Abstract Seventy-eight prepubertal children 3 to 10 years old (mean age 5,67 years, range 2.4 - 10.5 years), with symptoms suggestive of obstructive sleep apnea syndrome (OSAS) were studied. Based on overnight polysomnography (PSG) results, 32 children were classified as having OSAS, whereas 46 children were considered as primary snorers (PSs'), when an obstructive apnea-hypopnea index (AHIO) of over one was considered abnormal. Symptoms, signs and findings in these two groups were compared in a cross-sectional study. Fifty-eight of the children were retrieved for a follow-up visit, which was scheduled six months from the first visit. The children with an initial AHIO of 2 or over (n = 21) had been subjected to adenotonsillectomy swiftly after the first visit, whereas the others (n = 37) were observed without intervention. The changes in symptoms, signs and findings were analysed within and between these groups. Relative risk (RR) ratios were calculated in order to find clinical symptoms and signs predicting OSAS in snoring children. Observed apneas, restless sleep, constant snoring and tonsillar hypertrophy were significantly associated with an increased risk of OSAS. Dental arch measurements indicated that AHIO was significantly associated with the amount of overjet, suggesting that altered breathing may affect the dentofacial morphology. Nasalance measurements revealed no group differences between the OSAS children and PSs'. Adenotonsillectomy had no significant influence on the nasalence scores. Measurements of nasalance seem to contribute little to the diagnostics of OSAS in children. At the first visit the mean circulating concentrations of insulin-like growth factor-1 (IGF-1) were of the same magnitude in the OSAS children, the PSs' and the age-matched control group, but both the OSAS children and the PSs' had lower IGF-binding protein-3 (IGFBP-3) concentrations than the control subjects. At the second visit a significant increase of the peripheral concentrations of IGF-1 and IGFBP-3, along with increases in weight for height and BMI were observed in the surgically treated children, whose respiratory parameters and symptoms had improved highly significantly, as well. These results indicate that the growth of children with obstructed nighttime breathing is potentially affected through impaired growth hormone secretion. None of the primary snorers developed OSAS during the observation period, which finding suggests a favorable prognosis for primary snoring in children.

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Obstructive sleep apnea (OSA) is estimated to affect 2 to 4 percent of the adult population (Young T 1993, Skomro and Kryger 1999). However, an estimated 80 to 90 percent of adults with moderate to severe OSA may be clinically undiagnosed. Identification of those at risk and their subsequent diagnosis is, obviously, of great concern to clinicians. This investigation included three distinct research aims, which were the following: (1): In order to establish reliability of hemodynamic measures to be used during exercise testing, a study was conducted on the acetylene single-breath cardiac output (Qc) technique in 15 healthy subjects. This was completed in order to establish reliability of exercise Qc and total peripheral resistance (TPR), these responses could then be investigated acutely in the context of evaluating the relation of these measures to markers of disease in OSA patients. (2): The primary research aim was to describe the extent to which graded exercise testing may reveal abnormalities in hemodynamic function in obstructive sleep apnea (OSA) patients, particularly with respect to cardiac output (Qc), mean arterial pressure (MAP), and TPR that may be related to polysomnography (PSG) markers of OSA severity. Cardiorespiratory and hemodynamic responses that were evaluated included the following: peak oxygen consumption (VO2pk), end-tidal carbon dioxide production (PETCO2), end-tidal oxygen pressure (PETO2), heart rate (HR), blood pressure (systolic = SBP and diastolic = DBP), rate pressure product (RPP), TPR and its derivatives including MAP and Qc, in OSA patients. A global biochemical marker of vascular function, 24-hour urinary nitrite/ nitrate elimination was also determined for each patient. (3): The last aim was included in order to provide qualitative information concerning treatment, subjective sleep and daytime function, and physical activity levels of the OSA patients in this investigation as well as to give insights into the special challenges and potential for doing trials involving nCPAP and physical exercise training with OSA patients. Results from this study can be used to improve clinical evaluation procedures as well as to better understand underlying mechanisms relative to the link between cardiovascular disease and OSA / Ph. D.

Continuous positive airway pressure (CPAP) is the primary therapy administered for those afflicted with obstructive sleep apnea (OSA). We examined the effects of CPAP therapy on physiological variables during a ramped exercise. The five male, OSA patients had mean values and standard deviations for RDI=60.7 +/- 19.1, BMI=29.9 +/- 2.9, and age=56 +/- 16.1 yr. Subjects were examined before and after 4 wk of CPAP therapy. After 4 wk of CPAP therapy, patient responses to exercise showed a 17.6%, (p<0.05) improvement in rating of perceived exertion (RPE) at identical power outputs (60% of the individual's apparent functional capacity). Statistical significance was not attained (p>0.05) upon analysis of the following parameters at 60% of the individuals maximum workload although there was a trend showing a decrease in these variables: heart rate (6% improvement), VO2 (11.7% improvement) systolic blood pressure (4% improvement), and rate pressure product (8.6% improvement). This data shows that the decrease in RPE during 60% of the individual's maximum predicted HR reserve corresponded with an increase in sleep quality (mean increase of 40%, 3.2 units) as measured by the Pittsburgh Sleep Quality Index before and after 4 wk of CPAP therapy. It was concluded that the improvement in exercise tolerance could be attributed to the subjective feelings of improved sleep quality after 4 wk of CPAP therapy. Key Words: Obstructive sleep apnea---CPAP--- exercise---physiological responses. / Master of Science

In order to clarify the effects of a single night of CPAP titration on various cardiovascular, gas exchange, and perceptual measures, we conducted submaximal ramping exercise tests to an intensity of ~75% of the heart rate reserve in five male subjects. Means and standard deviation for their age and BMI were 57.0±14.7 years and 30.5±7.2, respectively. The baseline exercise test was administered immediately after the patients arose from bed, following an overnight PSG diagnostic evaluation. The exercise test was repeated within ~2 weeks of completion of an overnight CPAP evaluation trial. Patients reported experiencing improved sleep quality (50%) after the CPAP titration, based on comparison of morning questionnaire responses from the diagnostic PSG vs. CPAP titration. Statistical significance was not attained (p>0.05) upon analysis of the following parameters at 60% of the individuals maximum workload although there were changes in the mean values of the variables from the diagnostic PSG vs CPAP titration. The following changes were noted: heart rate increased by 6%, systolic blood pressure decreased by 6%, and the rate pressure product decreased by 5.8%. Respiratory variables changed as follows: VO2 decreased by 5.3% and VE decreased by 8.5%. The perceptual measure rate of perceived exertion (RPE) decreased by 17.5%. These preliminary findings demonstrate that self-reports of sleep quality in patients with diagnosed OSA improved after a single night of CPAP titration, even in a setting wherein the total time of CPAP sleep and reduction of apneas, hypopneas, and hypoxemic episodes are highly variable. Additionally, sleep structure revealed a marked increase in slow wave (53.2%) and REM (30.4%) sleep with CPAP titration in comparison to the diagnostic PSG. It was concluded that CPAP titration effectively improves sleep structure and patient ratings of sleep quality, but does not have significant effects on cardiorespiratory responses to submaximal endurance exercise. / Master of Science

Indiana University-Purdue University Indianapolis (IUPUI) / Efforts to encourage the medical community to prescribe exercise for disease prevention and management have increased significantly in recent years. In patients with obstructive sleep apnea (OSA), it is encouraging that exercise has been shown to improve sleep efficiency, daytime sleepiness, and disease severity. However, in order to better understand the dose-response relationship between exercise and OSA-related outcomes, accurate and reliable methods for assessing physical activity habits are needed. Purpose: To determine the test-retest reliability and validity of two self-report physical activity questionnaires [Physical Activity Vital Sign (PAVS); International Physical Activity Questionnaire-Short Form (IPAQ-SF)] in an OSA population. Methods: 39 adults with moderate-to-severe OSA wore an accelerometer for seven consecutive days and completed the PAVS and IPAQ-SF (twice within 10 d), along with questionnaires on quality of life, sleepiness, and treatment adherence. Test-retest reliability was determined using intraclass correlation coefficients (ICC). Criterion and construct validity were determined using Pearson (r) and Spearman correlation coefficients (ρ), respectively. Results: PAVS and IPAQ-SF scores were reported as total min/wk of moderate-vigorous physical activity (MVPA). Test-retest reliability for MVPA was excellent for PAVS (ICC = 0.982) and good for IPAQ-SF (ICC = 0.766). MVPA assessed via accelerometry was strongly correlated with PAVS (r = 0.802) and moderately with IPAQ-SF (r = 0.569). Both PAVS and IPAQ-SF were significantly correlated with body mass index (BMI) (ρ = -0.273 and -0.268, respectively), but no other variables. Conclusions: The PAVS and IPAQ-SF are reliable and valid PA questionnaires and may be utilized as a tool for accurately assessing physical activity levels in OSA patients.

Introduction: Little is known about the impact of spousal involvement on continuous positive airway pressure (CPAP) adherence. The aim of this study was to determine whether spouse involvement affects adherence with CPAP therapy, and how this association varies with gender. Methods: 194 subjects recruited from Apnea Positive Pressure Long Term Efficacy Study (APPLES) completed the Dyadic Adjustment Scale (DAS). The majority of participants were Caucasian (83%), and males (73%), with mean age of 56 years, mean BMI of 31 kg/m2. & 62% had severe OSA. The DAS is a validated 32-item self-report instrument measuring dyadic consensus, satisfaction, cohesion, and affectional expression. A high score in the DAS is indicative of a person’s adjustment to the marriage. Additionally, questions related to spouse involvement with general health and CPAP use were asked. CPAP use was downloaded from the device and self-report, and compliance was defined as usage > 4 h per night. Results: There were no significant differences in overall marital quality between the compliant and noncompliant subjects. However, level of spousal involvement was associated with increased CPAP adherence at 6 months (p=0.01). After stratifying for gender these results were significant only among males (p=0.03). Three years after completing APPLES, level of spousal involvement was not associated with CPAP compliance even after gender stratification. Conclusion: Spousal involvement is important in determining CPAP compliance in males in the 1st 6 months after initiation of therapy but is not predictive of longer-term adherence. Involvement of the spouse should be considered an integral part of CPAP initiation procedures. Support: HL068060

Background: Obstructive sleep apnea has become recognized as one of the most common, under-diagnosed chronic diseases. Recently studies have shown increased numbers among the pediatric and adolescent population. OSA in children is associated with behavioral problems, poor school achievements, and in severe cases, pulmonary hypertension. OSA is often the Achilles heel of pediatric sedation and analgesic programs; during sedation, children with OSA have an increased vulnerability of their airway undergoing pharyngeal collapse and of having upper airway obstruction. Consequently, pediatric dentists who practice sedation dentistry should exercise extra precautions when treating patients with risk of sleep apnea. Currently there is no screening tool used in pediatric dentistry for diagnosing OSA during the pre-operative appointment or consultation for patients undergoing minimal and moderate oral conscious sedation. The purpose of this study was to develop and test a concise and easy-to-use questionnaire as a screening tool to aid in the diagnosis of OSA in pediatric patients. Materials and Methods: A retrospective chart review of 180 patients under the age of 18, who completed a polysomnogram at the VCU Center for Sleep Medicine between February 2011 and February 2013. A validated adult questionnaire, STOPBANG, was modified using more typical pediatric risk factors for OSA: presence of snoring (S), tonsillar hypertrophy (T1), tiredness; pESS>10 (T2), observed obstruction (O), neuroPsych-behavioral symptoms such as ADHD or daytime irritability (P), BMI percentile for age (B), age at diagnostic screening (A), presence of neuromuscular disorder (N), and presence of genetic/congenital disorder (G). A positive scoring from these variables was measured against the standard OSA measure, Apnea-Hypopnea Index. A multiple logistic regression analysis tested for relationships. Results: There was a statistically significant relationship P= .0007 for the S(T1)OPBANG scale, with a minimum of 4 variables needed to have a sensitivity of 57% and a specificity of 78%. There was also a statistically significant relationship P= .0040 for the S(T2)OPBANG, the cutoff>5 yielding sensitivity=36%, and specificity=90%. Only obstruction, BMI, and age showed a strong significant relationship to OSA. The presence of an obstruction was positively related to apnea (P = 0.0010). Most of the other components had an odds-ratio larger than one (indicating a nominally positive relationship). Conclusions: While both STOPBANG screening tools showed a statistically significant relationship, only obstruction, BMI, and age showed a predictive relationship to OSA. Consequently, consideration of other risk factors may be beneficial for future studies.

Nonalcoholic fatty liver disease (NAFLD) afflicts approximately a quarter of the world’s general population and more than half of the world’s obese population. The disease is characterized by a spectrum of liver pathologies, ranging from simple steatosis or the accumulation of fat within hepatic tissue to steatohepatitis comprised of inflammation and fibrosis, also known as NASH. Simple steatosis is relatively asymptomatic and is considered benign, but NASH poses great risk for advanced forms of liver disease, such as cirrhosis and hepatocellular cancer. Obstructive sleep apnea(OSA) is a respiratory disorder involving the recurrent collapse of the upper airway during sleep. Consequently, the patient experiences constant arousals due to constant blockage followed reopening of the airway. Aside from poor quality and disruption of sleep, chronic intermittent hypoxia (CIH) is also present during OSA. The presence of CIH leaves many vital organs deprived of adequate oxygen to carry out normal physiological function. In response to this hypoxic state, the body upregulates many transcription factors, many of which control inflammatory processes. In recent studies, chronic and recurrent hypoxia generated from OSA has been implicated in the onset and progression of NAFLD. The pathogenesis of NAFLD is believed to be associated with metabolic imbalances, mainly obesity and insulin resistance, both of which also overlap with OSA. These conditions are the main factors in predisposing a patient suffering from OSA to the effects of CIH. Multiple lines of evidence suggest that CIH may accelerate the development of NAFLD through 1) Lipolysis of hepatic adipose tissue and increased hepatic free fatty acids; 2) Upregulation of lipid biosynthetic through CIH; 3) Upregulation of hypoxia-inducible factor 1-alpha by CIH inducing liver inflammation and fibrosis. The primary focus of this thesis will attempt to determine a possible link between OSA and NAFLD. Through citation of prior scientific studies, it will formulate the theory of OSA as a predisposing factor in the heightened risk of NAFLD pathogenesis and development to more severe, terminal stages. Primarily, the review of literature will highlight the metabolic imbalances of obesity and insulin resistance and how each is related to OSA and NAFLD. Ultimately, deposition of fat and inflammation triggered through various chemical factors connected to OSA will depict both the generation and progression of NAFLD.

SAS has became an increasingly important public-health problem since 1970. It can adversely affect neurocognitive, cardiovascular, respiratory diseases and can also cause behavior disorder. Moreover, up to 90% of these cases are obstructive sleep apnea (OSA). Presently, Polysomnography is considered as the gold standard for diagnosing sleep apnea syndrome (SAS). However, Polysomnography-based sleep studies are expensive and time-consuming because they require overnight evaluation in sleep laboratories with dedicated systems and attending personnel. In this study, based on the nocturnal oxygen saturation (SpO2) signals, this work develops a method to classify patients with different levels of respiratory disturbance index (RDI) values. To achieve this goal, this study uses neural network in conjunction with different sets of feature variables to perform classification.