The aim of my master degree project of Advanced Product Design was to develop a monitoring and medication device to empower people who are suffering from asthma. Asthma is a major non-communicable disease characterized by recurrent attacks of breathlessness and wheezing. It is not possible to cure asthma, but appropriate management can control the disease and enable people to enjoy a good quality of life. Asthma varies in severity and frequency from person to person and not every asthmatic will require the same level of treatment. Also asthma conditions can vary over time and the level of airways inflammation has to be reviewed and medication has to be adjusted. Asthma diagnostic takes place at a point-of-care environment and is usually based on the pattern of symptoms, response to therapy over time and by objective parameters like lung function tests. My degree project was focused on a home used diagnostic and medication system in order to adjust the dosage of asthma medication on a more frequently basis.

Part I of the thesis contains a brief review of the clinical importance of nocturnal asthma, and an account of the methods used to study breathing during sleep. The original work of the thesis is divided into three further parts: In Part II are described studies of breathing and oxygenation during sleep in normal subjects. These studies were performed to establish a normal range of apnoea, hypopnoea and oxygenation during sleep and to determine the effects of age and sex on these variables. Part III contains the results of similar studies in patients with asthma. Breathing patterns and oxygenation during sleep in asthmatic patients were compared with those of normal subjects and those of patients with chronic bronchitis and emphysema. The studies described in Part IV were designed to explore the relationship between sleep and bronchoconstriction. I wished to establish whether sleep was essential for nocturnal bronchoconstriction and to determine whether bronchoconstriction was associated with one particular stage of sleep. The results are summarised at the end of each section, and the clinical implications of the results are discussed in Part V.

Increased angiogenesis is an important characteristic of remodeling in asthmatic airways which stems from the imbalance between pro-angiogenic and anti-angiogenic factors. Surprisingly, the factors regulating this process in allergic asthma are poorly defined. The focus of this thesis is to investigate the effect of Semaphorin 3E (Sema3E) on angiogenesis events within the airways of murine model of allergic asthma. The role of Sema3E in asthma angiogenesis was tested in wild type and Sema3e-/- mice exposed to House Dust Mite (HDM) and monitored for changes in blood vessels number in the lungs. In addition, the potential of Sema3E, in reversing features of allergen inflammation, was tested in mouse model. In both cases immunohistochemistry and immunofluorescence staining of lung tissues used to assess the changes in the level of angiogenesis. Moreover, the expression of pro- and anti-angiogenic factors in total lung homogenate was assessed by ELISA and Real-Time PCR. The results showed that WT and Sema3e-/- mice both developed the HDM induced allergic asthma phenotype, but, the lung sections of HDM exposed Sema3e-/- mice had enhanced number of blood vessels compared to WT mice. The enhanced angiogenesis in Sema3-/- mice was coupled with increased level of angiogenesis driving factors VEGF and it receptor VEGFR-2. However, in WT mice the level of soluble VEGFR-1 secretion increased significantly which inhibited VEGF / VEGFR-2 binding. Besides, Sema3E treatment reduced the level of angiogenesis and inhibited HDM-induced secretion of VEGF and the expression of its receptor VEGFR-2 while increased the level of soluble VEGFR-1. Analyzing the ratio of VEGF / soluble VEGFR-1 revealed that in the presence of Sema3E in both models, soluble VEGFR-1 is the dominant factor which has an inhibitory role on angiogenic effect of VEGF. Taken together, this study provided the first evidence that Sema3E can modulate angiogenesis in allergic asthmatic airways. / February 2016

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Class of 2007 Abstract / Objectives: To explore the economic burden of illness and outcomes associated with in-patient related cases of asthma. Methods: This retrospective database study used Healthcare Cost and Utilization Project’s National Inpatient Survey to investigate the total number of discharges, length of stay and health care costs of patients with a primary diagnosis of asthma based on gender, payer and level of income. Data was analyzed using a non-parametric z-test to determine if results were significant. Results: A total of 418,789 patients (164,045 male, 251,264 female, 3,479 missing) were admitted with the category diagnosis of asthma in 2004. Females had a longer mean length of stay, higher mean charges and higher aggregate charges than males. These apparent differences were found to be significant. Medicaid had a larger number of total discharged and higher aggregate charges. Both these outcomes were found to be significant when compared to all other payers, expect there was no significance between Medicaid and Medicare in regards to aggregate charges. Medicare had a longer mean length of stay and higher mean charges which were found to be significant when compared to all other payers. Not low median income had more discharges, longer mean length of stay and higher mean and aggregate charges compared to low median income. These apparent differences were found to be significant. Conclusions: Being of female gender, or part of a government funded program (Medicaid or Medicare) or having an income of $36,000+ would result in higher discharge rates, longer mean length of stay and higher mean and aggregate charges in respect to asthma hospitalizations.

by Chan Hiu Shuen. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 123-135). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Monocytes and their subsets play an important role in immune and inflammatory diseases. In this study the focus was on their role of driving pathogenesis in asthmatic patients. The hypothesis was that although monocytes have not been identified as key players in atopic disease they are likely to be pro-inflammatory, be readily recruited to tissue and have a major role in the exacerbation of disease. This may relate to the prevailing pro-inflammatory microenvironment. Chemokines such as CCL2 and CX3CL1 are involved in monocyte recruitment and survival respectively in the inflamed tissues. Three subsets of monocytes namely CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocytes are known to express chemokine receptors. Alterations if any in the numbers or in the molecular inflammatory markers of these three monocyte subsets with contrasting potential of modulating inflammatory responses in the peripheral blood may provide some insight in the disease process. It is also believed that circulating fibrocytes in allergic asthma are the cause of fibrosis in chronically inflamed pulmonary tissues resulting in refractory asthma. Fibrocytes, also derived from the bone marrow, produce connective tissue components such a collagen-1 and can adopt a mesenchymal phenotype and contribute to granulomas, scar tissue and tissue remodeling. They appear to play an important role in chronic and refractory asthma but have also been found in lungs of patients with mild asthma indicating that they may play an as yet undefined role in the development of inflammation. Fibrocytes also express chemokine receptors and their recruitment in tissues may also depend upon chemokines. Using six-color flow-cytometry phenotypic analysis of human blood monocyte and fibrocyte populations from asthma patients was performed along with the isolation of mRNA from CD14+ monocytes for assessment of inflammatory markers expression and the data was compared with the normal healthy individuals. Based on the findings of gene expression an attempt was made to demonstrate the effect of routine treatment used by our patients on gene expression of selectively isolated monocytes from healthy individuals. Finally serum levels of chemokines between patients and normal healthy controls were also determined. XXI From the flow-cytometry analysis we demonstrated a significant increase in both CD45-positive monocytes and circulating fibrocytes in severe asthmatic patients. While CCR2 percentage was significantly increased, the CX3CR1 percentage was significantly decreased in the intermediate and non-classical monocyte subsets in both mild and moderate patients, however these changes were only observed in the non-classical monocytes in severe patients. In the gene expression the proinflammatory receptors CCR2, CCR5, CX3CR1, IL-17RA, and cytokine inhibitor SOCS3 in monocytes were all significantly reduced in the severe asthma patients. While CCR1 and CD36 were significantly decreased in mild and moderate asthmatic patients. No significant change in serum pro-inflammatory cytokines were detected although IL-5 was significantly increased in moderate and severe asthmatic patients. Analysis of monocyte gene expression in asthma by other groups although not highlighting a specific gene did indicate that inflammatory and TNF pathways might be involved. In conclusion there was a tendency toward more inflammatory monocytes in our asthma patients, however this was not clearly reflected in the patients serum profile given that inflamatory monocytes make up only a small percentage of the leukocytes in human blood. Finally increases in total monocytes and fibrocytes correlated with asthma severity.

This research focuses on investigating the vibration characteristics of branched circular cylindrical shells with applications to airway passages. Analytical modelling is carried out based on Donnell-Mushtari equations of thin elastic membrane type of shells while numerical validation is conducted using the Finite Element Method (COSMOS/Works). Further validation of the results is performed using experimental investigation of tracheobronchial tissues dissected from pigs. The analytical, numerical and experimental results are in acceptable agreement. Further investigation of the vibration characteristics of the airways for cases which cannot be dealt with analytically is carried out using COSMOS/Works. Results show a strong trend relationship which suggests that the natural frequency of the trachea and the primary tracheobronchi is approximately 10 Hz. Radial resonances of lower bronchi are predictable through trends found in this work that the resonant frequency is a linear function in certain region of generations.

Objectives: To improve the management of childhood asthma. Subjects & Setting: Children admitted with asthma from 1st January 2000 to 31st December 2000; and children discharged with asthma from Emergency Department (ED) of Sydney Children?s Hospital (SCH) between 16th October 2000 and 28th February 2002. Methods: There were two major studies addressing aspects of asthma management, namely the retrospective in-patient study and the prospective ED presentation study. Each of these was subdivided in two different studies to address different research questions. In the first retrospective study, a priori criteria for theoretical &quottime ready for discharge&quot (TRD) for asthmatic admissions were defined based on frequency of use of salbutamol. In the second retrospective study, we followed 361 children for 1 year from the date of their discharge, to find out whether those who received asthma education, written asthma action plan, and preventer medications at the time of discharge and whose follow?up was arranged prior to discharge, represented to the ED or were readmitted. The prospective study, which also addressed two different research questions, was a randomised-controlled trial in which parents of 310 children who had been discharged from ED with asthma, received written asthma materials only or received telephone consultation in addition to written materials. Background severity and control of asthma were assessed in baseline study from parent?s reported symptom frequency and medication uses. Outcome measures: readmission and representation to the ED, regular use of preventer medications, possession and use of written asthma action plan, and asthma symptom measures. Results: (1) 116 (27.7%) children were discharged before our theoretical TRD and only 2 child who were discharged after achieving TRD, developed symptoms which required oxygenation and more frequent doses of salbutamol. Both readmission and representation to ED within one week of discharge were uncommon. (2) 121 children represented within 1 year of their discharge, of whom 68 children were readmitted. Both receiving asthma education during admission and arranging follow-up prior to discharge were associated with a decreased likelihood of representation as well as readmission (P &gt 0.001). (3) In RCT, the baseline study showed that 14% of children were not receiving appropriate preventer therapy despite indications; and a further 34% had frequent symptoms despite receiving preventer therapy. 62% of the parents reported of having written asthma action plan but less than 50% of them reported using it regularly. At follow up we observed both possession and use of written asthma action plan (p = 0.002) as well as regular use of preventer medications (p = 0.001) were improved in the intervention group compared with the control group. Conclusions: Discharge on 3-hourly rather than 4-hourly doses of salbutamol appears safe and shortens length of stay by an average of 5.5 hrs. Both asthma education and follow-up at the time discharge appear to reduce readmission and representation to ED. Telephone consultation can increase the regular use of preventer medications and written asthma action plan.