Chinese herbal medicine for chronic obstructive pulmonary disease (COPD): systematic analyses of modern and classical approaches A thesis submitted in fulfilment of the requirements for Degree of Doctor of Philosophy XueDong An M. App Sci Chinese Medicine B.Med Discipline of Chinese Medicine School of Health Sciences RMIT University August 2012 Declaration I declare that all works in this thesis carried out during my Degree of Philosophy in Science in the Discipline of Chinese Medicine, School of Health Sciences, RMIT University were of my own. No part of this thesis has been submitted to this or any other university or institutions for any other award. To the best of my knowledge, this thesis contains no part that has been published previously by others except where due references are made. Xue Dong An Date 12/01/2013 II Acknowledgements I would like to thank the people, who have supported me during the period of completing my PhD study. Dr Brian May has spent much of his valuable time on proof reading my manuscript and advising me on statistical analyses of the Chinese classical literature and modern literature. For that I am grateful. I wish to express my sincere appreciation to Ms Chang Su-yueh for her patience in cross- checking the extensive amount of tedious data obtained from classical literature. I would also like to extend my sincere thanks to editors of Enago Crimson Interactive Pvt. Ltd for their professional copy-editing of the thesis at short notice. The time spent during this undertaking has been both joyful and hard. Fortunately a few colleagues and staff in the Discipline of Chinese Medicine and other departments at RMIT have assisted me in various ways throughout the past years. Without their friendship, encouragement and support it would have been very difficult. To them I wish to extend my heartfelt thanks. This project was funded by the Australian Postgraduate Award (APA). Co-operation was also provided by the IRN-TCM International Funding from Guangdong Provincial Hospital of Chinese Medicine. Finally, I wish to express my gratitude and appreciation to my family members and best friends for their patience and finance support and unwavering belief in me during these postgraduate years. III Table of Contents DECLARATION ........................................................................................................................... II ACKNOWLEDGEMENTS ........................................................................................................... III TABLE OF CONTENTS .............................................................................................................. IV LIST OF FIGURES .................................................................................................................... XII LIST OF TABLES ...................................................................................................................... XII PUBLICATION.......................................................................................................................... XX ABBREVIATION ...................................................................................................................... XXI SUMMARY .......................................................................................................................... XXIII 1 CHAPTER ONE: GENERAL INTRODUCTION ........................................................................ 1 1.1. BACKGROUND ............................................................................................................... 1 1.1.1 Definition of COPD .................................................................................................. 1 1.1.1.1 Development of COPD ...................................................................................... 1 1.1.1.2 Modern definition of COPD .............................................................................. 1 1.1.2 International variations of COPD prevalence .......................................................... 2 1.1.2.1 Geographic and racial factors ............................................................................ 2 1.1.2.2 Age and gender factors ...................................................................................... 4 1.1.3 Risk factors for COPD .............................................................................................. 4 1.1.3.1 Tobacco smoking (active and passive smoking) ................................................ 4 1.1.3.2 Genetic factors ................................................................................................... 5 1.1.3.3 Occupational exposure ....................................................................................... 5 1.1.3.4 Indoor air pollution ............................................................................................ 5 1.1.3.5 Outdoor air pollution .......................................................................................... 5 1.1.4 Co-morbidity in COPD patients ............................................................................... 5 1.1.5 Impact of COPD........................................................................................................ 6 1.1.5.1 Morbidity and mortality of COPD ..................................................................... 6 1.1.5.2 Burden of COPD ................................................................................................ 6 1.1.6 Management of COPD .............................................................................................. 6 1.1.7 Complementary and alternative medicine (Chinese medicine) ................................ 7 1.2. STUDY RATIONALE ......................................................................................................... 7 1.2.1 COPD is a significant global health problem ........................................................... 7 1.2.2 Limitations of pharmacotherapy and associated side effects ................................... 8 1.2.3 Promising results from CHM studies ........................................................................ 8 1.2.4 Potential benefit for COPD ....................................................................................... 8 1.3. AIMS AND OBJECTIVES ................................................................................................... 9 1.4. RESEARCH QUESTIONS ................................................................................................... 9 1.5. THESIS OUTLINE ............................................................................................................ 9 1.5.1 Analysis of Chinese classical literature relevant to COPD .................................... 12 1.5.2 Analyses of the modern literature and clinical trial results .................................... 12 2 CHAPTER TWO: REVIEW OF WESTERN MEDICINE-BASED LITERATURE CONCERNING CHRONIC OBSTRUCTIVE PULMONARY DISEASE ....................................................................... 13 2.1 INTRODUCTION ............................................................................................................ 13 2.2 DIAGNOSIS OF COPD .................................................................................................. 13 2.2.1 Symptoms of COPD ................................................................................................ 13 2.2.2 Physical signs of COPD .......................................................................................... 13 IV 2.2.3 Spirometry in COPD ............................................................................................... 14 2.2.4 Diagnostic imaging and other tests for COPD ....................................................... 14 2.2.5 Arterial blood gas measurement ............................................................................. 15 2.2.6 Alpha1-antitrypsin deficiency screening ................................................................. 16 2.3 CLASSIFICATION OF COPD SEVERITY .......................................................................... 16 2.4 STABLE COPD AND COPD EXACERBATIONS ............................................................... 17 2.5 DIFFERENTIAL DIAGNOSIS ........................................................................................... 17 2.5.1 Asthma ..................................................................................................................... 17 2.5.2 Bronchiectasis ......................................................................................................... 18 2.5.3 Tuberculosis) ........................................................................................................... 19 2.5.4 Obliterative bronchiolitis ........................................................................................ 19 2.5.5 Diffuse panbronchiolitis .......................................................................................... 19 2.5.6 Congestive heart failure ......................................................................................... 20 2.6 PATHOLOGICAL CHANGES IN COPD ............................................................................. 20 2.7 PATHOGENESIS OF COPD............................................................................................. 21 2.7.1 Roles of chronic inflammation and inflammatory cells in the pathogenesis of COPD ...............................................................................................................................