RESUMO
BACKGROUND: Obstructive sleep apnea (OSA) contributes to the generation, recurrence, and perpetuation of atrial fibrillation, and it is associated with worse outcomes. Little is known about the economic impact of OSA therapy in atrial fibrillation. This retrospective cohort study assessed the impact of positive airway pressure (PAP) therapy adherence on health care resource use and costs in patients with OSA and atrial fibrillation. METHODS AND RESULTS: Insurance claims data for ≥1 year before sleep testing and 2 years after device setup were linked with objective PAP therapy use data. PAP adherence was defined from an extension of the US Medicare 90-day definition. Inverse probability of treatment weighting was used to create covariate-balanced PAP adherence groups to mitigate confounding. Of 5867 patients (32% women; mean age, 62.7 years), 41% were adherent, 38% were intermediate, and 21% were nonadherent. Mean±SD number of all-cause emergency department visits (0.61±1.21 versus 0.77±1.55 [P=0.023] versus 0.95±1.90 [P<0.001]), all-cause hospitalizations (0.19±0.69 versus 0.24±0.72 [P=0.002] versus 0.34±1.16 [P<0.001]), and cardiac-related hospitalizations (0.06±0.26 versus 0.09±0.41 [P=0.023] versus 0.10±0.44 [P=0.004]) were significantly lower in adherent versus intermediate and nonadherent patients, as were all-cause inpatient costs ($2200±$8054 versus $3274±$12 065 [P=0.002] versus $4483±$16 499 [P<0.001]). All-cause emergency department costs were significantly lower in adherent and intermediate versus nonadherent patients ($499±$1229 and $563±$1292 versus $691±$1652 [P<0.001 and P=0.002], respectively). CONCLUSIONS: These data suggest clinical and economic benefits of PAP therapy in patients with concomitant OSA and atrial fibrillation. This supports the value of diagnosing and managing OSA and highlights the need for strategies to enhance PAP adherence in this population.
Assuntos
Fibrilação Atrial , Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Humanos , Feminino , Fibrilação Atrial/terapia , Fibrilação Atrial/economia , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/economia , Apneia Obstrutiva do Sono/epidemiologia , Pressão Positiva Contínua nas Vias Aéreas/economia , Estados Unidos/epidemiologia , Recursos em Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: The polysomnography (PSG) is the gold-standard for obstructive sleep apnea (OSA) syndrome diagnosis and assessment under positive airway pressure (PAP) therapies in children. Recently, an innovative digital medicine solution, including a mandibular jaw movement (MJM) sensor coupled with automated analysis, has been validated as an alternative to PSG for pediatric application. OBJECTIVE: This study aimed to assess the reliability of MJM automated analysis for the assessment of residual apnea/hypopnea events during sleep in children with OSA treated with noninvasive ventilation (NIV) or continuous PAP (CPAP). METHODS: In this open-label prospective non-randomized multicentric trial, we included children aged from 5 to 18 years with a diagnosis of severe OSA. The children underwent in-laboratory PSG with simultaneous MJM monitoring and at-home recording with MJM monitoring 3 months later. Agreement between PSG and MJM analysis in measuring the residual apnea-hypopnea index (AHI) was evaluated by the Bland-Altman method. The treatment effect on residual AHI was estimated for both PSG and MJM analysis. RESULTS: Fifteen (60% males) children were included with a median age of 12 years [interquartile range 8-15]. Two (17%) were ventilated with NIV and 13 (83%) with CPAP. There was a good agreement between MJM-AHI and PSG-AHI with a median bias of -0.25 (95% CI: -3.40 to +2.04) events/h. The reduction in AHI under treatment was consistently significant across the three measurement methods: in-laboratory PSG and MJM recordings in the laboratory and at home. CONCLUSION: Automated analysis of MJM is a highly reliable alternative method to assess residual events in a small population treated with PAP therapies.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Mandíbula , Polissonografia , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Criança , Masculino , Feminino , Estudos Prospectivos , Adolescente , Pressão Positiva Contínua nas Vias Aéreas/métodos , Mandíbula/fisiopatologia , Pré-Escolar , Reprodutibilidade dos Testes , Ventilação não Invasiva/métodosRESUMO
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a heterogeneous condition covering many clinical phenotypes in terms of the diversity of symptoms. Patient-based OSA screening questionnaires used in routine practice contain significantly varying contents that can impact the reliability and validity of the screening. We investigated to what extent common patient-based OSA screening questionnaires differ or overlap in their item content by conducting a rigorous, methodical, and quantified content overlap analysis. METHODS: We conducted an item content analysis of 11 OSA screening questionnaires validated in adult populations and characterized their overlap using a 4-step approach: (1) selection of OSA screening questionnaires, (2) item extraction and selection, (3) extraction of symptoms from items, and (4) assessment of content overlap with the Jaccard index (from 0, no overlap, to 1, full overlap). RESULTS: We extracted 72 items that provided 25 distinct symptoms from 11 selected OSA questionnaires. The overlap between them was weak (mean Jaccard index: 0.224; ranging from 0.138 to 0.329). All questionnaires contained symptoms of the "OSA symptom" dimension (eg, snoring or witnessed apneas). The STOP-BANG (0.329) and the Berlin (0.280) questionnaires exhibited the highest overlap content. Ten symptoms (40%) were investigated in only 1 questionnaire. CONCLUSIONS: The heterogeneity of content and the low overlap across these questionnaires reflect the challenges of screening OSA. The different OSA questionnaires potentially capture varying aspects of the disorder, with the risk of biased results in studies. Suggestions are made for better OSA screening and refinement of clinical OSA phenotypes. CITATION: Gauld C, Baillieul S, Martin VP, et al. Symptom content analysis of OSA questionnaires: time to identify and improve relevance of diversity of OSA symptoms? J Clin Sleep Med. 2024;20(7):1105-1117.
Assuntos
Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/diagnóstico , Inquéritos e Questionários/normas , Reprodutibilidade dos Testes , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Avaliação de Sintomas/métodos , Avaliação de Sintomas/estatística & dados numéricos , Avaliação de Sintomas/normas , Programas de Rastreamento/métodosRESUMO
Obstructive sleep apnea (OSA) is a highly prevalent yet underdiagnosed disease that creates a large economic burden on the United States healthcare system. In this retrospective study, we tested the hypothesis that adherence to positive airway pressure (PAP) therapy, the 'gold standard' treatment for OSA, is associated with reduced healthcare resource utilisation and costs. We linked de-identified payer-sourced medical claims and objective PAP usage data for patients newly diagnosed with OSA. Inverse probability of treatment weighting was used to create balanced groups of patients who were either adherent, intermediately adherent, or non-adherent to PAP therapy. From a sample of 179,542 patients (average age 52.5 years, 61% male), 37% were adherent, 40% intermediate, and 23% non-adherent. During the first year, PAP adherence was significantly associated with fewer emergency room visits (mean [SD] adherent: 0.39 [1.20] versus intermediate: 0.47 [1.30], p < 0.001; versus non-adherent: 0.54 [1.44], p < 0.001), all-cause hospitalisations (mean [SD] adherent: 0.09 [0.43] versus intermediate: 0.12 [0.51], p < 0.001; versus non-adherent: 0.13 [0.55], p < 0.001), and lower total costs (mean [SD] adherent $5874 [8045] versus intermediate $6523 [9759], p < 0.001; versus non-adherent $6355 [10,517], p < 0.001). Results were similar in the second year of PAP use. These results provide additional evidence from a large, diverse sample to support the diagnosis and treatment of OSA and encourage long-term adherence to PAP therapy.
RESUMO
INTRODUCTION: There is still a debate for the link between obstructive sleep apnoea (OSA) and cancer. The mechanisms underlying this causality are poorly understood. Several miRNAs are involved in cancer development and progression with expression being influenced by hypoxia. The aims of this work were (i) to compare miRNAs expression in controls versus patients affected by OSA without or with cancer (ONCO-OSA) and (ii) in colorectal cancer cells exposed to intermittent hypoxia (IH), to evaluate miRNAs impact on tumor progression in vitro. METHODS: We detected miRNAs by qRT-PCR in patients' sera and in CaCo2 cells exposed to 2-32h of IH with or without acriflavine (ACF), a HIF-1 inhibitor. Viability and transwell invasion test were applied to investigate the proliferation and migration of CaCo2 exposed to IH and treated with miRNA inhibitors or acriflavine. HIF-1α activity was evaluated in CaCo2 cells after IH. RESULTS: The levels of miR-21, miR-26a and miR-210 increased in OSA and ONCO-OSA patients compared to controls. MiR-23b increased in ONCO-OSA patients, and miR-27b and miR-145 increased in OSA but not ONCO-OSA patients. MiR-21, miR-26a, miR-23b and miR-210 increased in cells after IH. IH stimulated cell proliferation and migration. This effect was reduced after either miRNA inhibition or acriflavine treatment. MiRNA inhibition reduces HIF-1α gene expression. Conversely, acriflavine reduced the expression of these miRNAs. CONCLUSIONS: We identified a signature of miRNAs, induced by the IH environment. They could be implicated in cancer development and progression through a regulatory loop involving HIF-1.
Assuntos
MicroRNAs , Neoplasias , Apneia Obstrutiva do Sono , Humanos , MicroRNAs/genética , Células CACO-2 , Acriflavina , Hipóxia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/genéticaRESUMO
Obstructive sleep apnea (OSA) is an emerging risk factor for cancer occurrence and progression, mainly mediated by intermittent hypoxia (IH). Systemic IH, a main landmark of OSA, and local sustained hypoxia (SH), a classical feature at the core of tumors, may act separately or synergistically on tumor cells. Our aim was to compare the respective consequences of intermittent and sustained hypoxia on HIF-1, endothelin-1 and VEGF expression and on cell proliferation and migration in HepG2 liver tumor cells. Wound healing, spheroid expansion, proliferation and migration were evaluated in HepG2 cells following IH or SH exposure. The HIF-1α, endothelin-1 and VEGF protein levels and/or mRNA expression were assessed, as were the effects of HIF-1 (acriflavine), endothelin-1 (macitentan) and VEGF (pazopanib) inhibition. Both SH and IH stimulated wound healing, spheroid expansion and proliferation of HepG2 cells. HIF-1 and VEGF, but not endothelin-1, expression increased with IH exposure but not with SH exposure. Acriflavine prevented the effects of both IH and SH, and pazopanib blocked those of IH but not those of SH. Macitentan had no impact. Thus, IH and SH stimulate hepatic cancer cell proliferation via distinct signaling pathways that may act synergistically in OSA patients with cancer, leading to enhanced tumor progression.
Assuntos
Apneia Obstrutiva do Sono , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Hep G2 , Acriflavina , Hipóxia/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Fator 1 Induzível por Hipóxia , Proliferação de Células , Subunidade alfa do Fator 1 Induzível por Hipóxia/genéticaRESUMO
Over recent years, positive airway pressure (PAP) remote monitoring has transformed the management of OSA and produced a large amount of data. Accumulated PAP data provide valuable and objective information regarding patient treatment adherence and efficiency. However, the majority of studies that have analyzed longitudinal PAP remote monitoring have summarized data trajectories in static and simplistic metrics for PAP adherence and the residual apnea-hypopnea index by the use of mean or median values. The aims of this article are to suggest directions for improving data cleaning and processing and to address major concerns for the following data science applications: (1) conditions for residual apnea-hypopnea index reliability, (2) lack of standardization of indicators provided by different PAP models, (3) missing values, and (4) consideration of treatment interruptions. To allow fair comparison among studies and to avoid biases in computation, PAP data processing and management should be conducted rigorously with these points in mind. PAP remote monitoring data contain a wealth of information that currently is underused in the field of sleep research. Improving the quality and standardizing data handling could facilitate data sharing among specialists worldwide and enable artificial intelligence strategies to be applied in the field of sleep apnea.
Assuntos
Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/terapia , Inteligência Artificial , Ciência de Dados , Reprodutibilidade dos Testes , Resultado do Tratamento , Polissonografia , Pressão Positiva Contínua nas Vias Aéreas , Cooperação do PacienteRESUMO
The association between obstructive sleep apnea (OSA) and cancer is still debated and data are scarce regarding the link between OSA and breast cancer progression. Since conclusive epidemiological studies require large sample sizes and sufficient duration of exposure before incident cancer occurrence, basic science studies represent the most promising approach to appropriately address the topic. Here we assessed the impact of intermittent hypoxia (IH), the major hallmark of OSA, on the development of breast cancer and explored the specific involvement of the endothelin signaling pathway. Original in vitro and in vivo models were used where 3D-spheroids or cultures of murine 4T1 breast cancer cells were submitted to IH cycles, and nude NMRI mice, orthotopically implanted with 4T1 cells, were submitted to chronic IH exposure before and after implantation. The role of the endothelin-1 in promoting cancer cell development was investigated using the dual endothelin receptor antagonist, macitentan. In vitro exposure to IH significantly increased 4T1 cell proliferation and migration. Meta-analysis of 4 independent in vivo experiments showed that chronic IH exposure promoted tumor growth, assessed by caliper measurement (overall standardized mean difference: 1.00 [0.45-1.55], p < 0.001), bioluminescence imaging (1.65 [0.59-2.71]; p < 0.01) and tumor weight (0.86 [0.31-1.41], p < 0.01), and enhanced metastatic pulmonary expansion (0.77 [0.12-1.42]; p = 0.01). Both in vitro and in vivo tumor-promoting effects of IH were reversed by macitentan. Overall, these findings demonstrate that chronic intermittent hypoxia exposure promotes breast cancer growth and malignancy and that dual endothelin receptor blockade prevents intermittent hypoxia-induced tumor development.
Assuntos
Neoplasias , Apneia Obstrutiva do Sono , Animais , Endotelina-1/metabolismo , Hipóxia/metabolismo , Camundongos , Receptor de Endotelina ARESUMO
BACKGROUND: Obstructive sleep apnea (OSA) remains massively underdiagnosed, due to limited access to polysomnography (PSG), the highly complex gold standard for diagnosis. Performance scores in predicting OSA are evaluated for machine learning (ML) analysis applied to 3D maxillofacial shapes. METHODS: The 3D maxillofacial shapes were scanned on 280 Caucasian men with suspected OSA. All participants underwent single night in-home or in-laboratory sleep testing with PSG (Nox A1, Resmed, Australia), with concomitant 3D scanning (Sense v2, 3D systems corporation, USA). Anthropometric data, comorbidities, medication, BERLIN, and NoSAS questionnaires were also collected at baseline. The PSG recordings were manually scored at the reference sleep center. The 3D craniofacial scans were processed by geometric morphometrics, and 13 different supervised algorithms, varying from simple to more advanced, were trained and tested. Results for OSAS recognition by ML models were then compared with scores for specificity and sensitivity obtained using BERLIN and NoSAS questionnaires. RESULTS: All valid scans (n = 267) were included in the analysis (patient mean age: 59 ± 9 years; BMI: 27 ± 4 kg/m2). For PSG-derived AHI≥15 events/h, the 56% specificity obtained for ML analysis of 3D craniofacial shapes was higher than for the questionnaires (Berlin: 50%; NoSAS: 40%). A sensitivity of 80% was obtained using ML analysis, compared to nearly 90% for NoSAS and 61% for the BERLIN questionnaire. The auROC score was further improved when 3D geometric morphometrics were combined with patient anthropometrics (auROC = 0.75). CONCLUSION: The combination of 3D geometric morphometrics with ML is proposed as a rapid, efficient, and inexpensive screening tool for OSA. TRIAL REGISTRATION NUMBER: NCT03632382; Date of registration: 15-08-2018.
Assuntos
Cefalometria , Imageamento Tridimensional , Aprendizado de Máquina , Crânio , Apneia Obstrutiva do Sono , Idoso , Cefalometria/métodos , Cabeça/diagnóstico por imagem , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Polissonografia , Crânio/diagnóstico por imagem , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/diagnóstico por imagem , Inquéritos e QuestionáriosRESUMO
Preventing the cytokine storm observed in COVID-19 is a crucial goal for reducing the occurrence of severe acute respiratory failure and improving outcomes. Here, we identify Aldo-Keto Reductase 1B10 (AKR1B10) as a key enzyme involved in the expression of pro-inflammatory cytokines. The analysis of transcriptomic data from lung samples of patients who died from COVID-19 demonstrates an increased expression of the gene encoding AKR1B10. Measurements of the AKR1B10 protein in sera from hospitalised COVID-19 patients suggests a significant link between AKR1B10 levels and the severity of the disease. In macrophages and lung cells, the over-expression of AKR1B10 induces the expression of the pro-inflammatory cytokines Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß) and Tumor Necrosis Factor a (TNFα), supporting the biological plausibility of an AKR1B10 involvement in the COVID-19-related cytokine storm. When macrophages were stressed by lipopolysaccharides (LPS) exposure and treated by Zopolrestat, an AKR1B10 inhibitor, the LPS-induced production of IL-6, IL-1ß, and TNFα is significantly reduced, reinforcing the hypothesis that the pro-inflammatory expression of cytokines is AKR1B10-dependant. Finally, we also show that AKR1B10 can be secreted and transferred via extracellular vesicles between different cell types, suggesting that this protein may also contribute to the multi-organ systemic impact of COVID-19. These experiments highlight a relationship between AKR1B10 production and severe forms of COVID-19. Our data indicate that AKR1B10 participates in the activation of cytokines production and suggest that modulation of AKR1B10 activity might be an actionable pharmacological target in COVID-19 management.
Assuntos
Aldo-Ceto Redutases/fisiologia , COVID-19/genética , Síndrome da Liberação de Citocina/genética , Síndrome do Desconforto Respiratório/genética , Aldo-Ceto Redutases/antagonistas & inibidores , Aldo-Ceto Redutases/genética , Animais , COVID-19/complicações , COVID-19/metabolismo , COVID-19/patologia , Estudos de Casos e Controles , Células Cultivadas , Síndrome da Liberação de Citocina/metabolismo , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Citocinas/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Gravidade do Paciente , Células RAW 264.7 , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2/fisiologia , TranscriptomaRESUMO
Recent advances in obstructive sleep apnoea (OSA) pathophysiology and translational research have opened new lines of investigation for OSA treatment and management. Key goals of such investigations are to provide efficacious, alternative treatment and management pathways that are better tailored to individual risk profiles to move beyond the traditional continuous positive airway pressure (CPAP)-focused, "one size fits all" trial-and-error approach, which is too frequently inadequate for many patients. Identification of different clinical manifestations of OSA (clinical phenotypes) and underlying pathophysiological phenotypes (endotypes) that contribute to OSA have provided novel insights into underlying mechanisms and have underpinned these efforts. Indeed, this new knowledge has provided the framework for precision medicine for OSA to improve treatment success rates with existing non-CPAP therapies such as mandibular advancement devices and upper airway surgery, and newly developed therapies such as hypoglossal nerve stimulation and emerging therapies such as pharmacotherapies and combination therapy. Additionally, these concepts have provided insight into potential physiological barriers to CPAP adherence for certain patients. This review summarises the recent advances in OSA pathogenesis, non-CPAP treatment, clinical management approaches and highlights knowledge gaps for future research. OSA endotyping and clinical phenotyping, risk stratification and personalised treatment allocation approaches are rapidly evolving and will further benefit from the support of recent advances in e-health and artificial intelligence.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Inteligência Artificial , Humanos , Medicina de Precisão , Apneia Obstrutiva do Sono/terapia , Resultado do TratamentoRESUMO
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.
Assuntos
Avanço Mandibular , Apneia Obstrutiva do Sono , Adulto , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Placas Oclusais , Sistema Respiratório , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapiaRESUMO
BACKGROUND/OBJECTIVES: Although the benefits of bariatric surgery have been clearly established, it is not known whether they are as important in patients with obstructive sleep apnoea (OSA). Primary aim: to evaluate whether patients with moderate-to-severe OSA (apnoea-hypopnea index (AHI) ≥ 15 events/h) treated by continuous positive airway pressure/non-invasive ventilation (median [IQR] adherence 6.5 h/night [5; 7.9] at baseline) lose the same amount of body weight 1 year after bariatric surgery as patients with no or mild OSA. Secondary objectives: to compare the evolution of type 2 diabetes and hypertension after bariatric surgery, and surgical complication rates between groups. METHODS/SUBJECTS: Analyses were performed in 371 patients included in a prospective cohort of bariatric surgery, the Severe Obesity Outcome Network cohort. Subjects having moderate-to-severe OSA (n = 210) at baseline were compared with other subjects (n = 161). RESULTS: Excess weight loss (%EWL) at 1 year was lower in patients with moderate-to-severe OSA than in patients without (64.9%EWL [46.9; 79.5] vs. 73.8%EWL [56.6; 89.3], p < 0.01). Multivariable analysis showed that age, initial body mass index and type of surgery, but not OSA status, were associated with 1-year %EWL. Diabetes remitted in 25 (41%) patients with moderate-to-severe OSA and 16 (48%) patients with no or mild OSA (p = 0.48). Hypertension remitted in 28 (32.9%) patients with moderate-to-severe OSA and 9 (40.9%) with no or mild (p = 0.48). Complication rates were 28 (13.3%) in patients with moderate-to-severe OSA and 12 (7.5%) in patients with no or mild OSA (p = 0.07). CONCLUSIONS: Patients with OSA lose less body weight after bariatric surgery. This was related to older age and a higher baseline body mass index. However, the improvements of diabetes and hypertension were similar to that of patients without OSA, and the risk of surgical complications was not higher.
Assuntos
Cirurgia Bariátrica/normas , Obesidade Mórbida/cirurgia , Apneia Obstrutiva do Sono/cirurgia , Adulto , Idoso , Cirurgia Bariátrica/métodos , Índice de Massa Corporal , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/epidemiologia , Estudos Prospectivos , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/etiologiaRESUMO
BACKGROUND AND OBJECTIVE: Sleep Apnea Syndrome (SAS) is a multimorbid chronic disease with individual and societal deleterious consequences. Polysomnography (PSG) is the multi-parametric reference diagnostic tool that allows a manual quantification of the apnea-hypopnea index (AHI) to assess SAS severity. The burden of SAS is affecting nearly one billion people worldwide explaining that SAS remains largely under-diagnosed and undertreated. The development of an easy to use and automatic solution for early detection and screening of SAS is highly desirable. METHODS: We proposed an Accelerometry-Derived Respiratory index (ADR) solution based on a dual accelerometry system for airflow estimation included in a machine learning process. It calculated the AHI thanks to a RUSBoosted Tree model and used physiological and explanatory specifically developed features. The performances of this method were evaluated against a configuration using gold-standard PSG signals on a database of 28 subjects. RESULTS: The AHI estimation accuracy, specificity and sensitivity of the ADR index were 89%, 100% and 80% respectively. The added value of the specifically developed features was also demonstrated. CONCLUSION: Overnight physiological monitoring with the proposed ADR solution using a machine learning approach provided a clinically relevant estimate of AHI for SAS screening. The physiological component of the solution has a real interest for improving performance and facilitating physician's adhesion to an automatic AHI estimation.
Assuntos
Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Acelerometria , Humanos , Programas de Rastreamento , Polissonografia , Sensibilidade e Especificidade , Síndromes da Apneia do Sono/diagnósticoRESUMO
BACKGROUND: Obstructive sleep apnoea (OSA) causes intermittent hypoxia that in turn induces endothelial dysfunction and atherosclerosis progression. We hypothesised that VE-cadherin cleavage, detected by its released extracellular fragment solubilised in the blood (sVE), may be an early indicator of emergent abnormal endothelial permeability. Our aim was to assess VE-cadherin cleavage in OSA patients and in in vivo and in vitro intermittent hypoxia models to decipher the cellular mechanisms and consequences. METHODS: Sera from seven healthy volunteers exposed to 14â nights of intermittent hypoxia, 43 OSA patients and 31 healthy control subjects were analysed for their sVE content. Human aortic endothelial cells (HAECs) were exposed to 6â h of intermittent hypoxia in vitro, with or without an antioxidant or inhibitors of hypoxia-inducible factor (HIF)-1, tyrosine kinases or vascular endothelial growth factor (VEGF) pathways. VE-cadherin cleavage and phosphorylation were evaluated, and endothelial permeability was assessed by measuring transendothelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran flux. RESULTS: sVE was significantly elevated in sera from healthy volunteers submitted to intermittent hypoxia and OSA patients before treatment, but conversely decreased in OSA patients after 6â months of continuous positive airway pressure treatment. OSA was the main factor accounting for sVE variations in a multivariate analysis. In in vitro experiments, cleavage and expression of VE-cadherin increased upon HAEC exposure to intermittent hypoxia. TEER decreased and FITC-dextran flux increased. These effects were reversed by all of the pharmacological inhibitors tested. CONCLUSIONS: We suggest that in OSA, intermittent hypoxia increases endothelial permeability in OSA by inducing VE-cadherin cleavage through reactive oxygen species production, and activation of HIF-1, VEGF and tyrosine kinase pathways.
Assuntos
Células Endoteliais , Apneia Obstrutiva do Sono , Antígenos CD , Caderinas/metabolismo , Permeabilidade Capilar , Células Endoteliais/metabolismo , Humanos , Hipóxia , Permeabilidade , Fator A de Crescimento do Endotélio VascularRESUMO
BACKGROUND: Environmental research on multifactorial health outcomes calls for exposome approaches able to assess the joint effect of multiple exposures. OBJECTIVE: Our aim was to identify profiles of exposure to lifestyle/environmental factors associated with lung function in adults with asthma using a cluster-based approach. METHODS: We used data from 599 adults of the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) (mean age 39.0 years, 52% men) who ever had asthma. Exposures to 53 lifestyle/environmental factors were assessed by questionnaires or geographic information systems-based models. A two-step approach was developed: 1) exposome dimension reduction by selecting factors showing association with forced expiratory volume in 1 s (FEV1) (p < 0.20) in an exposome-wide association study (ExWAS), 2) clustering analysis using the supervised Bayesian Profile Regression (sBPR) to group individuals according to FEV1 level and to their profile of exposure to a reduced set of uncorrelated exposures (each paired correlation<0.70) identified in step 1. RESULTS: The ExWAS identified 21 factors showing suggestive association with FEV1 (none significant when controlling for multiple tests). The sBPR conducted on 15 uncorrelated exposures identified in step 1, revealed 3 clusters composed of 30, 115 and 454 individuals with a mean ± SD FEV1(%pred) of 79% ± 21, 90% ± 19 and 93% ± 16, respectively. Cluster 1 was composed of individuals with heavy smoking, poor diet, higher outdoor humidity and proximity to traffic, while cluster 2 and 3 included individuals with moderate/low levels of exposure to these factors. DISCUSSION: This exposome study identified a specific profile of joint lifestyle and environmental factors, associated with a low FEV1 in adults with asthma. None of the exposures revealed significant association when considered independently.
Assuntos
Asma , Expossoma , Adulto , Asma/epidemiologia , Teorema de Bayes , Exposição Ambiental/estatística & dados numéricos , Feminino , Volume Expiratório Forçado , Humanos , Pulmão , MasculinoRESUMO
INTRODUCTION: Recurrent vasovagal syncope (VVS) is associated with decreased quality-of-life and frequent use of emergency services. The evidence base for causality, diagnostic procedures and potential VVS treatments is poor. Scattered observations in the literature suggest a link between respiratory disturbances during sleep and VVS. Empirical observations lead us to further hypothesise that the appropriate management of sleep apnoea syndrome (SAS) may help resolve comorbid recurrent VVS in certain patients. We therefore designed this pilot study to provide a framework for the observation of changes in outcomes accompanying the deployment of SAS treatments in patients with VVS. METHODS AND ANALYSIS: This is a multicentre, registry-based study whose primary objective is to evaluate the effect of SAS management on the number of syncope/presyncope episodes in a population suffering from both VVS and SAS. To this effect, syncope rates prior to the treatment of SAS will be compared with those occurring after the initiation of the latter. In addition, yearly assessments will collect data for echocardiography, polysomnography, Holter monitoring, table tilt tests, multiple sleep latency tests, SAS management parameters and questionnaires describing fatigue, depression and quality-of-life. Sixty patients will be included with a minimum follow-up period of 12 months. The primary analysis will use comparisons of centrality for paired data to describe the changes in syncope rates before versus after the initiation of SAS management. Longitudinal data will be analysed using mixed models with patients set as a random effect. Subgroup analyses will be performed for SAS-treatment adherence and efficacy. ETHICS AND DISSEMINATION: The VVS-SAS registry was approved by an ethics committee (Comité pour la Protection des Personnes Ile-de-France VI, Reference number CPP/2-18) in accordance with French law. The princeps publication will present before-after SAS management results and longitudinal analyses. TRIAL REGISTRATION NUMBER: NCT04294524. Pre-results.
Assuntos
Síndromes da Apneia do Sono , Síncope Vasovagal , Estudos de Coortes , França , Humanos , Projetos Piloto , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/terapia , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/terapiaRESUMO
BACKGROUND: The Sleep Tiredness Observed Pressure-Body mass index Age Neck circumference Gender (STOP-Bang) questionnaire is a validated preoperative screening tool for identifying patients with obstructive sleep apnea (OSA). Although it has a high sensitivity at scores ≥3, its specificity is moderate, particularly for scores of 3-4. This study aimed to externally validate the STOP-Bang questionnaire and the alternative scoring models that have been proposed to improve its predictive performance. METHODS: This prospective cohort study included 115 surgical patients with preoperative STOP-Bang scores of 3-8. Type 3 sleep recordings identified moderate-to-severe OSA, reflected by an apnea-hypopnea index (AHI) of >15. Patients were categorized into 2 subgroups: patients with an intermediate (STOP-Bang 3-4) or a high risk of OSA (STOP-Bang 5-8). For patients with scores of 3-4, we tested approaches identified in previous studies: stepwise stratification of the STOP-Bang questionnaire and additional preoperative measurement of serum bicarbonate concentrations. RESULTS: The incidence of moderate-to-severe OSA was significantly higher in patients with STOP-Bang scores of 5-8 than in patients with scores of 3-4: 45 of 58 patients (78%) versus 30 of 57 patients (53%), respectively (P < .01). For patients with STOP-Bang scores of 3-4, we found no differences regarding their OSA diagnosis between patients included in the alternative scoring models and those not included. CONCLUSIONS: The STOP-Bang questionnaire detected moderate-to-severe OSA patients when scores reached 5-8. However, its performance was altered in patients with STOP-Bang scores of 3-4, and alternative scoring models with specific combinations of factors failed to improve the screening of these patients.
Assuntos
Índice de Massa Corporal , Pescoço/anatomia & histologia , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Idoso , Bicarbonatos/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Modelos Teóricos , Polissonografia , Cuidados Pré-Operatórios , Estudos Prospectivos , Reprodutibilidade dos Testes , Caracteres Sexuais , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Obstructive sleep apnea (OSA) is associated with cardiovascular co-morbidities and mortality. Arterial stiffness is an independent predictor of cardiovascular risk and mortality, and is influenced by the presence of OSA and related comorbidities. There is a paucity of data regarding long-term evolution of arterial stiffness in CPAP-treated OSA patients. We aimed to prospectively study long term PWV variations and determinants of PWV deterioration. METHODS: In a prospective obese OSA cohort, at time of diagnosis and after several years of follow-up we collected arterial stiffness measured by carotid-femoral pulse wave velocity (PWV), clinical and metabolic parameters, and CPAP adherence. Univariate and multivariate analyses were performed in order to determine contributing factors. RESULTS: Seventy two OSA patients (men: 52.8%, median age: 55.8 years and median BMI of 38.5 kg/m2) with a prevalence of hypertension: 58.3%, type 2 diabetes: 20.8%, hypercholesterolemia: 33.3%, current or past smoking: 59.7%, were evaluated after a median follow-up of 7.4 [5.8; 8.3] years. Over the period of follow-up, the median increase in PWV was 1.34 [0.10; 2.37] m/s. In multivariate analysis, the increase in PWV was associated with older age (10 extra years was associated with a 5.24 [1.35; 9.12] % increase in PWV) and hypertension (a significant increase in PWV of 8.24 [1.02; 15.57] %). No impact of CPAP adherence on PWV evolution was found. CONCLUSION: PWV progression in CPAP-treated OSA patients is mainly related to pre-existing cardio-metabolic comorbidities and not influenced by CPAP adherence. In this high cardiovascular risk population, it is crucial to associated weight management and exercise with CPAP treatment.