Introdução: A síndrome da apneia obstrutiva do sono (SAOS) tem sido cada vez mais estudada devido à sua prevalência e relação com problemas graves de saúde, como o aumento do risco de patologias cardiovasculares. O padrão-ouro para diagnóstico é a polissonografia (PSG), mas este método não fornece dados anatômicos da faringe dos pacientes. Objetivos: Avaliar, por meio de imagens de TC multislice (TCMS), o aspecto da faringe em indivíduos de um grupo controle e do grupo SAOS em vigília e durante o sono, observando as modificações sofridas nas estruturas faríngeas circunvizinhas e na coluna aérea; avaliar o comportamento faríngeo durante o ciclo respiratório nos indivíduos em vigília. Métodos: A amostra compreendeu 11 pacientes com SAOS grave, índice apneia/hipopneia maior que trinta, confirmados por PSG, e 7 indivíduos sem SAOS, controles, confirmados por PSG por Stardust, todos do sexo masculino. Os indivíduos foram submetidos a avaliação por TCMS com 16 canais (modelo Brilliance 16,Philips Medical Systems) e polissonografia simultânea. Os exames foram realizados com os indivíduos acordados e dormindo, em sono espontâneo. Foram realizadas aquisições volumétricas em ambos os estados (acordado e dormindo) e, posteriormente, avaliação das reformatações nos planos axiais, sagitais e das reconstruções em 3D. Foram realizadas medidas lineares e volumétricas: diâmetro mínimo anteroposterior e laterolateral, área mínima na orofaringe, retropalatal (RP) e retrolingual (RL), diâmetro transverso da língua, espessura da parede faríngea na região retropalatal, distância entre os ramos mandibulares, diâmetro anteroposterior da língua, comprimento e espessura do palato mole, espessura do tecido gorduroso subcutâneo na região submentoniana, distância MP-H (borda superior do hioide ao plano mandibular); volume da coluna aérea, volume das paredes faríngeas laterais, volume da gordura do espaço parafaríngeo e o volume da lingua. Resultados: As medidas significativamente menores encontradas no grupo SAOS, na região retropalatal, foram o diâmetro laterolateral e a área. Também houve diferença estatisticamente significativa nas medidas de espessura da língua, do palato, comprimento do palato, distância MP-H e ângulo mandibular. Foi realizado estudo comparativo entre as medidas lineares e volumétricas da faringe do grupo SAOS em estado de vigília e sono. Houve redução dos diâmetros retropalatal anteroposterior e laterolateral, da área e do volume da via aérea entre os estados acordado e dormindo. No grupo controle foram realizadas medidas lineares e volumétricas, porém não houve diferença significativa entre os diferentes estados. A variação da medida da área na região retropalatal foi significativa no grupo SAOS durante o estudo dinâmico. Conclusão: Em nossa amostra, as vias aéreas superiores de indivíduos do grupo SAOS diferem daquelas dos indivíduos do grupo controle. O grupo SAOS e o grupo controle sofrem modificações diferentes nas suas VAS, quando entram em estado de sono, de forma que as modificações do grupo SAOS são caracterizadas por mudanças significativas de medidas lineares e volumétricas, sugerindo maior suscetibilidade ao colapso faríngeo. O estudo dinâmico demonstrou que, na região retropalatal, indivíduos com SAOS são mais passíveis de colapso faríngeo. / Introduction: The obstructive sleep apnea syndrome (OSAS) has been increasingly studied because of the prevalence and relationship to serious healthy problems such as increased risk of cardiovascular diseases. The gold standard for diagnosis is polysomnography (PSG), but this method does not provide anatomical data of the pharynx of patients. Objectives: To evaluate the changes in upper airway and soft tissue structures surrounding the upper airway during wakefulness and sleep in patients with OSAS and a control group without OSAS. Methods: 11 patients with severe OSAS (apnea index > 30 event/hour) and 7 subjects without apnea and polysomnogram (Stardust) negative for OSAS were examined on a 16-channel multislice computed tomography. The exam was carried out with the patient awake and during spontaneous asleep, without any kind of sedation. The patients were monitored with a polysomnogram during the exam to assure the sleep and awaken state. Airway and soft-tissue 2-D measurements were performed in retropalatal and retroglossal level as well as, 3-D volumetric measurements. The measures were minimum anteroposterior and laterolateral diameter, the minimum area in the oropharynx in retropalatal and retroglossal levels, transverse and anteroposterior diameter of the tongue, pharyngeal wall thickness in RP, the distance between the mandibular branches, thickness and the length of the soft palate, the thickness of subcutaneous fat tissue in the submental region, MP-H distance (top edge of the hyoid to mandibular plane); volume of air column, volume of lateral pharyngeal wall, the volume of the parapharyngeal space fat, and the tongue volume. Results: Patients with OSAS had a small cross sectional area of retropalatal pharynx and the upper airway are significantly smaller when the patients were asleep. The measurements which presented significant decrease during sleep were the laterolateral and anteroposterior retropalatal diameter and minimal cross-seccional area. There was an inverse relationship between dimensions of lateral pharyngeal walls and the airway area, which was more pronounced during sleep. There was also a statistically significant difference in measures of the tongue thickness, palate thickness and length, MP-H distance and mandibular angle. There was a reduction of laterolateral, anteroposterior diameter, cross seccional area and upper airway volume, between awake and asleep states. Linear and volumetric measurements were performed in the control group but there was no significant difference between the different states. The variation of the cross seccional area in the OSAS group was significant during the dynamic study. Conclusion: The upper airway of subjects with severe OSAS differs from controls subjects. The OSAS group and the control group undergo different modifications in their upper airway after the sleep onset, and the changes of obstructive sleep apnea syndrome are characterized by significant changes of linear and volumetric measurements, suggesting greater pharyngeal collapsibility. There were significant differences in the patterns of dynamic airway motion between patients with and those without OSAS.

Objetivo: Estimar a prevalência de sintomas de apneia obstrutiva do sono (AOS), obstrução nasal (ON) e enurese em crianças com fissura labiopalatina unilateral, não sindrômicas. Local de execução: Unidade de Estudos do Sono do Laboratório de Fisiologia - HRAC/USP. Método: Estudo prospectivo transversal com a participação de 174 sujeitos que atenderam aos critérios de inclusão, de 6 a 12 anos de idade (média de 10,0 ± 1,8 anos, 58,62% do sexo masculino). A prevalência de sintomas de AOS e de ON foi estimada pela análise dos escores obtidos pelos instrumentos: Escala de Distúrbios do Sono em Crianças (EDSC); Índice de Congestão Nasal (CQ-5) e Escala Visual Analógica (EVA). A enurese foi considerada como presente quando relatada incontinência urinária intermitente durante o sono (no mínimo 1 episódio/mês, nos últimos 3 meses). Para caracterizar a enurese como monossintomática ou polissintomática, sintomas de disfunção do trato urinário inferior (DTUI) foram investigados pelo instrumento Dysfunctional Voiding Scoring System (DVSS), em Português. Foram colhidos dados sociodemográficos, antecedentes e comorbidades, índice de massa corpórea (IMC) e razão circunferência abdominal/altura (CA/A). Foram analisadas medidas de posição e dispersão, frequências percentuais e absolutas e razão de prevalências. Diferenças entre subgrupos foram analisadas a um nível de significância de 5%. Resultados: Escore EDSC positivo para AOS foi observado em 60 (34,48%) crianças da amostra; escore CQ-5 positivo para ON em 45 (25,86%), escore DVSS positivo para DTUI em 30 (17,24%) e 29 (16,67%) crianças apresentaram enurese. Ronco habitual foi observado em 75,00% no subgrupo AOS e sensação de nariz obstruído habitual em 75,56% no subgrupo ON. Não foram constatadas diferenças significativas quanto a sexo, raça, IMC e razão CA/A. A ocorrência de enurese foi maior aos 6 e 7 anos, com queda gradativa aos 8 anos e ausência aos 12 anos. Houve predomínio de enurese primária (65,52%), infrequente (68,96%) e polissintomática (72,41%). Comparativamente aos dados da literatura, as razões de prevalências de AOS, do sintoma nariz obstruído e de enurese foram até 6,75 vezes (IC 95% 5,3 - 8,7), 2,14 vezes (IC 95% 1,8 - 2,5) e 3,33 vezes (IC 95% 2,3 - 4,7) maiores, respectivamente. Foi identificada associação entre sintomas de AOS e ON (p=0,0001), com correlação positiva e moderada entre os escores médios do EDSC e do CQ-5 (0,545). Não se verificou maior prevalência de enurese nas crianças com sintomas de AOS. Conclusão: As crianças com FLPUNS tem alta prevalência de obstrução nasal e enurese e estão sob risco para apneia obstrutiva do sono / Objectives: To estimate the prevalence ratios of nasal obstruction (NO) symptoms, OSA-related symptoms and enuresis in Brazilian nonsyndromic children with repaired unilateral cleft lip and palate (UCLP/NS). Setting: Sleep Studies Unit, Laboratory of Physiology, HRAC/USP. Methods: 174 children with repaired UCLP/NS, meeting inclusion criteria, participated in this prospective, cross-sectional study (aged 6-12 y, 58.62% boys). Validated questionnaires were used to predict OSA and subjective NO, Sleep Disturbance Scale for Children (SDSC), Congestion Quantifier Five Item (CQ-5) and Visual Analog Scale (VAS), respectively. Enuresis was defined as intermittent incontinence of urine during sleeping (with a minimum of one episode per month and at least for 3 months). In order to identify non-monosymptomatic enuresis, lower urinary tract dysfunction was assessed by a validated questionnaire, the Dysfunctional Voiding Scoring System (DVSS). Sociodemographic data, medical history, comorbidities, body mass index (BMI) and waist-to-height ratio (WHR) were analyzed. Measures of central tendency and dispersion, absolute and relative frequencies and prevalence ratios were analyzed. Subgroups were compared at 5% significance level. Results: Positive screening for OSAS-related symptoms was seen in 60 (34.48%) children and subjective NO in 45 (25.86%). Enuresis was seen in 29 (16.67%) children and positive DVSS score in 30 (17.24%). Habitual snoring was seen in 75.00% of the children with OSA-related symptoms and sensation of nasal obstruction in 75.56% of the children with positive CQ-5 score. No differences were observed for gender, race, BMI and WHR. The occurrence of enuresis was higher at 6/7 y of age, with a gradual decline at 8 years and absence at 12 y. There was a predominance of primary (65.52%), infrequent (68.96%) and non-monosymptomatic (72.41%) enuresis. Compared to literature data, prevalence ratios of OSA-related symptoms, NO and enuresis were, respectively, 6.75 (95% CI 5.3 - 8.7), 2.14 (95% CI 1.8 - 2.5) and 3.33 (95% CI 2.3 - 4.7) times higher. Association was identified between symptoms of OSA and ON (p=0.0001), with a positive and moderate correlation between the average scores of the EDSC and CQ-5 (0.545). Prevalence of enuresis was not higher in children with symptoms of OSA. Conclusion: Nonsyndromic children with cleft lip and palate have a high prevalence of symptoms of nasal obstruction and enuresis, and are at risk for obstructive sleep apnea

Childhood OSA is increasingly recognized to be associated with a variety of complications including neurocognitive and cardiovascular diseases. The intermediate link between OSA and end organ damage has been suggested to be inflammation, and both local airway and systemic inflammation have been described in adults with OSA. A non-invasive technique of sputum induction was utilised to show that children with OSA also have airway inflammation, as characterized by a significant increase in neutrophils, and the severity of OSA also correlated significantly with the degree of neutrophilic inflammation (Chapter 7). This finding may lead to research on the use of anti-inflammatory therapeutic agents or antibiotics for the treatment of childhood OSA. Another marker of inflammation, C-reactive protein (CRP) was measured in a cohort of children with OSA before and after treatment (Chapter 8). Children with OSA had higher CRP levels compared to their non-OSA counterparts, and the raised CRP decreased significantly following treatment suggesting that the inflammatory response is potentially reversible. The cardiovascular risk factors of insulin levels and blood pressure (BP) were evaluated and children with OSA had higher serum insulin and greater systolic and diastolic BP compared to healthy controls (Chapters 9 and 10). These findings suggest that children with OSA may be at risk of developing metabolic syndrome and its devastating consequence. (Abstract shortened by UMI.) / The original research studies undertaken were based on nocturnal sleep examinations to explore childhood OSA in two main aspects, namely its assessment, and a better understanding of its complications in children. The gold standard for diagnosing OSA is overnight polysomnography (PSG), which is an expensive investigation that is not routinely available at all public hospitals in Hong Kong. Alternative valid assessment tools for OSA that are more cost-effective are needed. The feasibility of using radiographic techniques to assess severity of OSA was explored, and the size of the upper airway, as reflected by the tonsillar pharyngeal (TP) ratio obtained from lateral neck radiograph, correlated well with the severity of OSA (Chapter 4). A defined TP cutoff could accurately predict moderate-to-severe OSA with high sensitivity and specificity. This method could be used in clinical practice to prioritize patients with suspected OSA for further evaluation. A locally applicable questionnaire scale was examined for its validity and accuracy in diagnosing children with OSA (Chapter 5). The presence of three symptoms (snoring, mouth breathing and nocturnal sweating) was found to have high predictive value in correctly identifying children with the condition. The question of whether a single night PSG study is adequate in diagnosing OSA was examined together with the assessment for the presence of night-to-night variability in PSG and respiratory parameters in childhood sleep (Chapter 6). Forty-four obese children and 43 age and sex-matched healthy controls underwent two consecutive nights PSG examination. Although a first night effect was clearly documented, a single night PSG study would have correctly identified over 80% of children with OSA. This finding has significant resource implications. / Albert Martin Li. / Adviser: Tony Nelson. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3420. / Thesis (M.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves xxxv-lxxx). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English only. / School code: 1307.

O escopo dete trabalho é verificar a influência de episódios agudos de hipoxemia e subsequente reoxigenação sobre marcadores inflamatórios e sobre sinalizadores de integridade da função endotelial. / The aim of this study is to verify the effect of acute hipoxemia and subsequente reoxigenation over inflammatory markers and indicators of integrity of the endothelial function.

Background. Obstructive Sleep Apnoea (OSA) is associated with an increase in nocturnal gastro-oesophageal reflux (nocturnalGOR) events and symptoms, however the mechanism for this remains undefined. Treatment of OSA with continuous positive airway pressure (CPAP) has been shown to reduce nocturnalGOR in individuals with OSA however the reasons for this reduction are not clear. The combination of OSA and nocturnalGOR could be particularly problematic for individuals who have had a lung transplant in whom Bronchiolitis Obliterans Syndrome (BOS) limits survival. It is thought that GOR plays a role in the development of BOS in these individuals. Methods and Results. Five interrelated studies were undertaken. The first two studies sought to determine and compare the prevalence and risk factors of nocturnalGOR in OSA patients with the general population. To do this, a GOR questionnaire was completed by 2,042 members of the general community as part of the Busselton Health Survey and by 1,116 patients with polysomnography-diagnosed OSA. Risk of OSA in the general population was determined using a standardised sleep questionnaire. 137 of the OSA patients completed the questionnaire before and after treatment with CPAP. The prevalence of nocturnalGOR symptoms reported more than once a week (frequent symptoms) was greater in OSA patients (10.1%) than the general population (5.8%) (p<0.001), in individuals from the general population at high (11.2%) than low risk of OSA (4.5%) (p<0.001) and in patients with severe (14.7%) than mild OSA (5.2%) (p<0.001). Treatment of OSA with CPAP decreased the prevalence of frequent nocturnalGOR from 9.0% to 3.8% (p=0.04). In the general population, high risk of OSA was independently associated with a 2.4-fold increased risk of frequent ABSTRACT vi nocturnalGOR symptoms than low risk. In the OSA group, disease severity was independently associated with nocturnalGOR symptoms, with an adjusted odds ratio of 1.7 for frequent nocturnalGOR symptoms.

Sleep disruption has been implicated in morbidity after major surgery since 1974. Sleep-related upper airway obstruction has been associated with death after upper airway surgery and profound episodic hypoxaemia in the early postoperative period. There is also evidence for a rebound in rapid eye movement (REM) sleep that might be contributing to an increase in episodic sleep-related hypoxaemic events later in the first postoperative week. Speculation regarding the role of REM sleep rebound in the generation of late postoperative morbidity and mortality has evolved into dogma without any direct evidence to support it. The research presented in this thesis involved two main areas: a search for evidence of a clinically important contribution of REM sleep rebound to postoperative morbidity, and a re-examination of the role of sleep in the causation of postoperative episodic hypoxaemic events. To assess the latter, a relationship between airway obstruction under anaesthesia and the severity of sleep-disordered breathing was sought. In 148 consecutive sleep clinic patients, 49% of those with sleep-disordered breathing (SDB) had a number of events in non-rapid eye movement sleep (NREM) that was greater than or equal to that in REM and 51% had saturation nadirs in NREM that were equal to or worse than their nadirs in REM. This suggests SDB is not a REM-predominant phenomenon for most patients. Of 1338 postoperative deaths occurring over 6.5 years in one hospital only 37 were unexpected, most of which were one or two days after surgery with no circadian variation in the time of death, casting further doubt on the potential role of REM rebound. Five of nine subjects studied preoperatively had moderately severe SDB. Unrecognised and significant SDB is common in middle-aged and elderly patients presenting for surgery suggesting overall perioperative risk of important adverse events from SDB is probably small. In 17 postoperative patients, sleep macro-architecture was variably altered with decreases in REM and slow wave sleep while stage 1 sleep and a state of pre-sleep onset drowsiness, both associated with marked ventilatory instability, were increased. Sleep micro-architecture was also changed with an increase in power in the alpha-beta electroencephalogram range. These micro-architectural changes result in ambiguity in the staging of postoperative sleep that may have affected the findings of this and other studies. Twenty-four subjects with airway management difficulty under anaesthesia were all found to have some degree of SDB. Those with the most obstruction-prone airways while anaesthetised had a very high incidence of severe SDB. Such patients warrant referral to a sleep clinic.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

This thesis draws from music technology to create novel sonifications of heart rate information that may be of clinical utility to physicians. Current visually-based methods of analysis involve filtering the data, so that by definition some aspects are illuminated at the expense of others, which are decimated. However, earlier research has demonstrated the suitability of the auditory system for following multiple streams of information. With this in mind, sonification may offer a means to display a potentially unlimited number of signal processing operations simultaneously, allowing correlations among various analytical techniques to be observed. This study proposes a flexible listening environment in which a cardiologist or researcher may adjust the rate of playback and relative levels of several parallel sonifications that represent different processing operations. Each sonification "track" is meant to remain perceptually segregated so that the listener may create an optimal audio mix. A distinction is made between parameters that are suited for illustrating information and parameters that carry less perceptual weight, which are employed as stream separators. The proposed sonification model is assessed with a perception test in which participants are asked to identify four different cardiological conditions by auditory and visual displays. The results show a higher degree of accuracy in the identification of obstructive sleep apnea by the auditory displays than by visual displays. The sonification model is then fine-tuned to reflect unambiguously the oscillatory characteristics of sleep apnea that may not be evident from a visual representation. Since the identification of sleep apnea through the heart rate is a current priority in cardiology, it is thus feasible that sonification could become a valuable component in apnea diagnosis.

Sleep disruption has been implicated in morbidity after major surgery since 1974. Sleep-related upper airway obstruction has been associated with death after upper airway surgery and profound episodic hypoxaemia in the early postoperative period. There is also evidence for a rebound in rapid eye movement (REM) sleep that might be contributing to an increase in episodic sleep-related hypoxaemic events later in the first postoperative week. Speculation regarding the role of REM sleep rebound in the generation of late postoperative morbidity and mortality has evolved into dogma without any direct evidence to support it. The research presented in this thesis involved two main areas: a search for evidence of a clinically important contribution of REM sleep rebound to postoperative morbidity, and a re-examination of the role of sleep in the causation of postoperative episodic hypoxaemic events. To assess the latter, a relationship between airway obstruction under anaesthesia and the severity of sleep-disordered breathing was sought. In 148 consecutive sleep clinic patients, 49% of those with sleep-disordered breathing (SDB) had a number of events in non-rapid eye movement sleep (NREM) that was greater than or equal to that in REM and 51% had saturation nadirs in NREM that were equal to or worse than their nadirs in REM. This suggests SDB is not a REM-predominant phenomenon for most patients. Of 1338 postoperative deaths occurring over 6.5 years in one hospital only 37 were unexpected, most of which were one or two days after surgery with no circadian variation in the time of death, casting further doubt on the potential role of REM rebound. Five of nine subjects studied preoperatively had moderately severe SDB. Unrecognised and significant SDB is common in middle-aged and elderly patients presenting for surgery suggesting overall perioperative risk of important adverse events from SDB is probably small. In 17 postoperative patients, sleep macro-architecture was variably altered with decreases in REM and slow wave sleep while stage 1 sleep and a state of pre-sleep onset drowsiness, both associated with marked ventilatory instability, were increased. Sleep micro-architecture was also changed with an increase in power in the alpha-beta electroencephalogram range. These micro-architectural changes result in ambiguity in the staging of postoperative sleep that may have affected the findings of this and other studies. Twenty-four subjects with airway management difficulty under anaesthesia were all found to have some degree of SDB. Those with the most obstruction-prone airways while anaesthetised had a very high incidence of severe SDB. Such patients warrant referral to a sleep clinic.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.