Dissertations / Theses on the topic 'Lungs Diseases, Obstructive Australia'

This study was designed to gain an understanding of the family experience when an adult member has chronic obstructive pulmonary disease (COPD). It is recognized that illness within the family affects the well-being of the family unit and the health of all members. To understand the impact of COPD upon the family, however, the literature provides only knowledge of the experience of the individual who has COPD and the spouse, not that of the family unit. Thus, the purpose of this study was to describe and explain the COPD experience from the perspective of the family unit. A qualitative method, phenomenology, was chosen for this investigation. Data were collected through semi-structured interviews with eight families who shared their experiences. From the content analysis of these data, three themes that were common throughout the families' accounts were identified and developed to describe and explain family life with COPD. The first theme, disease-dictated family life, describes four aspects of a common lifestyle that is imposed on the family by the characteristics of COPD. The second theme, isolation, describes the isolation that accompanies the illness experience, for the family group and the individual members within the group. The final theme, family work, describes the four primary challenges the families face and the coping strategies they use to deal with them. These findings revealed that COPD acts as an intense stressor within the family, requiring extensive family work to cope with COPD in a way that maintains the well-being of the family unit. Furthermore, it was found that living with COPD in many ways inhibits the resources within the family and those external sources of support that foster the family's ability to manage the stress associated with living with COPD. The implications for nursing practice and nursing research were delineated in light of the research findings.
Applied Science, Faculty of
Nursing, School of
Graduate

To date, there is a scant amount of research on the long-term benefits of exercise training for individuals with moderate to severe chronic obstructive pulmonary disease. The purpose of this study was to evaluate standardized outcomes of a six-month maintenance pulmonary rehabilitation program to determine maintenance of functional capacity. Twenty-three subjects (sixteen men, seven women) diagnosed with clinical COPD ages 30-82 (65 + 12 years) participated in the retrospective study. The subjects were referred to an eight-week comprehensive pulmonary rehabilitation program after which upon twelve subjects continued onto a maintenance program. Eleven subjects chose not to participate in the maintenance program and were given a home exercise program and were encouraged to remain active. Hemodynamic, functional, and educational measures were taken prior to entry, upon completion of the hospital program, and again six-months post-program. Outcome tests were standardized using the Indiana Society of Cardiovascular and Pulmonary Rehabilitation Outcomes Manual. Significant differences were found between the maintenance and non-maintenance groups for systolic blood pressure in resting, exercise, and recovery measures at six monthsreevaluation. Differences in oxygen saturation were also found to reach significance between the two groups during recovery from the six-minute walk test. Interestingly, duration of exercise was found to be statistically significant between the two groups as well as emergency room visits and physician visits within the last six months. The maintenance group tended to have fewer emergency room and physician visits in addition to having self-reported higher durations of exercise. In conclusion, maintenance pulmonary rehabilitation programs have been shown to maintain physical activity levels for COPD patients and as a result, fewer quality of life consequences specifically the number of hospital admissions and emergency room visits.
School of Physical Education

Rationale. There is a need for the development of a field test to evaluate exertional dyspnea in the primary care setting. This study examined the applicability of a 3-minute constant rate step test in patients with COPD.
Methods. This test involved 4 stepping rates (18, 22, 26, 32 steps.min-1) equivalent to approximately 4.5, 5.3, 6.0, and 7.2 MET with the ultimate goal that in its final development, the assessment will be made a single stepping rate based on disease severity. Stable COPD patients (N = 43; 65 +/- 6.5 years; FEV1 = 49 +/- 16% pred.; SpO2 (%) rest: 95 +/- 2) were equipped with a portable Jaeger Oxycon MobileRTM metabolic system and followed an audio signal for stepping up and down a single 20 cm step for 3 minutes. Borg dyspnea scores were obtained at the end each stepping bout. A 10-min rest was given between each stepping bout.
Results. Of the 43 patients, 80% completed stages 1 and 2, 74 and 37% stages 3 and 4 while no patient of MRC class 4 or 5 (N = 8) completed stage 1. Breathing frequency (breaths.min-1) spanned from 26.5 +/- 4.1 to 39.0 +/- 6.4 but VT (L) remained unchanged (1.4 +/- 0.3 vs. 1.5 +/- 0.4) from stage 1 to 4 while Borg scores were 3 +/- 1, 4 +/- 1, 5 +/- 2, 6 +/- 3 respectively and SpO2 (%) were 92 +/- 5, 91 +/- 4, 91 +/- 4 and 90 +/- 4.
Conclusions. Preliminary findings indicate that a 3-minute constant rate step test may present a feasible alternative to laboratory testing to assess exertional dyspnea in moderately severe COPD. In this population, a stepping rate of 26 steps.min-1 could be sustained by the majority of patients while producing a level of dyspnea potentially amenable to therapy.
This study was supported by an unrestricted grant from Boehringer-Ingelheim/Pfizer.

Purpose: Exercise testing modalities to assess the effects of a given intervention should prove to be reliable and reproducible. This study reports on test-retest reproducibility of the 3-min shuttle walking and step testing exercise protocols to assess exertional dyspnea and exercise physiology in COPD patients.
Methods: Stable COPD patients (N=43; 65 +/- 6.5 years; FEV1 = 49 +/- 16% pred.) equipped with a portable Jaeger Oxycon MobileRTM metabolic system repeated the walking or stepping tests on two occasions separated by 7 to 14 days. At each visit, participants performed, in a randomized order, four externally paced 3-min bouts of shuttle walking at speeds of 1.5, 2.5, 4.0 and 6.0 km·h-1 or of stepping at a constant rate of 18, 22, 26 and 32 steps·min-1, respectively. Each exercise bout was separated by a 10-min rest period. Ventilation, heart rate, gas exchange parameters and Borg dyspnea score were obtained for each bout during the last 30-seconds of exercise.
Results: The majority of patients completed stepping or walking at the slowest cadence but only 33% completed walking at 6.0 km·h -1 and 40% completed stepping at 32 steps·min-1. Test-retest Pearson correlation coefficients for ventilation, heart rate, gas exchange parameters and dyspnea scores over the four exercise bouts, all exceeded 0.80 with the highest coefficient found for ventilation (r≥.95). Intra-class correlation coefficients were similar to Pearson. Bland & Altman representation showed that a similar proportion of dyspnea data points (92 vs. 96%) lied within 2 SD of the mean difference between test-retest values for dyspnea Borg scores during walking and stepping.
Conclusion: Results show very good reproducibility for both 3-min shuttle walking and stepping exercise protocols in patients with COPD.
This study was supported by an unrestricted grant from Boehringer-Ingelheim/Pfizer.

Ipratropium bromide is a short-acting, non-selective, muscarinic antagonist frequently prescribed for the treatment of Chronic Obstructive Pulmonary Disease (COPD) and as an emergency adjunct therapy for acute asthma. Within the past decade, there has been an accumulating wealth of clinical evidence which indicates that anti-muscarinic drugs, such as ipratropium, are responsible for an increased risk of stroke or, an adverse cardiovascular outcome (including increasing the risk and severity of myocardial infarction (MI)). MI remains the highest risk factor of death for COPD patients due to the systemic co-morbidities associated with COPD, which includes ischaemic heart disease (IHD). Despite the knowledge that approximately 22% of COPD patients also suffer from underlying IHD, the cardiovascular safety of muscarinic antagonists, such as ipratropium, has not been tested in a non-clinical setting of IHD or MI. In order to address this, the current project was designed to investigate, for the first time, the effects of ipratropium on the myocardium in a non-clinical setting. It was identified that under normoxic conditions, ipratropium did not have a significant effect on cardiac myocyte viability or infarction, from 3 month Sprague Dawley rats. In addition to this, following simulated ischaemia, ipratropium also did not appear to exacerbate myocardial injury. However, when ipratropium was administered in the context of simulated ischaemia followed by reperfusion, there was a significant exacerbation in myocardial injury which was characterised by increases in infarction, apoptosis, necrosis and a loss of resilience of oxidative stress. In order to characterise the mechanism by which ipratropium exerts the observed cardio-toxic effects, it was investigated whether acetylcholine (ACh) or cyclosporin A (CsA) were capable of attenuating the ipratropium induced cardiotoxicity. Both agents showed significant limitation of injury when co-administered with ipratropium indicating that ipratropium exerts its cardio-toxic effect through a mechanism which links muscarinic signalling to the mitochondrial permeability transition pore (mPTP). This supports previously published work where the protective signalling of ACh has been shown to promote the phosphorylation of pro-survival kinases, such as Akt and Erk1/2 and that this provides inhibition of the mPTP. Western blotting was employed to identify whether there was an involvement of the pro-survival kinases Akt and Erk1/2, as well as the stress induced kinase JNK. Ipratropium significantly increased levels of phospho-Akt and phospho-Erk1/2. However, JNK levels appeared to be insignificantly altered in comparison with the control groups. Both ACh and CsA were capable of limiting these increases. Further to this, an aged study was carried out, which showed that, within the aged myocardium, ipratropium is capable of eliciting further injury in comparison with the 3 month age groups. The effect of ipratropium on tolerance of oxidative stress was not significant, but, also, ACh and CsA were shown as unable to protect. Significant levels of JNK were also observed in the aged animals in comparison with the 3 month groups. In combination, the results presented here demonstrate, for the first time, that ipratropium is capable of exacerbating ischaemia/reperfusion injury in in vitro models of myocardial ischaemia/reperfusion. In addition, ACh and CsA are capable of limiting this injury, implying a role for pro-survival kinases and the mPTP in ipratropium induced myocardial injury. In the aged study, ipratropium still exacerbated injury, however, ACh and CsA appeared unable to protect, therefore promoting previous work that cellular signalling is altered in the senescent myocardium. In conclusion, further studies must be carried out in order to fully characterise the cardio-vascular safety profile of ipratropium.

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) patients show a marked reduction in exercise capacity compared to that of healthy age-matched individuals. While inadequate gas exchange and resulting hypoxemia appears as the primary factor in COPD, an impaired cardiac output is the predominant explanation for the reduced oxygen delivery in CHF. However, the extent of the contributions of other systemic factors remains unclear. In light of the potential interactions between cardiac output (Qc) and pulmonary hyperinflation, there is surprisingly little data thus far on ventilatory constraints in CHF and on the role of blood flow delivery in COPD which may further limit the exercise capacity. Thus, the purpose of this study was to compare the slope of the Qc versus oxygen uptake (VO2) response through several submaximal cycling loads in patients with moderately severe COPD and with that of moderate to severe CHF patients as well as age-matched healthy control subjects (CTRL). Also examined was the possibility that ventilatory constraints such as dynamic hyperinflation contribute to an abnormal stroke volume response in both diseases. Cardiac output was measured using the CO 2-rebreathing equilibrium technique during baseline conditions and cycling at 20, 40 and 65% of peak power in 17 COPD (Age: 64 +/- 8 yrs; FEV 1/FVC: 37 +/- 11%; FEV1: 41 +/- 15 % predicted), 10 CHF (Age: 57+/- 10 yrs; FEV1/FVC: 73.8 +/- 5.6%; FEV 1: 93 +/- 13% predicted) and 10 age-matched CTRL subjects. Inspiratory capacity (IC) was also measured for the determination of dynamic hyperinflation during the steady state exercise bouts. The results indicate that while the absolute Qc values are lower in COPD and in CHF than in CTRL during 65% peak power cycling (11.30 +/- 2.38 vs 12.40 +/- 2.08 vs 15.63 +/- 2.15 L•min-1 respectively, p < 0.01), likely due to their lower exercise metabolic demand. The Qc/VO2 response to increasing levels of exercise intensity was lower or normal in CHF patients compared to CTRL, while normal or hyperdynamic in most COPD patients. Indeed, the majority of patients with COPD exhibited Qc/VO2 slopes greater than 7.0, which may be indicative of a peripheral muscle bioenergetic disturbance that may drive the need for greater oxygen delivery, and thus result in an exaggerated central circulatory response.

Malnutrition, as evidenced by low weight for height, low triceps skinfold thickness and low midarm muscle circumference, is prevalent among COPD patients. A stepped decline in nutritional status has been postulated as a mechanism for malnutrition wherein patients progressively suffer weight loss with each COPD exacerbation. A randomized clinical trial of continuous enteral nutrition could not successfully address whether or not the stepped decline in weight can be prevented. Despite this, sixteen patients admitted for a COPD exacerbation, participated in an observational prospective study wherein anthropometric, biochemical, dynamometric, respiratory, general well-being and energy consumption measures were obtained. Twelve patients had body weights below 90% of ideal weight. The mean energy intake was 107% $ pm$ 30 of estimated resting energy expenditure. Measures were repeated to assess changes during hospitalization. Weight change was a poor indicator of nutritional status. Midarm muscle circumference and handgrip strength appear to be useful as nutritional status indicators among unstable hospitalized COPD patients. Changes in handgrip strength and midarm muscle circumference were closely linked (r =.78, p $<$ 0.0005) and tended to decrease over the course of hospitalization despite clinical improvement. In the absence of adequate nutrition, COPD patients have at least as much risk of developing iatrogenic malnutrition as are other hospitalized medical patients.

Total body fat and muscle mass depletion has been reported in some patients with COPD. This study used simple anthropometric measurements to compare the body composition of patients with moderate-severe COPD to that of healthy controls, and examines relationships between body composition, disease severity, habitual physical activity and resting and exercise energy expenditure. Results show no significant differences in overall Heath-Carter somatotype characteristics, percent body fat, fat free mass and girth measurements between COPD and control subjects although when stratified by gender, female COPD patients exhibited a greater body fat component. Measured VO2 (L/min) at rest or during steady-state exercise was not significantly different between COPD and control subjects despite a higher exercise ventilation in patients. Neither resting or exercise energy expenditure was related to body composition, however it was related to DLCO/VA (ml·min-1·mmHg -1·L-1). Findings from this study suggest that COPD patients capable of participating in dynamic exercise studies do not exhibit total body fat and muscle depletion. Findings in women suggest that the relative decrease in FFM may be related to a relatively higher proportion of body fat and not a decrease in absolute muscle mass.

Chronic obstructive pulmonary disease (COPD) is characterized by an expiratory flow limitation, as well as an evident reduced exercise capacity compared to that of healthy age-matched individuals. Clearly, the expiratory flow limitation plays a significant role in this exercise intolerance; however, the extent of the contributions of other systemic factors remains unclear. More specifically, there is little data thus far on the role of blood flow delivery as a possible exercise limitation in COPD, especially in light of the potential interactions between cardiac output (Qc) and pulmonary hyperinflation. Thus, the purpose of this study was to compare the slope of the Qc versus oxygen uptake (VO 2) response through several submaximal cycling loads in patients with moderately severe COPD with that of age-matched healthy control subjects (CTRL). Also examined was the possibility that ventilatory constraints such as dynamic hyperinflation contribute to an abnormal Qc response. Cardiac output was measured using the CO2-rebreathing equilibrium technique during baseline conditions and cycling at 20, 40 and 65% of peak power in 17 COPD (Age: 64 +/- 8 yrs; FEV1/FVC: 37 +/- 11%; FEV1: 41 +/- 15% predicted) and 10 age-matched CTRL subjects. Inspiratory capacity (IC) was also measured for the determination of dynamic hyperinflation during the steady state exercise bouts. The results indicate that while the absolute Qc values are lower in COPD than in CTRL during moderately intense (65% peak power) cycling (11.30 +/- 2.38 vs. 15.63 +/- 2.15 L⋅min -1, p < 0.01), likely due to their lower exercise metabolic demand, the Qc/VO2 response to increasing levels of exercise intensity is normal or hyperdynamic in COPD. Indeed, the majority of patients with COPD exhibited Qc/VO2 slopes greater than 7.0, which may be indicative of a peripheral muscle bioenergetic disturbance that may drive the need for greater oxygen delivery, and thus result in an exaggerated ce

Chronic obstructive pulmonary disease (COPD) is one of the world’s most common chronic diseases, and consists of chronic bronchitis that involves chronic inflammation of the bronchi, or emphysema that involves destruction of lung alveoli. In COPD patients, the airways become narrowed, and the airflow is irreversibly obstructed. This leads to a limitation of the flow of air to and from the lungs, causing shortness of breath (dyspnea), as well as abnormal inflammatory response in the lung. Nowadays, COPD is often under-diagnosed, as spirometry was not performed until patient has significant symptoms of dyspnea, cough and sputum production. At that stage, the COPD patients may have reached an advanced stage with considerable loss of lung function. Thus, biomarkers are of great interest for research and clinical purposes in COPD, especially for early diagnosis of COPD. In this study, the relationship between plasma levels of different biomarkers, including monocyte chemoattractant protein-1 (MCP)-1 (a primary chemoattractant biomarker), matrix metalloproteinase nine (MMP)-9, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) (injury and repair biomarkers), and growth differentiation factor 15 (GDF)-15 (a novel biomarker), in 29 healthy ever-smokers and 116 COPD patients was investigated using commercially available enzyme-linked immunosorbent assay (ELISA) kits. We also investigated the correlations between these biomarkers and lung function. There were significant increases in plasma MCP-1, MMP-9, HGF and GDF-15 in COPD patients compared to healthy smokers. Among ever-smokers with or without COPD, plasma MCP-1, MMP-9 and HGF levels were inversely correlated with force expiratory volume in one second![FEV1 (% predicted)] after adjustment for age, smoking status and packyears smoked. Correlation was also found between plasma MCP-1 and HGF, plasma MMP-9 and HGF or GDF-15, plasma HGF and GDF-15 after adjustment for age, smoking status and pack-years smoked. Further multiple linear regression analyses demonstrated that plasma MMP-9 level increased with the COPD GOLD stages. In conclusion, our findings suggest that MMP-9 might be as an important biomarker for COPD initiation and progression. As this study provides only evidence of association rather than of causation, prospective studies are required to assess biological significance of these associations between the plasma biomarkers.
published_or_final_version
Medicine
Master
Master of Medical Sciences

Pulmonary patients attending outpatient rehabilitation experience an enhanced ability for physical activity. The current study assessed and characterized domestic physical activity levels of new and maintenance patients to 1) compare physical activity levels of pulmonary patients on rehabilitation and non-rehabilitation days, 2) to identify factors that may contribute to low physical activity levels and 3) to compare step count levels between 2 activity monitors.Eighteen patients (age, 66.2 ± 8.8 y; FEV1, 52.1 ± 11.8%) participating in pulmonary rehabilitation wore an accelerometer and pedometer for 7 consecutive days. Patients new to pulmonary rehabilitation and maintenance patients participated in the study. Upon returning the monitors, patients returned a log sheet with the times monitors were put on and taken off each morning and night.The participants who completed the one week assessment had an average step count of 3,800 ± 1,651 steps/day, with a significant difference (p < .05) between rehabilitation days (5,468 ± 2,810 steps/day) and non-rehabilitation days (2,874 ± 1,490 steps/day). The number of minutes/day spent in moderate walking activities was also significant (p < .05) between rehabilitation (10.9 ± 16.0 minutes/day) and non-rehabilitation days (3.1 ± 5.8 minutes/day). Male waist circumference and occupational status were significantly correlated with low physical activity levels. The pedometer and accelerometer step count values were not significantly different from each other.Patients participating in pulmonary rehabilitation have significantly different activity levels between rehabilitation and non-rehabilitation days. To increase activity benefits, patients with COPD should increase activity levels on rehabilitation and non-rehabilitation days. Special consideration should be taken to help patients increase physical activity levels on non-rehabilitation days.(key words: chronic obstructive pulmonary disease, pedometer, accelerometer, pulmonary rehabilitation.
School of Physical Education, Sport, and Exercise Science

A nursing concern for patients with chronic obstructive airway disease (COAD) is to assist the patient/family in improving adaptation strategies and self-care abilities. Identification of emotional and behavioral characteristics impacting on symptoms and life quality may predict individuals at risk for greater utilization of health care resources. The purpose of this descriptive study was to apply Traver's Prediction Formula for Emergent Use to a more general COAD population to determine if the formula would accurately predict those subjects who have high versus low emergent use of institutional health care resources. Fifty subjects with a range of COAD severity were studied. Subjects completed instruments which measured symptoms and life quality: the Bronchitis-Emphysema Symptom Checklist and the Sickness-Impact Profile. Findings demonstrated Traver's Formula predicted low emergent subjects with 76 percent accuracy, high emergent subjects with 53 percent accuracy and predicted the overall emergent status of subjects with 67 percent accuracy.

Despite the acknowledged importance of nutritional support for COPD patients, it is difficult to accomplish in acutely stressed individuals. A randomized trial of nutritional supplementation during an acute exacerbation was carried out in 16 hospitalized patients for a 2 week period. Six control patients consumed a standard diet supplying 1,951 $ pm$ 130 (mean $ pm$ SEM) kcal and 80 $ pm$ 6 g protein/d, while ten treatment patients, in addition to the usual diet received oral supplements (Ensure) or snacks, resulting in an intake of 2,516 $ pm$ 129 kcal (p = 0.012) and 99 $ pm$ 6 g protein/d (p = 0.059). Although the treatment subjects improved their intake over the control group, no significant improvement in nutritional status occurred in either group.
Forced vital capacity (FVC % predicted) improved significantly over the study period in treated vs control subjects (+11.10 $ pm$ 4.63 vs $-$4.50 $ pm$ 2.14; p = 0.026). Nitrogen balances were calculated for 9 subjects, and all were in negative balance ($-$8.42 $ pm$ 1.74 g nitrogen/d) with no difference between groups.
Because of the high doses of methylprednisolone administered (69.6 $ pm$ 8.3 mg/d), and their known catabolic effects, we examined whether the dose affected nitrogen balance and muscle strength. Both nitrogen balance (r = $-$0.73; p = 0.025) and grip strength (r = $-$0.76; p $<$ 0.001) worsened with higher doses of steroids. The catabolic process may have resulted from elevated energy requirements, inadequate intake of protein and energy or been induced by high doses of steroids.
Hospitalized COPD patients are highly stressed and catabolic, and the means to preventing protein wasting during an acute exacerbation of their disease remains to be established. (Abstract shortened by UMI.)

Cigarette smoking is a major risk factor in the development of age-related chronic obstructive pulmonary disease (COPD) with chronic airway inflammation as a key feature. Currently, no effective treatment can reduce the protracted inflammation in the lung of COPD. Further research on the inflammatory mechanisms would therefore be important in determining new potential therapeutic targets in COPD. Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that plays an important role in pulmonary functions and inflammatory responses. The serotoninergic system including serotonin transporter (SERT), serotonin receptors (5-HTR) and its metabolic enzyme monoamine oxidase (MAO) have been reported to associate with cigarette smoking and/or COPD. Blockade of serotonin receptor 2A (5-HTR2A) with its selective antagonist ketanserin has been shown to improve lung function in COPD patients. In this study, we hypothesize that the serotoninergic system is involved in cigarette smoke-induced oxidative stress, inflammation and COPD. Exposure to cigarette smoke medium (CSM) caused the elevation of interleukin (IL)-8 levels in primary normal human bronchial epithelial (NHBE) cells and a human bronchial epithelial cell line (BEAS-2B) in vitro via activation of p38 and extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway. Besides, CSM was found to disrupt the glutathione (GSH) system, resulting in the translocation of nuclear factor-erythroid 2 related factor 2 (Nrf2) to the nucleus. Knock-down of Nrf2 by small interference RNA (siRNA) blocked CSM-induced IL-8 release. Pretreatment with ketanserin was found to attenuate CSM-induced IL-8 release by inhibiting the p38, ERK1/2, and Nrf2 signaling pathways, and by partially restoring the GSH system. On the other hand, CSM reduced MAO activity in BEAS-2B, indicating a reduced catabolism of 5-HT. Furthermore, 5-HT was found to share the common p38 and ERK1/2 signaling pathway with CSM in IL-8 release. In the cigarette smoke-exposed rat model, the GSH system in the lung was found to be disrupted compared to the sham-air control, supporting our in vitro findings. Interestingly, we found an increased MAO-A activity in the lung of cigarette smoke-exposed rats in comparison to sham air-exposed rats. The increased MAO-A activity in the lung was associated with the reduction of 5-HT levels in bronchoalveolar lavage (BAL) and lung homogenates, while the increased metabolism of 5-HT may be involved in cigarette smoke-induced superoxide anion levels. On the other hand, serum, but not plasma level of 5-HT was elevated in cigarette smoke-exposed group, which may be due to platelet activation caused by cigarette smoke. In the clinical study, the elevated plasma 5-HT levels were found to be associated with an increased odds ratio for COPD and positively correlated with age in COPD patients. Furthermore, plasma 5-HT was also demonstrated to be a significant mediator on the relation between cigarette smoking and COPD. In summary, our study supports the hypothesis that the serotoninergic system contributes to cigarette smoke-induced oxidative stress, inflammation and COPD. The serotoninergic system (e.g. 5-HTR2A) may constitute potential therapeutic targets for the treatment of COPD, which is worthy for further investigation.
published_or_final_version
Medicine
Doctoral
Doctor of Philosophy

Introduction: COPD is a progressive disease, characterised by symptoms of dyspnoea, fatigue, exercise intolerance and reduced physical activity, resulting in impaired quality of life. Furthermore, the disease poses a significant burden on healthcare systems around the world. SPACE FOR COPD is a new self-management programme which aims to support individuals in acquiring the knowledge and skills required to optimise their emotional and medical well-being. Methods: This thesis describes a randomised controlled trial which aims to establish the effectiveness of a SPACE FOR COPD compared with usual care alone. 184 people with COPD were recruited from primary care. Individuals were randomly allocated to receive either the SPACE FOR COPD intervention or to continue with their usual care. The primary outcome was a measure of health-related quality of life (HRQoL), the Chronic Respiratory Questionnaire – Self Report (CRQ-SR) dyspnoea domain. Secondary measures included exercise performance, anxiety, depression, knowledge, self-efficacy and physical activity. Outcome measures were recorded at baseline, six weeks and six months. Results: There was no significant between-group difference in the change in dyspnoea at six months, therefore our hypothesis was rejected. In secondary outcomes, there were significant gains in HRQoL, exercise, performance, anxiety, knowledge and steps at six weeks, and at six months changes in exercise performance and anxiety remained statistically significant. Correction for multiple comparisons, however, had not been made. Conclusions: SPACE FOR COPD did not result in improved dyspnoea, over and above usual care at six months. The programme may confer significant benefits in HRQoL, exercise performance, anxiety, knowledge and physical activity over and above usual care in the short-term, and gains in anxiety and exercise performance maintained at six months. Although these patients were relatively early within the course of their disease, physical activity was low, highlighting the need for a lifestyle intervention in this group of patients. Exploration of the potential benefit of additional on-going support, and delivery within group settings may of value in order to support the maintenance of these benefits in the medium- and longer-term.

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.

Thesis (PhD)--Stellenbosch University, 2015.
ENGLISH ABSTRACT: Tuberculosis (TB) in children is a common infectious disease in the world affecting approximately 550 000 children annually and contributing to approximately 10-15% of the TB caseload. The estimate is that 75% of the children who have TB live in the 22 countries that have the highest burden of TB disease. In these 22 countries, the technology required to make the diagnosis and manage complicated cases is limited. The epidemiological data required to estimate the proportion of children with severe disease requiring intervention at a global level are lacking. Airway involvement is commonly seen in children with primary TB, but only in a small group of children the compression is severe, needing intervention. The incidence of children with airway obstruction requiring intervention due to primary TB in the chemotherapeutic era is not known. The incidence of complicated lymph node disease in two recent reports varied from 8-38% in children younger than 15 years of age. Flexible bronchoscopy (FB) is an invasive procedure performed under general anesthetic is used to assess the airways of children. Few studies have been published on the use of FB in the diagnosis of paediatric TB and most have concentrated on the use of bronchoscopy as an intervention for obtaining samples to diagnose pulmonary TB (PTB). All previous studies only examined broncho-alveolar lavage (BAL) for Ziehl Neelsen (ZN) positive organisms and mycobacterial culture. All the published studies are from developed countries with a very low incidence of PTB in children. It has been postulated that HIV positive children with TB are more likely to have airway obstruction, but this hypothesis has not been studied. The same is true for children infected with drug-resistant strains of tuberculosis. Similarly, there have been few reports on the correlation between the findings at bronchoscopy and those found on chest computer tomography (CT). The aim of this research project was to systematically determine airways involvement in childhood pulmonary TB and assess the role paediatric bronchoscopy plays in the diagnosis, sample collection and the management of severe airway obstruction. The first part of the thesis describes the bronchoscopic assessment of airway obstruction due to pulmonary TB in children, specifically concentrating on the areas of the airway involved and the severity of the obstruction. We investigated which factors determine the severity of airway obstruction and this included age, sex, HIV status and drug sensitivities. We have shown that there was no difference in airway obstruction in HIV positive children and in children with drug resistance TB. More severe airway obstruction was seen in the younger child. The second question that was analysed is the value of flexible bronchoscopy in collecting samples for TB culture and drug sensitivity testing. It has previously been reported that BAL culture was inferior to gastric lavage in isolating the bacilli. We set out to evaluate which factors determine if a child will be culture-positive on BAL. Most childhood pulmonary TB is postulated to have a low yield of ZN positive cases. We found a higher yield from BAL as was previously reported, and the yield was increased if segmental or lobar pneumonia was present on the chest radiography. We developed novel interventions of finding the organism and increasing the yield from BAL. About 80% of children with PTB have enlarged subcarinal lymph nodes. We performed a trans-bronchial needle aspiration (TBNA) biopsy of these lymph nodes for culture. This technique enables us to differentiate the cause of enlarged mediastinal lymph nodes. This is especially important in children who are HIV positive, as they are prone to have other causes of enlarged lymph nodes. We successfully performed TBNA, even in very young infants, which resulted in a diagnostic yield of 55%. The use of Xpert has been described on other tissue, but not on BAL. We wanted to test if the use of Xpert on BAL is feasible in children, and determine if it will increase the diagnostic yield by using BAL samples. The third aspect of this research was to compare flexible bronchoscopy findings with those of chest CT scan finding. Firstly, the aim was to describe the CT scan findings of mediastinal glands and lungs in children with significant airway obstruction due to PTB. The second aim was to investigate how these two investigations of airway obstruction compared, with particular emphasis on their advantages and disadvantages. The areas of airway obstruction as well as the severity of the obstruction as determined by CT scan were very similar to the findings with bronchoscopy. The final part under this aspect of the study was to analyze airway shape using a computer model to asses if this could predict TB. This was done by extracting components of the airway surface mesh and branch radius and orientation features. This method showed the potential of computer-assisted detection of TB and other airway pathology by using airway shape deformation analysis. The fourth aspect investigated was to determine which children with severe airway obstruction would benefit from a surgical intervention. Surgical enucleation is done via a lateral thoracotomy in children with severe airway obstruction. We investigated which factors determine the need for surgical enucleation, the optimal timing of this intervention, and – if surgical enucleation was done as an emergency intervention – which factors would predict for this. The combination of trachea, left main bronchus and bronchus intermedius involvement was the best predictor for children requiring surgical enucleation. Involvement of the smaller airway divisions did not play a significant role. Children needing enucleation were younger and had more severe airway obstruction. The fifth aspect of this thesis was to measure the outcome following surgical enucleation. Measurements used included clinical measurements, radiological measurements and bronchoscopy. The response in children treated surgically were compared to those treated medically by estimating airway size with flexible bronchoscopy. Both groups showed significant improvement with the magnitude of improvement greater in those surgically treated. We have demonstrated in this thesis that the site and severity of severe airway obstruction can be assessed by either bronchoscopy or chest CT scan. Approximately one third of children with severe airway compression due to TB lymph nodes can be successfully treated surgically with a low morbidity and mortality.
AFRIKAANSE OPSOMMING: Tuberkulose (TB) by kinders is wêreldwyd ’n algemene siekte wat jaarliks ongeveer 550 000 kinders raak en sowat 10-15% van die algehele TB-siektelas uitmaak. Na raming kom 75% van alle kinders met TB van die 22 lande met die hoogste TB-siektelas. Hierdie 22 lande beskik oor beperkte tegnologie om die siekte te diagnoseer en ingewikkelde gevalle te bestuur. Die vereiste epidemiologiese data om te raam watter persentasie kinders wêreldwyd ernstig siek is en intervensie vereis, ontbreek ook. Lugwegaantasting word algemeen by kinders met primêre TB aangetref. Tog is die kompressie by slegs ’n klein groepie kinders so erg dat dit intervensie vereis. Die voorkoms van kinders in die chemoterapeutiese era met primêre-TB-verwante obstruksie van die lugweë wat intervensie vereis, is onbekend. In twee onlangse verslae het die voorkoms van gekompliseerde limfkliersiekte by kinders jonger as 15 jaar van 8% tot 38% gewissel. Buigbare brongoskopie is ’n indringende prosedure wat onder algemene verdowing uitgevoer word om kinders se lugweë te ondersoek. ’n Paar studies is reeds gepubliseer oor die gebruik van buigbare brongoskopie om pediatriese TB te diagnoseer. Die meeste daarvan het gekonsentreer op die gebruik van brongoskopie as intervensie vir die insameling van monsters om pulmonêre TB (PTB) te diagnoseer. Alle vorige studies het uitsluitlik ondersoek ingestel na brongo-alveolêre spoeling (BAS) vir die opsporing van Ziehl Neelsen- (ZN-)positiewe materiaal en vir kweking. Geen ander diagnostiese tegnieke is tot dusver ondersoek nie, wat die waarde daarvan vir populasies met ’n hoë siektelas beperk. Boonop is alle gepubliseerde studies in ontwikkelde lande met ’n baie lae voorkoms van PTB by kinders onderneem. Daar word aangevoer dat MIV-positiewe kinders met TB meer waarskynlik aan obstruksie van die lugweë sal ly, hoewel hierdie hipotese nog nie bestudeer is nie. Dieselfde geld vir kinders wat aan middelweerstandige vorme van TB ly. Daar is ook weinig verslae oor die verband tussen die bevindinge van brongoskopie en dié van rekenaartomografie (RT) van die borskas. Die doel van hierdie navorsing was om stelselmatig vas te stel hoe pulmonêre TB by kinders die lugweë aantas, en watter rol pediatriese brongoskopie in diagnose, monsterinsameling en die hantering van ernstige obstruksie van die lugweë speel. Die eerste deel van die tesis beskryf die brongoskopiese voorkoms van PTB-verwante obstruksie van die lugweë, met bepaalde klem op die aangetaste dele van die lugweg en die erns van die obstruksie. Daar is ondersoek ingestel na watter faktore die erns van die obstruksie bepaal, onder meer ouderdom, geslag, MIV-status en middelsensitiwiteit. Die resultate toon geen verskil in obstruksie by MIV-positiewe kinders en kinders met middelweerstandige TB nie, hoewel ernstiger obstruksie van die lugweë by die jonger kind opgemerk is. Die tweede kwessie wat ontleed is, is die waarde van buigbare brongoskopie in die verkryging van monsters vir TB-kweking en toetse vir middelsensitiwiteit. Daar is voorheen aangemeld dat BAS-kweking minder doeltreffend is as gastriese spoeling om die basille te isoleer. Hierdie studie was daarop toegespits om te beoordeel watter faktore bepaal of ’n kind kwekingspositief met BAS sal wees. Die meeste PTB by kinders toon na bewering ’n lae opbrengs van ZN-positiewe gevalle. Tog het BAS in hierdie studie ’n hoër opbrengs gehad as wat voorheen aangemeld is, welke opbrengs hoër was met die aanwesigheid van segmentale of lobêre pneumonie op die borskasradiogram. Innoverende intervensies is ontwikkel om die organisme op te spoor en die opbrengs met BAS te verhoog. Sowat 80% van kinders met PTB het vergrote subkarinale limfkliere. ’n Transbrongiale naaldaspirasie- (TBNA-)biopsie is gevolglik vir die doeleinde van kweking op hierdie kliere uitgevoer. Hierdie tegniek het die navorser in staat gestel om tussen die verskillende oorsake vir vergrote mediastinale limfkliere te onderskei. Dít is veral belangrik by MIVpositiewe kinders, wat geneig is om ander oorsake vir vergrote limfkliere te toon. Die TBNA-biopsies is selfs by baie jong babas suksesvol uitgevoer, wat tot ’n diagnostiese opbrengs van 55% gelei het. Die gebruik van Xpert op ander weefsel as BAS is al voorheen beskryf. Die navorser wou dus vasstel of die gebruik van Xpert by BAS haalbaar is by kinders, en of dit die diagnostiese opbrengs deur die gebruik van BAS-monsters sal verhoog. Die derde aspek van hierdie navorsing was om die bevindinge van buigbare brongoskopie met dié van RT-skanderings van die borskas te vergelyk. Die doel was eerstens om die bevindinge van die RT-skanderings van mediastinale kliere en longe by kinders met beduidende PTB-verwante lugweg-obstruksie te beskryf. Tweedens wou die navorser vasstel wat die verskille tussen hierdie twee ondersoeke van lugweg-obstruksie is, met bepaalde klem op die voordele en nadele daarvan. Die RT-skandering en die bevindinge van brongoskopie lewer betreklik soortgelyke resultate op wat die aangetaste gedeeltes van die lugweg sowel as die erns van sodanige obstruksie betref. Die laaste doel onder hierdie studieaspek was om die vorm van die lugweg met behulp van ’n rekenaarmodel te ontleed om te bepaal of dit TB kan voorspel. Dít is gedoen deur komponente van die die erns van die obstruksie. Daar is ondersoek ingestel na watter faktore die erns van die obstruksie bepaal, onder meer ouderdom, geslag, MIV-status en middelsensitiwiteit. Die resultate toon geen verskil in obstruksie by MIV-positiewe kinders en kinders met middelweerstandige TB nie, hoewel ernstiger obstruksie van die lugweë by die jonger kind opgemerk is. Die tweede kwessie wat ontleed is, is die waarde van buigbare brongoskopie in die verkryging van monsters vir TB-kweking en toetse vir middelsensitiwiteit. Daar is voorheen aangemeld dat BAS-kweking minder doeltreffend is as gastriese spoeling om die basille te isoleer. Hierdie studie was daarop toegespits om te beoordeel watter faktore bepaal of ’n kind kwekingspositief met BAS sal wees. Die meeste PTB by kinders toon na bewering ’n lae opbrengs van ZN-positiewe gevalle. Tog het BAS in hierdie studie ’n hoër opbrengs gehad as wat voorheen aangemeld is, welke opbrengs hoër was met die aanwesigheid van segmentale of lobêre pneumonie op die borskasradiogram. Innoverende intervensies is ontwikkel om die organisme op te spoor en die opbrengs met BAS te verhoog. Sowat 80% van kinders met PTB het vergrote subkarinale limfkliere. ’n Transbrongiale naaldaspirasie- (TBNA-)biopsie is gevolglik vir die doeleinde van kweking op hierdie kliere uitgevoer. Hierdie tegniek het die navorser in staat gestel om tussen die verskillende oorsake vir vergrote mediastinale limfkliere te onderskei. Dít is veral belangrik by MIVpositiewe kinders, wat geneig is om ander oorsake vir vergrote limfkliere te toon. Die TBNA-biopsies is selfs by baie jong babas suksesvol uitgevoer, wat tot ’n diagnostiese opbrengs van 55% gelei het. Die gebruik van Xpert op ander weefsel as BAS is al voorheen beskryf. Die navorser wou dus vasstel of die gebruik van Xpert by BAS haalbaar is by kinders, en of dit die diagnostiese opbrengs deur die gebruik van BAS-monsters sal verhoog. Die derde aspek van hierdie navorsing was om die bevindinge van buigbare brongoskopie met dié van RT-skanderings van die borskas te vergelyk. Die doel was eerstens om die bevindinge van die RT-skanderings van mediastinale kliere en longe by kinders met beduidende PTB-verwante lugweg-obstruksie te beskryf. Tweedens wou die navorser vasstel wat die verskille tussen hierdie twee ondersoeke van lugweg-obstruksie is, met bepaalde klem op die voordele en nadele daarvan. Die RT-skandering en die bevindinge van brongoskopie lewer betreklik soortgelyke resultate op wat die aangetaste gedeeltes van die lugweg sowel as die erns van sodanige obstruksie betref. Die laaste doel onder hierdie studieaspek was om die vorm van die lugweg met behulp van ’n rekenaarmodel te ontleed om te bepaal of dit TB kan voorspel. Dít is gedoen deur komponente van die lugwegoppervlaknetwerk en vertakkingsradius- en oriëntasiekenmerke te onttrek. Hierdie metode het daarop gedui dat rekenaargesteunde opsporing van TB en ander lugwegpatologie deur middel van ’n ontleding van lugwegvervorming wél potensiaal toon. Die vierde aspek was om te bepaal watter kinders met ernstige obstruksie van die lugweë by intervensie sal baat vind. By sulke kinders word chirurgiese enukleëring deur ’n laterale torakotomie uitgevoer. Die studie het ondersoek ingestel na watter faktore die behoefte aan chirurgiese enukleëring bepaal, wat die optimale tyd vir sodanige intervensie sou wees, en – indien chirurgiese enukleëring as noodintervensie uitgevoer word – watter faktore so ’n noodintervensie sou vereis. Die kombinasie van aantasting van die tragea, linkerhoofbrongus en brongus intermedius was die beste voorspeller van kinders wat chirurgiese enukleëring benodig. Aantasting van die kleiner lugwegverdelings het nie ’n beduidende rol gespeel nie. Kinders wat enukleëring vereis, was jonger en het aan ernstiger obstruksie van die lugweë gely. Die vyfde aspek van hierdie tesis was om die uitkoms na afloop van chirurgiese enukleëring te meet. Kliniese metings, radiologiese metings en brongoskopie is hiervoor gebruik. Die reaksie by kinders wat chirurgies behandel is, is vergelyk met diegene wat medies behandel is deur lugweggrootte met behulp van buigbare brongoskopie te raam. Albei groepe het beduidende verbetering getoon. In die studie het ons getoon dat die ligging en die erns van ernstige lugwegobstruksie kan geassesseer word deur óf brongoskopie of rekenaartomografie van die borskas. Ongeveer een derde van kinders met 'n ernstige lugweg-obstruksie weens TB limfkliersiekte kan suksesvol chirurgies met 'n lae morbiditeit en mortaliteit behandel word.

Thesis (MScSportSc)--University of Stellenbosch, 2004.
ENGLISH ABSTRACT: The purpose of the study was to measure the responses of chronic obstructive pulmonary disease patients to an exercise programme in a South Africa setting. Nine subjects were evaluated before and after aerobic and resistance training three times a week for the total of 12 weeks. Each evaluation measured forced expiratory lung function; health-related quality of life; functional capacity; level of dyspnea; body composition; physician global evaluation; and the patient global evaluation. The exercise programme consisted of one-hour exercise sessions, three times a week for 12 weeks. The exercise sessions included elements of aerobic and resistance training of the upper and lower extremities. Functional capacity improved drastically (p < 0.01), as did the physician and the patient global evaluations (p < 0.01 and p < 0.01, respectively). Levels of dyspnea also improved (p < 0.01). Health-related quality of life improved marginally (p = 0.03). No significant change was noted in lung function and body composition. The study concluded that an exercise programme consisting of aerobic and resistance training improves chronic obstructive pulmonary disease patients' health-related quality of life, functional capacity and levels of dyspnea. Exercise also reduces the symptoms of chronic obstructive pulmonary disease as are perceived by the physician and patient alike. Exercise does not change lung function or body composition of chronic obstructive pulmonary disease patients. Exercise in conjunction with appropriate medical treatment has the potential to benefit all chronic obstructive patients in South Africa. Keywords: COPD, quality oflife, functional capacity, rehabilitation, exercise.
AFRIKAANSE OPSOMMING: Die doel van die studie was om die reaksies te meet van pasiënte met chroniese obstruktiewe pulmonêre siekte op 'n oefenprogram in 'n Suid-Afrikaanse konteks. Nege proefpersone is voor en na aërobiese en weerstandsoefening drie keer per week vir 'n totaal van 12 weke geëvalueer. Elke evaluering het die volgende gemeet: geforseerde ekspiratoriese longfunksie, gesondheidsverwante lewenskwalitiet, funksionele kapasiteit; dispneevlak, liggaamsamestelling; geneesheer algehele evaluering asook pasiënt algehele evaluering. Die oefenprogram het uit een-uur sessies bestaan, wat drie keer per week vir 12 weke plaasgevind het. Die oefensessies het elemente van aërobiese en weerstandsoefeninge van die boonste en onderste ledemate ingesluit. Funksionele kapasiteit het drasties verbeter (p < 0.01), net so ook die geneesheer en pasiënt algehele evaluerings (p < 0.01 en p < 0.01, respektiewelik). Dispneevlakke het ook verbeter (p < 0.01). Gesondheidsverwante lewenskwaliteit het marginaal verbeter (p = 0.03). Geen beduidende veranderinge is in die longfunksie en liggaamsamestelling gevind nie. Die studie het bevind dat 'n oefenprogram wat uit aërobiese en weerstandsoefening bestaan gesondheidsverwante lewenskwaliteit, funksionele kapasiteit asook dispneevlakke van pasiënte met chroniese obstruktiewe pulmonêre siekte verbeter. Oefening verminder ook die simptome van chroniese obstruktiewe pulmonêre siekte soos waargeneem deur beide die geneesheer en pasiënt. Oefening verander ook nie longfunksie of liggaamsamestelling van pasiënte met chroniese obstruktiewe pulmonêre siekte nie. Oefening tesame met die geskikte mediese behandeling kan voordelig wees vir chronies obstruktiewe pasiënte in Suid- Afrika. Keywords: KOPS, lewenskwaliteit, funksionele kapasiteit, rehabilitasie, oefening.

The problem of this study is to determine the vitamin B-6 status of patients who have chronic obstructive pulmonary disease (COPD). Erythrocyte aspartate transaminase assay was the method for measuring vitamin B-6 status. The vitamin B-6 status was examined in thirty subjects (ten COPD subjects and twenty control subjects). An unpaired t-test was used to compare the vitamin B-6 status of the COPD group versus the control group. Four determinants (percentage stimulation, ratio of basal to stimulated activity, basal activity, and stimulated activity) were used to determine vitamin B-6 status in both groups of subjects. Percentage stimulation and ratio of basal to stimulated activity were not significantly different (control group versus COPD group) at the .05 level. However, two of ten COPD subjects had values for percentage stimulation that were two standard deviations above the mean, indicating a poor B-6 status. In contrast, basal activity and stimulated activity of erythrocyte aspartate transaminase were found to be significantly lower at the .05 level in the COPD group than the control group. Therefore, the COPD subjects as a group had some biochemical characteristics of a lower level of vitamin B-6 than the controls.

Introduction: COPD is a worldwide public health issue, while anxiety and depression are highly prevalent comorbidities in COPD, some reviews in overseas reported prevalence rates of up to 75% for anxiety and up to 80% for depression among COPD patients. The situation in Hong Kong is largely unclear and information is lacking. Objective: To assess the prevalence of anxiety and depression in a regional hospital in Hong Kong and to evaluate the odds ratio of different stages of severity in COPD. Method: COPD patients before hospital discharge from E3 ward in Princess Margaret Hospital (in-patient) and COPD patients who attend out-patient clinic in block K7 in PMH (out-patient) will be asked for consent to participate in the study. Baseline demographic and clinical information includes staging of COPD, questionnaires of HADS, MMRC, CAT score will be collected by research nurses after consent is obtained. Result: A total of 260 patients have been approached, with a response rate of 58.08%. 75 in-patients and 76 out-patients were eligible for the study. Our study showed the overall prevalence of depression and anxiety among COPD population are 61.6% and 23.2% respectively. Odds Ratio of depression and anxiety were increased when severity of COPD increased from stage I to IV. Compared with stage I COPD patients, the respective crude odds ratio of depression for stage II is 1.25 (95% CI: 0.15-10.23), stage III is 1.44 (95% CI: 0.19-10.89), while stage IV is 2.09 (95% CI: 0.26-16.86); But in anxiety, the value is insignificant as the odds ratio is less than 1. Conclusion: This is the first study in Hong Kong which is targeted on estimating the prevalence of depression and anxiety among COPD population and to correlate the finding with the COPD severity. Depression and anxiety are prevalent among the COPD patients as suggested in the study. The possibility of depression increased when severity of COPD stage increases, but the result in anxiety cannot be confirmed. No specific risk factors were found to have statistical significant association with the presence of depression and anxiety, but the current study still warrant attention. Further large scale study may be needed to reveal the situation. A more comprehensive and holistic approach to the COPD patients should be employed to tackle their special need during disease progress, in order to reduce the whole health care system burden.
published_or_final_version
Public Health
Master
Master of Public Health

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by persistent airway obstruction that is only partially reversible. It is the fourth leading cause of death and is predicted to be the third by 2030. The progression of the disease involves chronic inflammation, oxidative stress, excess protease activity, increased lung cell apoptosis and accelerated lung aging, but the exact pathogenesis is still unclear. The major cause of COPD is cigarette smoking(CS). Although COPD is associated with increasing social and economical burden, there have been few advances in pharmacological therapy of COPD. Mesenchymal stem cells (MSCs) are fibroblast-like multipotent stem cells which can be isolated from a broad range of sources including bone marrow (BM) and adipose tissue. Administration of BM-derivedMSCs (BM-MSC) or adipose tissue-derived MSCs was reported to attenuate CS-induced emphysema in murine models. Induced pluripotent stem cell-derived MSC (IPSC-MSC) are MSCs differentiated from induced pluripotent stem cells(IPSCs), which are pluripotent cells generated by somatic cell reprogramming in vitro. IPSC-MSCs have several advantages over BM-MSC, including more abundant sources and high capacity of doubling without loss of differentiation potency. A general exploration and comparison on the effects of human IPSC-MSC and BM-MSC treatments were carried out in a 56-day CS-exposed rat model. Compared to BM-MSC, IPSC-MSC showed a higher capacity to reside in lung tissue. The two treatments shared similar efficacy to attenuate CS-induced lung cell apoptosis, to restore CS-induced reduction of lungIL-10and to alleviate CS-induced elevation of systemic TGF-β1. In addition, IPSC-MSC was found to cause reduction in CS-induced elevation of systemic oxidative stress and reversal of CS-induced reduction of lung adiponectin. Furthermore, in order to understand the possible paracrine mechanism involved, human airway epithelial cells were treated with IPSC-MSC or BM-MSC-conditioned medium in a cell culture system in the presence of cigarette smoke medium (CSM). Potentiation rather than attenuation of CSM-induced release of pro-inflammatory cytokine IL-8, MCP-1 and IL-6 was observed with IPSC-MSC or BM-MSC conditioned medium. It is currently unknown whether cultured IPSC-MSCs or BM-MSCs will release pro-inflammatory mediators into the conditioned medium or not. In order to study CS-induced oxidative stress and inflammation in a short time frame, anacute (5-day) CS-exposed rat model was established in juvenile and adult groups. An age-dependent alteration of CS-induced oxidative and inflammatory responses was demonstrated in this model. In summary, our in vivo rat model provides a platform for elucidating the effects of stem cell treatment in CS-induced oxidative stress and inflammation, leading to lung damage. Our findings suggest that treatment of IPSC-MSC or BM-MSC might be able to slow down CS-induced disease progression, possibly through anti-oxidant, anti-inflammatory and anti-apoptotic properties. However, caution should be taken as our in vitro data revealed that conditioned medium from MSCs may provoke pro-inflammatory responses. Further studies on the regulation of the activity of MSCs in vivo will be needed before developing IPSC-MSC into cell therapies for COPD to halt the progression over time.
published_or_final_version
Medicine
Master
Master of Philosophy

The objective of this study was to assess the oxygen cost of various intensities of steady-state cycling. VO2 (ml·min -1·kg-1) was measured at rest, during unloaded cycling (UL), 20 Watts, 50% (SS50) & 65% (SS65) of peak watts in 40 COPD patients (64 +/- 9 yrs; FEV1/FVC: 48 +/- 17 % predicted; FEV1:36 +/- 14 % predicted) and 28 age-matched healthy controls (CTRL). Despite higher VE (L·min -1) in COPD vs. CTRL (UL: 20.6 +/- 3.4 vs. 15.4 +/- 4.1; 20W: 24.3 +/- 4.5 vs. 17.8 +/- 4.2), VO2 at rest, at UL and 20W was not higher in COPD compared to CTRL. In addition, comparable slope and intercept coefficients for the VO2 vs. Watt relationship were obtained in COPD and CTRL for submaximal cycling of low to moderate intensity. (Abstract shortened by UMI.)

To investigate the possibility that malnutrition is an important factor that prolongs respiratory failure (PRF), I studied the effects of pharmacologic injections of recombinant human growth hormone (rhGH), an important anabolic stimulus, on nutritional and respiratory parameters in patients requiring mechanical ventilation for more than three days. Patients were excluded from consideration if dominating factors known to prolong ventilatory failure had not been stabilized. Over ten months, 106 patients in PRF were evaluated, but only six met the selection criteria. Three patients were randomized to receive standard nutritional support, and three into a group that received the equivalent nutrition plus 5 mg/day of rhGH for 14 days or until withdrawal of mechanical ventilation. Baseline characteristics of the selected patients were divergent as demonstrated by body mass indexes ranging from 14 to 42 (kg/m$ sp2),$ baseline maximal inspiratory pressures (PI$ sb{ max}$ from $-$15 to $-$70 cm H$ sb2$O, and Day 1 N balances from $-$13.5 to 1.2 g N/day. Despite increased plasma insulin-like growth factor-1 concentrations, the mean daily N balances of the rhGH-treated group were no better than the controls (1.3 $ pm$ 5.0 vs. 0.4 $ pm$ 2.6 g N/day; Mean $ pm$ SD), nor were there differences in PI$ sb{ max},$ level of ventilatory assistance required, and days to weaning. The persistence of respiratory failure in the overwhelming majority of patients in PRF appears to be due to factors already known to prevent weaning from mechanical ventilation. Even the carefully selected patients enrolled in the present study were insufficiently homogeneous or stable enough to allow proper testing of the experimental hypothesis.

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Introdução: Não está claro na literatura se os valores do índice bispectral (BIS) e da taxa de supressão do traçado de eletroencefalograma (TS), estão relacionados à disfunção cognitiva pós-operatória (DCPO). Objetivo: Avaliar os valores de BIS e TS e sua relação com a DCPO após cirurgia de revascularização do miocárdio (CRM) em pacientes submetidos a anestesia com sevoflurano (SEVO) guiada pelo BIS. Tipo de estudo: Observacional prospectivo. Local do estudo: Hospital de ensino. Pacientes: Noventa pacientes adultos programados para CRM com ou sem circulação extra-corpórea (CEC). Intervenções: A anestesia foi induzida com propofol, remifentanil e atracúrio e mantida com concentrações expiradas de SEVO (ETSEVO) em valores de concentração alveolar mínima (CAMSEVO) adaptada à idade, tendo como alvo valores de BIS de 40-60. O Mini-Exame do Estado Mental (MEEM) para avaliação cognitiva dos pacientes foi aplicado na admissão hospitalar e três meses após a cirurgia. Variáveis estudadas: Os valores de BIS, TS, ETSEVO e CAMSEVO foram registrados a cada 5 minutos durante o procedimento. Redução de um desvio padrão (DP) ou mais no MEEM basal foi definida como DCPO. Resultados: A proporção de DCPO foi de 40%. Os pacientes foram alocados em dois grupos: com (n = 36) ou sem DCPO (n = 54). Não houve diferença significativa na incidência de DCPO entre os pacientes que foram submetidos à CRM com ou sem CEC (p = 1,0). Quanto às características dos pacientes, somente os valores de índice de massa corporal (IMC) foram maiores no grupo sem DCPO (p = 0,009). Valores médios de BSR, ETSEV e MACSEV foram maiores no grupo sem DCPO (p < 0,05). Em uma análise multivariada, valores menores de TS (Razão de Chances-RC 0,008, Intervalo de Confiança-IC 95% [0,001-0,53], p = 0,02), CAMSEVO (RC 0,001, IC 95% [0,001-0,08], p = 0,008), ETSEVO (RC 0,03, IC 95% [0,002-0,66], p = 0,02) e ...
Background: It is still controversial whether bispectral index (BIS) and burst suppression ratio (BSR) values are related to postoperative cognitive dysfunction (POCD). OBJECTIVE: To evaluate BIS and BSR values and their relation to POCD after coronary artery bypass grafting (CABG) surgery in patients undergoing BIS-guided sevoflurane (SEVO) anaesthesia. DESIGN: Prospective, observational study. SETTING: Teaching hospital. PATIENTS: Ninety adult patients scheduled for on- or off-pump CABG surgery. INTERVENTIONS: Anaesthesia was induced with propofol, remifentanil and atracurium and maintained with end-tidal SEVO (ETSEVO) at age-adapted minimum alveolar concentration (MACSEVO) targeting BIS values of 40-60. Mini-Mental State Examination (MMSE) for cognitive assessment of the patients was applied on hospital admission and at 3 months after surgery. MAIN OUTCOME MEASUREMENTS: BIS, BSR, ETSEVO and MACSEVO values were recorded every 5 minutes during the procedure. A decrease of 1 standard deviation or more from the basal MMSE was defined as POCD. RESULTS: The POCD proportion was 40%. The patients were allocated into two groups: with POCD (n=36) or no POCD (n=54). There was no difference of POCD incidence between patients who were submitted to on- versus off-pump CABG (P=1.0). With regard to the patient’s characteristics, only body mass index (BMI) was higher in the no-POCD group (P=0.009). Mean BSR, ETSEVO and MACSEVO values were higher in the no-POCD group (P<0.05). In a multivariable analysis, lower values of BSR (odds ratio-OR 0.008; 95%CI [0.001-0.53]; P=0.02), MACSEVO (OR 0.001; 95%CI [0.001-0.08]; P=0.008), ETSEVO (OR 0.03; 95%CI [0.002-0.66]; P=0.02) and BMI (OR 0.82; 95%CI [0.70-0.96]; P=0.01) were independent predictors of risk for POCD incidence. BIS values did not influence POCD incidence (OR 1.0; 95%CI [0.95-1.11]; P=0.40). CONCLUSION: BIS-guided SEVO anaesthesia titrated to a range between 40 and 60 is not a predictive factor ...

Orientador: Silke Anna Theresa Weber
Banca: Camila Renata Corrêa Camacho
Banca: Márcia Guimarães da Silva
Banca: Ricardo Beneti
Banca: Aline Roberta Danaga
Resumo: Introdução: A prevalência da DPOC e da SAOS e o comportamento das atividades inflamatória e metabólica destas doenças, isoladamente, já foi estudada. Entretanto, a sobreposição entre elas (Overlap) e a associação com a obesidade, ainda necessita de investigações. Objetivos: Verificar a incidência da SAOS em portadores de DPOC obeso e as atividades inflamatória e metabólica desta tríade. Métodos: Foram incluídos portadores de DPOC moderado e grave com índice de massa corpórea (IMC) ≥ 27 Kg/cm2 . Além da espirometria que classificou a DPOC, foi realizada polissonografia que diagnosticou ou não a SAOS. Foram avaliados os marcadores bioquímicos de glicemia, hemoglobina glicada (HBC), insulina, leptina, adiponectina, grelina, proteína C-reativa (PCR) e interleucina 6 (IL-6). Resultados: Este estudo transversal incluiu portadores de DPOC com (N=46) e sem (N=20) SAOS com médias de idade, IMC e VEF1, respectivamente, 61.57±11.31 x 59.75±9.68 anos, 34.00±5.67 x 33.89±6.75 kg/cm2, 57.20±16.81 x 53.85±17.65 %pred. As médias de glicemia, HBC, insulina, leptina e adiponectina com ou sem SAOS foram semelhantes. A grelina aumentou com a maior gravidade da SAOS na overlap (186.16±25.56 x 137.10±21.78 pg/ml). Não foi observado aumento da PCR para nenhum grupo. A maior gravidade da DPOC aumentou a IL-6 (5.17±5.79 x 11.18±13.10). Conclusão: A prevalência de SAOS é elevada em pacientes portadores de DPOC com obesidade. A SAOS grave elevou a atividade metabólica pelo aumento da grelina, sem influencia na expressão inflamatória, na tríade com DPOC e obesidade. A gravidade da DPOC produziu maior atividade inflamatória de IL-6.
Abstract: Introduction: The prevalence of COPD and OSA and the behaviour of inflammatory and metabolic activities of each diseases has already been studied. However, the overlap between OSA and COPD, associated to obesity, still needs investigation. Objectives: To determine the incidence of OSA in obese patients with COPD, and inflammatory and metabolic activities of this triad. Methods: moderate and severe COPD patients were included with a body mass index (BMI) ≥ 27 kg / cm2. In addition to spirometry which ranked COPD, polysomnography was performed for OSA diagnosis. Blood glucose, glycated hemoglobin (GH), insulin, leptina, adiponectin, ghrelin, C-reactive protein (CRP) and interleukin 6 (IL-6) were assesed. Results: This cross-sectional study included COPD patients with (N = 46) and without (N = 20) OSA mean age, BMI and FEV1, respectively, 61.57 ±11.31 x 59.75 ±9.68 years, 34.00 ±5.67 x 33.89 ±6.75 kg/cm2, 57.20 ±16.81 x 53.85 ±17.65% pred. Mean blood glucose, GH, insulin, adiponectin and leptin with or without OSA were similar. Ghrelin increased with greater severity of OSA in the overlap group(186.16 ±25.56 x 137.10 ±21.78 pg/ml). There was no difference for CRP, but IL-6 (5.17 ±5.79 x 18.11 ±10.13) was increased in the more severe COPD. Conclusion: The prevalence of OSA is high in COPD patients with obesity. The severe OSAS increased metabolic activity by increasing ghrelin. The severity of COPD produced greater inflammatory activity.
Doutor

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Introdução: Exacerbação aguda (EA) é uma importante causa de perda de funções em pacientes que sofrem de doença pulmonar obstrutiva crônica (DPOC). Afeta negativamente a qualidade de vida, a função pulmonar, a fraqueza muscular, a utilização dos recursos da saúde e a sobrevida. Entretanto, o exercício físico realizado durante a exacerbação pode melhorar a qualidade de vida e a capacidade física do paciente. Nesse contexto, o presente estudo visa avaliar a influência da realização do exercício físico em pacientes hospitalizado por exacerbação da DPOC (EADPOC). Objetivo: O presente estudo visa avaliar os efeitos do exercício fisico aeróbio de curta duração nos pacientes hospitalizados por exacerbação aguda de DPOC no escore da dispneia, na qualidade de vida e na capacidade física. Pacientes e Métodos: Vinte e dois pacientes foram randomizados em dois grupos, o grupo controle que recebeu o tratamento clínico padrão e o grupo de intervenção que realizou o treinamento de exercício físico juntamente com os cuidados clínicos. Os pacientes foram submetidos às seguintes avaliações após 48 horas da hospitalização e após um mês da alta: espirometria, avaliação nutricional, distância percorrida no teste de caminhada de seis minutos (DP6), qualidade de vida, ansiedade e depressão, índice de BODE e intensidade de dispneia. O programa de exercício físico foi composto por treinamento aeróbio em esteira ergométrica, duas vezes ao dia, por 15 minutos cada sessão até o período da alta hospitalar. Resultados: O domínio impacto e o escore total da qualidade de vida apresentaram maior incremento no grupo intervenção em relação ao grupo controle (p < 0,001) quando comparado os momentos. Houve melhora de ambos os grupos após um mês de alta hospitalar no domínio atividade quando comparado ao momento basal, mas sem diferença entre os grupos. Além disso, apenas o grupo de intervenção apresentou...
Introduction: Acute Exacerbation (AE) is an important cause of impairment of function in chronic obstructive pulmonary disease (COPD) patients. Negatively affects the quality of life, lung function, muscle weakness, the use of health resources and survival. However, physical exercise performed during the exacerbation can improve the quality of life and the physical capacity of the patient. In this context, this study aims to evaluate the influence of aerobic exercise in hospitalized COPD patients with exacerbation (AECOPD). Objective: To evaluate the effects of short duration aerobic exercise in AECOPD on dyspnea score, quality of life and exercise capacity. Patients and Methods: Twenty-two patients were randomized in two groups; the control group received standard medical treatment and the intervention group that performed aerobic exercise training. All patients performed spirometry, nutritional assessment, distance covered on the six-minute walk test (6MWD), quality of life (Saint George Respiratory Questionnaire- SGRQ), anxiety and depression ( The Hospital Anxiety and Depression Scale), BODE index and intensity of dyspnea (Baseline Dyspnea Index and Modified Medical Research Council Score) after 48 hours of hospitalization and after one month of discharge. The exercise program consisted of aerobic training on a treadmill twice a day for 15 minutes until to the discharge. Results: The impact domain and the total score of quality of life showed a higher increase in the intervention group compared to the control group (p<0.001) when compared to the moments. Both groups showed improvement in the activity domain of SGRQ after one month of hospital discharge, but they did not show difference between groups. Furthermore, only the intervention group showed significant improvement in the symptom domain of SGRQ (p<0.001) and baseline dyspnea index (p=0.006) after one month. 6MWD and BODE did not show difference between ...

Orientador: José Reinaldo Cerqueira Braz
Banca: Paulo do Nascimento Junior
Banca: Maria Angela Tardelli
Resumo: Introdução: Não está claro na literatura se os valores do índice bispectral (BIS) e da taxa de supressão do traçado de eletroencefalograma (TS), estão relacionados à disfunção cognitiva pós-operatória (DCPO). Objetivo: Avaliar os valores de BIS e TS e sua relação com a DCPO após cirurgia de revascularização do miocárdio (CRM) em pacientes submetidos a anestesia com sevoflurano (SEVO) guiada pelo BIS. Tipo de estudo: Observacional prospectivo. Local do estudo: Hospital de ensino. Pacientes: Noventa pacientes adultos programados para CRM com ou sem circulação extra-corpórea (CEC). Intervenções: A anestesia foi induzida com propofol, remifentanil e atracúrio e mantida com concentrações expiradas de SEVO (ETSEVO) em valores de concentração alveolar mínima (CAMSEVO) adaptada à idade, tendo como alvo valores de BIS de 40-60. O Mini-Exame do Estado Mental (MEEM) para avaliação cognitiva dos pacientes foi aplicado na admissão hospitalar e três meses após a cirurgia. Variáveis estudadas: Os valores de BIS, TS, ETSEVO e CAMSEVO foram registrados a cada 5 minutos durante o procedimento. Redução de um desvio padrão (DP) ou mais no MEEM basal foi definida como DCPO. Resultados: A proporção de DCPO foi de 40%. Os pacientes foram alocados em dois grupos: com (n = 36) ou sem DCPO (n = 54). Não houve diferença significativa na incidência de DCPO entre os pacientes que foram submetidos à CRM com ou sem CEC (p = 1,0). Quanto às características dos pacientes, somente os valores de índice de massa corporal (IMC) foram maiores no grupo sem DCPO (p = 0,009). Valores médios de BSR, ETSEV e MACSEV foram maiores no grupo sem DCPO (p < 0,05). Em uma análise multivariada, valores menores de TS (Razão de Chances-RC 0,008, Intervalo de Confiança-IC 95% [0,001-0,53], p = 0,02), CAMSEVO (RC 0,001, IC 95% [0,001-0,08], p = 0,008), ETSEVO (RC 0,03, IC 95% [0,002-0,66], p = 0,02) e ...
Abstract: BACKGROUND: It is still controversial whether bispectral index (BIS) and burst suppression ratio (BSR) values are related to postoperative cognitive dysfunction (POCD). OBJECTIVE: To evaluate BIS and BSR values and their relation to POCD after coronary artery bypass grafting (CABG) surgery in patients undergoing BIS-guided sevoflurane (SEVO) anaesthesia. DESIGN: Prospective, observational study. SETTING: Teaching hospital. PATIENTS: Ninety adult patients scheduled for on- or off-pump CABG surgery. INTERVENTIONS: Anaesthesia was induced with propofol, remifentanil and atracurium and maintained with end-tidal SEVO (ETSEVO) at age-adapted minimum alveolar concentration (MACSEVO) targeting BIS values of 40-60. Mini-Mental State Examination (MMSE) for cognitive assessment of the patients was applied on hospital admission and at 3 months after surgery. MAIN OUTCOME MEASUREMENTS: BIS, BSR, ETSEVO and MACSEVO values were recorded every 5 minutes during the procedure. A decrease of 1 standard deviation or more from the basal MMSE was defined as POCD. RESULTS: The POCD proportion was 40%. The patients were allocated into two groups: with POCD (n=36) or no POCD (n=54). There was no difference of POCD incidence between patients who were submitted to on- versus off-pump CABG (P=1.0). With regard to the patient's characteristics, only body mass index (BMI) was higher in the no-POCD group (P=0.009). Mean BSR, ETSEVO and MACSEVO values were higher in the no-POCD group (P<0.05). In a multivariable analysis, lower values of BSR (odds ratio-OR 0.008; 95%CI [0.001-0.53]; P=0.02), MACSEVO (OR 0.001; 95%CI [0.001-0.08]; P=0.008), ETSEVO (OR 0.03; 95%CI [0.002-0.66]; P=0.02) and BMI (OR 0.82; 95%CI [0.70-0.96]; P=0.01) were independent predictors of risk for POCD incidence. BIS values did not influence POCD incidence (OR 1.0; 95%CI [0.95-1.11]; P=0.40). CONCLUSION: BIS-guided SEVO anaesthesia titrated to a range between 40 and 60 is not a predictive factor ...
Mestre

Orientador: Suzana Erico Tanni Minamoto
Coorientador: Victor Zuniga Dourado
Banca: Irma de Godoy
Banca: Oliver Augusto Nascimento
Resumo: Introdução: Exacerbação aguda (EA) é uma importante causa de perda de funções em pacientes que sofrem de doença pulmonar obstrutiva crônica (DPOC). Afeta negativamente a qualidade de vida, a função pulmonar, a fraqueza muscular, a utilização dos recursos da saúde e a sobrevida. Entretanto, o exercício físico realizado durante a exacerbação pode melhorar a qualidade de vida e a capacidade física do paciente. Nesse contexto, o presente estudo visa avaliar a influência da realização do exercício físico em pacientes hospitalizado por exacerbação da DPOC (EADPOC). Objetivo: O presente estudo visa avaliar os efeitos do exercício fisico aeróbio de curta duração nos pacientes hospitalizados por exacerbação aguda de DPOC no escore da dispneia, na qualidade de vida e na capacidade física. Pacientes e Métodos: Vinte e dois pacientes foram randomizados em dois grupos, o grupo controle que recebeu o tratamento clínico padrão e o grupo de intervenção que realizou o treinamento de exercício físico juntamente com os cuidados clínicos. Os pacientes foram submetidos às seguintes avaliações após 48 horas da hospitalização e após um mês da alta: espirometria, avaliação nutricional, distância percorrida no teste de caminhada de seis minutos (DP6), qualidade de vida, ansiedade e depressão, índice de BODE e intensidade de dispneia. O programa de exercício físico foi composto por treinamento aeróbio em esteira ergométrica, duas vezes ao dia, por 15 minutos cada sessão até o período da alta hospitalar. Resultados: O domínio impacto e o escore total da qualidade de vida apresentaram maior incremento no grupo intervenção em relação ao grupo controle (p < 0,001) quando comparado os momentos. Houve melhora de ambos os grupos após um mês de alta hospitalar no domínio atividade quando comparado ao momento basal, mas sem diferença entre os grupos. Além disso, apenas o grupo de intervenção apresentou...
Abstract: Introduction: Acute Exacerbation (AE) is an important cause of impairment of function in chronic obstructive pulmonary disease (COPD) patients. Negatively affects the quality of life, lung function, muscle weakness, the use of health resources and survival. However, physical exercise performed during the exacerbation can improve the quality of life and the physical capacity of the patient. In this context, this study aims to evaluate the influence of aerobic exercise in hospitalized COPD patients with exacerbation (AECOPD). Objective: To evaluate the effects of short duration aerobic exercise in AECOPD on dyspnea score, quality of life and exercise capacity. Patients and Methods: Twenty-two patients were randomized in two groups; the control group received standard medical treatment and the intervention group that performed aerobic exercise training. All patients performed spirometry, nutritional assessment, distance covered on the six-minute walk test (6MWD), quality of life (Saint George Respiratory Questionnaire- SGRQ), anxiety and depression ( The Hospital Anxiety and Depression Scale), BODE index and intensity of dyspnea (Baseline Dyspnea Index and Modified Medical Research Council Score) after 48 hours of hospitalization and after one month of discharge. The exercise program consisted of aerobic training on a treadmill twice a day for 15 minutes until to the discharge. Results: The impact domain and the total score of quality of life showed a higher increase in the intervention group compared to the control group (p<0.001) when compared to the moments. Both groups showed improvement in the activity domain of SGRQ after one month of hospital discharge, but they did not show difference between groups. Furthermore, only the intervention group showed significant improvement in the symptom domain of SGRQ (p<0.001) and baseline dyspnea index (p=0.006) after one month. 6MWD and BODE did not show difference between ...
Mestre

Thesis (M.S.)--Worcester Polytechnic Institute.
Keywords: latent class model; Poisson regression model; Metropolis-Hastings sampler; order restriction; disease mapping. Includes bibliographical references.

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Estudos mostram que os valores médios da Interleucina 6 (IL-6) e Proteína CReativa (PCR) não mudam significativamente em pacientes com DPOC no período de um ano. No entanto, o acompanhamento de longo prazo desses mediadores não está estabelecido. Portanto, o objetivo do atual estudo é verificar a evolução dos marcadores inflamatórios sistêmicos de pacientes com DPOC após três anos e verificar a associação entre eles e os demais marcadores da doença. Uma coorte de 77 pacientes com DPOC estável foi avaliada no momento basal e 53 (VEF1=56±21%) foram incluídos no estudo. Nós avaliamos IL-6, PCR, distância percorrida em seis minutos (DP6) e índice de massa corporal (IMC) no momento basal e após três anos. A concentração plasmática de IL-6 foi avaliada por meio de ensaios imunoenzimáticos (ELISA) ultrassensíveis e a PCR foi obtida por meio de imunonefelometria com uso de kits ultrassensíveis. Os valores da IL-6 aumentaram significativamente após três anos em comparação ao momento basal [0,8 (0,5-1,3) vs 2,4 (1,3-4,4) pg/ml, p <0,001] e foram associados com piora da DP6. Os resultados da análise de regressão de Cox mostraram que os valores aumentados de IL-6 no momento basal foram associados com a mortalidade [Hazard Ratio (95% CI)=2,68 (0,13; 1,84); p=0,02]. Os valores médios da PCR não apresentaram alteração significativa [5 (1,6-7,9) vs 4,7 (1,7-10) mg/ L, p=0,84]; embora, onze pacientes (21%) apresentaram aumento >3 mg/L da PCR no período de três anos. O processo inflamatório sistêmico, avaliado pela IL-6, parece ser persistente e progressivo e associado com mortalidade e piora da performance física em pacientes com DPOC
Past studies have shown that mean values of Interleukin-6 (IL-6) and Creactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers. A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study. We evaluated IL-6, CRP, six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry. IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p<0.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI)=2.68 (0.13, 1.84); p=0.02]. CRP mean values did not change [5 (1.6- 7.9) vs 4.7 (1.7-10) pg/L; p=0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years. The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients

Orientador: Irma Godoy
Banca: Suzana Erico Tanni
Banca: Hugo Hyung Bok Yoo
Banca: Oliver Augusto Nascimento
Banca: Marcia Maria Faganello
Resumo: Estudos mostram que os valores médios da Interleucina 6 (IL-6) e Proteína CReativa (PCR) não mudam significativamente em pacientes com DPOC no período de um ano. No entanto, o acompanhamento de longo prazo desses mediadores não está estabelecido. Portanto, o objetivo do atual estudo é verificar a evolução dos marcadores inflamatórios sistêmicos de pacientes com DPOC após três anos e verificar a associação entre eles e os demais marcadores da doença. Uma coorte de 77 pacientes com DPOC estável foi avaliada no momento basal e 53 (VEF1=56±21%) foram incluídos no estudo. Nós avaliamos IL-6, PCR, distância percorrida em seis minutos (DP6) e índice de massa corporal (IMC) no momento basal e após três anos. A concentração plasmática de IL-6 foi avaliada por meio de ensaios imunoenzimáticos (ELISA) ultrassensíveis e a PCR foi obtida por meio de imunonefelometria com uso de kits ultrassensíveis. Os valores da IL-6 aumentaram significativamente após três anos em comparação ao momento basal [0,8 (0,5-1,3) vs 2,4 (1,3-4,4) pg/ml, p <0,001] e foram associados com piora da DP6. Os resultados da análise de regressão de Cox mostraram que os valores aumentados de IL-6 no momento basal foram associados com a mortalidade [Hazard Ratio (95% CI)=2,68 (0,13; 1,84); p=0,02]. Os valores médios da PCR não apresentaram alteração significativa [5 (1,6-7,9) vs 4,7 (1,7-10) mg/ L, p=0,84]; embora, onze pacientes (21%) apresentaram aumento >3 mg/L da PCR no período de três anos. O processo inflamatório sistêmico, avaliado pela IL-6, parece ser persistente e progressivo e associado com mortalidade e piora da performance física em pacientes com DPOC
Abstract: Past studies have shown that mean values of Interleukin-6 (IL-6) and Creactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers. A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study. We evaluated IL-6, CRP, six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry. IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p<0.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI)=2.68 (0.13, 1.84); p=0.02]. CRP mean values did not change [5 (1.6- 7.9) vs 4.7 (1.7-10) pg/L; p=0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years. The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients
Doutor

COPD is the third leading cause of death in the United States and is the sixth leading cause of death for low-to middle income countries (Downs & Appel, 2006; GOLD, 2011). COPD is a largely preventable disease due to the lifestyle factors that heavily contribute to disease onset and severity. Although traditionally COPD research has focused on health outcomes related to risk factors, compliance, comorbid psychological and physical conditions, and treatment interventions, a growing body of research suggests religious and spiritual factors may play an equally important role in health outcomes for several medical conditions, including pulmonary disease. However, studies of this kind have not specifically examined COPD nor have they examined the role of religious and spiritual beliefs in COPD management among ethnic minority patients. As such, the current study aimed to examine whether spiritual ethnic minority patients with COPD hold religious fatalistic attitudes and less active religious problem solving . A sample of 35 ethnic minority patients from the Louis. B. Stokes Cleveland VA Medical Center (LSCVAMC) Outpatient Pulmonary Clinic in Cleveland, OH. were recruited to participate in the study. Due to the acknowledgeable limitations of the present study, results are preliminary but convey associations between religious health fatalistic beliefs and religious problem solving approaches. Implications and areas of future study are discussed.

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Foi realizado estudo transversal para avaliar e comparar a associação entre estresse oxidativo e estado inflamatório e suas relações com a força muscular, a massa muscular sistêmica, a capacidade funcional de exercício e o estado geral de saúde em tabagistas, pacientes com doença pulmonar obstrutiva crônica (DPOC) leve/moderado e controles não tabagistas. Foram avaliados 32 tabagistas ativos (carga tabágica >10 anos/maço) sem DPOC, 32 pacientes com DPOC leve/moderado [tabagistas ativos ou ex-tabagistas (carga tabágica >10 anos/maço)] e 32 indivíduos não tabagistas. Todos os indivíduos foram submetidos à avaliação clínica e do estado tabágico, espirometria pré e pósbroncodilatador, oximetria de pulso e as concentrações de mediadores inflamatórios [proteína C-reativa (PCR), interleucina (IL) 6, receptores do fator de necrose tumoral alfa (TNFR1 e TNFR2)] e indicadores de estresse oxidativo [produtos finais de glicação avançada (AGEs) e receptor solúvel do produto final de glicação (sRAGE)] foram avaliadas no soro. Foi realizada avaliação da composição do corpo por bioimpedância, da força muscular periférica por dinamometria, da capacidade funcional de exercício (distância percorrida em seis minutos) e da avaliação do estado geral de saúde, por meio do Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) e da Escala Hospitalar de Ansiedade e Depressão (HAD). Tabagistas (p<0,001) e pacientes com DPOC (p<0,001) apresentaram valores superiores de AGEs quando comparados aos controles. Não houve diferença estatisticamente significante entre tabagistas e pacientes com DPOC. As concentrações de sRAGE não diferiram entre os grupos (p=0,92). Tabagistas (p=0,01) e pacientes com DPOC (p=0,01) apresentaram valores superiores da PCR em comparação aos controles, sem diferenças nas demais comparações. As concentrações de IL6 (p=0,07) e TNFR1 (p=0,07) não diferiram entre os grupos. Os valores...
The aim of this study was to evaluate the association between oxidative stress and inflammatory markers and their relationship with muscle strength, systemic muscle mass, exercise capacity, quality of life in smokers, mild/moderate COPD patients and nonsmokers controls. Were evaluated 32 active smokers (smoking history> 10 pack/years) without COPD, 32 mild/moderate COPD patients [current smokers or former smokers (smoking history> 10 pack/years) and 32 nonsmokers. All individuals underwent to medical and smoking status evaluations, spirometry pre and post-bronchodilator and pulse oximetry. The concentration of inflammatory mediators [C-reactive protein (CRP), interleukin (IL) 6, and tumor necrosis factor-alpha receptors (TNFR1 and TNFR2)] and indicators of oxidative stress [advanced glycation end-products (AGEs) and soluble receptors for advanced glycation end-products (sRAGE)] were measured in serum. We assessed body composition by bioimpedance, peripheral muscle strength by dynamometry, exercise capacity (six minutes walk distance) and the health status through the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HAD). Smokers (p<0.001) and COPD patients (p<0.001) had higher values of AGEs when compared to controls there was no statistically significant difference between smokers and COPD patients. The sRAGE concentrations did not differ between groups (p=0.92). Smokers (p=0.01) and patients with COPD (p=0.01) showed higher values of CRP compared to controls, there was no statistical significant difference between smokers and COPD groups. The concentrations of IL-6 (p=0.07) and TNFR1 (p=0.07) did not differ between groups. Regarding concentrations of TNFR2, COPD patients showed higher values when compared to smokers (p=0.004) and controls (p=0.004). We identified positive association of smoking (p=0.04), CRP (p=0.03) and IL6 (p=0.03) with the concentrations of AGEs. The ...

Orientador: Irma de Godoy
Coorientador: Susana Erico Tanni Minamoto
Coorientador: Camila Renata Corrêa
Banca: José Antonio Baddini Martinez
Banca: Mariana Gobbo Braz
Banca: Oliver Augusto Nascimento
Banca: Ângela Victoriano de Campos Soares
Resumo: Foi realizado estudo transversal para avaliar e comparar a associação entre estresse oxidativo e estado inflamatório e suas relações com a força muscular, a massa muscular sistêmica, a capacidade funcional de exercício e o estado geral de saúde em tabagistas, pacientes com doença pulmonar obstrutiva crônica (DPOC) leve/moderado e controles não tabagistas. Foram avaliados 32 tabagistas ativos (carga tabágica >10 anos/maço) sem DPOC, 32 pacientes com DPOC leve/moderado [tabagistas ativos ou ex-tabagistas (carga tabágica >10 anos/maço)] e 32 indivíduos não tabagistas. Todos os indivíduos foram submetidos à avaliação clínica e do estado tabágico, espirometria pré e pósbroncodilatador, oximetria de pulso e as concentrações de mediadores inflamatórios [proteína C-reativa (PCR), interleucina (IL) 6, receptores do fator de necrose tumoral alfa (TNFR1 e TNFR2)] e indicadores de estresse oxidativo [produtos finais de glicação avançada (AGEs) e receptor solúvel do produto final de glicação (sRAGE)] foram avaliadas no soro. Foi realizada avaliação da composição do corpo por bioimpedância, da força muscular periférica por dinamometria, da capacidade funcional de exercício (distância percorrida em seis minutos) e da avaliação do estado geral de saúde, por meio do Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) e da Escala Hospitalar de Ansiedade e Depressão (HAD). Tabagistas (p<0,001) e pacientes com DPOC (p<0,001) apresentaram valores superiores de AGEs quando comparados aos controles. Não houve diferença estatisticamente significante entre tabagistas e pacientes com DPOC. As concentrações de sRAGE não diferiram entre os grupos (p=0,92). Tabagistas (p=0,01) e pacientes com DPOC (p=0,01) apresentaram valores superiores da PCR em comparação aos controles, sem diferenças nas demais comparações. As concentrações de IL6 (p=0,07) e TNFR1 (p=0,07) não diferiram entre os grupos. Os valores...
Abstract: The aim of this study was to evaluate the association between oxidative stress and inflammatory markers and their relationship with muscle strength, systemic muscle mass, exercise capacity, quality of life in smokers, mild/moderate COPD patients and nonsmokers controls. Were evaluated 32 active smokers (smoking history> 10 pack/years) without COPD, 32 mild/moderate COPD patients [current smokers or former smokers (smoking history> 10 pack/years) and 32 nonsmokers. All individuals underwent to medical and smoking status evaluations, spirometry pre and post-bronchodilator and pulse oximetry. The concentration of inflammatory mediators [C-reactive protein (CRP), interleukin (IL) 6, and tumor necrosis factor-alpha receptors (TNFR1 and TNFR2)] and indicators of oxidative stress [advanced glycation end-products (AGEs) and soluble receptors for advanced glycation end-products (sRAGE)] were measured in serum. We assessed body composition by bioimpedance, peripheral muscle strength by dynamometry, exercise capacity (six minutes walk distance) and the health status through the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HAD). Smokers (p<0.001) and COPD patients (p<0.001) had higher values of AGEs when compared to controls there was no statistically significant difference between smokers and COPD patients. The sRAGE concentrations did not differ between groups (p=0.92). Smokers (p=0.01) and patients with COPD (p=0.01) showed higher values of CRP compared to controls, there was no statistical significant difference between smokers and COPD groups. The concentrations of IL-6 (p=0.07) and TNFR1 (p=0.07) did not differ between groups. Regarding concentrations of TNFR2, COPD patients showed higher values when compared to smokers (p=0.004) and controls (p=0.004). We identified positive association of smoking (p=0.04), CRP (p=0.03) and IL6 (p=0.03) with the concentrations of AGEs. The ...
Doutor

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A doença pulmonar obstrução crônica (DPOC) é caracterizada pela limitação de fluxo parcialmente reversível, classificada por níveis de obstrução pós-broncodilatador. Há várias evidências de que o FEV1 sozinho não é capaz de mostrar a broncodilatação de pacientes com DPOC, mesmo naqueles que apresentam melhora clínica. A técnica de oscilações forçadas (TOF) tem mostrado alta sensibilidade na detecção precoce de alterações mecânicas na DPOC, contudo o efeito broncodilatador na impedância respiratória de pacientes com DPOC ainda não está esclarecido. Objetiva avaliar a utilidade da TOF nos diferentes estágios de obstrução das vias aéreas; (2) avaliar a resposta da impedância respiratória ao salbutamol em indivíduos saudáveis ao exame espirométrico e pacientes com DPOC em diferentes graus de gravidade. Foram avaliados 25 indivíduos saudáveis sem história de tabagismo, 24 tabagistas e 151 pacientes com DPOC classificados em graus I, II, III e IV. Todos os sujeitos foram avaliados pela TOF seguida da espirometria, antes e após o uso do salbutamol spray. As curvas de resistência e reatância demonstraram alteração em todos os estágios de obstrução das vias aéreas após o uso do salbutamol. O grupo de risco apresentou alterações mecânicas semelhantes ao grupo leve (p=ns). Os parâmetros R0, Rm, Csr,din e Z4Hz apresentam desempenho diagnóstico adequado (AUC > 0,85) em todos os estágios de gravidade da doença. Todos os parâmetros de TOF e espirometria apresentaram diminuição após uso do salbutamol. Os indivíduos saudáveis apresentaram uma pequena diminuição comparada aos subgrupos de DPOC. A variação em termos absolutos da ΔZ4Hz e das derivadas da resistência, ΔR0, ΔRm, ΔS, apresentaram variação significativa (p<0,0001, p<0,003; p<0,04; p<0,0002, respectivamente) com o aumento da obstrução brônquica. Nas derivadas da reatância o ΔXm aumentou com a gravidade da doença (p<0,0002). Por outro lado, a ΔCrs,dyn não demonstrou diferença significativa com a gravidade da DPOC. Em termos percentuais os parâmetros da TOF apresentaram variação expressiva em ΔRm% (p<0,02), ΔS% (p<0,02) e ΔXm% (p<0,004) com o aumento da obstrução nas vias aéreas. Por outro lado, ΔR0%, ΔCrs,dyn% e ΔZ4Hz% não variaram entre os estágios da DPOC. A associação entre a broncodilatação nas vias aéreas e a impedância pulmonar foi fraca entre ΔXm vs ΔFVC (r=0,32, p<0,0001) e ΔZ4Hz% vs ΔFEV1% vs ΔFVC% (r=0.28, p<0,0005; r=0,29, p<0,0003, respectivamente). A TOF é útil na avaliação das alterações mecânicas nos diferentes níveis de obstrução das vias aéreas na DPOC. Demonstramos o benefício da medicação broncodilatadora, quantificando a melhora da ventilação através da TOF. A impedância respiratória diminui em todos os estágios da DPOC, o estágio leve melhorou tanto quanto o estágio muito grave. Isto sugere que a medida da impedância pulmonar não é dependente do volume como ocorre na espirometria e que a broncodilatação ocorre em todas as fases da progressão da DPOC.
Chronic obstructive pulmonary disease (COPD) is characterized by partially reversible flow limitation, classified by the post-bronchodilator level of airway obstruction. There is abundant evidence that FEV1 alone is not able to show bronchodilation in COPD patients, even in patients with clinical improvement. The forced oscillation technique (FOT) has shown high sensitivity for early detection of mechanical changes in COPD. However, the bronchodilator effect on respiratory impedance is still unclear. Objective to evaluate the utility of FOT in the diagnosis of different stages of airway obstruction, (2) to investigate the response to salbutamol in healthy, smoking and COPD patients in different degrees of severity. We evaluated 25 healthy subjects with no history of smoking, 24 smokers and 151 COPD patients classified into grades I, II, III and IV of severity. All subjects were assessed by the FOT followed by spirometry before and after the use of salbutamol spray. The resistance and reactance curves showed change at all stages of airway obstruction after the use of salbutamol. The smoking group showed similar mechanical changes to the mild group (p=ns). The parameters R0, Rm, Csr,din and Z4Hz presented adequate diagnostic accuracy (AUC>0.85) in all stages of disease severity. All FOT and spirometry parameters showed decreased after salbutamol use. Healthy individuals showed a small decrease compared with the subgroups of COPD. The variations of the impedance module (ΔZ4Hz) and resistance parameters, (ΔR0, ΔRm, Δs) were significant (p<0.0001, p<0.003, p<0.04 and p<0.0002, respectively) with increased bronchial obstruction. Mean reactance (ΔXm) increased with disease severity (p<0.0002). The ΔCrs,dyn showed no significant change with the severity of COPD. In percentage terms, FOT parameters showed significant variation in ΔRm% (p<0.02), Δs (p<0.02) and ΔXm% (p<0.004) with increased airway obstruction. ΔR0% ΔCrs,dyn% and ΔZ4Hz% did not vary between different stages of COPD. The association between bronchodilation in the airways and lung impedance was weak between ΔXm vs ΔFVC (r=0.32, p<0.0001) and ΔZ4Hz% vs ΔFEV1% vs ΔFVC% (r=0.28, p<0.0005, r=0.29, p<0.0003, respectively). The FOT is useful in the evaluation of the mechanical changes at different levels of airway obstruction in COPD. We demonstrate the benefit of a bronchodilator, quantifying the improvement of ventilation through the FOT. The respiratory impedance decreases in all stages of COPD. This suggests that the impedance changes are not dependent on lung volume as in spirometry and that bronchodilation occurs at all stages of the progression of COPD.

Chronic obstructive pulmonary disease (COPD) is characterized by periodic episodes of worsening symptom (e.g., shortness of breath, irregular breathing, and worse coughing with increased phlegm production), also called pulmonary exacerbations. Inflammation is an important cause of reduced lung function as inflammation contributes to airflow obstruction in the small airways and lung parenchyma. Even in individuals with mild COPD, inflammation reduces lung function, accelerates decline in lung function overtime, and increases the risk for respiratory exacerbations. Agents that reduce systemic inflammation are hypothesized to decrease the inflammation in the lungs, resulting in improvements in lung function and a decrease in exacerbation frequency. We hypothesize that antidepressants have a beneficial effect on lung function. In addition to having anti-inflammatory properties, antidepressants act upon serotonin, which is integral in central breathing control. The combination of the anti-inflammatory and serotonergic effects may provide users of selective serotonin reuptake inhibitors with a lung function benefit while avoiding the side effects of steroids. This dissertation assesses whether selective serotonin reuptake inhibitors increase concurrent lung function and reduce the risk for respiratory exacerbations. It consists of three parts: a systematic literature review and two analytic papers using large prospective databases. The systematic review of the literature identified limitations concerning the effect of selective serotonin reuptake inhibitors on lung function. Overall, the analytic papers found no support for a beneficial association between selective serotonin reuptake inhibitors and spirometry, dyspnea or pulmonary exacerbations; indeed the association was in the opposite direction as hypothesized. In addition, there was no support for meaningful mediation by inflammatory markers. Further research is needed to determine if selective serotonin reuptake inhibitors have a harmful effect on lung function and pulmonary exacerbations.