Ambulatory blood pressure monitoring in children with obstructive sleep apnea and primary snoring

Objective: To evaluate the systemic blood pressure (BP) during daytime and nighttime in children with sleep breathing disorders (SBD) and compare parameters of BP in children with diagnosis of obstructive sleep apnea syndrome (OSA) to those one with primary snoring (PS).Methods: Children, both genders, aged from 8 to 12 years, with symptoms of SBD realized an overnight polysomnography followed by a 24 h recording of ambulatory BP.Results: All subjects presented with a history of snoring 7 nights per week. Children who have apnea/hipoapnea index >= four or a apnea index >= one presented a mean BP of 93 +/- 7 mmHg and 85 +/- 9 mmHg diurnal and nocturnal respectively whereas children who have a apnea/hipoapnea < four or a apnea index < one presented 90 +/- 7 mmHg and 77 +/- 2 mmHg. Eight children out of fourteen, from OSA group, lost the physiologic nocturnal dipping of the blood pressure. Among OSA children 57% were considered non-dippers. Two (16%) have presented absence of nocturnal dipping among children with primary snoring. The possibility of OSA children loosing physiologic blood pressure dipping was 6.66 higher than the possibilities of patients from PS group.Discussion: Our results indicate that children with sleep apnea syndrome exhibit a higher 24 h blood pressure when compared with those of primary snoring in form of decreased degree of nocturnal dipping and increased levels of diastolic and mean blood pressure, according to previous studies in literature. OSA in children seems to be associated to the development of hypertension or other cardiovascular disease. (C) 2012 Elsevier B.V. All rights reserved.

Ambulatory blood pressure monitoring in children with obstructive sleep apnea and primary snoring

Objective: To evaluate the systemic blood pressure (BP) during daytime and nighttime in children with sleep breathing disorders (SBD) and compare parameters of BP in children with diagnosis of obstructive sleep apnea syndrome (OSA) to those one with primary snoring (PS). Methods: Children, both genders, aged from 8 to 12 years, with symptoms of SBD realized an overnight polysomnography followed by a 24 h recording of ambulatory BP. Results: All subjects presented with a history of snoring 7 nights per week. Children who have apnea/hipoapnea index >= four or a apnea index >= one presented a mean BP of 93 +/- 7 mmHg and 85 +/- 9 mmHg diurnal and nocturnal respectively whereas children who have a apnea/hipoapnea < four or a apnea index < one presented 90 +/- 7 mmHg and 77 +/- 2 mmHg. Eight children out of fourteen, from OSA group, lost the physiologic nocturnal dipping of the blood pressure. Among OSA children 57% were considered non-dippers. Two (16%) have presented absence of nocturnal dipping among children with primary snoring. The possibility of OSA children loosing physiologic blood pressure dipping was 6.66 higher than the possibilities of patients from PS group. Discussion: Our results indicate that children with sleep apnea syndrome exhibit a higher 24 h blood pressure when compared with those of primary snoring in form of decreased degree of nocturnal dipping and increased levels of diastolic and mean blood pressure, according to previous studies in literature. OSA in children seems to be associated to the development of hypertension or other cardiovascular disease. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Two new tools for assessing patients' knowledge and beliefs about obstructive sleep apnea and continuous positive airway pressure therapy

Background and purpose: Patients' knowledge and beliefs about their illnesses are known to influence a range of health related variables, including treatment compliance. It may, therefore, be important to quantify these variables to assess their impact on compliance, particularly in chronic illnesses such as Obstructive Sleep Apnea (OSA) that rely on self-administered treatments. The aim of this study was to develop two new tools, the Apnea Knowledge Test (AKT) and the Apnea Beliefs Scale (ABS), to assess illness knowledge and beliefs in OSA patients. Patients and methods: The systematic test construction process followed to develop the AKT and the ABS included consultation with sleep experts and OSA patients. The psychometric properties of the AKT and ABS were then investigated in a clinical sample of 81 OSA patients and 33 healthy, non-sleep disordered adults. Results: Results suggest both measures are easily understood by OSA patients, have adequate internal consistency, and are readily accepted by patients. A preliminary investigation of the validity of these tools, conducted by comparing patient data to that of the 33 healthy adults, revealed that apnea patients knew more about OSA, had more positive attitudes towards continuous positive airway pressure (CPAP) treatment, and attributed more importance to treating sleep disturbances than non-clinical groups. Conclusions: Overall, the results of psychometric analyses of these tests suggest these measures will be useful clinical tools with numerous beneficial applications, particularly in CPAP compliance studies and apnea education program evaluations. (C) 2004 Elsevier B.V. All rights reserved.

Evaluation of antihypertensive drugs in patients with obstructive sleep apnea and in rats submitted to chronic intermittent hypoxia

RESUMO: A hipertensão arterial (HA) é uma patologia altamente prevalente, embora claramente subdiagnosticada, em doentes com síndrome de apneia obstrutiva do sono (SAOS). Estas duas patologias apresentam uma estreita relação e a monitorização ambulatória da pressão arterial (MAPA), por um período de 24 horas, parece ser o método mais preciso para o diagnóstico de hipertensão em doentes com SAOS. No entanto, esta ferramenta de diagnóstico para além de ser dispendiosa e envolver um número acrescido de meios técnicos e humanos, é mais morosa e, por conseguinte, não é utilizada por rotina no contexto do diagnóstico da SAOS. Por outro lado, apesar da aplicação de pressão positiva contínua nas vias aéreas (CPAP – Continous Positive Airway Pressure) ser considerada a terapêutica de eleição para os doentes com SAOS, o seu efeito no abaixamento da pressão arterial (PA) parece ser modesto, exigindo, por conseguinte, a implementação concomitante de terapêutica anti-hipertensora. Acontece que são escassos os dados relativos aos regimes de fármacos anti-hipertensores utilizados em doentes com SAOS e, acresce ainda que, as guidelines terapêuticas para o tratamento farmacológico da HA, neste grupo particular de doentes, permanecem, até ao momento, inexistentes. A utilização de modelos animais de hipóxia crónica intermitente (CIH), que mimetizam a HA observada em doentes com SAOS, revela-se extremamente importante, uma vez que se torna imperativo identificar fármacos que promovam um controle adequado da PA neste grupo de doentes. No entanto, estudos concebidos com o intuito de investigar o efeito anti-hipertensor dos fármacos neste modelo animal revelam-se insuficientes e, por outro lado, os escassos estudos que testaram fármacos anti-hipertensores neste modelo não foram desenhados para responder a questões de natureza farmacológica. Acresce ainda que se torna imprescindível garantir a escolha de um método para administração destes fármacos que seja não invasivo e que minimize o stress do animal. Embora a gavagem seja uma técnica indiscutivelmente eficaz e amplamente utilizada para a administração diária de fármacos a animais de laboratório, ela compreende uma sequência de procedimentos geradores de stress para os animais e, que podem por conseguinte, constituir um viés na interpretação dos resultados obtidos. O objectivo global da presente investigação translacional foi contribuir para a identificação de fármacos anti-hipertensores mais efectivos para o tratamento da HT nos indivíduos com SAOS e investigar mecanismos subjacentes aos efeitos sistémicos associadas à SAOS bem como a sua modulação por fármacos anti-hipertensores. Os objectivos específicos foram: em primeiro lugar,encontrar novos critérios, baseados nas medidas antropométricas, que permitam a identificação de doentes com suspeita de SAOS, que erroneamente se auto-classifiquem como nãohipertensos, e desta forma promover um uso mais criterioso do MAPA; em segundo lugar, investigar a existência de uma hipotética associação entre os esquemas de fármacos antihipertensores e o controle da PA (antes e após a adaptação de CPAP) em doentes com SAOS em terceiro lugar, avaliar a eficácia do carvedilol (CVD), um fármaco bloqueador β-adrenérgico não selectivo com actividade antagonista α1 intrínseca e propriedades anti-oxidantes num modelo animal de hipertensão induzida pela CIH; em quarto lugar, explorar os efeitos da CIH sobre o perfil farmacocinético do CVD; e, em quinto lugar, investigar um método alternativo à gavagem para a administração crónica de fármacos anti-hipertensores a animais de laboratório. Com este intuito, na primeira fase deste projecto, fizemos uso de uma amostra com um número apreciável de doentes com SAOS (n=369), que acorreram, pela primeira vez, à consulta de Patologia do Sono do CHLN e que foram submetidos a um estudo polissonográfico do sono, à MAPA e que preencheram um questionário que contemplava a obtenção de informação relativa ao perfil da medicação anti-hipertensora em curso. Numa segunda fase, utilizámos um modelo experimental de HT no rato induzida por um paradigma de CIH. Do nosso trabalho resultaram os seguintes resultados principais: em primeiro lugar, o índice de massa corporal (IMC) e o perímetro do pescoço (PP) foram identificados como preditores independentes de “auto-classificação errónea” da HA em doentes com suspeita de SAOS; em segundo lugar, não encontramos qualquer associação com significado estatístico entre os vários esquemas de fármacos anti-hipertensores bem como o número de fármacos incluídos nesse esquemas, e o controle da PA (antes e depois da adaptação do CPAP); em terceiro lugar, apesar das doses de 10, 30 e 50 mg/kg de carvedilol terem promovido uma redução significativa da frequência cardíaca, não foi observado qualquer decréscimo na PA no nosso modelo animal; em quarto lugar, as razões S/(R+S) dos enantiómeros do CVD nos animais expostos à CIH e a condições de normóxia revelaram-se diferentes; e, em quinto lugar, a administração oral voluntária mostrou ser um método eficaz para a administração diária controlada de fármacos anti-hipertensores e que é independente da manipulação e contenção do animal. Em conclusão, os resultados obtidos através do estudo clínico revelaram que o controle da PA, antes e após a adaptação do CPAP, em doentes com SAOS é independente, quer do esquema de fármacos anti-hipertensores, quer do número de fármacos incluídos num determinado esquema. Os nossos resultados salientam ainda a falta de validade da chamada self-reported hypertension e sugerem que em todos os doentes com suspeita de SAOS, com HA não diagnosticada e com um IMC e um PP acima de 27 kg/m2 e 39 cm, respectivamente, a confirmação do diagnóstico de HA deverá ser realizada através da MAPA, ao invés de outros métodos que com maior frequência são utilizados com este propósito. Os resultados obtidos no modelo animal de HA induzida pela CIH sugerem que o bloqueio do sistema nervoso simpático, juntamente com os supostos efeitos pleiotrópicos do CVD, não parece ser a estratégia mais adequada para reverter este tipo particular de hipertensão e indicam que as alterações farmacocinéticas induzidas pela CIH no ratio S/(R+S) não justificam a falta de eficácia anti-hipertensora do CVD observada neste modelo animal. Por último, os resultados do presente trabalho suportam ainda a viabilidade da utilização da administração oral voluntária, em alternativa à gavagem, para a administração crónica de uma dose fixa de fármacos anti-hipertensores.---------------------------- ABSTRACT: Hypertension (HT) is a highly prevalent condition, although under diagnosed, in patients with obstructive sleep apnea (OSA). These conditions are closely related and 24-hour ambulatory blood pressure monitoring (ABPM) seems to be the most accurate measurement for diagnosing hypertension in OSA. However, this diagnostic tool is expensive and time-consuming and, therefore, not routinely used. On the other hand, although continuous positive airway pressure (CPAP) is considered the gold standard treatment for symptomatic OSA, its lowering effect on blood pressure (BP) seems to be modest and, therefore, concomitant antihypertensive therapy is still required. Data on antihypertensive drug regimens in patients with OSA are scarce and specific therapeutic guidelines for the pharmacological treatment of hypertension in these patients remain absent. The use of animal models of CIH, which mimic the HT observed in patients with OSA, is extremely important since it is imperative to identify preferred compounds for an adequate BP control in this group of patients. However, studies aimed at investigating the antihypertensive effect of antihypertensive drugs in this animal model are insufficient, and most reports on CIH animal models in which drugs have been tested were not designed to respond to pharmacological issues. Moreover, when testing antihypertensive drugs (AHDs) it becomes crucial to ensure the selection of a non-invasive and stress-free method for drug delivery. Although gavage is effective and a widely performed technique for daily dosing in laboratory rodents, it comprises a sequence of potentially stressful procedures for laboratory animals that may constitute bias for the experimental results. The overall goal of the present translational research was to contribute to identify more effective AHDs for the treatment of hypertension in patients with OSA and investigate underlying mechanisms of systemic effects associated with OSA, as well as its modulation by AHDs. The specific aims were: first, to find new predictors based on anthropometric measures to identify patients that misclassify themselves as non-hypertensive, and thereby promote the selective use of ABPM; second, to investigate a hypothetical association between ongoing antihypertensive regimens and BP control rates in patients with OSA, before and after CPAP adaptation; third, to determine, in a rat model of CIH-induced hypertension, the efficacy of carvedilol (CVD), a nonselective beta-blocker with intrinsic anti-α1-adrenergic activity and antioxidant properties; fourth, to explore the effects of CIH on the pharmacokinetics profile of CVD and fifth, to investigate an alternative method to gavage, for chronic administration of AHDs to laboratory rats. For that, in the first phase of this project, we used a sizeable sample of patients with OSA (n=369), that attended a first visit at Centro Hospitalar Lisboa Norte, EPE Sleep Unit, and underwent overnight polysomnography, 24-h ABPM and filled a questionnaire that included ongoing antihypertensive medication profile registration. In the second phase, a rat experimental model of HT induced by a paradigm of CIH that simulates OSA was used. The main findings of this work were: first, body mass index (BMI) and neck circumference (NC) were identified as independent predictors of hypertension misclassification in patients suspected of OSA; second, in patients with OSA, BP control is independent of both the antihypertensive regimen and the number of antihypertensive drugs, either before or after CPAP adaptation; third, although the doses of 10, 30 and 50 mg/Kg of CVD promoted a significant reduction in heart rate, no decrease in mean arterial pressure was observed; fourth, the S/(R+S) ratios of CVD enantiomers, between rats exposed to CIH and normoxic conditions, were different and fifth, voluntary ingestion proved to be an effective method for a controlled daily dose administration, with a define timetable, that is independent of handling and restraint procedures. In conclusion, the clinical study showed that BP control in OSA patients is independent of both the antihypertensive regimen and the number of antihypertensive drugs. Additionally, our results highlight the lack of validity of self-reported hypertension and suggest that all patients suspected of OSA with undiagnosed hypertension and with a BMI and NC above 27 Kg/m2 and 39 cm should be screened for hypertension, through ABPM. The results attained in the rat model of HT related to CIH suggest that the blockade of the sympathetic nervous system together with the putative pleiotropic effects of carvedilol is not able to revert hypertension induced by CIH and point out that the pharmacokinetic changes induced by CIH on S/(R+S) ratio are not apparently responsible for the lack of efficacy of carvedilol in reversing this particular type of hypertension. Finally, the results here presented support the use of voluntary oral administration as a viable alternative to gavage for chronic administration of a fixed dose of AHDs.

Position paper on the management of patients with obstructive sleep apnea and hypertension: joint recommendations by the European Society of Hypertension, by the European Respiratory Society and by the members of European COST (COoperation in Scientific and Technological research) ACTION B26 on obstructive sleep apnea

This article is aimed at addressing the current state of the art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnea (OSA) in cardiovascular (particularly hypertensive) patients, as well as for the management of cardiovascular diseases (particularly arterial hypertension) in OSA patients. The present document is the result of the work done by a panel of experts participating in the European Union COST (COoperation in Scientific and Technological research) ACTION B26 on OSA, with the endorsement of the European Respiratory Society (ERS) and the European Society of Hypertension (ESH). These recommendations are particularly aimed at reminding cardiovascular experts to consider the occurrence of sleep-related breathing disorders in patients with high blood pressure. They are at the same time aimed at reminding respiration experts to consider the occurrence of hypertension in patients with respiratory problems at night.

Condutas terapêuticas para tratamento da Síndrome da Apnéia e Hipopnéia Obstrutiva do Sono (SAHOS) e da Síndrome da Resistência das Vias Aéreas Superiores (SRVAS) com enfoque no Aparelho Anti-Ronco (AAR-ITO)

Os autores apresentam uma revisão da literatura referente às alternativas de tratamento cirúrgicas e não-cirúrgicas para a Síndrome da Apnéia e Hipopnéia Obstrutiva do Sono (SAHOS) e para a Síndrome da Resistência das Vias Aéreas superiores (SRVAS) com enfoque no princípio de ação e evolução dos aparelhos de avanço mandibular e, em particular, no mecanismo dinâmico de ação do Aparelho Anti-Ronco® (AAR-ITO).

Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after Hemodialysis.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with significantly increased cardiovascular morbidity and mortality. Fluid overload may promote obstructive sleep apnea in patients with ESRD through an overnight fluid shift from the legs to the neck soft tissues. Body fluid shift and severity of obstructive sleep apnea before and after hemodialysis were compared in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventeen patients with hemodialysis and moderate to severe obstructive sleep apnea were included. Polysomnographies were performed the night before and after hemodialysis to assess obstructive sleep apnea, and bioimpedance was used to measure fluid overload and leg fluid volume. RESULTS: The mean overnight rostral fluid shift was 1.27±0.41 L prehemodialysis; it correlated positively with fluid overload volume (r=0.39; P=0.02) and was significantly lower posthemodialysis (0.78±0.38 L; P<0.001). There was no significant difference in the mean obstructive apnea-hypopnea index before and after hemodialysis (46.8±22.0 versus 42.1±18.6 per hour; P=0.21), but obstructive apnea-hypopnea index was significantly lower posthemodialysis (-10.1±10.8 per hour) in the group of 12 patients, with a concomitant reduction of fluid overload compared with participants without change in fluid overload (obstructive apnea-hypopnea index +8.2±16.1 per hour; P<0.01). A lower fluid overload after hemodialysis was significantly correlated (r=0.49; P=0.04) with a lower obstructive apnea-hypopnea index. Fluid overload-assessed by bioimpedance-was the best predictor of the change in obstructive apnea-hypopnea index observed after hemodialysis (standardized r=-0.68; P=0.01) in multivariate regression analysis. CONCLUSIONS: Fluid overload influences overnight rostral fluid shift and obstructive sleep apnea severity in patients with ESRD undergoing intermittent hemodialysis. Although no benefit of hemodialysis on obstructive sleep apnea severity was observed in the whole group, the change in obstructive apnea-hypopnea index was significantly correlated with the change in fluid overload after hemodialysis. Moreover, the subgroup with lower fluid overload posthemodialysis showed a significantly lower obstructive sleep apnea severity, which provides a strong incentive to further study whether optimizing fluid status in patients with obstructive sleep apnea and ESRD will improve the obstructive apnea-hypopnea index.

Frequency of insomnia report in patients with obstructive sleep apnoea hypopnea syndrome (OSAHS)

Background and purpose: Insomnia and Obstructive Sleep Apnoea Hypopnea Syndrome (OSAHS) are the two most common sleep disorders, and both have significant associated health costs. Despite this, relatively little is known about the prevalence or impact of insomnia in those with OSAHS, although a recent study suggested there may be substantial comorbidity between these disorders [Chest 120 (2001) 1923-9]. The primary aim of this study was to further explore the prevalence of insomnia in OSAHS. A secondary aim was to assess the effect of factors that may impact on both conditions, including mood and sleep-beliefs. Patients and methods: Consecutive patients referred to an accredited Sleep Investigations Unit (n = 105) completed a brief standardized battery of validated questionnaires assessing sleep-related variables and mood. Results: Results showed a high rate of prevalence of clinical insomnia in this OSAHS population, and a strong positive correlation between OSAHS and insomnia symptom severity. Further, OSAHS patients with comorbid insomnia had increased levels of depression, anxiety and stress compared to patients with OSAHS-only, and both patient groups reported similar and significant levels of dysfunctional beliefs about sleep. Findings in relation to habitual sleep, assessed using subjective (diary) and objective criteria (polysomnogram), were mixed but generally showed greater sleep disturbance among those with OSAHS-insomnia compared to those with OSAHS-only. Conclusions: Overall these findings suggest that comorbidity of insomnia in OSAHS patients may lead to increased OSAHS severity and that patients with both conditions may experience more symptoms relating to depression, anxiety and stress. These findings underscore the need for insomnia assessment and management services, even in clinics that primarily service patients with OSAHS. (C) 2004 Elsevier B.V. All rights reserved.

Do optic nerve head and visual field parameters in patients with obstructive sleep apnea syndrome differ from those in control individuals?

BACKGROUND It has been suggested that sleep apnea syndrome may play a role in normal-tension glaucoma contributing to optic nerve damage. The purpose of this study was to evaluate if optic nerve and visual field parameters in individuals with sleep apnea syndrome differ from those in controls. PATIENTS AND METHODS From the records of the sleep laboratory at the University Hospital in Bern, Switzerland, we recruited consecutive patients with severe sleep apnea syndrome proven by polysomnography, apnea-hypopnea index >20, as well as no sleep apnea controls with apnea-hypopnea index <10. Participants had to be unknown to the ophtalmology department and had to have no recent eye examination in the medical history. All participants underwent a comprehensive eye examination, scanning laser polarimetry (GDx VCC, Carl Zeiss Meditec, Dublin, California), scanning laser ophthalmoscopy (Heidelberg Retina Tomograph II, HRT II), and automated perimetry (Octopus 101 Programm G2, Haag-Streit Diagnostics, Koeniz, Switzerland). Mean values of the parameters of the two groups were compared by t-test. RESULTS The sleep apnea group consisted of 69 eyes of 35 patients; age 52.7 ± 9.7 years, apnea-hypopnea index 46.1 ± 24.8. As controls served 38 eyes of 19 patients; age 45.8 ± 11.2 years, apnea-hypopnea index 4.8 ± 1.9. A difference was found in mean intraocular pressure, although in a fully overlapping range, sleep apnea group: 15.2 ± 3.1, range 8-22 mmHg, controls: 13.6 ± 2.3, range 9-18 mmHg; p<0.01. None of the extended visual field, optic nerve head (HRT) and retinal nerve fiber layer (GDx VCC) parameters showed a significant difference between the groups. CONCLUSION Visual field, optic nerve head, and retinal nerve fiber layer parameters in patients with sleep apnea did not differ from those in the control group. Our results do not support a pathogenic relationship between sleep apnea syndrome and glaucoma.

Microscopical Evaluation of Extracellular Matrix and Its Relation to the Palatopharyngeal Muscle in Obstructive Sleep Apnea

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Apnea and oxygen desaturations in children treated with opioids after adenotonsillectomy for obstructive sleep apnea syndrome: a prospective pilot study

Recent case reports have alerted the medical community of fatality in children receiving codeine after tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome.

Patent Foramen Ovale Closure in Obstructive Sleep Apnea Improves Blood Pressure and Cardiovascular Function.

UNLABELLED Obstructive sleep apnea (OSA) is a frequent syndrome characterized by intermittent hypoxemia and increased prevalence of arterial hypertension and cardiovascular morbidity. In OSA, the presence of patent foramen ovale (PFO) is associated with increased number of apneas and more severe oxygen desaturation. We hypothesized that PFO closure improves sleep-disordered breathing and, in turn, has favorable effects on vascular function and arterial blood pressure. In 40 consecutive patients with newly diagnosed OSA, we searched for PFO. After initial cardiovascular assessment, the 14 patients with PFO underwent initial device closure and the 26 without PFO served as control group. Conventional treatment for OSA was postponed for 3 months in both groups, and polysomnographic and cardiovascular examinations were repeated at the end of the follow-up period. PFO closure significantly improved the apnea-hypopnea index (ΔAHI -7.9±10.4 versus +4.7±13.1 events/h, P=0.0009, PFO closure versus control), the oxygen desaturation index (ΔODI -7.6±16.6 versus +7.6±17.0 events/h, P=0.01), and the number of patients with severe OSA decreased significantly after PFO closure (79% versus 21%, P=0.007). The following cardiovascular parameters improved significantly in the PFO closure group, although remained unchanged in controls: brachial artery flow-mediated vasodilation, carotid artery stiffness, nocturnal systolic and diastolic blood pressure (-7 mm Hg, P=0.009 and -3 mm Hg, P=0.04, respectively), blood pressure dipping, and left ventricular diastolic function. In conclusion, PFO closure in OSA patients improves sleep-disordered breathing and nocturnal oxygenation. This translates into an improvement of endothelial function and vascular stiffening, a decrease of nighttime blood pressure, restoration of the dipping pattern, and improvement of left ventricular diastolic function. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01780207.

Evaluación de la contribución y el impacto de las tecnologías del habla en la detección automática del Síndrome de la Apnea Obstructiva del Sueño = Contributions and impact assessment of speech technologies on the automatic detection of severe Obstructive Sleep Apnea syndrome

La presente Tesis analiza las posibilidades que ofrecen en la actualidad las tecnologías del habla para la detección de patologías clínicas asociadas a la vía aérea superior. El estudio del habla que tradicionalmente cubre tanto la producción como el proceso de transformación del mensaje y las señales involucradas, desde el emisor hasta alcanzar al receptor, ofrece una vía de estudio alternativa para estas patologías. El hecho de que la señal emitida no solo contiene este mensaje, sino también información acerca del locutor, ha motivado el desarrollo de sistemas orientados a la identificación y verificación de la identidad de los locutores. Estos trabajos han recibido recientemente un nuevo impulso, orientándose tanto hacia la caracterización de rasgos que son comunes a varios locutores, como a las diferencias existentes entre grabaciones de un mismo locutor. Los primeros resultan especialmente relevantes para esta Tesis dado que estos rasgos podrían evidenciar la presencia de características relacionadas con una cierta condición común a varios locutores, independiente de su identidad. Tal es el caso que se enfrenta en esta Tesis, donde los rasgos identificados se relacionarían con una de la patología particular y directamente vinculada con el sistema de físico de conformación del habla. El caso del Síndrome de Apneas Hipopneas durante el Sueno (SAHS) resulta paradigmático. Se trata de una patología con una elevada prevalencia mundo, que aumenta con la edad. Los pacientes de esta patología experimentan episodios de cese involuntario de la respiración durante el sueño, que se prolongan durante varios segundos y que se reproducen a lo largo de la noche impidiendo el correcto descanso. En el caso de la apnea obstructiva, estos episodios se deben a la imposibilidad de mantener un camino abierto a través de la vía aérea, de forma que el flujo de aire se ve interrumpido. En la actualidad, el diagnostico de estos pacientes se realiza a través de un estudio polisomnográfico, que se centra en el análisis de los episodios de apnea durante el sueño, requiriendo que el paciente permanezca en el hospital durante una noche. La complejidad y el elevado coste de estos procedimientos, unidos a las crecientes listas de espera, han evidenciado la necesidad de contar con técnicas rápidas de detección, que si bien podrían no obtener tasas tan elevadas, permitirían reorganizar las listas de espera en función del grado de severidad de la patología en cada paciente. Entre otros, los sistemas de diagnostico por imagen, así como la caracterización antropométrica de los pacientes, han evidenciado la existencia de patrones anatómicos que tendrían influencia directa sobre el habla. Los trabajos dedicados al estudio del SAHS en lo relativo a como esta afecta al habla han sido escasos y algunos de ellos incluso contradictorios. Sin embargo, desde finales de la década de 1980 se conoce la existencia de patrones específicos relativos a la articulación, la fonación y la resonancia. Sin embargo, su descripción resultaba difícilmente aprovechable a través de un sistema de reconocimiento automático, pero apuntaba la existencia de un nexo entre voz y SAHS. En los últimos anos las técnicas de procesado automático han permitido el desarrollo de sistemas automáticos que ya son capaces de identificar diferencias significativas en el habla de los pacientes del SAHS, y que los distinguen de los locutores sanos. Por contra, poco se conoce acerca de la conexión entre estos nuevos resultados, los sé que habían obtenido en el pasado y la patogénesis del SAHS. Esta Tesis continua la labor desarrollada en este ámbito considerando específicamente: el estudio de la forma en que el SAHS afecta el habla de los pacientes, la mejora en las tasas de clasificación automática y la combinación de la información obtenida con los predictores utilizados por los especialistas clínicos en sus evaluaciones preliminares. Las dos primeras tareas plantean problemas simbióticos, pero diferentes. Mientras el estudio de la conexión entre el SAHS y el habla requiere de modelos acotados que puedan ser interpretados con facilidad, los sistemas de reconocimiento se sirven de un elevado número de dimensiones para la caracterización y posterior identificación de patrones. Así, la primera tarea debe permitirnos avanzar en la segunda, al igual que la incorporación de los predictores utilizados por los especialistas clínicos. La Tesis aborda el estudio tanto del habla continua como del habla sostenida, con el fin de aprovechar las sinergias y diferencias existentes entre ambas. En el análisis del habla continua se tomo como punto de partida un esquema que ya fue evaluado con anterioridad, y sobre el cual se ha tratado la evaluación y optimización de la representación del habla, así como la caracterización de los patrones específicos asociados al SAHS. Ello ha evidenciado la conexión entre el SAHS y los elementos fundamentales de la señal de voz: los formantes. Los resultados obtenidos demuestran que el éxito de estos sistemas se debe, fundamentalmente, a la capacidad de estas representaciones para describir dichas componentes, obviando las dimensiones ruidosas o con poca capacidad discriminativa. El esquema resultante ofrece una tasa de error por debajo del 18%, sirviéndose de clasificadores notablemente menos complejos que los descritos en el estado del arte y de una única grabación de voz de corta duración. En relación a la conexión entre el SAHS y los patrones observados, fue necesario considerar las diferencias inter- e intra-grupo, centrándonos en la articulación característica del locutor, sustituyendo los complejos modelos de clasificación por el estudio de los promedios espectrales. El resultado apunta con claridad hacia ciertas regiones del eje de frecuencias, sugiriendo la existencia de un estrechamiento sistemático en la sección del tracto en la región de la orofaringe, ya prevista en la patogénesis de este síndrome. En cuanto al habla sostenida, se han reproducido los estudios realizados sobre el habla continua en grabaciones de la vocal /a/ sostenida. Los resultados son cualitativamente análogos a los anteriores, si bien en este caso las tasas de clasificación resultan ser más bajas. Con el objetivo de identificar el sentido de este resultado se reprodujo el estudio de los promedios espectrales y de la variabilidad inter e intra-grupo. Ambos estudios mostraron importantes diferencias con los anteriores que podrían explicar estos resultados. Sin embargo, el habla sostenida ofrece otras oportunidades al establecer un entorno controlado para el estudio de la fonación, que también había sido identificada como una fuente de información para la detección del SAHS. De su estudio se pudo observar que, en el conjunto de datos disponibles, no existen variaciones que pudieran asociarse fácilmente con la fonación. Únicamente aquellas dimensiones que describen la distribución de energía a lo largo del eje de frecuencia evidenciaron diferencias significativas, apuntando, una vez más, en la dirección de las resonancias espectrales. Analizados los resultados anteriores, la Tesis afronta la fusión de ambas fuentes de información en un único sistema de clasificación. Con ello es posible mejorar las tasas de clasificación, bajo la hipótesis de que la información presente en el habla continua y el habla sostenida es fundamentalmente distinta. Esta tarea se realizo a través de un sencillo esquema de fusión que obtuvo un 88.6% de aciertos en clasificación (tasa de error del 11.4%), lo que representa una mejora significativa respecto al estado del arte. Finalmente, la combinación de este clasificador con los predictores utilizados por los especialistas clínicos ofreció una tasa del 91.3% (tasa de error de 8.7%), que se encuentra dentro del margen ofrecido por esquemas más costosos e intrusivos, y que a diferencia del propuesto, no pueden ser utilizados en la evaluación previa de los pacientes. Con todo, la Tesis ofrece una visión clara sobre la relación entre el SAHS y el habla, evidenciando el grado de madurez alcanzado por la tecnología del habla en la caracterización y detección del SAHS, poniendo de manifiesto que su uso para la evaluación de los pacientes ya sería posible, y dejando la puerta abierta a futuras investigaciones que continúen el trabajo aquí iniciado. ABSTRACT This Thesis explores the potential of speech technologies for the detection of clinical disorders connected to the upper airway. The study of speech traditionally covers both the production process and post processing of the signals involved, from the speaker up to the listener, offering an alternative path to study these pathologies. The fact that utterances embed not just the encoded message but also information about the speaker, has motivated the development of automatic systems oriented to the identification and verificaton the speaker’s identity. These have recently been boosted and reoriented either towards the characterization of traits that are common to several speakers, or to the differences between records of the same speaker collected under different conditions. The first are particularly relevant to this Thesis as these patterns could reveal the presence of features that are related to a common condition shared among different speakers, regardless of their identity. Such is the case faced in this Thesis, where the traits identified would relate to a particular pathology, directly connected to the speech production system. The Obstructive Sleep Apnea syndrome (OSA) is a paradigmatic case for analysis. It is a disorder with high prevalence among adults and affecting a larger number of them as they grow older. Patients suffering from this disorder experience episodes of involuntary cessation of breath during sleep that may last a few seconds and reproduce throughout the night, preventing proper rest. In the case of obstructive apnea, these episodes are related to the collapse of the pharynx, which interrupts the air flow. Currently, OSA diagnosis is done through a polysomnographic study, which focuses on the analysis of apnea episodes during sleep, requiring the patient to stay at the hospital for the whole night. The complexity and high cost of the procedures involved, combined with the waiting lists, have evidenced the need for screening techniques, which perhaps would not achieve outstanding performance rates but would allow clinicians to reorganize these lists ranking patients according to the severity of their condition. Among others, imaging diagnosis and anthropometric characterization of patients have evidenced the existence of anatomical patterns related to OSA that have direct influence on speech. Contributions devoted to the study of how this disorder affects scpeech are scarce and somehow contradictory. However, since the late 1980s the existence of specific patterns related to articulation, phonation and resonance is known. By that time these descriptions were virtually useless when coming to the development of an automatic system, but pointed out the existence of a link between speech and OSA. In recent years automatic processing techniques have evolved and are now able to identify significant differences in the speech of OSAS patients when compared to records from healthy subjects. Nevertheless, little is known about the connection between these new results with those published in the past and the pathogenesis of the OSA syndrome. This Thesis is aimed to progress beyond the previous research done in this area by addressing: the study of how OSA affects patients’ speech, the enhancement of automatic OSA classification based on speech analysis, and its integration with the information embedded in the predictors generally used by clinicians in preliminary patients’ examination. The first two tasks, though may appear symbiotic at first, are quite different. While studying the connection between speech and OSA requires simple narrow models that can be easily interpreted, classification requires larger models including a large number dimensions for the characterization and posterior identification of the observed patterns. Anyhow, it is clear that any progress made in the first task should allow us to improve our performance on the second one, and that the incorporation of the predictors used by clinicians shall contribute in this same direction. The Thesis considers both continuous and sustained speech analysis, to exploit the synergies and differences between them. On continuous speech analysis, a conventional speech processing scheme, designed and evaluated before this Thesis, was taken as a baseline. Over this initial system several alternative representations of the speech information were proposed, optimized and tested to select those more suitable for the characterization of OSA-specific patterns. Evidences were found on the existence of a connection between OSA and the fundamental constituents of the speech: the formants. Experimental results proved that the success of the proposed solution is well explained by the ability of speech representations to describe these specific OSA-related components, ignoring the noisy ones as well those presenting low discrimination capabilities. The resulting scheme obtained a 18% error rate, on a classification scheme significantly less complex than those described in the literature and operating on a single speech record. Regarding the connection between OSA and the observed patterns, it was necessary to consider inter-and intra-group differences for this analysis, and to focus on the articulation, replacing the complex classification models by the long-term average spectra. Results clearly point to certain regions on the frequency axis, suggesting the existence of a systematic narrowing in the vocal tract section at the oropharynx. This was already described in the pathogenesis of this syndrome. Regarding sustained speech, similar experiments as those conducted on continuous speech were reproduced on sustained phonations of vowel / a /. Results were qualitatively similar to the previous ones, though in this case perfomance rates were found to be noticeably lower. Trying to derive further knowledge from this result, experiments on the long-term average spectra and intraand inter-group variability ratios were also reproduced on sustained speech records. Results on both experiments showed significant differences from the previous ones obtained from continuous speech which could explain the differences observed on peformance. However, sustained speech also provided the opportunity to study phonation within the controlled framework it provides. This was also identified in the literature as a source of information for the detection of OSA. In this study it was found that, for the available dataset, no sistematic differences related to phonation could be found between the two groups of speakers. Only those dimensions which relate energy distribution along the frequency axis provided significant differences, pointing once again towards the direction of resonant components. Once classification schemes on both continuous and sustained speech were developed, the Thesis addressed their combination into a single classification system. Under the assumption that the information in continuous and sustained speech is fundamentally different, it should be possible to successfully merge the two of them. This was tested through a simple fusion scheme which obtained a 88.6% correct classification (11.4% error rate), which represents a significant improvement over the state of the art. Finally, the combination of this classifier with the variables used by clinicians obtained a 91.3% accuracy (8.7% error rate). This is within the range of alternative, but costly and intrusive schemes, which unlike the one proposed can not be used in the preliminary assessment of patients’ condition. In the end, this Thesis has shed new light on the underlying connection between OSA and speech, and evidenced the degree of maturity reached by speech technology on OSA characterization and detection, leaving the door open for future research which shall continue in the multiple directions that have been pointed out and left as future work.

The roles of depression and anxiety in the understanding and treatment of Obstructive Sleep Apnea Syndrome

Obstructive Sleep Apnea Syndrome (OSAS) is a debilitating condition stemming from disruption to the respiratory system during sleep. At present, the nature of the relationship between OSAS and mood, specifically depression and anxiety, is still unclear. The purpose of this paper is to shed some light on this relationship. PsycINFO was used to locate relevant papers on this topic. This literature search formed the basis of our investigation. Results showed that the anxiety and depression methodology is weak. It is now clear that there is an urgent need to better understand the roles of anxiety and depression in OSAS. For example, the research literature suggests that depression and anxiety covary with OSAS. However, because of methodological issues, such as difficulties involved in diagnosis and the use of inappropriate instruments, this conclusion remains tenuous. Future directions are discussed. (C) 2004 Elsevier Ltd. All rights reserved.

Inflammatory Markers and Obstructive Sleep Apnea in Obese Children: The NANOS Study

Introduction. Obesity and obstructive sleep apnea syndrome (OSA) are common coexisting conditions associated with a chronic low-grade inflammatory state underlying some of the cognitive, metabolic, and cardiovascular morbidities. Aim. To examine the levels of inflammatory markers in obese community-dwelling children with OSA, as compared to no-OSA, and their association with clinical and polysomnographic (PSG) variables. Methods. In this cross-sectional, prospective multicenter study, healthy obese Spanish children (ages 4-15 years) were randomly selected and underwent nocturnal PSG followed by a morning fasting blood draw. Plasma samples were assayed for multiple inflammatory markers. Results. 204 children were enrolled in the study; 75 had OSA, defined by an obstructive respiratory disturbance index (RDI) of 3 events/hour total sleep time (TST). BMI, gender, and age were similar in OSA and no-OSA children. Monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in OSA children, with interleukin-6 concentrations being higher in moderate-severe OSA (i.e., AHI > 5/hrTST; P < 0.01), while MCP-1 levels were associated with more prolonged nocturnal hypercapnia (P < 0.001). Conclusion. IL-6, MCP-1, and PAI-1 are altered in the context of OSA among community-based obese children further reinforcing the proinflammatory effects of sleep disorders such as OSA. This trial is registered with ClinicalTrials.gov NCT01322763.