a prominent symptom and can persist despite adherence to CPAP, the first-line therapy for OSA. Pitolisant was effective in reducing daytime sleepiness in two 12-week randomized controlled trials (RCTs), one in patients adherent to CPAP (BF2.649 in Patients With OSA and Treated by CPAP But Still Complaining of EDS [HAROSA 1]) and the other in patients refusing or not tolerating CPAP (BF2.649 in Patients With OSA, Still Complaining of EDS and Refusing to be Treated by CPAP [HAROSA 2]). RESEARCH QUESTION: Does the efficacy and safety of pitolisant persist when these patients take it long-term? STUDY DESIGN AND METHODS: All adults included in the HAROSA 1 and HAROSA 2 RCTs (both pitolisant and placebo arms) were offered pitolisant (up to 20 mg/d) after completion of the short-term double-anonymized phase (ie, from week 13) in an open-label cohort study. The primary efficacy outcome was the change in Epworth Sleepiness Scale score between baseline and week 52. Safety outcomes were treatment-emergent adverse event(s) (TEAE[s]), serious TEAEs, and special interest TEAEs. RESULTS: Out of 512 adults included in the two RCTs, 376 completed the 1-year follow-up. The pooled mean difference in Epworth Sleepiness Scale score from baseline to 1 year for the intention-to-treat sample was -8.0 (95% CI, -8.3 to -7.5). The overall proportions of TEAEs, serious TEAEs, and TEAEs of special interest were 35.1%, 2.0%, and 11.1%, respectively, without any significant difference between patients in the initial pitolisant and placebo arms. No cardiovascular safety issues were reported. INTERPRETATION: Pitolisant is effective in reducing daytime sleepiness over 1 year in adults with OSA, with or without CPAP treatment. Taken for 1 year, it has a good safety profile (including cardiovascular). TRIAL REGISTRATION: ClinicalTrials.gov; Nos.: NCT01071876 and NCT01072968; URL: www. CLINICALTRIALS: gov.
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Distúrbios do Sono por Sonolência Excessiva , Apneia Obstrutiva do Sono , Adulto , Humanos , Sonolência , Piperidinas/efeitos adversos , Distúrbios do Sono por Sonolência Excessiva/etiologia , Distúrbios do Sono por Sonolência Excessiva/tratamento farmacológico , Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Resultado do TratamentoRESUMO
Sleep-disordered breathing, ranging from habitual snoring to severe obstructive sleep apnea, is a prevalent public health issue. Despite rising interest in sleep and awareness of sleep disorders, sleep research and diagnostic practices still rely on outdated metrics and laborious methods reducing the diagnostic capacity and preventing timely diagnosis and treatment. Consequently, a significant portion of individuals affected by sleep-disordered breathing remain undiagnosed or are misdiagnosed. Taking advantage of state-of-the-art scientific, technological, and computational advances could be an effective way to optimize the diagnostic and treatment pathways. We discuss state-of-the-art multidisciplinary research, review the shortcomings in the current practices of SDB diagnosis and management in adult populations, and provide possible future directions. We critically review the opportunities for modern data analysis methods and machine learning to combine multimodal information, provide a perspective on the pitfalls of big data analysis, and discuss approaches for developing analysis strategies that overcome current limitations. We argue that large-scale and multidisciplinary collaborative efforts based on clinical, scientific, and technical knowledge and rigorous clinical validation and implementation of the outcomes in practice are needed to move the research of sleep-disordered breathing forward, thus increasing the quality of diagnostics and treatment.
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Síndromes da Apneia do Sono , Adulto , Humanos , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/terapia , RoncoRESUMO
Aims: We analysed longitudinal blood pressure (BP) data from hypertensive obstructive sleep apnoea (OSA) patients in the European Sleep Apnea Database cohort. The study investigated the interaction between positive airway pressure (PAP)-induced BP change and antihypertensive treatment (AHT). Methods and results: Hypertensive patients with AHT [monotherapy/dual therapy n = 1283/652, mean age 59.6 ± 10.7/60.6 ± 10.3 years, body mass index (BMI) 34.2 ± 6.5/34.8 ± 7.0â kg/m2, apnoea-hypopnoea index 46 ± 25/46 ± 24 n/h, proportion female 29/26%, respectively] started PAP treatment. Office BP at baseline and 2- to 36-month follow-up were assessed. The interaction between AHT drug classes and PAP on BP was quantified and the influences of age, gender, BMI, co-morbidities, BP at baseline, and study site were evaluated. Following PAP treatment (daily usage, 5.6 ± 1.6/5.7 ± 1.9â h/day), systolic BP was reduced by -3.9 ± 15.5/-2.8 ± 17.7â mmHg in mono/dual AHT and diastolic BP by -3.0 ± 9.8/-2.7 ± 10.8â mmHg, respectively, all P < 0.0001. Systolic and diastolic BP control was improved following PAP treatment (38/35% to 54/46% and 67/67% to 79/74%, mono/dual AHT, respectively). PAP treatment duration predicted a larger BP improvement in the monotherapy group. Intake of renin-angiotensin blockers [angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)] alone or in any AHT combination was associated with better BP control. The AHT-dependent BP improvement was independent of confounders. Conclusion: In this pan-European OSA patient cohort, BP control improved following initiation of PAP. Longer PAP treatment duration, was associated with a favourable effect on BP. Our study suggests that ACEI/ARB, alone or in combination with other drug classes, provides a particularly strong reduction of BP and better BP control when combined with PAP in OSA.
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Rationale: Positive airway pressure (PAP) is standard treatment for obstructive sleep apnea. Telemedicine has been introduced for improved PAP follow-up. Objectives: Our study aim was to evaluate the clinical utility of and patient satisfaction with PAP follow-up with an early intervention telemedical protocol. Methods: A randomized controlled trial was conducted at four sleep clinics of the same county. Treatment-naive patients with obstructive sleep apnea were randomized to standard PAP follow-up (203 patients, fixed follow-up procedures) or early intervention telemedical follow-up (AirView, ResMed; 206 patients, continuous follow-up) for 3 months. Evaluated variables included PAP adherence at 3 months, patient-reported outcome measures (Epworth Sleepiness Scale, 36-item Short Form Health Survey, Insomnia Severity Index, Hospital Anxiety and Depression Scale), and staff time. Group differences were analyzed with linear mixed regression models adjusted for age, body mass index, apnea-hypopnea index, and study center. Results: The study groups were comparable at baseline (N = 409; mean age, 59 ± 12 yr; body mass index, 31.9 ± 6 kg/m2, apnea-hypopnea index, 41.5 ± 21 events/h). PAP adherence was higher in the proactive telemedicine group than in the control group (4.3 ± 2.4 and 4.1 ± 2.6 h/night; P = 0.01, respectively), and mean mask pressure at follow-up was significantly lower in the telemedicine group than in the control group (8.7 ± 2.1 cm H2O vs. 9.2 ± 2.5 cm H2O; P = 0.028). In post hoc analysis, the difference in PAP adherence between groups was most pronounced in patients with depression (4.8 ± 2.6 h/night vs. 2.7 ± 2.3 h/night; P = 0.03). Relevant mask leakage (>24 L/min) was lower in the telemedicine group (5.4% vs. 12.1%, P = 0.024). Improvement of patient-reported outcome measures and patient satisfaction was equivalent between groups. Conclusions: Proactive telemedical management of the initial follow-up of PAP treatment compared favorably with conventional follow-up in terms of adherence, pressure level, and mask leakage. Patients with depression may particularly benefit from telemedical follow-up. Specific clinical routines are required to establish this practice in sleep clinics. Clinical trial registered with www.clinicaltrials.gov (NCT03446560).
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Apneia Obstrutiva do Sono , Telemedicina , Humanos , Pessoa de Meia-Idade , Idoso , Pressão Positiva Contínua nas Vias Aéreas , Seguimentos , Apneia Obstrutiva do Sono/terapia , Inquéritos Epidemiológicos , Cooperação do PacienteRESUMO
Aim: The impact of obstructive sleep apnoea (OSA)-COPD overlap syndrome (OVS) on sleep quality and cardiovascular outcomes has not been fully explored. We aimed to compare clinical and polysomnographic characteristics of patients with OVS versus patients with OSA, and to explore pathophysiological links between OVS and comorbidities. Study design and methods: This cross-sectional analysis initially included data from 5600 patients with OSA and lung function in the European Sleep Apnoea Database. Two subgroups of patients with OSA (n=1018) or OVS (n=509) were matched (2:1) based on sex, age, body mass index and apnoea-hypopnea index at baseline. Results: After matching, patients with OVS had more severe hypoxia, lower sleep efficiency and presented with higher prevalences of arterial hypertension, ischaemic heart disease and heart failure compared with patients with OSA. OVS was associated with a significant decrease in sleep efficiency (mean difference (ß) -3.0%, 95% CI -4.7 to -1.3) and in nocturnal mean peripheral oxyhaemoglobin saturation (SpO2) (ß -1.1%, 95% CI -1.5 to -0.7). Further analysis revealed that a decrease in forced expiratory volume in 1â s and arterial oxygen tension was related to a decrease in sleep efficiency and in mean nocturnal SpO2. A COPD diagnosis increased the odds of having heart failure by 1.75 (95% CI 1.15-2.67) and systemic hypertension by 1.36 (95% CI 1.07-1.73). Nocturnal hypoxia was strongly associated with comorbidities; the mean nocturnal SpO2 and T90 (increase in time below SpO2 of 90%) were associated with increased odds of systemic hypertension, diabetes and heart failure but the oxygen desaturation index was only related to hypertension and diabetes. Conclusion: Patients with OVS presented with more sleep-related hypoxia, a reduced sleep quality and a higher risk for heart failure and hypertension.
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STUDY OBJECTIVES: Cheyne - Stokes respiration (CSR) is prevalent in patients with chronic heart failure (CHF). Adaptive Servo Ventilation (ASV) alleviates CSR and improves objective sleep quality. We investigated the effects of ASV on neurocognitive function in the symptomatic phenotype of patients with CSR and CHF. METHODS: This case series included patients diagnosed with stable CHF (NYHA ≥ II) and CSR (N = 8). Sleep and neurocognitive function were assessed at baseline and after 1- and 6-months following initiation of ASV treatment. RESULTS: In CHF patients (n = 8, median age 78.0[64.5-80.8] years and BMI 30.0[27.0-31.5] kg/m2, median ejection fraction 30[24-45]%, Epworth Sleepiness Scale (ESS) score 11.5[9.0-15.0]), ASV markedly improved respiration during sleep (Apnea-Hypopnea Index (AHI) 44.1[39.0-51.5]n/h at baseline, 6.3[2.4-9.7]n/h at 6 months treatment, respectively, p < 0.01). The 6-min-walk test distance increased by treatment from (295.0[178.8-385.0] m to 356.0[203.8-495.0] m (p = 0.05)). Sleep structure was modified, and Stage 3 increased markedly from 6.4[1.7-20.1] % to 20.8[14.2-25.3] %, p < 0.02). Sleep latency in the Maintenance of Wakefulness Test increased from 12.0[6.0-30.0] min to 26.3[12.0-30.0] min, (p = 0.04). In the Attention Network Test, evaluating neurocognition, the number of lapses decreased from 6.0[1.0-44.0] to 2.0[0.3-8.0], (p = 0.05) and the overall number of responses to a preset stimulus increased after treatment (p = 0.04). CONCLUSIONS: ASV treatment in CHF patients with CSR may improve sleep quality, neurocognition and daytime performance.
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Respiração de Cheyne-Stokes , Cognição , Pressão Positiva Contínua nas Vias Aéreas , Distúrbios do Sono por Sonolência Excessiva , Insuficiência Cardíaca , Distúrbios do Sono por Sonolência Excessiva/complicações , Distúrbios do Sono por Sonolência Excessiva/psicologia , Distúrbios do Sono por Sonolência Excessiva/terapia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/psicologia , Insuficiência Cardíaca/terapia , Doença Crônica , Respiração de Cheyne-Stokes/etiologia , Respiração de Cheyne-Stokes/psicologia , Respiração de Cheyne-Stokes/terapia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Projetos PilotoRESUMO
Background: The prevalence of obstructive sleep apnoea (OSA) is growing as the population is ageing. However, data on the clinical characteristics of elderly patients with OSA and their adherence to positive airway pressure (PAP) treatment are scarce. Methods: Data from 23â 418 30-79-year-old OSA patients prospectively collected into the ESADA database during 2007-2019 were analysed. Information on PAP use (h·day-1) in association with a first follow-up visit was available for 6547 patients. The data was analysed according to 10-year age groups. Results: The oldest age group was less obese, less sleepy and had a lower apnoea-hypopnoea index (AHI) compared with middle-aged patients. The insomnia phenotype of OSA was more prevalent in the oldest age group than in the middle-aged group (36%, 95% CI 34-38 versus 26%, 95% CI 24-27, p<0.001). The 70-79-year-old group adhered to PAP therapy equally well as the younger age groups with a mean PAP use of 5.59â h·day-1 (95% CI 5.44-5.75). PAP adherence did not differ between clinical phenotypes based on subjective daytime sleepiness and sleep complaints suggestive of insomnia in the oldest age group. A higher score on the Clinical Global Impression Severity (CGI-S) scale predicted poorer PAP adherence. Conclusion: The elderly patient group was less obese, less sleepy, had more insomnia symptoms and less severe OSA, but were rated to be more ill compared with the middle-aged patients. Elderly patients with OSA adhered to PAP therapy equally well as middle-aged patients. Low global functioning (measured by CGI-S) in the elderly patient predicted poorer PAP adherence.
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OBJECTIVE: New drug treatments are under development in obstructive sleep apnea (OSA). The placebo effect is well recognized in various conditions, but its relevance in OSA is debated. In the current study we determined the influence of a placebo effect in studies of drug therapy in OSA. METHODS: A systematic review and meta-analysis (PROSPERO CRD42021229410) with searches in MEDLINE, Scopus, Web of Science and Cochrane CENTRAL from inception to 2021-01-19. Inclusion criteria were (i) RCTs of adults with OSA, (ii) drug intervention with placebo baseline and follow-up sleep study (iii) outcomes: apnea hypopnea index (AHI), mean oxygen saturation (mSaO2), oxygen desaturation index (ODI) and/or Epworth Sleepiness Scale (ESS). Risk-of-bias was assessed with Cochrane RoB 2. RESULTS: 7436 articles were identified and 29 studies included (n = 413). Studies were generally small (median n = 14), with 78% men, baseline AHI range 9-74 events/h and treatment duration range 1-120 days. Meta-analyses were conducted for main outcomes. Mean change of the primary outcome, AHI, was -0.84 (95% CI -2.98 to 1.30); mSaO2 and ODI estimations were also non-significant. ESS showed a trend towards a reduction of -1 unit. Subgroup analysis did not show significant differences. Risk-of-bias assessment indicated mostly low risk but studies were small with wide confidence intervals. CONCLUSIONS: In this meta-analysis we did not identify systematic placebo effects on the AHI, ODI or mSaO2 while ESS score showed a trend for a small reduction. These results have an impact on the design and interpretation of drug trials in OSA.
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Apneia Obstrutiva do Sono , Humanos , Oxigênio/metabolismo , Efeito Placebo , Apneia Obstrutiva do Sono/tratamento farmacológico , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/fisiopatologia , SonolênciaRESUMO
Background: Coexisting obstructive sleep apnoea (OSA) in patients with COPD, defined as overlap syndrome (OVS), is prevalent and underdiagnosed. Routine assessment of OSA is not common practice in COPD care. Our study assessed the clinical impact of sleep assessment by peripheral arterial tonometry (PAT) in COPD patients. Methods: 105 COPD patients (mean age 68.1±9â years, body mass index (BMI) 28.3±6.0â kg·m-2, 44% males, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I to IV in 2%, 40%, 42% and 16%, respectively) underwent assessment at an outpatient COPD clinic including anthropometrics, arterial blood gas (ABG) and spirometry in this clinical cohort study. PAT-based sleep studies were performed. Predictors of OVS and ABG were determined. Rapid eye movement (REM) sleep-related OSA (REM-OSA) was analysed in OVS. Results: 49 COPD patients (47%) suffered from moderate to severe OSA (OVS group, mean apnoea-hypopnoea index 30.8±18â events·h-1, REM-oxygen desaturation index (REM-ODI) 26.9±17â events·h-1). OVS was more prevalent in males compared to females (59% and 37%, p=0.029, respectively). Age (70.1±8 versus 66.3±10â years), BMI (30.0±6 versus 26.4±7â kg·m-2) and hypertension prevalence (71% versus 45%) were elevated (all p<0.03, respectively), while deep sleep (12.7±7% and 15.4±6%, p=0.029) and mean overnight oxygenation (90.6±3% and 92.3±2%, p=0.003) were lower in OVS compared to COPD alone. REM-ODI was independently associated with daytime arterial carbon dioxide tension (P aCO2 ) (ß=0.022, p<0.001). REM-OSA was associated with an elevated prevalence of atrial fibrillation compared to no REM-OSA (25% and 3%, p=0.022). Conclusions: OVS was highly prevalent, specifically in obese males. REM-related OSA showed strong association with elevated daytime P aCO2 and prevalent cardiovascular disease. PAT was feasible for sleep assessment in COPD.
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INTRODUCTION: This paper describes the development of "Swedish Guidelines for OSA treatment" and the underlying managed care process. The Apnea Hypopnea Index (AHI) is traditionally used as a single parameter for obstructive sleep apnea (OSA) severity classification, although poorly associated with symptomatology and outcome. We instead implement a novel matrix for shared treatment decisions based on available evidence. METHODS: A national expert group including medical and dental specialists, nurses, and patient representatives developed the knowledge-driven management model. A Delphi round was performed amongst experts from all Swedish regions (N = 24). Evidence reflecting treatment effects was extracted from systematic reviews, meta-analyses, and randomized clinical trials. RESULTS: The treatment decision in the process includes a matrix with five categories from a "very weak"" to "very strong" indication to treat, and it includes factors with potential influence on outcome, including (A) OSA-related symptoms, (B) cardiometabolic comorbidities, (C) frequency of respiratory events, and (D) age. OSA-related symptoms indicate a strong incitement to treat, whereas the absence of symptoms, age above 65 years, and no or well-controlled comorbidities indicate a weak treatment indication, irrespective of AHI. CONCLUSIONS: The novel treatment matrix is based on the effects of treatments rather than the actual frequency of respiratory events during sleep. A nationwide implementation of this matrix is ongoing, and the outcome is monitored in a prospective evaluation by means of the Swedish Sleep Apnea Registry (SESAR).
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OBJECTIVE: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA. METHODS: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), and percentage of time with SpO2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively. RESULTS: The [HCO3-] level was normal in most patients (average 24.0 ± 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030, <0.001, <0.001, and <0.001, respectively). [HCO3-] was independently associated with ODI, mean SpO2, minimum SpO2, and T90% after adjusting for confounders (ß value [95%CI]: 1.21 [0.88-1.54], -0.16 [-0.20 to -0.11], -0.51 [-0.64 to -0.37], 1.76 [1.48-2.04], respectively, all p < 0.001). 1 mmol/L elevation of [HCO3-] was associated with a 4% increased odds of uncontrolled hypertension (OR: 1.04 [1.01-1.08], p = 0.013). CONCLUSION: We first demonstrated an independent association between [HCO3-] and nocturnal hypoxic burden as well as uncontrolled hypertension in OSA patients. Bicarbonate levels as an adjunctive measure provide insight into the pathophysiology of hypertension in OSA.
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Hipertensão , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Humanos , Bicarbonatos , Estudos Transversais , Hipertensão/epidemiologia , Hipertensão/complicações , Síndromes da Apneia do Sono/complicações , Hipóxia/complicações , OxigênioRESUMO
BACKGROUND: Emerging data suggest that determination of physiologic endotypic traits (eg, loop gain) may enable precision medicine in OSA. RESEARCH QUESTION: Does a single-night assessment of polysomnography-derived endotypic traits provide reliable estimates in moderate to severe OSA? STUDY DESIGN AND METHODS: Two consecutive in-lab polysomnography tests from a clinical trial (n = 67; male, 69%; mean ± SD age, 61 ± 10 years; apnea-hypopnea index [AHI] 53 ± 22 events/h) were used for the reliability analysis. Endotypic traits, reflecting upper airway collapsibility (ventilation at eupneic drive [Vpassive]), upper airway dilator muscle tone (ventilation at the arousal threshold [Vactive]), loop gain (stability of ventilatory control, LG1), and arousal threshold (ArTh) were determined. Reliability was expressed as an intraclass correlation coefficient (ICC). Minimal detectable differences (MDDs) were computed to provide an estimate of maximum spontaneous variability. Further assessment across four repeated polysomnography tests was performed in a subcohort (n = 22). RESULTS: Reliability of endotypic traits between the two consecutive nights was moderate to good (ICC: Vpassive = 0.82, Vactive = 0.76, LG1 = 0.72, ArTh = 0.83). Variability in AHI, but not in body position or in sleep stages, was associated with fluctuations in Vpassive and Vactive (r = -0.49 and r = -0.41, respectively; P < .001 for both). MDDs for single-night assessments were: Vpassive = 22, Vactive = 34, LG1 = 0.17, and ArTh = 21. Multiple assessments (mean of two nights, n = 22) further reduced MDDs by approximately 20% to 30%. INTERPRETATION: Endotypic trait analysis using a single standard polysomnography shows acceptable reliability and reproducibility in patients with moderate to severe OSA. The reported MDDs of endotypic traits may facilitate the quantification of relevant changes and may guide future evaluation of interventions in OSA.
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Apneia Obstrutiva do Sono , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Apneia Obstrutiva do Sono/diagnóstico , Reprodutibilidade dos Testes , Polissonografia , RespiraçãoRESUMO
We recruited 5,970 hypertensive patients with obstructive sleep apnea (OSA) on current antihypertensive treatment from the European Sleep Apnea Database (ESADA) cohort. The group was subdivided into those receiving monotherapy (n = 3,594) and those receiving dual combined therapy (n = 2,376). We studied how major OSA confounders like age, gender, and body mass index as well as the degree of sleep apnea modified office systolic and diastolic blood pressure. Beta-blockers alone or in combination with a diuretic were compared with other antihypertensive drug classes. Monotherapy with beta-blocker was associated with lower systolic blood pressure, particularly in non-obese middle-aged males with hypertension. Conversely, the combination of a beta-blocker and a diuretic was associated with lower systolic and diastolic blood pressure in hypertensive patients with moderate-severe OSA. Systolic blood pressure was better controlled in female patients using this combined treatment. Our cross-sectional data suggest that specific clinical characteristics and type of antihypertensive medication influence the degree of blood pressure control in hypertensive OSA patients. Controlled trials are warranted.
Assuntos
Hipertensão , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Medicina de Precisão , Estudos Transversais , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/terapia , Pressão Sanguínea , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Diuréticos/farmacologia , Diuréticos/uso terapêutico , PolissonografiaRESUMO
Introduction: The European Sleep Apnea Database was used to identify distinguishable obstructive sleep apnoea (OSA) phenotypes and to investigate the clinical outcome during positive airway pressure (PAP) treatment. Method: Prospective OSA patient data were recruited from 35 sleep clinics in 21 European countries. Unsupervised cluster analysis (anthropometrics, clinical variables) was performed in a random sample (n=5000). Subsequently, all patients were assigned to the clusters using a conditional inference tree classifier. Responses to PAP treatment change in apnoea severity and Epworth sleepiness scale (ESS) were assessed in relation to baseline patient clusters and at short- and long-term follow-up. Results: At baseline, 20 164 patients were assigned (mean age 54.1±12.2â years, 73% male, median apnoea-hypopnoea index (AHI) 27.3 (interquartile range (IQR) 14.1-49.3) events·h-1, and ESS 9.8±5.3) to seven distinct clusters based on anthropometrics, comorbidities and symptoms. At PAP follow-up (median 210 [IQR 134-465] days), the observed AHI reduction (n=1075) was similar, whereas the ESS response (n=3938) varied: largest reduction in cluster 3 (young healthy symptomatic males) and 6 (symptomatic males with psychiatric disorders, -5.0 and -5.1 units, respectively (all p<0.01), limited reduction in clusters 2 (obese males with systemic hypertension) and 5 (elderly multimorbid obese males, -4.2 (p<0.05) and -3.7 (p<0.001), respectively). Residual sleepiness in cluster 5 was particularly evident at long-term follow-up (p<0.05). Conclusion: OSA patients can be classified into clusters based on clinically identifiable features. Importantly, these clusters may be useful for prediction of both short- and long-term responses to PAP intervention.
RESUMO
PURPOSE OF REVIEW: This review provides a condensed description of pharmacological remedies explored in patients with obstructive sleep apnoea (OSA) as well as projections of what we might expect in terms of clinical performance of these drugs. RECENT FINDINGS: Conventional drug therapies explored in OSA have generally produced disappointing results and there is a shortage of pharmacological treatment alternatives in this disorder. Recent insights into pathophysiological mechanisms potentially involved in OSA suggest that the condition may be divided into distinct subgroups based on clusters or defined by means of unique functional endotypic criteria. In fact, positive outcomes in clinical trials have now resulted in several drug candidates that show a convincing reduction of sleep disordered breathing in both short and intermediate term. Such drugs may be particularly useful in certain variants of OSA but not in others. These insights have also raised the ambition to create personalized therapies in OSA. Another recent development is the insight that OSA-linked conditions such as obesity, daytime somnolence and various forms of cardiovascular/metabolic disease may provide drug-based targets. For instance, pharmacological obesity therapy may provide not only positive metabolic effects but may also be a way to eliminate the anatomic component in obese OSA patients. SUMMARY: Recent insights into the pathophysiology of OSA have opened possibilities to develop personalized therapy. Drugs addressing fundamental aspects of the sleep and breathing disorder provide a particularly promising avenue for development of novel forms of treatment in OSA.