Pharmacology of Asthma

This volume forms part of a prestigious series and covers the latest advances in our understanding of the pathophysiology and treatment of asthma. Our understanding of asthma has changed dramatically in recent years, and much of this new information is brought together in this volume written by inter­ nationally recognised authorities. The aim of the book is to review in depth the changing concepts of inflammatory processes in asthma and to discuss the implications for research of this common chronic disease. Many of the advances in and future therapy our understanding of asthma have originated from a pharmacological approach, and this volume highlights the promising new options for pharma­ cological intervention. It is hoped this book will be invaluable for research scientists and clinic­ ians involved in asthma research and will be a major reference resource for chest physicians and those involved in the development of novel pharmaceu­ tical entities. Each chapter is extensively referenced, generously illustrated with clear diagrams and photographs, and represents a state-of-the-art review of this growing area. c.P. PAGE P.l. BARNES Contents CHAPTER 1 The Pathology of Asthma: An Overview L.A. LAmNEN and A. LAmNEN. With 10 Figures ...................... 1 A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 1 . . . . . . . . . . . . . . . B. Methods to Investigate the Pathology of Human Asthma ............ 1 C. Bronchial Epithelium and Inflammatory Cells in Asthmatic Patients Between Attacks ........................... 2 I. Mast Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 4 . . . . . . . . . . . . . . II. Eosinophils ............................................... 7 III.Neutrophils.............................................. 10 D. Bronchial Epithelial Inflammation During an Asthma Attack. . . . . .. . 10 E. Epithelial Regeneration .... . . . . . . . . . . . . . . . . . . . . . . .. . . 12 . . . . . . . . .

1 The Pathology of Asthma: An Overview.- A. Introduction.- B. Methods to Investigate the Pathology of Human Asthma.- C. Bronchial Epithelium and Inflammatory Cells in Asthmatic Patients Between Attacks.- D. Bronchial Epithelial Inflammation During an Asthma Attack.- E. Epithelial Regeneration.- F. Airway Smooth Muscle.- G. Bronchial Glands.- H. Neural Pathways.- I. Nerves and Other Airway Structures.- J. Bronchial Circulation.- K. Leakage of the Bronchial Vascular Bed in Patients with Asthma.- L. Conclusion.- References.- 2 The Contribution of Inflammatory Cells to the Pathogenesis of Asthma.- A. Inflammation and Inflammatory Cells.- B. Pathological Evidence for Inflammation in Asthma.- C. Microvascular Leakage.- D. Neutrophils.- E. Eosinophils.- F. Mast Cells and Basophils.- G. Monocytes and Macrophages (Mononuclear Phagocytes).- H. Platelets.- I. Lymphocytes.- J. Concluding Comments.- References.- 3 Inflammatory Mediators.- A. Introduction.- B. Histamine.- C. Cyclooxygenase Products.- D. Lipoxygenase Products.- E. PAF.- F. Kinins.- G. Adenosine.- H. Complement.- I. Serotonin.- J. Chemotactic Factors.- K. Oxygen Radicals.- L. Conclusions.- References.- 4 Pharmacology of Airway Smooth Muscle.- A. Introduction.- B. E/C Coupling Mechanisms.- C. E/C Uncoupling Mechamisms.- D. Future Trends in the Development of Bronchodilator Drugs.- References.- 5 Neural Mechanisms in Asthma.- A. Introduction.- B. Cholinergic Mechanisms.- C. Adrenergic Mechanisms.- D. NANC Nerves and Neuropeptides.- E. Conclusions.- References.- 6 Pharmacology and Therapeutics of ?-Adrenoceptor Agonists.- A. Introduction.- B. The Molecular Nature of the ?-Adrenoceptor and Its Relationship to Adenylate Cyclase.- C. Density and Distribution of ?-Adrenoceptors in the Lung.- D. Therapeutic Sites ofAction.- E. The Status of ?-Adrenoceptor Function in Asthma.- F. The Importance of ?2-Adrenoceptor Selectivity and Efficacy.- G. Adverse Reactions to ?-Adrenoceptor Agonists.- H. Therapeutic Actions of ?-Agonists.- I. Concluding Remarks.- References.- 7 Pharmacology of Anti-Asthma Xanthines.- A. Introduction.- B. Clinical Use.- C. Mode of Action of Xanthines.- D. Conclusion.- References.- 8 Glucocotricosteroids in Asthma.- A. Mechanism of Action of Glucocorticosteroids.- B. Clinical Use.- C. Future Developments.- References.- 9 Pharmacology of Prophylactic Anti-Asthma Drugs.- A. Cromoglycate and Nedocromil.- B. Ketotifen.- C. Pharmacological Analysis.- References.- 10 Pathophysiology and Pharmacology of Aspirin-Induced Asthma.- A. Introduction.- B. Definition and Main Clinical Features.- C. Pathogenesis.