No description available.

Aim: To determine whether the addition of nebulised ipratropium to the therapy of acute asthma leads to a cost-effective reduction in the mean duration of admission and time to maximum peak expiratory flow rate (PEFR). Method: Patients with an admission diagnosis of acute asthma were studied in a double-blind, placebo-controlled trial in which they received a standard therapeutic regimen of continuous intravenous aminophylline, 4-hourly fenoterol nebulisation, intravenous methylprednisolone 125mg 12-hourly, and, every four hours, either nebulised saline placebo or ipratropium bromide 500mcg in 3ml saline. Data on age, gender, initial and maximum PEFR, time to maximum PEFR, and duration of hospital stay was collected from the hospital record after discharge. Statistical techniques: 2-way contingency tables for categorical variables, 1-way ANOVA for treatment effects, and life-table analysis of the time till discharge. Results: Records of 279 of the 400 patients entered in the study were suitable for analysis after excluding re-admissions, non-asthmatics and incomplete records. Baseline comparisons of age and severity on presentation showed no significant differences. The trial group did not differ significantly from the control group with respect to either time to PEFR (respectively 21.11 hours (SD 14.3) versus 22.89 (SD 15.82)) or duration of admission (5.02 (SD 3.65) versus 5.38 (SD 3.13) 6-hour units). In a sub-group of patients (n=155) demonstrating more than 100% improvement in PEFR, the time to maximum PEFR was significantly shorter in the ipratropium group (20.35 hours SD 12.4) versus 25.20 hours (SD 17.0); p= 0.045). Conclusion: The addition of ipratropium bromide to a standard treatment regimen for acute asthma reduced the time to achieve maximum PEFR in a sub-group of patients with markedly reversible airflow limitation. Overall, however, the addition did not prove cost-effective.

No description available.

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.

Lun Samantha Wei Man. / "August 2006." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 181-206). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

Ng, Chor Fung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 130-144). / Abstracts in English and Chinese. / ABSTRACT (ENGLISH VERSION) --- p.i / ABSTRACT (CHINESE VERSION) --- p.iv / ACKNOWLEDGEMENTS --- p.vi / TABLE OF CONTENTS --- p.viii / LIST OF TABLES AND FIGURES --- p.xii / ABBREVIATIONS --- p.xiv / Chapter CHAPTER 1. --- GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- Definition of asthma --- p.1 / Chapter 1.2 --- Asthma epidemiology --- p.2 / Chapter 1.3 --- Pathogenesis of Asthma --- p.3 / Chapter 1.3.1 --- Gene-environment interaction --- p.3 / Chapter 1.3.2 --- Allergens and atopic sensitization --- p.4 / Chapter 1.3.3 --- Other environmental factors --- p.5 / Chapter 1.4 --- House dust mite (HDM) --- p.5 / Chapter 1.4.1 --- Characteristics of HDM allergens --- p.5 / Chapter 1.4.2 --- HDM and asthma --- p.6 / Chapter 1.5 --- Pathophysiology of asthma --- p.8 / Chapter 1.5.1 --- Airway inflammation --- p.8 / Chapter 1.5.1.1 --- Cellular mechanism --- p.8 / Chapter 1.5.1.2 --- Characteristics of chronic inflammation --- p.9 / Chapter 1.5.1.3 --- Inflammatory cells in airway inflammation --- p.10 / Chapter 1.5.1.3.1 --- Mast cell --- p.10 / Chapter 1.5.1.3.2 --- Macrophages --- p.11 / Chapter 1.5.1.3.3 --- T lymphocytes --- p.12 / Chapter 1.5.1.3.4 --- Eosinophils --- p.12 / Chapter 1.5.1.3.5 --- Epithelial cells --- p.13 / Chapter 1.5.1.4 --- Cytokines in asthma --- p.14 / Chapter 1.5.1.4.1 --- Inflammatory cytokines --- p.14 / Chapter 1.5.1.4.1.1 --- Interleukin-4 --- p.14 / Chapter 1.5.1.4.1.2 --- Interleukin-5 --- p.14 / Chapter 1 5.1.4.1.3 --- Interleukin-6 --- p.15 / Chapter 1.5.1.4.1.4 --- Granulocyte Monocyte Colony Stimulating Factor (GM-CSF) --- p.15 / Chapter 1.5.1.4.1.5 --- Tumor Necrosis Factor-α (TNF-α) --- p.16 / Chapter 1.5.1.4.2 --- Anti-inflammatory cytokines --- p.17 / Chapter 1.5.1.4.2.1 --- Interleukin-10 --- p.17 / Chapter 1.5.1.4.2.2 --- Interferon-γ(IFN-γ) --- p.17 / Chapter 1.5.2 --- Airway hyperresponsiveness (AHR) --- p.18 / Chapter 1.5.3 --- A irway remodeling --- p.19 / Chapter 1.6 --- Asthma therapy --- p.21 / Chapter 1.6.1 --- β2-agonists --- p.21 / Chapter 1.6.2 --- Cromolyn and nedocromil --- p.21 / Chapter 1.6.3 --- Theophylline --- p.22 / Chapter 1.6.4 --- Leukotriene modifiers --- p.22 / Chapter 1.6.5 --- Corticosteroids --- p.23 / Chapter 1.7 --- Traditional Chinese Medicine --- p.24 / Chapter 1.7.1 --- Introduction --- p.24 / Chapter 1.7.2 --- Traditional Chinese Medicine (TCM) --- p.24 / Chapter 1.7.3 --- "Chinese herbal formula, CU Formula 2 (CUF2) and Kuan Dong Hua" --- p.26 / Chapter 1.8 --- Objectives of our studies --- p.28 / Chapter CHAPTER 2. --- ESTABLISHMENT OF A HDM-INDUCED ASTHMATIC ANIMAL MODEL IN SD RATS --- p.32 / Chapter 2.1 --- Introduction --- p.32 / Chapter 2.2 --- Materials and methods --- p.33 / Chapter 2.2.1 --- Buffers and solutions --- p.33 / Chapter 2.2.2 --- Animals --- p.33 / Chapter 2.2.3 --- Preparation of aluminum hydroxide gel --- p.34 / Chapter 2.2.4 --- HDMAllergen --- p.34 / Chapter 2.2.5 --- Sensitization Procedure --- p.35 / Chapter 2.2.6 --- Intratracheal instillation challenge --- p.35 / Chapter 2.2.7 --- Bronchoalveolar lavage (BAL) and BAL Cell counting --- p.36 / Chapter 2.2.8 --- Lung Histopathological Analysis --- p.37 / Chapter 2.2.9 --- Measurement of cytokine and chemokine by Enzyme-Linked Immunosorbent Assay (ELISA) --- p.39 / Chapter 2.2.10 --- Statistical Analysis --- p.40 / Chapter 2.3 --- Results --- p.41 / Chapter 2.3.1 --- Cellular Analysis of BALF --- p.41 / Chapter 2.3.2 --- Histopathology --- p.42 / Chapter 2.3.3 --- Cytokine and chemokine --- p.43 / Chapter 2.4 --- Discussion --- p.44 / Chapter CHAPTER 3. --- IMMUNOMODULATORY EFFECT OF CUF2 AND KUAN DONG HUA IN A RAT MODEL OF HDM-INDUCED ASTHMA --- p.65 / Chapter 3.1 --- Introduction --- p.65 / Chapter 3.2 --- Materials and methods --- p.67 / Chapter 3.2.1 --- Herbal materials and extraction method --- p.67 / Chapter 3.2.2 --- "Antigen sensitization, challenge, and treatment" --- p.68 / Chapter 3.2.3 --- Bronchoalveolar lavage and cell differential counts --- p.69 / Chapter 3.2.4 --- Histological Studies --- p.69 / Chapter 3.2.5 --- Measurement of BALF cytokines and chemokines --- p.70 / Chapter 3.2.6 --- "Body weight, thymus index and spleen index" --- p.70 / Chapter 3.2.7 --- Statistical analysis --- p.70 / Chapter 3.3 --- Results --- p.71 / Chapter 3.3.1 --- Effect of herbs and DXA on total cells and eosinophils in BALF --- p.71 / Chapter 3.3.2 --- Effect of herb and DXA on lung histology --- p.72 / Chapter 3.3.3 --- Effect of herbs and DXA on cytokine and chemokine level in BALF --- p.73 / Chapter 3.3.4 --- "Effect of herb and DXA on body weight, thymus index and spleen index" --- p.75 / Chapter 3.4 --- Discussion --- p.77 / Chapter CHAPTER 4. --- IMMUNOMODULATORY EFFECT OF KUAN DONG HUA ON HUMAN MAST CELLS (HMC-1) --- p.109 / Chapter 4.1 --- Introduction --- p.109 / Chapter 4.2 --- Materials and methods --- p.110 / Chapter 4.2.1 --- Reagents --- p.110 / Chapter 4.2.2 --- Cell line and Cell Culture --- p.111 / Chapter 4.2.3 --- Herb and extraction procedure --- p.111 / Chapter 4.2.4 --- Cell Viability Assay --- p.112 / Chapter 4.2.5 --- Assay of cytokine secretion --- p.113 / Chapter 4.2.6 --- Quantitative Analysis of cytokines --- p.113 / Chapter 4.2.7 --- Bacterial endotoxin contamination --- p.114 / Chapter 4.2.8 --- Statistical analysis --- p.115 / Chapter 4.3 --- Results --- p.116 / Chapter 4.3.1 --- Effect of Kuan Dong Hua on cell viability of HMC-I --- p.116 / Chapter 4.3.2 --- Effect of Kuan Dong Hua on cytokine release from HMC-I --- p.116 / Chapter 4.3.3 --- Effect of endotoxin contamination in the extract --- p.117 / Chapter 4.4 --- Discussion --- p.118 / Chapter CHAPTER 5. --- GENERAL CONCLUSION --- p.125 / Chapter 5.1 --- Conclusion --- p.125 / Chapter 5.2 --- Limitations of this study and Future work --- p.128 / REFERENCES --- p.130 / APPENDICES --- p.145 / Appendix A. Wright-Giemsa Stain for cytospin preparations --- p.145 / Appendix B. Hematoxylin & eosin (H&E) staining --- p.145 / Appendix C. Congo Red staining --- p.146 / Appendix D. Periodic acid-Schiff (PAS) staining --- p.146