Significant cardiovascular morbidity and mortality exists in chronic obstructive pulmonary disease independent of traditional risk factors. A number of different hypotheses exist to explain this association including the contribution arterial stiffness and lung hyperinflation. Non-invasive cardiovascular imaging and assessment are ideal methods through which this relationship can be further studied although a number of the techniques have yet to be validated in COPD. In this thesis we aimed to achieve a number of goals. First, we aimed to assess the reproducibility and level of agreement between different measures of arterial stiffness in stable hyperinflated COPD. Second, we hoped to establish the utility of 3 different measurement techniques for measuring intrinsic cardiac function in stable hyperinflated COPD. Third, in a case-control study we compared surrogates of cardiovascular risk in hyperinflated COPD patients and a group matched for cardiovascular risk with normal lung function. Finally, we sought to understand the impact of pharmacologically reducing lung hyperinflation on cardiovascular structure, function and arterial stiffness. We have firstly demonstrated that non-invasive measures of arterial stiffness are reproducible in stable hyperinflated COPD. Secondly, we have established the level of agreement and reproducibility of three different CMR techniques for measuring intrinsic myocardial function which will provide important information for the powering of future CMR studies in COPD. Thirdly, we have shown that surrogates for cardiovascular outcomes are adversely affected in COPD compared to a group matched for global cardiovascular risk, suggesting that current scoring systems may be suboptimal in risk prediction in COPD. Finally, we have demonstrated that pharmacological lung deflation has consistent and physiologically plausible beneficial effects on cardiac structure, function and the pulmonary vasculature. Whether intrinsic myocardial function can be modulated through prolonged periods of lung deflation is as yet unverified and should be the focus of future clinical trials.

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / Chronic obstructive pulmonary disease is a common, avoidable and treatable disease characterized by persistent obstruction of the airways and lungs. This disease is usually progressive and associated with a chronic inflammatory response set off by noxious particles or gases. Patients with chronic obstructive pulmonary disease, represents a great impact on the increase of clinical care, as well as the economic health spending to provide better quality of life. This study characterizes the pharmacoepidemiological profile, adherence to drug therapy, pharmacotherapy complexity and performance of using inhalation devices in outpatientâs subjects of a referral hospital for treatment of pulmonary diseases. This is a descriptive, exploratory and transversal study. 83 individuals were interviewed, with a predominance of males, a mean age of 68.22 years, and low schooling. The average number of medications per patient was 5.58, characterizing the polypharmacy, and 81.9% had some type of comorbidity. The founded prevalence was mean adherence rate (45.8%). The most frequent response among the questions asked to measure adherence was related to forgettings (38.6%). The complexity therapy had a mean value of 15.9 points, a high score that reveals the difficulties in following the treatment. After evaluation of inhalation devices was found that as the use of dry powder inhaler Aerolizer, the technique was considered good in 62.5% of patients, the use of Respimat  inhaler was "good" in 70.96% of cases and the use of metered-dose aerosol showed to be regular in 64.7%. The evaluation of the use of the devices found flaws in several steps considered essential for their proper management. From these data, are needed strategies that aimed at enhancing actions to improve adherence to therapy and ongoing evaluation of inhalation devices, minimizing complications for the patient. / A DoenÃa pulmonar obstrutiva crÃnica, à uma doenÃa comum, evitÃvel e tratÃvel, caracterizada por obstruÃÃo persistente das vias aÃreas e dos pulmÃes, geralmente progressiva e associada a uma resposta inflamatÃria crÃnica desencadeada por partÃculas ou gases nocivos. Os pacientes portadores de DoenÃa pulmonar obstrutiva crÃnica representam um grande impacto no aumento dos atendimentos clÃnicos, assim como nos gastos econÃmicos com a saÃde para proporcionar melhor qualidade de vida. Este trabalho caracteriza o perfil farmacoepidemiolÃgico, a adesÃo à terapia medicamentosa, complexidade da farmacoterapia e o desempenho do uso de dispositivos inalatÃrios em indivÃduos atendidos em um ambulatÃrio de um hospital de referÃncia em tratamento de doenÃas pulmonares. Trata-se de um estudo descritivo, exploratÃrio e transversal. Foram entrevistados 83 indivÃduos, com predominÃncia do sexo masculino, idade mÃdia de 68,22 anos e baixa escolaridade. A mÃdia do nÃmero de medicamentos por paciente foi de 5,58, caracterizando a polifarmÃcia, e 81,9% tinham algum tipo de comorbidade. A prevalÃncia encontrada foi de mÃdia adesÃo (45,8%). A resposta mais frequente entre as perguntas realizadas para mensurar a adesÃo foi a referente aos esquecimentos dos pacientes em tomarem seus medicamentos diariamente (38,6%). A complexidade terapÃutica teve valor mÃdio de 15,9 pontos, um escore elevado que revela as dificuldades existentes no seguimento do tratamento. ApÃs avaliaÃÃo dos dispositivos inalatÃrios constatou-se que quanto ao uso de inaladores de pà seco Aerolizer a tÃcnica foi considerada boa em 62,5% dos pacientes, o uso de inalador Respimat foi âbomâ em 70,96% dos casos e o uso de aerossol dosimetrado mostrou-se regular em 64,7%. A avaliaÃÃo do uso dos dispositivos encontrou falhas em vÃrias etapas consideradas essenciais para o seu manejo adequado. A partir destes dados, se fazem necessÃrias estratÃgias que visem potencializar aÃÃes para melhorar a adesÃo à terapia e uma avaliaÃÃo contÃnua do uso dos dispositivos inalatÃrios, minimizando complicaÃÃes para o paciente.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / O objetivo deste estudo foi verificar a presenÃa de parÃmetros morfolÃgicos maxilares na SÃndrome da ApnÃia Obstrutiva do Sono (SAOS) A amostra consistiu nos modelos de gesso da maxila de 23 indivÃduos (11 masculinos e 12 femininos) com diagnÃstico polissonogrÃfico de SÃndrome da ApnÃia Obstrutiva do Sono leve 34 indivÃduos (17 masculinos e 17 femininos) com sÃndrome moderada e 17 indivÃduos com sÃndrome grave (14 masculinos e 3 femininos) O grupo controle era composto por modelos de gesso da maxila de 50 jovens brasileiros de ambos os sexos com oclusÃo normal e sem indÃcios de SÃndrome da ApnÃia Obstrutiva do Sono Os resultados encontrados demonstraram que os parÃmetros morfolÃgicos da maxila avaliados nÃo apresentaram associaÃÃo com o Ãndice de apnÃia e hipopnÃia (IAH) mas ocorreram menores dimensÃes transversais da arcada dentÃria superior principalmente ao nÃvel de molares associado a um aumento da dessaturaÃÃo de oxi-hemoglobina (SaO2mÃn)IndivÃduos com SÃndrome da ApnÃia Obstrutiva do Sono tambÃm apresentaram dimensÃes transversais da maxila mais estreitas e maior profundidade do palato na regiÃo de prÃ-molares e molares quando comparados ao grupo controle / The objective of this study was to verify the presence of maxillary morphologic parameters on the Obstructive Sleep Apnea Syndrome (OSA) The sample was consisted on maxilla dental models of 23 individuals (11 males and 12 females) with the polyssonographic diagnosis of mild SAOS, 34 individuals (17 males and 17 females) with moderate SAOS and 17 individuals with severe SAOS (14 males and 3 females) Measures of maxilla dental models of 50 young Brazilians were used for the control group, both males and females and with normal occlusion and without any indication OSA The results found show that the maxillary morphologic parameters evaluated didnât show the association with the apnea/hypopnea index (AHI) but minor transversal dimensions of the maxilla mainly at the level of the molars associated to the increase of the dessaturation of oxyhemoglobin (minSaO2) The individuals with OSA also presented maxilla transversal dimensions narrower and more height on the palate at the region of pre-molars and molars when compared to the control group

Masters of Science in Medicine / The relationship between COPD and laryngopharyngeal sensitivity has not been previously determined. Limited research into the relationship between COPD and swallow function suggests that patients with COPD are at increased risk of aspiration. One possible mechanism for this is a reduction in laryngopharyngeal sensitivity (LPS). Reduced laryngopharyngeal sensitivity (LPS) has been associated with an increased risk of aspiration in pathologies such as stroke, however impaired LPS has not been examined with respect to aspiration risk in COPD. The Aims of this study were to investigate the effect of COPD on laryngopharyngeal sensation using Laryngopharyngeal Sensory Discrimination Testing (LPSDT) and to determine whether a relationship between LPS and swallow function in patients with proven COPD exists. Method: 20 patients with proven COPD and 11 control subjects underwent LPSDT utilising an air-pulse stimulator (Pentax AP4000) via a nasendoscope (Pentax FNL10AP). The threshold of laryngopharyngeal sensation was measured by the air pressure required to elicit the laryngeal adductor reflex (LAR). A number of further examinations were also completed for COPD subjects. These included respiratory function testing, self-reporting questionnaire on swallowing ability (SSQ), bedside clinical examination of swallowing (MASA) and endoscopic assessment of swallowing (EAS). Results: subjects with COPD had a significantly higher LAR threshold when compared to their normal healthy counterparts (p<0.001). Positive correlations were identified for the relationships between MASA score and EAS results for presence of laryngeal penetration / aspiration (p<0.04), vallecular residue (p<0.01) and piriform residue (p<0.01). Conclusion: Patients with COPD have significantly reduced mechanosensitivity in the laryngopharynx. Patients with COPD also have impaired swallow function characterised primarily by pharyngeal stasis. These changes may place patients with COPD at increased risk of aspiration.

Doctor of Philosophy (Medicine) / Sleepiness is an important source of morbidity in the community, with potentially catastrophic consequences of occupational or driving injuries or accidents. Although many measures of sleepiness exist, there is no gold standard. The electroencephalograph (EEG) has been studied as an indicator of sleep pressure in the waking organism, or sleep depth. A mathematical model has been developed, relating the observed EEG to interactions between groups of neurons in the cortex and thalamus (Robinson, Rennie, Rowe, O'Connor, & Gordon, 2005; Robinson, Rennie, & Wright, 1997). These interactions are thought to be important in the transition from wake to sleep. Sleepiness is common in obstructive sleep apnea (OSA). The measurement of sleepiness would have great utility in quantifying the disease burden, measuring treatment response, or determining fitness for work or driving. This study will evaluate parameters derived from the EEG mathematical model as a measure of sleepiness. It is divided into the following four parts: 1. Subjects with likely OSA based on symptoms and demographics from an international database were compared with matched non-OSA controls. The OSA group showed deficits in executive function and abnormalities on evoked response potential testing. 2. Outcomes from a cross-sectional study in a sleep-clinic OSA population were aggregated by factor analysis into a five summary variables relevant to sleepiness: subjective sleepiness, mood & anxiety, memory & learning, driving, and executive functioning. 3. EEG mathematical model parameters from wake EEG recordings were related to the five summary outcomes. Executive function correlated with a parameter Z, representing the negative feedback loop between the thalamic reticular nucleus and the thalamocortical relay nuclei. 4. EEG model parameters during first NREM sleep cycle of 8 subjects with regular sleep architecture were studied. Net cortical excitation (parameter X) is predicted to increase across the cycle, while there was, as predicted, a greater inhibitory effect of the thalamic reticular nucleus upon thalamocortical relay cells (parameter Z). In this preliminary assessment, EEG model parameters reflecting thalamocortical interactions are sensitive to prefrontal lobe tasks such as executive function, which are known to be vulnerable to sleep loss and sleepiness, and these parameters also show variation with increasing sleep depth.

Accumulating evidence suggests that volume overload in drug-resistant hypertension (RH) may contribute to the high prevalence of obstructive sleep apnea-hypopnea (OSAH). Upon recumbency, leg fluid volume moves rostrally causing an increase in nuchal and peripharyngeal fluid content, subsequently obstructing airflow. Rostral fluid displacement following lower body positive pressure (LBPP) application and occurring spontaneously overnight were evaluated in subjects with RH (n = 25) and controlled hypertension (n = 15). In both groups, the reduction in mean upper airway cross-sectional area with LBPP strongly related to the amount of fluid displaced from the legs (R2 = 0.41; p<0.0001), although its magnitude was greater in the RH group (p=0.001; adjusted for propensity score). In both groups, the apnea-hypopnea index strongly related to the amount of fluid spontaneously displaced from the legs during sleep (R2 = 0.56; p<0.0001), although its magnitude was greater in the RH group (p=0.01; adjusted for propensity score).

Accumulating evidence suggests that volume overload in drug-resistant hypertension (RH) may contribute to the high prevalence of obstructive sleep apnea-hypopnea (OSAH). Upon recumbency, leg fluid volume moves rostrally causing an increase in nuchal and peripharyngeal fluid content, subsequently obstructing airflow. Rostral fluid displacement following lower body positive pressure (LBPP) application and occurring spontaneously overnight were evaluated in subjects with RH (n = 25) and controlled hypertension (n = 15). In both groups, the reduction in mean upper airway cross-sectional area with LBPP strongly related to the amount of fluid displaced from the legs (R2 = 0.41; p<0.0001), although its magnitude was greater in the RH group (p=0.001; adjusted for propensity score). In both groups, the apnea-hypopnea index strongly related to the amount of fluid spontaneously displaced from the legs during sleep (R2 = 0.56; p<0.0001), although its magnitude was greater in the RH group (p=0.01; adjusted for propensity score).

名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成7年12月20日 北川喜己氏の博士論文として提出された

The diagnosis of obstructive sleep apnea (OSA) syndrome is overnight PSG (mutli-channel system). But it¡¦s hard to be popularized for the general population (about twenty channel signals). In recent decades, several researches were devoted to a replacement system with only one channel signal (oxyhemoglobin saturation). However, it¡¦s hard to match PSG system¡¦s report without EEG wake information. Consequently, two channels (oxyhemoglobin saturation and EEG) were used of this study to enhance the AHI (estimation index for sleep apnea) prediction performance. After surveying the most recent studies, this work proposes a new basleline removal technique for oxygen saturation signal (SpO2) by using median filter. It was proved this technique improves the diagnostic accuracy for OSA. Furthermore, it is also found that by removing the wake periods, diagnostic accuracy can be improved further. By counting the number of times that the desaturation level has dropped more than 2% for at least 3 seconds, the correlation coefficient between AHI and proposed feature is 0.9218. In addition, by removing the wake period, this correlation increases to 0.9425. By using this feature to classify patients with AHI value larger than 5, the proposed approach achieves 93.78% accuracy, 95.94% sensitivity, 78.87% specificity f. Such results demonstrate the feasibility of using single SpO2 channel system for OSA diagnosis.

published_or_final_version / Nursing Studies / Master / Master of Nursing