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Obstructive sleep apnea syndrome (OSAS) is a serious disorder that affects an estimated 24% of middle-age males, and 9% of middle-aged females. In addition, a large portion of individuals with OSAS go undiagnosed. OSAS is associated with several adverse health problems, including the metabolic syndrome. Therefore, there is a clear need to identify new methods for assessing OSAS risk. The exercise test has been used effectively as a diagnostic and prognostic tool for those at high risk for cardiovascular disease and hypertension. Research into the cardiopulmonary responses to exercise testing in young adult men with OSAS has not been examined. Objectives: The objectives of this study were to: 1) evaluate whether OSAS is characterized by exaggerated ventilatory responses to ramp exercise testing, with a secondary aim to evaluate if variations in serum leptin concentration might exert a regulatory in ventilatory responses during exercise; 2) To evaluate whether autonomic control of the cardiovascular response during exercise is distorted by OSAS in young overweight men, as manifested by a blunting of heart rate and exaggeration of blood pressure responses.; 3) To explore whether various simple clinical measures and response patterns from graded exercise testing might serve to discriminate between young men with and without OSAS. Methods: For objectives one and two, 14 obese men with OSAS [age = 22.4 ± 2.8; body mass index (BMI) = 32.0 ± 3.7; apnea-hypopnea index (AHI) = 22.7 ± 18.5], 16 obese men without OSAS (age = 21.4 ± 2.6; BMI = 31.4 ± 3.7), and 14 normal weight subjects (objective 2) (age = 21.4 ± 2.1; BMI = 22.0 ± 1.3) were recruited. For objective three, 91 men (age = 21.6 ± 2.8; AHI range = 0.6 – 60.5; BMI range = 19.0 – 43.9) were recruited. Subjects completed a ramp cycle ergometer exercise test, and a fasting blood sample was obtained to measure plasma leptin and blood lipid levels. Repeated measures ANOVA and stepwise linear regression was used to examine objectives 1 and 2. For objective 3, stepwise linear regression and receiver operator curve (ROC) analysis was utilized. Results: Ventilation (VE), the ventilatory equivalents for oxygen (VE/VO₂) and carbon dioxide (VE/VCO₂) were greater in the OSAS subjects vs. the overweight subjects without OSAS (P = 0.05, P < 0.05 and P < 0.005, respectively) at all exercise intensities. Heart rate (HR) recovery was attenuated in the overweight OSAS subjects compared to the No-OSAS and Control groups throughout 5 minutes of active recovery (P = 0.009). Oxygen uptake, HR, and blood pressure did not differ throughout exercise. Leptin was not associated with ventilatory responses at any exercise intensity. Linear regression analysis revealed hip-to-height ratio (HHR), hip circumference (HC), triglyceride levels, and recovery systolic blood pressure ratio (SBPR) at 2 and 4 minutes were independent predictors of AHI (model fit: R² = 0.68, p <0.0001). ROC analysis determined that percent body fat, HHR, and recovery HR at 2 minutes and 4 minutes were the best single predictors of OSAS risk (AUC = 0.77 for each measure, p = 0.003). Conclusions: Unique ventilatory and hemodynamic characteristics to maximal exercise testing are exhibited in young men with OSAS. These characteristics may be related to alterations in the sympathetic nervous system and chemoreceptor activation, and may be early clinical signs in the progression of OSAS. These exercise characteristics, along with anthropometric and body composition measures may provide useful information in identifying young men at risk for OSAS. / Ph. D.

Background and Purpose: Little is known about influences of obstructive sleep apnea syndrome (OSAS) on dietary intake and body composition. The purpose of this study was to evaluate dietary status, body fat distribution and leptin in overweight young men with and without OSAS in comparison to published values for normal weight counterparts. Methods: Groups were comprised of 24 sedentary overweight young men with and without OSAS, who had a body mass index (BMI) greater than 25 kg/m². Serum leptin concentration was measured in the 24 subjects using radioimmunoassay, while OSAS assessment was done using nighttime home somnography. Analysis of 4-day diet recalls was performed using Nutritionist Pro (First DataBank, Inc., San Bruno, CA). A Healthy Eating Index (HEI) score was calculated for the 24 overweight subjects. Results: There were no differences between the two overweight groups for total fat mass, central abdominal fat, BMI, waist circumference, leptin, or the HEI. The HEI was not predictive of overall OSAS severity; however, BMI was moderately related to OSAS severity (r = 0.39; p=0.05). The normal weight group did have a 50% higher report of carbohydrate intake, and consumed on average, 500 more kilocalories per day. The normal weight group consumed 50% less sodium, and 50% more Vitamin's C and E including a 13% increase in the HEI. Conclusions: Regulation of eating behavior and related influences on diet composition may be affected by a number of neurohormonal disturbances associated with OSAS and/or obesity, itself. Further research is needed to quantify these possible differences on dietary status and the underlying mechanism involved. / Master of Science

Heart Rate Variability (HRV) currently is utilized when assessing the risk of mortality in individuals suffering from coronary heart disease or diabetic neuropathy. Research has shown that patients with Obstructive Sleep Apnea (OSA) also show a decrease in HRV, as well as an increase in sympathetic drive characterized by an increase in the low-frequency component of HRV. HRV, in conjunction with other indicators, may represent a non-invasive, low cost method for the confirmation of severity of OSA in some patients and therefore may represent an additional tool for the assessment of risk in these individuals. This becomes especially true when urinary catecholamines, fitness level, and quality of life (QOL) assessment are included. The purpose of this study was to determine if a correlation exists between severity of OSA as assessed by respiratory distress index (RDI) and the selected measures HRV, fitness, QOL, and catecholamine output. Subjects were 6 men and 5 women who were recently diagnosed with OSA by polysomnographic (PSG) study. HRV and blood pressure was measured during two consecutive trials consisting of 512 heartbeats. Catecholamine levels were determined by HPLC following 24-hour urine collection. Fitness levels were established following cycle ergometer testing and QOL following questionnaire completion. Subjects with lower weight, BMI, and neck circumference had significantly higher parasympathetic influence as analyzed through the amount of high frequency component of HRV (r =.738, .726, .789, respectively; p<0.05). Respiratory distress index (RDI) was negatively related to the average heart rate (HR=RR average, r = -.610, p<0.05), while the amount of total sleep (r = .657, p<0.05) and REM sleep (r = .739, p<0.01) increased as HR increased. The average HR was correlated to the predicted VO2max (r = .677, p<0.05). When the frequency components of HRV, fitness, QOL, and catecholamines were combined, the association to RDI increased dramatically (r = .984, p = .02). The results indicate that as the severity of OSA increases, markers of fitness, QOL, and sleep decrease. There is also an inverse relationship between autonomic function and severity of OSA. It is concluded that HRV and fitness levels are inversely related to the severity of OSA, and that these measures may be developed into a risk assessment tool for use in OSA patient evaluatio / Master of Science

Obstructive sleep apnea syndrome (OSAS) is a complex disorder characterized by repetitive bouts of upper airway collapse during sleep, causing subsequent intermittent hypoxia, hypercapnia, and fragmented sleep and is also associated with significant morbidity including daytime sleepiness, hypertension, and elevated cardiovascular risk. OSAS affects at least 4% of men and 2% of women; unfortunately, it is estimated that 80% to 90% of adults with OSAS remain undiagnosed. Both clinical characteristics and complex genetic and environmental interactions have made it difficult to understand OSAS disease etiology and identifying patients at risk is still elusive. A pattern of gene expression in cells or tissues related to a disease state for OSAS would provide beneficial information to be most effective in screening or diagnosing this disease. Objectives: The objectives of this study were to: 1) map out the study design and bench assay strategies by which to investigate this issue; 2) find out if there are specific differences in the global gene expression profiles of adult females with OSAS compared to those without OSAS, under conditions in which subjects were clinically similar (BMI, diabetes, cardiovascular disease, etc.); and 3) assess the protein expression differences that could potentially be linked via well-established molecular pathways associated with any differences found in global gene expression profiles in the presence and absence of OSAS. Methods: Subjects were overweight premenopausal Caucasian women with untreated OSAS (n=6; age = 40.7 ± 3.4; BMI = 49.04 ± 6.97; apnea-hypopnea index = 27.3 ± 16.02), and control subjects (n=10) (age = 38.2 ± 7.6; BMI = 47.94 ± 6.15; apnea-hypopnea index < 5), and matched for other clinical characteristics (diabetes, cardiovascular disease status, medications, etc.) recruited from either Carilion Clinic Pulmonary/Sleep Medicine or Carilion Clinic Bariatric Surgery practices. Subjects provided a fasting blood sample in which the monocytes were isolated from whole blood. The RNA was extracted from the monocytes, assessed for purity and quantity, frozen and shipped to collaborators at Dana-Farber Cancer Institute and hybridized to Affymetrix whole human genome chips on a gene chip. The initial computational evaluation and interpretation generated the hypothesis. Two-step quantitative real time polymerase chain reaction (qPCR) was performed to verify the results from the microarray analysis. The laminin enzyme immunoassay (EIA), and cellular adhesion assays were performed to determine if genomic changes resulted in proteomic and phenotypic assessments. Results: OSAS subjects had nine aberrantly regulated genes, of which three genes (LAMC-1, CDC42, and TACSTD2) showed a pattern in segregation between OSAS and controls subjects based on expression patterns. In addition, qPCR indicated a 2.1 fold increase in LAMC-1 and a 1.1 fold increase CDC42 expression unique to the tissue samples of patients with OSAS. Though the serum laminin EIA did not differ between groups, a statistically significant increase in peripheral blood mononuclear cells (PBMC) cellular adhesion in OSAS patients versus control subjects was found. The OSAS subjects had a well cell count of 9.27 ± 1.54 cells vs. controls 5.75 ± 0.78 cells (p Ë‚ 0.05), which is relative to the 103 cells/field that were plated. Conclusions: Cells isolated from women with moderate-severe OSAS show an abnormality in cellular adhesion, a process driven in part by the gene LAMC-1, which was also aberrantly expressed in these subjects. This suggests that inflammation may be linked to the pathogenesis of OSAS. This pilot study has provided the framework and preliminary data needed to propose a larger study with extramural research funding. / Ph. D.

Yes / The increasing prevalence and associated cost of treating chronic obstructive pulmonary disease (COPD) is unsustainable, and focus is needed on self-management and prevention of hospital admissions. Telehealth monitoring of patients’ vital signs allows clinicians to prioritise their workload and enables patients to take more responsibility for their health. This paper reports the results of a pilot randomised controlled trial (RCT) of Telehealth-supported care within a community-based COPD supported-discharge service. Methods: A two-arm pragmatic pilot RCT was conducted comparing the standard service with a Telehealth-supported service and assessed the potential for progressing into a full RCT. The co-primary outcome measures were the proportion of COPD patients readmitted to hospital and changes in patients’ self-reported quality of life. The objectives were to assess the suitability of the methodology, produce a sample size calculation for a full RCT, and to give an indication of cost-effectiveness for both pathways. Results: Sixty three participants were recruited (n = 31 Standard; n = 32 Telehealth); 15 participants were excluded from analysis due to inadequate data completion or withdrawal from the Telehealth arm. Recruitment was slow with significant gaps in data collection, due predominantly to an unanticipated 60% reduction of staff capacity within the clinical team. The sample size calculation was guided by estimates of clinically important effects and COPD readmission rates derived from the literature. Descriptive analyses showed that the standard service group had a lower proportion of patients with hospital readmissions and a greater increase in self-reported quality of life compared to the Telehealth-supported group. Telehealth was cost-effective only if hospital admissions data were excluded. Conclusions: Slow recruitment rates and service reconfigurations prevented progression to a full RCT. Although there are advantages to conducting an RCT with data collection conducted by a frontline clinical team, in this case, challenges arose when resources within the team were reduced by external events. Gaps in data collection were resolved by recruiting a research nurse. This study reinforces previous findings regarding the difficulty of undertaking evaluation of complex interventions, and provides recommendations for the introduction and evaluation of complex interventions within clinical settings, such as prioritisation of research within the clinical remit.

No / Dear Editor In undertaking studies of palliative care in heart failure and chronic obstructive pulmonary disease (COPD) in the UK, we identified procedural, conceptual and ethical challenges that may arise from one feature of The End of Life Care Strategy for England.1 The strategy presents the question, ‘Would I be surprised if the person in front of me was to die in the next six months or one year?’ as a prompt to initiate discussion of endof-life care needs and preferences (paragraph 3.23). We believe this question is inappropriate in heart failure and COPD and its use will inhibit the initiation of a palliative care approach with these patients.

Thesis (MScPhysio)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: Acute exacerbation is an important event of COPD as it causes significant disability and mortality. Especially repeated hospitalisation of patients with acute exacerbation has been associated with reduce quality of life and excessive hospitalisation cost. Chronic Obstructive Pulmonary Disease causes significant functional limitations that translate into enormous economic and societal burden. Study Aim: To describe the profile and selected outcomes of Chronic Obstructive Pulmonary Disease (COPD) patients admitted with acute exacerbation to hospitals in the northern suburbs of the Western Cape. Study design: A multicenter retrospective descriptive single subject design was used. Method: Patients admitted with the diagnosis of COPD with acute exacerbation in the time period 01June 2004-01June 2005 were followed up retrospectively for a period of 12 months. The demographics, medical condition on admission and past presentation of acute exacerbation, length of stay in hospital and the number of readmissions for acute exacerbation in the 12 month period were collected and recorded on a self designed data capture sheet. Results: One hundred and seventy eight patients were admitted with acute exacerbation at the three hospitals. The mean age of the patients were 63 (±11.73), more males than females (103: 75) were admitted. Subjects spent a mean of 5.67 (±6.55), days in hospital with every admission and admission frequency of up to eight periods were recorded. Of the n=178 admitted, 56% had one admission and 44% had 2 or more admissions in the study year. This resulted in a total of 338 hospital admissions with the 78 subjects responsible for the majority of admissions (238) Subjects presenting with two or more co-morbidities had a significantly greater risk of multiple re admissions. Subjects with three or more admissions had two or more co morbidities (p=0.001), comparatively those with one admission had only one co morbidity. Congestive cardiac failure (p=0.01) as well as the lack of Long Term Oxygen Therapy p=0.017) were associated with increase risk of three or more admissions. Conclusion: Patients admitted with acute exacerbation to the hospitals where the study was conducted presented with an age ranging from 30-95 years. Patients with 2 or more admissions experience up to eight readmissions episodes in the study year. This is a cause of concern in respect of the burden of disease on especially the younger economically viable South African population. In the current study factors that influenced readmission were the presence of two or more co morbid diseases, specifically the presence of congestive cardiac failure as well as the lack of LTOT. Interventions including a pulmonary rehabilitation programme post discharge should be aimed at decreasing frequency of hospitalisation especially in those patients who are a risk of readmission. / AFRIKAANSE OPSOMMING: Verergering van simptome in Kroniese Obstruktiewe Lugweg Siekte (KOLS) is baie belangrik as gevolg van die ongeskiktheid en mortalitieit wat dit veroorsaak. Dit veroorsaak vermindering in die kwaliteit van lewe en verhoog hospitaal koste verbind met die siekte. Die beperkings toe te skrywe aan die Kroniese Obstruktiewe Lugweg Siekte veroorsaak ontsettende ekonomiese en sosiale druk. Doelstelling: Om die profiel en geselekteerde uitkomste van pasiente met Kroniese Obstruktiewe Lugweg Siekte toegelaat met verergering in die hospitale van die noordelike voorstede van die Wes Kaap te beskryf. Studie ontwerp: ʼn Multisentrum retrospektiewe beskrywende enkel persoon studie. Studie metode: Pasiente toegelaat met verergering van Kroniese Obstruktiewe Lugweg Siekte in die periode 01Junie 2004-01Junie 2005 was retrospektief opgevolg vir ‘n periode van 12-maande. Demografiese data, mediese toestand op toelating en ontslag, lengte van hospitaal verblyf en getal toelatings in die 12- maande was gekollekteer en gedokumenteer op self ontwerpde vorms. Resultate: Een-honderd agt en seventig pasiente was toegelaat met verergering by die drie hospitale. Die gemiddelde ouderdom van die studie populasie was 63 (±11.73) met meer mans as vrouens (103: 75) toegelaat. Die studie populasie het gemiddelde dae van 5.67 (±6.55), in die hospitaal deurgebring en toelating frekwensie van agt episodes was gedokumenteer. Van die n=178 toegelaat was 56% eenkeer toegelaat en 44% het 2 of meer toelatings in die studie jaar gehad. Dit het in 338 hospital toelaatings veroorsaak en 78 van die studie populasie verantwoordelik vir die meeste van die toelatings (238). Die groep met drie of meer toelatings in die studie jaar het twee of meer siektetoestande (p=0.001) gehad, teenorgesteld met die wat net een toelaat was met een siektetoestand. Hart versaaking (p=0.01) en die gebrek aan suurstof by die huis (p=0.017) was verbind met meer risiko van drie of meer toelating. Samevatting: Die ouderdoms verskil was wydbeskrywend van 30-95 jaar van die pasiente wat in die studie jaar toegelaat is by die drie hospitale. Pasiente wat 2 of meer keer toegelaat is het tot agt hertoelatings in die studie jaar gehad. Kommerwekkend is die uitwerking van die siekte op die jonger werkend populasie in Suid Afrika. In die studie was hertoelating beinvloed deur die teenwoordigheid van twee of meer siektetoestande, spesifiek hart versaaking sowel as die gebrek aan suurstof by die huis. Intervensies insluitende pulmonale rehabilitasie na ontslag se doel moet wees om vermindering van heraaldelike hospitalisasie in hoë risiko pasiente vir hospitalisasie.