Fung, Kit Ching. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 134-144). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Some appendixes in Chinese.

Asthma has long been considered as one of the most common health problems in the world. In Hong Kong, the prevalence of childhood asthma has increased from 4.8% in 1989, to 10.2% in 2002. In spite of the popularity of using Chinese herbs to treat asthma in Hong Kong, evidence on the effectiveness of herbal treatments is lacking. The Chinese herbal formula CUF2 is an innovative formula developed in the Institute of Chinese Medicine, The Chinese University of Hong Kong and it is composed of 5 commonly used Chinese herbs: Radix astragali, Cordyceps sinesis, Radix Scutellaria, Bulbus fritillariae cirrhosae and Radix stemonae. These herbs are chosen because of their well-known effects on either reducing coughing and sputum production, or anti-inflammatory and immunomodulatory activities. Based on the theoretical benefits of CUF2, we conducted a series of animal, in vitro and clinical studies to explore the efficacy, safety and mechanism of action of CUF2. / Following the establishment of the animal model, we have investigated the effect of CUF2 using this model of asthma. We found that 28 days pretreatment with CUF2 could reduce total cell number and eosinophilia in bronchoalveolar lavage fluid (BALF), prevent the eosinophil infiltration of airways, decrease pulmonary inflammatory cells, and reduce mucus and goblet cell hyperplasia. Especially in the reduction of goblet cell hyperplasia, we demonstrated that there was no significant difference between the effects of high dose CUF2 and dexamethasone (DEX). The eosinophilic immune-inflammatory responses in the airways in OA-sensitized/challenged rats were completely blocked by DEX returning to almost the same as those in normal rats, but the loss of thymus index and body weight were also observed. In contrast to the overall immunosuppressive effects of DEX, decreased production of inflammatory cytokines and chemokines [interleukin (IL)-4, tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-2 and monocyte chemotactic protein-1 (MCP-1)], increased production of IL-10 and interferon-gamma (IFN-gamma) in BALF and no suppression of body weight and thymus index were demonstrated in the CUF2-treated groups. There was a dose-response relationship with more prominent effects seen with higher doses of CUF2. These findings indicate that the CUF2 has anti-airway inflammatory activity and exhibits immunomodulatory effect on Th1/Th2 responses in ovalbumin sensitized rats after allergen challenge, and this may imply its potential application to patients with allergic asthma. / In order to evaluate the clinical efficacy and safety, we conducted a multicenter, randomized, double blind, parallel and placebo controlled clinical trial. The same Chinese herbal formula was used in this clinical trial in 85 children aged 7-15 years with mild to moderate perennial asthma as an adjuvant therapy for 6 months. The primary outcome measure was the steroid dosage reduction. Other outcome measures included changes in disease severity score (DSS), lung function, serum concentrations of total IgE and the levels of some key allergy and inflammatory markers in peripheral blood, fractional exhaled nitric oxide (FENO), frequency of asthma attacks and quality of life (QOL). To assess safety, we did urinalysis, complete blood count, liver function and renal function at baseline and the end of the study. Drug compliance and adverse effects were also checked at each monthly visit. All patients were maintained on inhaled corticosteroid at their usual dose and dosing interval, and continued to receive short-acting, inhaled beta2-agonists as needed. There were no serious adverse events reported in the 6-month study period by any of the subjects. Hematological (except eosinophils count) and biochemical profiles (including renal function and liver function) remained within normal limits in the CUF2 group and placebo group at the end of the study. CUF2 was well tolerated in asthmatic children. Both CUF2 group and placebo group showed an improvement in most of clinical parameters. The dosage of inhaled corticosteroid was successfully reduced in both groups. Both groups had similar decrease in DSS, improved QOL and improved lung function parameter PEFR (L/min). Although these parameters showed no statistically significant difference between two groups, the percentage of eosinophils and lymphocytes were significantly decreased in CUF2 group as compared with the placebo group. The CUF2 group also showed improved diary symptom score, reduced expression of TNF-alpha and slight increase in anti-inflammation cytokine IL-18 in the blood. A trend of greater improvement in frequency of upper respiratory infection (URI) in CUF2 group was noted, but no statistical significance was attained. The changes in lung function parameter FEV1%, FENO, frequency of asthma attacks and serum concentrations of total IgE, IgE HDM, IgE cat, cockroach, TARC, LTB4 and LTC4D4E4 showed no statistically significant difference CUF2 group and placebo group. Overall, our data demonstrated that CUF2 treatment had some immunomodulatory effect in childhood asthma. Our findings should support further investigations of Chinese herbal medicine in the area of asthma without steroid therapy. / In the animal study, firstly we attempted to establish a novel murine model of asthma. We adopted a modified sensitization procedure using 10-point subcutaneous and intraperitoneal injections of Ovalbumin (OA) with freshly prepared Al(OH)3 and successfully induced severe airway allergic reactions in young Sprague Dawley (SD) rats. In this SD rat model, allergen exposure triggered accumulation of inflammation cells and eosinophils in the airway submucosa and goblet cells hyperplasia in mucosa, lung function test revealed obstructive lung function changes that included increase of lung resistance (RL) and decrease of dynamic lung compliance (Cdyn). Cytokine and chemokine assays showed that there was a change of the TH1/Th2 balance as illustrated by the high Th2 (interleukin-4)/Th1 (interferon-gamma) ratio. These results demonstrated the feasibility and validity of the SD rat model for studying allergic asthma. This SD model is much cheaper and readily available than the Brown Norway rat model and may facilitate further drug trial in asthma. / In the in vitro study, we investigated the effect of CUF2 on the release of cytokines and/or gene expression using human mast cell line HMC-1, human bronchial epithelial cell line BEAS-2B, peripheral blood mononuclear cells (PBMCs) from healthy subjects and airway cells present in induced sputum from asthmatic patients. We have shown (1) the CUF2 had no cytotoxic effects in final working concentration; (2) CUF2 had inhibitory effects on IL-6, TNF-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion from HMC-1 in a dose-dependent manner. However, no reduction of IL-8 production in HMC-1 was demonstrated. (3) In addition, study of the effect of CUF2 on the expression of cytokine gene from HMC-1 showed that IL-4, IL-6 and GM-CSF mRNA expressions were down regulated at 24 hours, 24 hours, 16 hours and 24 hours of time points, respectively. No effects on IL-8 and TNF-alpha mRNA expression was observed. (4) Furthermore, CUF2 also significantly inhibited in vitro IL-6 and GM-CSF secretion in TNF-alpha stimulated BEAS-2B cell and reduced GM-CSF production in airway cells present in induced sputum from asthmatic children. (5) We observed that CUF2 enhanced TNF-alpha and IL-6 production but did not alter the levels of GM-CSF and IL-8 in mitogen-stimulated PBMCs from health subject. These findings suggest that pharmacological activities of the CUF2 may be mediated by regulating the production of cytokines in human mast cell, bronchial epithelial cell, airway cell and PBMCs. / In this study, a novel animal asthma model has been established. This model has extensively characterized and exhibited several inflammatory, immunological features that resemble those of human asthma and may facilitate further drug trial in asthma. CUF2 showed its efficacy treating the animal model of allergic asthma. In vitro study also provided evidence of its beneficial dichotomous effects on cytokine and chemokine production in HMC-1, PBMCs and airway cells. A multi-center, randomized, double blind, placebo controlled clinical trial showed that CUF2 had a certain degree of clinical efficacy. Furthermore, the use of CUF2, with the study dose and treatment period, was safe. The efficacy of individual ingredient and the mechanism of CUF2 have not been clarified and further investigations are warranted. In conclusion, our results provided evidence of the potential beneficial effect of CUF2 on immune system functions and supported the potential use of TCM as therapeutic drugs for allergic inflammatory diseases. / by Wong Yeuk Oi. / "September 2005." / Advisers: Yn Tz Sung; Kowk Pui Fung. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6296. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 330-349). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Wong, Yun Sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 142-162). / Abstracts in English and Chinese. / Abstract (in English) --- p.ii / Abstract (in Chinese) --- p.vi / Acknowledgement --- p.ix / Statement of Work --- p.x / Table of Contents --- p.xi / List of Tables --- p.xiv / List of Figures --- p.xvi / Glossary of Terms and Abbreviations --- p.xviii / Chapter Section I: --- Introduction --- p.1 / Chapter Chapter 1: --- General Overview of Asthma --- p.2 / Chapter 1.1 --- Asthma definition and its phenotype --- p.2 / Chapter 1.2 --- Asthma epidemiology and its prevalence in past decades --- p.4 / Chapter 1.3 --- Hygiene hypothesis and asthma development --- p.8 / Chapter 1.4 --- Asthma pathogenesis and innate immunity --- p.12 / Chapter 1.5 --- The environmental factors and genetic makeup in relation with asthma --- p.17 / Chapter Chapter 2: --- Study Plan and Obj ective --- p.21 / Chapter Section II: --- Literature Review --- p.24 / Chapter Chapter 3: --- Indoor Environmental factors of Asthma --- p.25 / Chapter 3.1 --- Overview of the indoor environmental factors --- p.25 / Chapter 3.2 --- House dust endotoxin --- p.27 / Chapter 3.2.1 --- Determinants of endotoxin exposure in home environment --- p.21 / Chapter 3.2.2 --- Protective role of endotoxin in allergy and asthma development --- p.29 / Chapter 3.2.3 --- Deleterious effect of endotoxin exposure in asthma: the dark side --- p.31 / Chapter 3.3 --- Allergen --- p.34 / Chapter 3.3.1 --- Allergens: an update --- p.34 / Chapter 3.3.2 --- Determinants of allergens in home environment --- p.35 / Chapter 3.3.3 --- Allergens avoidance: environmental intervention --- p.36 / Chapter 3.4 --- Nitrogen dioxide --- p.40 / Chapter 3.4.1 --- Determinants of indoor nitrogen dioxide and its relation with gas cooking --- p.40 / Chapter 3.4.2 --- The adverse effects of nitrogen dioxide on respiratory symptoms --- p.41 / Chapter 3.4.3 --- Reactive nitrogen species and nitrosative stress in asthma --- p.42 / Chapter Chapter 4: --- CD14 Single Nucleotide Polymorphisms and Asthma --- p.45 / Chapter 4.1 --- Overview of CD14 receptor --- p.45 / Chapter 4.2 --- Action of CD14 receptor in endotoxin response --- p.47 / Chapter 4.3 --- Relation of CD14 with asthma --- p.48 / Chapter 4.3.1 --- Associations between CD14 polymorphisms and asthma phenotypes --- p.48 / Chapter 4.3.2 --- Endotoxin switch concept: from gene to gene - environment --- p.52 / Chapter Section III: --- Study Core --- p.55 / Chapter Chapter 5: --- Methodology in indoor environment investigation and its result --- p.57 / Chapter 5.1 --- Study Population --- p.57 / Chapter 5.2 --- Home Visiting Protocol --- p.60 / Chapter 5.2.1 --- The International Study of Asthma and Allergies in Childhood (ISAAC) --- p.60 / Chapter 5.2.2 --- ISAAC questionnaire --- p.61 / Chapter 5.2.3 --- House dust collection procedures --- p.62 / Chapter 5.2.4 --- Indoor nitrogen dioxide measurements --- p.65 / Chapter 5.2.4.1 --- Ogawa passive sampler --- p.65 / Chapter 5.2.4.2 --- Preparation and measurement procedures --- p.66 / Chapter 5.2.4.3 --- Indoor nitrogen dioxide quantification --- p.67 / Chapter 5.3 --- House dust extraction --- p.69 / Chapter 5.4 --- House dust endotoxin measurement --- p.70 / Chapter 5.5 --- Allergen measurement --- p.72 / Chapter 5.6 --- Statistical Analysis --- p.75 / Chapter 5.7 --- Results --- p.77 / Chapter 5.7.1 --- Demographic data and subjects characteristics --- p.77 / Chapter 5.7.2 --- "Dust weight, endotoxin and allergen levels and their determinants in household" --- p.82 / Chapter 5.7.3 --- Indoor NO〕2levels and its determinant in household --- p.95 / Chapter 5.7.4 --- Associations between indoor environmental factors and respiratory health --- p.96 / Chapter 5.7.4.1 --- Clinical symptoms --- p.96 / Chapter 5.7.4.2 --- Exhaled NO levels --- p.101 / Chapter 5.7.4.3 --- Spirometric indices --- p.103 / Chapter Chapter 6： --- Methodology in genotyping CD14 polymorphisms and its result --- p.105 / Chapter 6.1 --- Study population --- p.105 / Chapter 6.2 --- Serum Total and allergen-specific IgE measurement --- p.106 / Chapter 6.3 --- CD14 Genotyping s --- p.107 / Chapter 6.3.1 --- Genotyping promoter SNPs ofCD14/-159 and -1359 --- p.107 / Chapter 6.3.2 --- Genotyping promoter SNP of CD14/-1619 --- p.109 / Chapter 6.3.3 --- Validation of genotyping by sequencing --- p.111 / Chapter 6.4 --- Statistical Analysis --- p.112 / Chapter 6.5 --- Results --- p.113 / Chapter 6.5.1 --- Subjects characteristics and clinical features. --- p.113 / Chapter 6.5.2 --- Associations between CD14 SNPs and asthma phenotypes --- p.114 / Chapter Chapter 7: --- Discussion --- p.120 / Chapter 7.1 --- Influence of indoor factors on asthmatic children --- p.120 / Chapter 7.2 --- CD14 polymorphisms in modifying asthma phenotypes --- p.135 / Chapter Chapter 8: --- Conclusion and Further Works --- p.138 / References --- p.141 / Appendix 1 Questionnaire / Appendix 2 Publications

published_or_final_version / Community Medicine / Master / Master of Public Health

Childhood asthma is one of the commonest chronic respiratory conditions in developed communities. Chest physiotherapy has traditionally been one of the interventions used mainly after an attack and for a relatively short-period on an outpatient basis. The purpose of the study was to determine the perceptions of physiotherapists and caregivers about the importance of chest physiotheraphy in asthmatic children in Kigali. To achieve this aim the author attempted to identify the perceived benefits of chest physiotherapy for asthmatic children among caregivers / to determine the perception of physiotherapists about the importance of chest physiotherapy for asthmatic children and / to identify the physiotherapists experiences with doctors referrals and the caregivers compliance in the management of asthmatic children.

Background: Asthma is characterized by chronic airway inflammation in which leukocytes are attracted into the inflamed airway under the influence of chemokines. Molecular studies and allergen bronchoprovocation suggested that chemokines such as thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), eotaxin and regulated upon activation normal T-cell expressed and secreted (RANTES) were involved in the airway responses to allergen exposure. / Conclusions: Chemokines are important mediators in the pathophysiology of asthma and atopy. TARC in plasma and MDC in EBC appear to be useful biomarkers for assessing childhood asthma. Besides, MDC concentrations in UCB may predict the susceptibility to develop wheezing during infancy. / Methods: Asthmatic patients, non-allergic controls and healthy singleton newborns were recruited from attendants of a university teaching hospital. Atopy-related chemokines in peripheral blood and EBC were measured by enzyme-linked immunosorbent assays. Genomic DNA from asthmatics and controls was genotyped by restriction fragment length polymorphism to characterize single nucleotide polymorphisms (SNPs) in the genes encoding TARC, RANTES, interleukin-13 and CD14. / Objectives: This thesis investigated the relation between chemokines and asthma and atopy by: (a) measuring their concentrations in peripheral blood and exhaled breath condensate (EBC); (b) performing case-control association studies for genes encoding atopy-related chemokines and related molecules; and (c) analyzing chemokines in umbilical cord blood (UCB) in relation to wheezing phenotypes during infancy. / Results: Plasma TARC concentrations were higher in children with chronic asthma than controls, and also correlated with plasma total IgE. Among children with asthmatic exacerbation, plasma TARC concentrations showed inverse correlation with peak expiratory flow rates at presentation. When measured in EBC, MDC but not TARC or eotaxin was higher in asthmatics than controls. In our genetic association studies, SNPs in IL13, RANTES and TARC were associated with serum total and/or allergen-specific IgE. TARC C-431T was also linked to peripheral eosinophilia. However, none of these polymorphisms was associated with physician-diagnosed asthma. Interestingly, C-159T in CD14 was also associated with serum total IgE, but only among atopic asthmatic children. In the last part involving 124 singleton healthy newborns, MDC concentrations in UCB were significantly increased in newborns who wheezed during infancy. / Leung Ting-fan. / Adviser: Gary W.K. Wong. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (M.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 196-231). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

Asthma prevalence in children under age 18 has risen steadily in the U.S. since the mid-1970s. Most researchers attribute this increase to air pollutants, socioeconomic status or urban residence. This study examined asthma prevalence in Lane County, Oregon, using children's asthma hospital discharges (1990-1995), and data from 10 of 16 school districts. The overall asthma prevalence in Lane County was 5.8%, ranging from 1.9% (coastal Siuslaw District) to 10% (urban, industrial Bethel District). Asthma prevalence during 1988-1997 was examined for the largest school district, Eugene 4J (43% of the total study population). Eugene 4J is divided into four regions: North, South, Churchill, and Sheldon. The largest asthma prevalence increase during this time was detected in North Region (2.5%-8%), while the overall district prevalence nearly doubled (3.3%-6.2%). No correlation was found between socioeconomic status and asthma prevalence, and there was not a consistent pattern between asthma prevalence and location of each school district (urban vs. rural). Two out of the three urban school districts had higher asthma prevalence than five of the rural school districts. However, three school districts did not follow this pattern, either being lower than expected for an urban area or higher than expected for a rural area. Asthma hospitalization rates increased for most children between 1990 and 1995, with a 20-fold increase for ages 15-19 years. The results of this study show an increase in prevalence and severity of asthma in school children in Lane County. Further studies are warranted to investigate the contribution that geography, meteorology, and proximity to industry have in asthma prevalence in Lane County. / Graduation date: 1999

Thesis (Ph. D.)--UCLA, 2008. / Vita. Description based on print version record. Includes bibliographical references (leaves 138-163).

Childhood asthma is one of the commonest chronic respiratory conditions in developed communities. Chest physiotherapy has traditionally been one of the interventions used mainly after an attack and for a relatively short-period on an outpatient basis. The purpose of the study was to determine the perceptions of physiotherapists and caregivers about the importance of chest physiotheraphy in asthmatic children in Kigali. To achieve this aim the author attempted to identify the perceived benefits of chest physiotherapy for asthmatic children among caregivers / to determine the perception of physiotherapists about the importance of chest physiotherapy for asthmatic children and / to identify the physiotherapists experiences with doctors referrals and the caregivers compliance in the management of asthmatic children.

Includes bibliography (v. 2, leaves 80-93) / 2 v. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aims to develop a tool to measure parents' approaches to the management of their children's asthma, and to also identify the influence of psychosocial factors on parents' management of childhood asthma. In order to do this the author developed a questionnaire asking parents to describe their management approaches to typical asthma scenarios. / Thesis (Ph.D.)--University of Adelaide, Dept. of Psychiatry, 1998