Tracheal respiratory sounds analysis has been investigated as a non-invasive method to estimate respiratory flow and upper airway obstruction. However, the flow-sound relationship is highly variable among subjects which makes it challenging to estimate flow in general applications. Therefore, a robust model for acoustical flow estimation in a large group of individuals did not exist before. On the other hand, a major application of acoustical flow estimation is to detect flow limitations in patients with obstructive sleep apnea (OSA) during sleep. However, previously the flow--sound relationship was only investigated during wakefulness among healthy individuals. Therefore, it was necessary to examine the flow-sound relationship during sleep in OSA patients. This thesis takes the above challenges and offers innovative solutions. First, a modified linear flow-sound model was proposed to estimate respiratory flow from tracheal sounds. To remove the individual based calibration process, the statistical correlation between the model parameters and anthropometric features of 93 healthy volunteers was investigated. The results show that gender, height and smoking are the most significant factors that affect the model parameters. Hence, a general acoustical flow estimation model was proposed for people with similar height and gender. Second, flow-sound relationship during sleep and wakefulness was studied among 13 OSA patients. The results show that during sleep and wakefulness, flow-sound relationship follows a power law, but with different parameters. Therefore, for acoustical flow estimation during sleep, the model parameters should be extracted from sleep data to have small errors. The results confirm reliability of the acoustical flow estimation for investigating flow variations during both sleep and wakefulness. Finally, a new method for sleep apnea detection and monitoring was developed, which only requires recording the tracheal sounds and the blood's oxygen saturation level (SaO2) data. It automatically classifies the sound segments into breath, snore and noise. A weighted average of features extracted from sound segments and SaO2 signal was used to detect apnea and hypopnea events. The performance of the proposed approach was evaluated on the data of 66 patients. The results show high correlation (0.96,p < 0.0001) between the outcomes of our system and those of the polysomnography. Also, sensitivity and specificity of the proposed method in differentiating simple snorers from OSA patients were found to be more than 91%. These results are superior or comparable with the existing commercialized sleep apnea portable monitors.

Tracheal respiratory sounds analysis has been investigated as a non-invasive method to estimate respiratory flow and upper airway obstruction. However, the flow-sound relationship is highly variable among subjects which makes it challenging to estimate flow in general applications. Therefore, a robust model for acoustical flow estimation in a large group of individuals did not exist before. On the other hand, a major application of acoustical flow estimation is to detect flow limitations in patients with obstructive sleep apnea (OSA) during sleep. However, previously the flow--sound relationship was only investigated during wakefulness among healthy individuals. Therefore, it was necessary to examine the flow-sound relationship during sleep in OSA patients. This thesis takes the above challenges and offers innovative solutions. First, a modified linear flow-sound model was proposed to estimate respiratory flow from tracheal sounds. To remove the individual based calibration process, the statistical correlation between the model parameters and anthropometric features of 93 healthy volunteers was investigated. The results show that gender, height and smoking are the most significant factors that affect the model parameters. Hence, a general acoustical flow estimation model was proposed for people with similar height and gender. Second, flow-sound relationship during sleep and wakefulness was studied among 13 OSA patients. The results show that during sleep and wakefulness, flow-sound relationship follows a power law, but with different parameters. Therefore, for acoustical flow estimation during sleep, the model parameters should be extracted from sleep data to have small errors. The results confirm reliability of the acoustical flow estimation for investigating flow variations during both sleep and wakefulness. Finally, a new method for sleep apnea detection and monitoring was developed, which only requires recording the tracheal sounds and the blood's oxygen saturation level (SaO2) data. It automatically classifies the sound segments into breath, snore and noise. A weighted average of features extracted from sound segments and SaO2 signal was used to detect apnea and hypopnea events. The performance of the proposed approach was evaluated on the data of 66 patients. The results show high correlation (0.96,p < 0.0001) between the outcomes of our system and those of the polysomnography. Also, sensitivity and specificity of the proposed method in differentiating simple snorers from OSA patients were found to be more than 91%. These results are superior or comparable with the existing commercialized sleep apnea portable monitors.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro / Introdução: a apneia obstrutiva do sono (AOS) é considerada um fator de risco para as doenças cardiovasculares. Os mecanismos responsáveis pelo desenvolvimento da aterosclerose potencializados pela AOS não são completamente conhecidos. Entretanto, existem evidências de que a AOS está associada com aumento no estresse oxidativo, elevação nos mediadores inflamatórios, resistência à insulina, ativação do sistema nervoso simpático, elevação da pressão arterial (PA) e a disfunção endotelial. Objetivo: avaliar a relação da AOS com a função endotelial, o estresse oxidativo, os biomarcadores inflamatórios, o perfil metabólico, a adiposidade corporal, a atividade simpática e a PA em indivíduos obesos. Métodos: estudo transversal envolvendo 53 pacientes obesos, com índice de massa corporal (IMC) &#8805; 30 e < 40 Kg/m2, sem distinção de raça e gênero, apresentando idade entre 20 e 55 anos. O estudo do sono foi realizado com o equipamento Watch-PAT 200, sendo feito o diagnóstico de AOS quando índice apneia-hipopneia (IAH) &#8805; 5 eventos/h. Todos os participantes foram submetidos à avaliação do (a): adiposidade corporal (peso, % gordura corporal e circunferências da cintura, quadril e pescoço); PA; atividade do sistema nervoso simpático (concentrações plasmáticas de catecolaminas); biomarcadores inflamatórios (proteína C reativa ultrassensível (PCR-us) e adiponectina); estresse oxidativo (malondialdeído); metabolismo glicídico (glicose, insulina e HOMA-IR) e lipídico (colesterol total e frações e triglicerídeos); e função endotelial (índice de hiperemia reativa (RHI) avaliado com o equipamento Endo-PAT 2000 e moléculas de adesão celular). A análise estatística foi realizada com o software STATA versão 10. Resultados: dos 53 pacientes avaliados 20 foram alocados no grupo sem AOS (grupo controle; GC) (IAH: 2,550,35 eventos/h) e 33 no grupo com AOS (GAOS) (IAH: 20,163,57 eventos/h). A faixa etária (39,61,48 vs. 32,52,09 anos) e o percentual de participantes do gênero masculino (61% vs. 25%) foram significativamente maiores no GAOS do que no GC (p=0,01). O GAOS em comparação o GC apresentou valores significativamente mais elevados de circunferência do pescoço (CP) (40,980,63 vs. 38,650,75 cm; p=0,02), glicemia (92,541,97 vs. 80,21,92 mg/dL; p=0,0001), PA sistólica (126,051,61 vs.118,16 1,86 mmHg; p=0,003) e noradrenalina (0,160,02 vs. 0,120,03 ng/mL; p=0,02). Após ajustes para fatores de confundimento, a glicose e a PCR-us foram significativamente mais elevadas no GAOS. Os 2 grupos apresentaram valores semelhantes de IMC, insulina, HOMA-IR, perfil lipídico, adiponectina, PA diastólica, adrenalina, dopamina, moléculas de adesão celular e malondialdeído. A função endotelial avaliada pelo RHI também foi semelhante nos 2 grupos (GAOS:1,850,2 vs. GC:1,980,1; p=0,31). Nas análises de correlação, considerando todos os participantes do estudo, o IAH apresentou associação positiva e significativa com CP e PCR-us após ajustes para fatores de confundimento. A saturação mínima de O2 se associou de forma negativa e significativa com a CP, os níveis séricos de insulina e o HOMA-IR, mesmo após ajustes para fatores de confundimento. Conclusões: o presente estudo sugere que em obesos a AOS está associada com valores mais elevados de glicemia e inflamação; o aumento do IAH apresenta associação significativa com a obesidade central e com a inflamação; e a queda na saturação de oxigênio se associa com resistência à insulina. / Introduction: obstructive sleep apnea (OSA) is considered a risk factor for cardiovascular disease. The mechanisms responsible for the development of atherosclerosis triggered by OSA are not completely known. However, there is evidence that OSA is associated with increased oxidative stress, higher levels of inflammatory mediators, insulin resistance, increased sympathetic nervous system activity, elevated blood pressure (BP) and endothelial dysfunction. Objective: to evaluate the relation of OSA with endothelial function, oxidative stress, inflammatory biomarkers, metabolic profile, body adiposity, sympathetic activity and BP in obese individuals. Methods: cross-sectional study involving 53 obese patients with body mass index (BMI) > 30 and < 40 kg/m2, without distinction of race and gender, aged between 20 and 55 years. The sleep study was performed with the equipment Watch-PAT200 and the diagnosis of OSA was made when apnea-hipopnea index (AHI) &#8805; 5 events/h. All participants underwent evaluation of: body adiposity (weight, % body fat and circumferences of waist, hip and neck); BP; sympathetic nervous system activity (plasma levels of catecholamines); inflammatory biomarkers (high sensible c-reactive protein (hs-CRP) and adiponectin); oxidative stress (malondialdehyde); metabolism of glucose (glucose, insulin and HOMA-IR) and lipids (total cholesterol and fractions and triglycerides); and endothelial function (reactive hyperemia index (RHI) evaluated by Endo-PAT 2000 and cellular adhesion molecules). Statistical analysis was performed with software STATA version 10. Results: of the 53 evaluated patients, 20 were included in the group without OSA (Control group; CG) (AHI: 2.550.35 events/h) and 33 in the group with OSA (OSAG) (IAH: 20.163.57 events/h). The mean age (39.61.48 vs. 32.52.09 years) and the percentage of male participants (61% vs. 25%) were significantly higher in OSAG than in CG (p=0.01). The OSAG compared the CG showed significantly higher values of neck circumference (NC) (40.980.63 vs. 38.650.75 cm, p=0.02), glucose (92.541.97 vs. 80.21.92 mg/dL, p=0.0001), systolic BP (126.051.61 vs. 118.161.86 mmHg, p=0.003) and noradrenaline (0.160.02 vs. 0.120.03 ng/mL, p=0.02). After adjustment for confounders, glucose and hs-CRP were significantly higher in OSAG. Both groups presented similar values of BMI, insulin, HOMA-IR, lipid profile, adiponectin, diastolic BP, adrenaline, dopamine, adhesion cellular molecules and malondialdehyde. Endothelial function evaluated by RHI was also similar in both groups (OSAG: 1.850.2 vs. CG: 1.980.1, p=0.31). In correlation analysis, considering the whole group of patients, AHI presented a positive and significant association with NC and hs-CRP after adjustments for confounders. The minimum oxygen saturation was associated negatively and significantly with NC, insulin and HOMA-IR even after adjustments for confounders. Conclusions: the present study suggests that in obese individuals, OSA is associated with higher values of glucose and inflammation; higher AHI presents significant association with central adiposity and with inflammation; and lower oxygen saturation is associated with insulin resistance.

Esta tese de doutorado aborda o assunto apneia do sono, especialmente a síndrome de apneia e hipopneia obstrutiva do sono (SAHOS) como principal motivo de investigação. Nosso estudo teve como objetivo estudar o mecanismo fisiológico de funcionamento da válvula expiratória nasal (nEPAP) denominada Provent. Trata-se de um dispositivo descartável utilizado em ambas as narinas e que permite a inspiração normal, porém oferece resistência à expiração, fazendo com que o próprio paciente gere uma determinada pressão expiratória nasal. Este mecanismo de atuação da válvula determina algum grau de modificação na via aérea superior e no pulmão. Embora já se saiba que este dispositivo é efetivo no tratamento de pacientes com SAHOS leve e moderada3 o seu mecanismo fisiológico de funcionamento ainda não está completamente entendido. Utilizamos um método de ressonância magnética para avaliar a via aérea superior e o pulmão de pacientes em utilização do Provent nasal. Estudamos dez pacientes, 7 homens e 3 mulheres, entre 30 e 62 anos, com diagnóstico clínico de SAHOS e confirmado pela polissonografia (IAH>5 ev/h). Realizamos então, em diferentes momentos, polissonografia diagnóstica, polissonografia em uso da válvula nasal e exame de imagem (ressonância magnética). A faringe e o pulmão foram inspecionados e medidos durante alguns ciclos respiratórios, com e sem a válvula nasal. Neste estudo, validamos o exame de Ressonância Magnética para a avaliação da área transversal da via aérea superior e da capacidade residual funcional durante a respiração através da válvula nasal. Com os nossos resultados reforçamos os achados anteriores da literatura referentes aos três possíveis mecanismos de funcionamento desta válvula nasal: hiperinflação pulmonar importante aumentando a tração na traqueia, uma tendência à dilatação da faringe durante a expiração que se mantém no início da inspiração reduzindo a colapsabilidade da faringe e, finalmente, hipoventilação e aumento de PCO2. Considerando estes resultados, podemos dizer que a pressão expiratória positiva nasal pode ser uma alternativa de tratamento da SAHOS. Os resultados deste estudo são apresentados sob a forma de artigo já publicado em revista internacional de alto impacto científico (Journal of Applied Physiology). Adicionalmente, na forma de apêndice, realizamos outro estudo objetivando estudar o comportamento da SAHOS na Doença de Parkinson e as alterações ocasionadas em marcadores periféricos de lesão neuronal, especificamente a proteína S100B e a Enolase. Os transtornos do sono, incluindo os distúrbios respiratórios, são frequentes nos pacientes com Doença de Parkinson (DP), e, estudos já realizados mostram que a proteína S100B pode estar aumentada tanto em pacientes com SAHOS1 como naqueles com Doença de Parkinson2, sugerindo a possibilidade de algum grau de dano neuronal nestes pacientes quando comparados com indivíduos normais. Estes achados serviram de motivação para o estudo das variáveis neurofisiológicas do sono e do comportamento de biomarcadores em pacientes com Parkinson e, supostamente, SAHOS concomitantemente. / The issue of this doctoral thesis is Obstructive Sleep Apnea (OSA). Our study intended to clarify the mechanism of action of nEPAP (Nasal Expiratory Positive Airway Pressure), delivered with a disposable device (Provent, Ventus Medical). It has been shown to improve sleep disordered breathing (SDB) in some subjects3, but how it works is still not completely understood. We studied 10 patients, 7 males and 3 females, age between 30 and 62 years old, with clinic OSA and confirmed by sleep study (IHA>5). Sleep studies were performed in different nights, a night for diagnostic of OSA and other night under nasal valve. We did use MRI (Magnetic Resonance Imaging) to see upper airway and lung in patients wearing Provent. The present study demonstrate that significant hyperinflation (an increase in end expiratory lung volume) occurs during breathing through the device. In addition, there may be some trend to dilate the UA during expiration, and this may carry over into inspiration, providing a second mechanism to reduce the tendency of the UA to collapse in patients with SDB. Finally, we were able to show significant hypoventilation and a rise in PCO2 during breathing through the nEPAP during wakefulness, which may persist into sleep. Results are presented in the format of a paper published in a international journal with high scientific impact (Journal of Applied Physiology). In addition, as appendix, we did perform other protocol intended to study OSA in the Parkinson Disease (PD) and correlation with detectable levels of S100B and NSE, biochemical markers of neuronal damage. Sleep breathing disorders are frequent in Parkinson Disease and there are some studies showing that S100B, a known biochemical marker of astrocyte damage, is increased in both SAOS and PD1 2, suggesting a possible neuronal damage while compared to controls. These findings were motivation to investigate biochemical markers and sleep in patients with Parkinson. Our results suggest that sleep disturbance in PD causes a worse sleep quality and leads to S100B elevation during the night. Probably PD patients are suffering some degree of brain damage during the night that trigger a S100B response.

Chez l'homme, l'hypoxie correspond à une inadéquation entre les besoins tissulaires et les apports en oxygène. Cet état est une caractéristique commune à l'exposition à l'altitude et au syndrome d'apnées obstructives du sommeil (SAOS), bien que celle-ci soit continue dans le premier cas et intermittente et nocturne dans le second.L'hypoxie d'altitude entraine une altération des performances cognitives et motrices. La réduction de la performance à l'exercice en altitude a longtemps été attribuée à une altération du métabolisme musculaire du fait d'une réduction de l'apport en oxygène. Les perturbations cérébrales induites par l'hypoxie pourraient également avoir un rôle majeur dans cette limitation.Le SAOS, véritable enjeu de santé publique, est associé à des troubles cognitifs pouvant ainsi influencer le fonctionnement quotidien des patients souffrant de ce syndrome et résulter en une somnolence diurne excessive, une baisse de la qualité de vie ou encore une réduction de la productivité au travail et des performances scolaires. Le fait que ces altérations cérébrales puissent influencer les capacités motrices et à l'effort des patients atteints d’apnées obstructives du sommeil reste en revanche à investiguer.Au cours de ce travail de thèse, nous nous sommes intéressés à deux modèles d’exposition hypoxique et à leurs conséquences cérébrales et neuromusculaires. Nous avons tout d’abord étudié l'effet d'une exposition à l'hypoxie d'altitude aigue (quelques heures) et prolongée (plusieurs jours) sur la fonction neuromusculaire et ses répercussions à l'exercice chez le sujet sain. Nous avons ensuite étudié l'influence du modèle d'hypoxie intermittente associé au SAOS sur la fonction neuromusculaire et la tolérance à l'exercice de ces patients. Nous avons ainsi cherché à caractériser les altérations cérébrales à l'exercice en lien avec ce syndrome et leur réversibilité suite à un traitement en ventilation par pression positive continue.Chez le sujet sain, nous avons démontré que la performance à l'exercice impliquant une masse musculaire réduite (fléchisseurs du coude) n'était pas limitée par une fatigue centrale accrue après 1 et 5 jours d'exposition à une altitude de 4350 m. Nous avons mis en évidence que la dysfonction musculaire (force et endurance réduites) observée chez le patient SAOS est associée à un déficit d'activation supraspinal et une augmentation de l'inhibition intracorticale. De plus, nos résultats suggèrent qu'une altération de la réponse cérébrovasculaire à l'exercice puissent impacter négativement la tolérance à l'exercice des patients souffrant d'un SAOS sévère. Ces altérations neuromusculaires et cérébrovasculaires n'étaient pas corrigées après un traitement de huit semaines par ventilation nocturne en pression positive continue soulignant la nature persistante de ces altérations cérébrales. / In humans, hypoxia is defined as the mismatch between tissue requirement and oxygen delivery. This condition is a common feature between high-altitude exposure and obstructive sleep apnea syndrome (OSA), although it is continuous in the first instance and intermittent and nocturnal in the second one.High-altitude exposure causes an impairment in cognitive and motor performance. The reduction in exercise performance observed under hypoxic condition has been mainly attributed to altered muscle metabolism due to impaired oxygen delivery. However, hypoxia-induced cerebral perturbations may also play a major role in exercise limitation.OSA, a major public health concern, is associated with cognitive impairment that can alter patients' daytime functioning and result in excessive daytime sleepiness, reduced quality of life and lowered work productivity and school performance. The fact that these cerebral alterations can influence motor and exercise performance in patients with obstructive sleep apnea remains to be investigated.In this thesis, we investigated two different models of hypoxic exposure and their cerebral and neuromuscular consequences. First, we assessed the effect of acute (several hours) and prolonged (several days) high-altitude exposure on the neuromuscular function and its repercussions during exercise in healthy subject. Then, we then investigated the model of intermittent hypoxia associated with OSA and its influence on the neuromuscular function and exercise tolerance in these patients. We seeked to characterize cerebral alterations during exercise associated with this syndrome and their reversibility following continuous positive airway pressure treatment.In healthy subject, we showed that exercise performance involving a small muscle mass (elbow flexors) was not limited by an exacerbated amount of central fatigue after 1 and 5 days of high-altitude exposure (4,350 m). We highlighted that muscle dysfunction (reduced strength and endurance) was associated with a supraspinal activation deficit and an increase in intracortical inhibition. Moreover, our results suggest that an alteration in cerebrovascular response during exercise may contribute to reduced exercise tolerance observed in patients with severe OSA syndrome. The neuromuscular and cerebrovascular abnormalities were not reversed following an eight-week continuous positive airway pressure treatment, highlighting the persistent nature of the cerebral alterations.

Bakgrund: Obstruktiv sömnapné (OSA) innebär luftflödeshinder under sömnen vilket leder till andningsuppehåll. OSA är vanligast förekommande vid övervikt och hos män. Individer med OSA lider oftare av depression än övriga befolkningen. Fysisk aktivitet har visat sig vara en effektiv behandlingsmetod för depression. Syfte: Att undersöka om förändring av fysisk aktivitet korrelerar med förändring av självskattade depressiva symptom, samt om det finns skillnader gällande kön eller intensitetsnivå. Metod: En retrospektiv, deskriptiv, korrelerande och jämförande studie. Data inhämtades från en tidigare studie. Fysisk aktvitet och självskattade depressiva symptom mättes med SenseWear Pro3 Armband respektive MADRS-S vid baslinjen och vid 6 månaders uppföljning. Resultat: Ett samband mellan ökning av fysisk aktivitet och minskning av MADRS-S-poäng förelåg, r= -0,27, p=0,04. Uppdelat på kön förstärktes sambandet hos männen, r= -0,35 (p=0,02). För kvinnorna förelåg ett samband mellan en ökning av fysisk aktivitet och en ökning av MADRS-S-poäng, r=0,7 ej statistiskt signifikant, p=0,16. Det fanns ingen skillnad i MADRS-S-poäng mellan grupperna på måttlig 5 (5,5) median (kvartilavstånd), respektive hög fysisk intensitetsnivå 4,5 (9,25), p= 0,68. Konklusion: Det förelåg ett samband mellan ökning av fysisk aktivitet och minskning av MADRS-S-poäng. Gällande skillnader mellan kön och intensitetsnivå gjorde det låga antalet kvinnor och högintensivt aktiva att inga slutsatser gick att dra. / Background: Obstructive sleep apnea (OSA) is obstruction of airflow during sleep leading to respiratory arrest. OSA is most common with obesity and among men. Individuals with OSA have a higher depression rate than the rest of the population. Physical activity (PA) has proven to be an effective treatment for depression. Aim: To investigate whether change in PA correlates with change in self-assessed depressive symptoms and if there are differences regarding gender or intensity levels. Method: A retrospective, descriptive, correlative and comparative study. Data was obtained from a previous study. PA and self-assessed depressive symptoms were measured with SenseWear Pro3 Armband and MADRS-S at baseline and at 6 months follow-up. Results: There was a correlation between an increase of PA and a decrease of MADRS-S score, r = -0.27, p = 0.04. The correlation for men was stronger r = -0.35 (p = 0.02). Women had a correlation between an increase in PA and an increase of MADRS-S score, r = 0.7 not statistically significant, p = 0.16. There was no difference in MADRS-S score between the groups performing PA at moderate intensity 5 (5.5) median (interquartile), respectively high intensity 4.5 (9.25), p=0.68 Conclusion: The results showed a correlation between an increase in PA and a reduction of MADRS-S score. Regarding differences between genders or intensity levels the low number of women and physically active at high intensity meant no conclusions could be drawn.

O refluxo gastroesofágico (RGE) tem sido diagnosticado em uma elevada proporção de lactentes com apnéia e episódios de ALTE (apparent life threatening events) ou eventos com aparente risco de vida, entretanto, a relação entre eles per-manece pouco entendida. A proposta deste estudo é avaliar a coexistência de apnéia e refluxo gastroesofágico em um grupo de lactentes durante o sono e vigília, através da utilização da polissonografia e, pela inclusão de um canal para aferição do pH na porção distal do esôfago, determinar a relação temporal entre estes dois eventos e aferir a associação entre ALTE e RGE. Método: A população em estudo constituiu-se de lactentes com história clínica compatível com eventos sugestivos de RGE, além de alguma anormalidade do ponto de vista ventilatório, os quais realizaram polissonografia com a inclusão de um canal para registro contínuo do pH esofágico. Os estudos polissonográficos foram analisados individualmente, em três etapas assim constituídas: Etapa 1 - realização do escore dos eventos respiratórios e dos estágios de sono e vigília, com o pesquisador cego para a ocorrência de RGE; Etapa 2 - indicação do escore isolado dos eventos de RGE; Etapa 3 - reintrodução de canal do pH e estabelecimento da correlação temporal entre os dois eventos, levando-se em consideração o período compreendido entre um minuto antes da queda do pH abaixo de 4,0, até um minuto após a elevação do pH acima de 4,0. A relação entre a história clínica de ALTE e a ocorrência de RGE durante o estudo polissonográfico também foi aferida. A partir de dados publicados na literatura, foi calculada uma amostra de 88 indivíduos (lactentes). A amostra final constituiu-se de 89 pacientes. Resultados: Quarenta pacientes apresentaram RGE e quarenta e nove não. Ambos os grupos tinham composição semelhante quanto à idade, peso, duração total do estudo polissonográfico, duração do tempo total de sono durante o estudo e história de ALTE. Ocorreu uma média de 2,82 episódios de RGE por paciente (1-20 episódios/ paciente). Os episódios de RGE foram mais freqüentes e longos durante o sono que durante os períodos de vigília. O número de eventos obstrutivos/minuto de sono (densidade de apnéias) foi significativamente maior durante os períodos de RGE (mediana 0,4), se comparados aos períodos sem RGE (mediana 0,2), p = 0,002. Em relação às apnéias centrais, não houve diferença estatisticamente significativa, p = 0, 039. Em 62% dos períodos de RGE, houve associação temporal com eventos obstrutivos, dos quais a apnéia obstrutiva precedeu o RGE em 67% dos casos. A correlação entre história de ALTE e a presença de RGE não foi estatisticamente significativa. Conclusões: Os resultados sugerem que a apnéia obstrutiva em lacten-tes está freqüentemente associada com RGE do ponto de vista de temporalidade, e é mais provável que ela ocorra precedendo um episódio de refluxo. Especula-se que a apnéia obstrutiva no lactente possa, em algumas circunstâncias, ser a causa e não a conseqüência do RGE. / Gastroesophageal Reflux (GER) has been diagnosed in a high proportion of infants with apnea and ALTE (APPARENT LIFE THREATENING EVENTS), however, the temporal relationship between these episodes remain unclear. The purpose of this study was, using polysomnographyc studies, during sleep and wakefulness, with an addition of an esophageal pH probe, evaluate the coexistence of apnea and GER, determine the temporal relationship between these two events and assess whether a relationship exists between the presence of ALTE and GER. Methods: Study population was infants with a clinical suspicion of GER and a presence of a respiratory abnormality who underwent polysomnography with a distal pH probe. Polysomnographic studies were evaluated in three steps: Step 1 - scoring of respiratory events and sleep stages disregarding pH channel; Step 2 - scoring of GER episodes; Step 3 - using all channels at the same time, a temporal correlation between the GER and apnea was assessed taking into account a period of one minute before a pH drop less than 4.0 for more than 15 seconds up to one minute after elevation of pH more than 4.0. The relationship between clinical history of ALTE and the occurrence of GER during polysomnography was also evaluated. From literature data, a sample size was calculated as 88 subjects (infants). A final sample of 89 patients was included. Results: Forty patients had GER, forty- nine did not have. Both groups had the same status regarding age, weight, total polysomnographic study duration, total sleep time duration and history of ALTE. There was a mean of 2.82 episodes of GER per patient (1-20 episodes/ patient). GER episodes were more frequent and longer during sleep than wakefulness. The number of obstructive events/ minute of sleep (apnea density) was significantly higher during GER episodes (median 0.4) compared to free GER periods (median 0.2), p = 0.002; while for central apneas there was no statistically significance, p = 0.039. In sixty-two percent (62%) of GER episodes there were a temporal association with obstructive episodes, where obstructive apnea preceded GER in 67% of these episodes. There was no correlation between clinical story of ALTE and the occurrence of GER. Conclusion: The results indicates that obstructive apnea in infants is often temporally related to gastroesophageal reflux and more likely to follow than precede obstructive apnea. The authors speculate that obstructive apnea may be the cause rather than a consequence of GER.

INTRODUÇÃO: A síndrome da apneia e hipopneia obstrutiva do sono (SAHOS) é uma doença crônica que se caracteriza por ronco e apneias que causam microdespertares e fragmentação do sono. O impacto da doença sobre o humor e a qualidade de vida não é bem conhecido. OBJETIVO: Avaliar o impacto do uso da pressão positiva contínua nas vias aéreas (CPAP) sobre sintomas depressivos e qualidade de vida em pacientes com SAHOS. MATERIAL E MÉTODOS: Pacientes com diagnóstico polissonográfico de SAHOS foram avaliados antes e seis meses após o tratamento com CPAP. Foram coletadas as seguintes medidas antropométricas: peso, altura, índice de massa corporal (IMC), circunferência do pescoço, medida da cintura e do quadril. A sonolência foi avaliada pela escala de sonolência diurna de Epworth, o sono pelo índice de qualidade do sono de Pittsburgh, a qualidade de vida através dos questionários SF-36 e FOSQ e os sintomas depressivos pelo inventário de depressão de Beck. RESULTADOS: Foram estudados 61 pacientes, sendo 42 homens e 19 mulheres, com índice de apneias e hipopneias (IAH) de 40,3 ± 27,2 eventos/hora. A média de idade foi de 53,2 ± 9,0 anos e do IMC 30,36 ± 3,93 kg/m², sendo que 96,7% dos pacientes apresentavam sobrepeso ou obesidade. Valores acima do normal para a circunferência do pescoço foram observados em 73,8% e da cintura em 72% dos indivíduos. Com o tratamento com CPAP observou-se redução da sonolência (13,2 ± 4,8 vs 7,9 ± 3,3 pontos; p=0,0001), melhora da qualidade do sono (escore 10,1 ± 4,5 vs 4,1 ± 2,5; bons dormidores pré 9 vs 36 pós; p<0, 01), melhora da qualidade de vida em todos os domínios do FS-36 (p<0,01) e do FOSQ (81,9 ± 19,5 vs 91,7 ± 14,4 pontos; p=0,00001). Os sintomas depressivos melhoraram após o uso do CPAP (12,0 ± 8,6 vs 7,5 ± 5,1; p<0,01), os quais estavam presentes em 33 pacientes antes do tratamento e em 19 após 6 meses de seguimento. Não houve associação entre sintomas depressivos e sonolência. Houve correlação fraca entre sintomas depressivos e IAH (r=0,28; p=0,02), e moderada a forte com todos os domínios do SF-36 (r entre -0,58 e - 0,72; p=0,0001). CONCLUSÕES: Nosso estudo demonstra que a terapia com CPAP tem impacto positivo sobre a sonolência, qualidade do sono e melhora a qualidade de vida e os sintomas depressivos dos portadores de SAHOS. Os sintomas depressivos não se relacionaram com a sonolência e com a gravidade da doença, mas se associaram com a qualidade de vida. / INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a chronic disease characterized by snoring and apneas that cause microarrousals and sleep fragmentation. The effects of the disease on mood and health related quality of life is not well known. OBJECTIVE: To evaluate the impact of the use of continuous positive airway pressure (CPAP) on depressive symptoms and quality of life in patients with OSAS. MATERIAL AND METHODS: Patients with OSAS diagnosed by polyssomnography underwent evaluation before and after 6 months treatment with CPAP. Weight, height, body mass index (BMI), neck, waist and hip circumference were measured. Daytime sleepiness was evaluated using the Epworth scale, sleep quality using the Pittsburgh sleep quality index and quality of life using SF-36 and FOSQ. Depressive symptoms were detected through the Beck Depression Inventory. Data were analized by Student T test, McNemar test and Pearson correlation test. RESULTS: We studied 61 patients with OSAS, 42 males and 19 females, with apnea hypopnea index (AHI) of 40.3 ± 27.2 events/hour. The mean age was 53.2 ± 9.0 years, BMI was 30.4 ± 3.9 kg/m², and 90.7% of the patients were overweight or obese. Abnormal neck and waist circumference were observed in 73.8% and 72% of patients, respectively. After treatment with CPAP there was a decrease in daytime sleepiness (13.2 ± 4.8 vs 7.9 ± 3.3 points; p=0.0001), an increase in sleep quality (10.1 ± 4.5 vs 4.1 ± 2.5; the number of good sleepers 9 before vs 36 after CPAP; p<0.01), and in quality of life as shown by SF-36 (p<0.01) and FOSQ (81.9 ± 19.5 vs 91.7 ± 14.4 points; p=0.00001). Depressive symptoms improved after use of CPAP (12.0 ± 8.6 vs 7.5 ± 5.1; p<0,01), they were reported by 33 patients before treatment and by 19 after six months of follow up. There was a weak correlation between depressive symptoms and AHI (r=0.28; p=0.02) and no association between depressive symptoms and daytime sleepiness. The correlation among depressive symptoms and SF-36 domains varied from r=-0.58 and r=-0.72 (p=0.0001). CONCLUSIONS: Our study demonstrates that the CPAP therapy has a positive impact on daytime sleepiness and sleep quality and improves quality of life and depressive symptoms in patients with OSAS. Depressive symptoms were not related to daytime sleepiness or disease severity, but were associated with quality of life.

Esta tese de doutorado aborda o assunto apneia do sono, especialmente a síndrome de apneia e hipopneia obstrutiva do sono (SAHOS) como principal motivo de investigação. Nosso estudo teve como objetivo estudar o mecanismo fisiológico de funcionamento da válvula expiratória nasal (nEPAP) denominada Provent. Trata-se de um dispositivo descartável utilizado em ambas as narinas e que permite a inspiração normal, porém oferece resistência à expiração, fazendo com que o próprio paciente gere uma determinada pressão expiratória nasal. Este mecanismo de atuação da válvula determina algum grau de modificação na via aérea superior e no pulmão. Embora já se saiba que este dispositivo é efetivo no tratamento de pacientes com SAHOS leve e moderada3 o seu mecanismo fisiológico de funcionamento ainda não está completamente entendido. Utilizamos um método de ressonância magnética para avaliar a via aérea superior e o pulmão de pacientes em utilização do Provent nasal. Estudamos dez pacientes, 7 homens e 3 mulheres, entre 30 e 62 anos, com diagnóstico clínico de SAHOS e confirmado pela polissonografia (IAH>5 ev/h). Realizamos então, em diferentes momentos, polissonografia diagnóstica, polissonografia em uso da válvula nasal e exame de imagem (ressonância magnética). A faringe e o pulmão foram inspecionados e medidos durante alguns ciclos respiratórios, com e sem a válvula nasal. Neste estudo, validamos o exame de Ressonância Magnética para a avaliação da área transversal da via aérea superior e da capacidade residual funcional durante a respiração através da válvula nasal. Com os nossos resultados reforçamos os achados anteriores da literatura referentes aos três possíveis mecanismos de funcionamento desta válvula nasal: hiperinflação pulmonar importante aumentando a tração na traqueia, uma tendência à dilatação da faringe durante a expiração que se mantém no início da inspiração reduzindo a colapsabilidade da faringe e, finalmente, hipoventilação e aumento de PCO2. Considerando estes resultados, podemos dizer que a pressão expiratória positiva nasal pode ser uma alternativa de tratamento da SAHOS. Os resultados deste estudo são apresentados sob a forma de artigo já publicado em revista internacional de alto impacto científico (Journal of Applied Physiology). Adicionalmente, na forma de apêndice, realizamos outro estudo objetivando estudar o comportamento da SAHOS na Doença de Parkinson e as alterações ocasionadas em marcadores periféricos de lesão neuronal, especificamente a proteína S100B e a Enolase. Os transtornos do sono, incluindo os distúrbios respiratórios, são frequentes nos pacientes com Doença de Parkinson (DP), e, estudos já realizados mostram que a proteína S100B pode estar aumentada tanto em pacientes com SAHOS1 como naqueles com Doença de Parkinson2, sugerindo a possibilidade de algum grau de dano neuronal nestes pacientes quando comparados com indivíduos normais. Estes achados serviram de motivação para o estudo das variáveis neurofisiológicas do sono e do comportamento de biomarcadores em pacientes com Parkinson e, supostamente, SAHOS concomitantemente. / The issue of this doctoral thesis is Obstructive Sleep Apnea (OSA). Our study intended to clarify the mechanism of action of nEPAP (Nasal Expiratory Positive Airway Pressure), delivered with a disposable device (Provent, Ventus Medical). It has been shown to improve sleep disordered breathing (SDB) in some subjects3, but how it works is still not completely understood. We studied 10 patients, 7 males and 3 females, age between 30 and 62 years old, with clinic OSA and confirmed by sleep study (IHA>5). Sleep studies were performed in different nights, a night for diagnostic of OSA and other night under nasal valve. We did use MRI (Magnetic Resonance Imaging) to see upper airway and lung in patients wearing Provent. The present study demonstrate that significant hyperinflation (an increase in end expiratory lung volume) occurs during breathing through the device. In addition, there may be some trend to dilate the UA during expiration, and this may carry over into inspiration, providing a second mechanism to reduce the tendency of the UA to collapse in patients with SDB. Finally, we were able to show significant hypoventilation and a rise in PCO2 during breathing through the nEPAP during wakefulness, which may persist into sleep. Results are presented in the format of a paper published in a international journal with high scientific impact (Journal of Applied Physiology). In addition, as appendix, we did perform other protocol intended to study OSA in the Parkinson Disease (PD) and correlation with detectable levels of S100B and NSE, biochemical markers of neuronal damage. Sleep breathing disorders are frequent in Parkinson Disease and there are some studies showing that S100B, a known biochemical marker of astrocyte damage, is increased in both SAOS and PD1 2, suggesting a possible neuronal damage while compared to controls. These findings were motivation to investigate biochemical markers and sleep in patients with Parkinson. Our results suggest that sleep disturbance in PD causes a worse sleep quality and leads to S100B elevation during the night. Probably PD patients are suffering some degree of brain damage during the night that trigger a S100B response.