京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19400号 / 医博第4051号 / 新制||医||1012(附属図書館) / 32425 / 京都大学大学院医学研究科医学専攻 / (主査)教授 横出 正之, 教授 福原 俊一, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20261号 / 医博第4220号 / 新制||医||1020(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 福田 和彦, 教授 木村 剛, 教授 大森 孝一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(人間健康科学) / 甲第23574号 / 人健博第94号 / 新制||人健||7(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 任 和子, 教授 木下 彩栄, 教授 平井 豊博 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

No description available.

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is characterised by repeated cycles of upper airway obstruction during sleep, leading to diurnal symptoms. Individuals with Down syndrome (DS) are predisposed to this as the DS phenotype overlaps with OSAHS risk factors. Around 2-4% of the general adult population and 55% of children with DS have OSAHS but, to date, no large-scale study has assessed OSAHS prevalence or efficacy of treatment in DS adults. This study aimed to: 1) Systematically assess subjective and objective OSAHS prevalence; 2) Assess the effectiveness of continuous positive airway pressure (CPAP) in an adult DS population. Standard questionnaires including pictorial Epworth Sleepiness Scale (pESS) and Developmental Behaviour Checklist for Adults (DBC-A) were sent to UK adults aged ≥16yr with DS and their caregivers. All questionnaire responders were invited to undergo home polygraphy. Symptomatic adults with DS with ≥10 apnoeas/hypopnoeas per hour in bed (AH) on home polygraphy were invited to participate in a prospective randomised controlled trial (RCT) of CPAP v. lifestyle advice, with review at 1, 3, 6 and 12m. Participants in the lifestyle arm were offered CPAP at 1m. Standard measurements of sleepiness, behaviour, cognitive function and general health were undertaken. Standard statistical analyses were conducted, with significance set at p < 0.001 to control for multiple testing. Of 5270 questionnaires sent, 1105 responses were valid (21%). Responders (55% males) were overweight/obese young adults: mean BMI 29.0±6.8kg/m2; mean age 28±9 years. Women had a higher BMI (p < 0.0001), but collar size was greater in men (p < 0.0001). Mean pESS scores were broadly within the normal range (7±5/24). No significant gender differences in OSAHS symptoms were noted. Individuals with probable OSAHS had higher pESS and DBC-A scores, and significantly more symptoms of OSAHS. Subjective OSAHS prevalence was estimated at 35%. Of the 790 individuals invited, 149 underwent polygraphy, with 134 valid studies obtained: mean AH 21.8(10.9-42.7); mean oximetry desaturation index (ODI) 6.6(2.3-20.0). No significant gender differences were observed. Forty-two percent of participants met standard clinical diagnostic criteria for OSAHS. Twenty-eight eligible adults with DS (19 male) were randomised: age 28±9yr; BMI 31.5±7.9kg/m2; AH 28.6(14.8-47.9); ODI 7.3(1.8-21.9); pESS 11±6/24. Groups did not differ significantly at baseline. By 12m, 4 participants had withdrawn (all remaining participants on CPAP). The pESS (p=0.001), DBC-A Disruptive (p < 0.0001) and Kaufmann Brief Intelligence Test verbal subscale (p=0.001) scores improved significantly. This first large study of OSAHS prevalence in the adult DS population estimates a prevalence of 35-42% - around 10 times higher than in the general adult population. Sustained, significant improvements in sleepiness, cognitive function and behavioural/emotional outcomes with CPAP use over a 12m period were demonstrated during this first RCT of CPAP in adults with DS. A larger trial of CPAP in this population is warranted.

A pressão positiva contínua nas vias aéreas(CPAP) é a forma mais simples de ventilação não invasiva. O objetivo deste estudo é comparar o desempenho de dois modelos de gerador de fluxo com um ventilador projetado especificamente para ventilação não invasiva no modo CPAP, através de um modelo mecânico de pulmão e em voluntários sadios, em três diferentes alimentações de pressão e em CPAP de 5, 10 e 15 cm H2O. Conclui-se que os geradores de fluxo têm capacidade similar ao ventilador específico para manter o nível de CPAP, se ajustados para sua melhor pressão de alimentação, que foi ao redor de 100 L/min / Continuous positive airway pressure (CPAP) is the simplest form of noninvasive ventilation. Mechanical ventilators designed to invasive ventilation, ventilators specifically designed to noninvasive ventilation (NIV-Ventilator) and continuous flow generators can provide CPAP. The objectives of this study is compare the performance of two continuous flow generators with a ventilator designed to NIV to deliver continuous positive airway pressure (CPAP) and compare flow generators using different oxygen pressure supplies in lung model and healthy subjects, in CPAP of 5, 10 and 15 cm H2O. It was observed that flow generators had similar performance to noninvasive ventilator if they were adjust in their best output flow, that was around 100 L/min

Introduction: Obstructive sleep apnoea (OSA) is common and is caused by repetitive obstruction of the upper airway during sleep. OSA is associated with increased cardiovascular morbidity and mortality and is an independent risk factor for hypertension. The immediate physiological effects of OSA include intermittent hypoxia, repeated arousal from sleep and intra-thoracic pressure swings. The resulting activation of the sympathetic nervous system, systemic inflammation and oxidative stress may result in increased arterial stiffness and endothelial dysfunction, potentially explaining any causal link between OSA and cardiovascular disease (CVD). Continuous positive airway pressure (CPAP) therapy improves excessive daytime sleepiness (EDS) and in non-randomised studies, reduces cardiovascular mortality. Prior to starting this study, there was a limited amount of evidence suggesting that CPAP therapy improved arterial stiffness and endothelial function, but the effects in subjects without pre-existing CVD were unclear. Aims: i) to determine whether CPAP therapy has an effect upon measures of arterial stiffness and endothelial function in patients with OSA, in the absence of known CVD. ii) To compare arterial stiffness and endothelial function in a subset of patients with OSAHS (defined as OSA and EDS), with a group of well-matched control subjects. Methods: Fifty three patients with OSA, defined as an apnoea/hypopnoea index of ≥15, and without known CVD, entered a double-blind placebo-controlled crossover trial of 12 weeks CPAP therapy, of whom forty three completed the study protocol. Sham CPAP was used in the placebo arm of the study and vascular assessments were made at baseline and after each arm of the study. Arterial stiffness was determined by measuring aortic distensibility using cardiovascular magnetic resonance imaging and by measuring the augmentation index (AIx) and aortic pulse wave velocity (PWV) by applanation tonometry. Endothelial function was assessed non-invasively by measuring vascular reactivity after administration of salbutamol and glyceryl trinitrate. In a subset of twenty patients with OSAHS, arterial stiffness and endothelial function at baseline were compared to readings obtained from healthy control subjects, matched on a one-to-one basis for age, sex and BMI. Results: Patients with OSAHS (n=20) had increased arterial stiffness [AIx 19.3(10.9) vs. 12.6(10.2) %; p=0.017] and impaired endothelial function, measured as the change in AIx following salbutamol [-4.3(3.2) vs. -8.0(4.9) %; p=0.02] compared to controls. Twelve weeks of CPAP therapy had no significant effect upon any measure of arterial stiffness or endothelial function in patients with OSA (n=43). A trend towards a reduction in AIx following CPAP therapy was seen, but this was non-significant. There was a reduction in systolic blood pressure following CPAP therapy [126(12) vs. 129(14) mmHg]. Sub group analysis showed CPAP to have no effect on arterial stiffness or endothelial function in patients with EDS or in patients using CPAP for ≥4 hours per night. Conclusions: This study demonstrates that even in the absence of known CVD, patients with OSAHS have evidence of increased arterial stiffness and impaired endothelial function. However, in patients with OSA, free from CVD, CPAP therapy did not lead to an improvement in any measure of arterial stiffness or endothelial function after 12 weeks.

Objetivos: Determinar o tempo de espera para o diagnóstico e início do tratamento da síndrome da apneia obstrutiva do sono (SAOS) em hospital público brasileiro. Desenho do estudo: Estudo transversal. Métodos: Foi avaliada, com um questionário específico, uma amostra de conveniência composta por 68 pacientes com síndrome da apneia obstrutiva do sono (SAOS), com indicação de tratamento com pressão positiva em vias aéreas (PAP) e que utilizaram o aparelho durante acompanhamento ambulatorial, no período de janeiro de 2005 a dezembro de 2009. Foram excluídos os pacientes menores de 18 anos, incapazes de responder ao questionário ou que se negaram a participar. Resultados: Dos pacientes avaliados, a maioria era de homens (62%), com média de idade de 54,4 (+ 10,7) anos e obesos (IMC médio 33,7 + 7,1 Kg/m2); 76% eram hipertensos, 22% portadores de diabete melito e igual número de doença arterial coronariana; 10% destes apresentavam hipoventilação associada. A mediana do tempo entre a primeira consulta médica e a realização da PSG diagnóstica foi de 8,3 (intervalos interquartis [IQ] 3,3-14,3) meses e a mediana do tempo da indicação da PAP até a aquisição do aparelho foi de 10,5 (IQ 3,1-16,7) meses. Sessenta e quatro pacientes (94%) eram usuários de CPAP e 4 usuários de bilevel (6%). A maioria dos aparelhos (57%) foi obtida de forma gratuita por meio da rede pública de saúde. Conclusão: O presente estudo evidenciou a demora excessiva para diagnóstico e tratamento dos pacientes portadores de SAOS em atendimento em um hospital público de referência no Brasil. / Objectives: To determine the waiting time for the diagnosis and beginning of treatment of syndrome of obstructive sleep apnea (OSA) in Brazilian public hospital. Study design: cross-sectional study Methods: A convenience sample composed of 68 patients with syndrome of obstructive sleep apnea (OSA) was assessed through a specific questionnaire. All patients were indicated a treatment with positive airway pressure (PAP) and that used the unit during de period between January 2005 and December 2009. Patients who were under 18 years old, who were uncapable of answering the questionnaire or who refused to answer were excluded. Results: Among the patients, the majority were men (62%), with an average age of 54.4 (+10.7) years and obese (mean BMI 33.7 + 7.1 kg/m2); 76% were hypertensive, 22% diabetes mellitus patients and an equal number with coronary artery disease, 10% of them had associated hypoventilation. The average time between the first medical consultation and the implementation of diagnostic PSG was 8.3 (interquartile range [IQ] 3.3 to 14.3) months and the average time indication of the PAP until the purchase of the equipment was 10,5 (CI 3.1 to 16.7) months. Sixty-four patients (94%) were users of CPAP and 4 were users of bilevel (6%). Most appliances (57%) were obtained free of charge through the public health system. Conclusion: The present study demonstrated the excessive delay to diagnosis and treatment of patients with OSAS in attendance at a public hospital of reference in Brazil.

Objetivos: Determinar o tempo de espera para o diagnóstico e início do tratamento da síndrome da apneia obstrutiva do sono (SAOS) em hospital público brasileiro. Desenho do estudo: Estudo transversal. Métodos: Foi avaliada, com um questionário específico, uma amostra de conveniência composta por 68 pacientes com síndrome da apneia obstrutiva do sono (SAOS), com indicação de tratamento com pressão positiva em vias aéreas (PAP) e que utilizaram o aparelho durante acompanhamento ambulatorial, no período de janeiro de 2005 a dezembro de 2009. Foram excluídos os pacientes menores de 18 anos, incapazes de responder ao questionário ou que se negaram a participar. Resultados: Dos pacientes avaliados, a maioria era de homens (62%), com média de idade de 54,4 (+ 10,7) anos e obesos (IMC médio 33,7 + 7,1 Kg/m2); 76% eram hipertensos, 22% portadores de diabete melito e igual número de doença arterial coronariana; 10% destes apresentavam hipoventilação associada. A mediana do tempo entre a primeira consulta médica e a realização da PSG diagnóstica foi de 8,3 (intervalos interquartis [IQ] 3,3-14,3) meses e a mediana do tempo da indicação da PAP até a aquisição do aparelho foi de 10,5 (IQ 3,1-16,7) meses. Sessenta e quatro pacientes (94%) eram usuários de CPAP e 4 usuários de bilevel (6%). A maioria dos aparelhos (57%) foi obtida de forma gratuita por meio da rede pública de saúde. Conclusão: O presente estudo evidenciou a demora excessiva para diagnóstico e tratamento dos pacientes portadores de SAOS em atendimento em um hospital público de referência no Brasil. / Objectives: To determine the waiting time for the diagnosis and beginning of treatment of syndrome of obstructive sleep apnea (OSA) in Brazilian public hospital. Study design: cross-sectional study Methods: A convenience sample composed of 68 patients with syndrome of obstructive sleep apnea (OSA) was assessed through a specific questionnaire. All patients were indicated a treatment with positive airway pressure (PAP) and that used the unit during de period between January 2005 and December 2009. Patients who were under 18 years old, who were uncapable of answering the questionnaire or who refused to answer were excluded. Results: Among the patients, the majority were men (62%), with an average age of 54.4 (+10.7) years and obese (mean BMI 33.7 + 7.1 kg/m2); 76% were hypertensive, 22% diabetes mellitus patients and an equal number with coronary artery disease, 10% of them had associated hypoventilation. The average time between the first medical consultation and the implementation of diagnostic PSG was 8.3 (interquartile range [IQ] 3.3 to 14.3) months and the average time indication of the PAP until the purchase of the equipment was 10,5 (CI 3.1 to 16.7) months. Sixty-four patients (94%) were users of CPAP and 4 were users of bilevel (6%). Most appliances (57%) were obtained free of charge through the public health system. Conclusion: The present study demonstrated the excessive delay to diagnosis and treatment of patients with OSAS in attendance at a public hospital of reference in Brazil.

Objetivos: Determinar o tempo de espera para o diagnóstico e início do tratamento da síndrome da apneia obstrutiva do sono (SAOS) em hospital público brasileiro. Desenho do estudo: Estudo transversal. Métodos: Foi avaliada, com um questionário específico, uma amostra de conveniência composta por 68 pacientes com síndrome da apneia obstrutiva do sono (SAOS), com indicação de tratamento com pressão positiva em vias aéreas (PAP) e que utilizaram o aparelho durante acompanhamento ambulatorial, no período de janeiro de 2005 a dezembro de 2009. Foram excluídos os pacientes menores de 18 anos, incapazes de responder ao questionário ou que se negaram a participar. Resultados: Dos pacientes avaliados, a maioria era de homens (62%), com média de idade de 54,4 (+ 10,7) anos e obesos (IMC médio 33,7 + 7,1 Kg/m2); 76% eram hipertensos, 22% portadores de diabete melito e igual número de doença arterial coronariana; 10% destes apresentavam hipoventilação associada. A mediana do tempo entre a primeira consulta médica e a realização da PSG diagnóstica foi de 8,3 (intervalos interquartis [IQ] 3,3-14,3) meses e a mediana do tempo da indicação da PAP até a aquisição do aparelho foi de 10,5 (IQ 3,1-16,7) meses. Sessenta e quatro pacientes (94%) eram usuários de CPAP e 4 usuários de bilevel (6%). A maioria dos aparelhos (57%) foi obtida de forma gratuita por meio da rede pública de saúde. Conclusão: O presente estudo evidenciou a demora excessiva para diagnóstico e tratamento dos pacientes portadores de SAOS em atendimento em um hospital público de referência no Brasil. / Objectives: To determine the waiting time for the diagnosis and beginning of treatment of syndrome of obstructive sleep apnea (OSA) in Brazilian public hospital. Study design: cross-sectional study Methods: A convenience sample composed of 68 patients with syndrome of obstructive sleep apnea (OSA) was assessed through a specific questionnaire. All patients were indicated a treatment with positive airway pressure (PAP) and that used the unit during de period between January 2005 and December 2009. Patients who were under 18 years old, who were uncapable of answering the questionnaire or who refused to answer were excluded. Results: Among the patients, the majority were men (62%), with an average age of 54.4 (+10.7) years and obese (mean BMI 33.7 + 7.1 kg/m2); 76% were hypertensive, 22% diabetes mellitus patients and an equal number with coronary artery disease, 10% of them had associated hypoventilation. The average time between the first medical consultation and the implementation of diagnostic PSG was 8.3 (interquartile range [IQ] 3.3 to 14.3) months and the average time indication of the PAP until the purchase of the equipment was 10,5 (CI 3.1 to 16.7) months. Sixty-four patients (94%) were users of CPAP and 4 were users of bilevel (6%). Most appliances (57%) were obtained free of charge through the public health system. Conclusion: The present study demonstrated the excessive delay to diagnosis and treatment of patients with OSAS in attendance at a public hospital of reference in Brazil.