This book sums up the mechanistic basis, current status, and future prospects of steroid inhalation as the cornerstone of prophylactic asthma therapy, identifying its kinetic basis-especially the essential airway selectivity-and including a historical account of inhaled glucocorticoid development. Makes connections among the underlying pharmacol

Robert P. Schleimer The Johns Hopkins University School of Medicine and The Johns Hopkins Asthma & Allergy Center Baltimore, Maryland Paul M. O'Byrne McMaster University and St. Joseph's Hospital Hamilton, Ontario, Canada Stanley J. Szefler University of Colorado Health Sciences Center and National Jewish Medical and Research Center Denver, Colorado Ralph Brattsand AstraZeneca Research and Development Lund, Sweden.

Part One INTRODUCTION 1. Drug Development of Inhaled Steroids: A Pharmacologist's View Based on Experiences from the Budesonide Project Part Two USE OF INHALED STEROIDS 2. How Inhaled Corticosteroids Changed Asthma Therapy 3. Side Effects of Inhaled Corticosteroids Part Three MOLECULAR ASPECTS OF STEROID ACTION 4. Mechanisms of Gene Regulation by the Glucocorticoid Receptor Discussion 5. Relationship of Dose- and Time-Dependent Corticosteroid Responses to Receptor Turnover 6. Blockade of Chemokine Production/Function as an Example of Glucocorticoid Anti-inflammatory Actions 7. Newly Recognized Glucocorticoid Targets Part Four DETERMINANTS OF AIRWAY-LUNG SELECTIVITY 8. Aerosol Delivery Devices and Airways/Lung Deposition 9. Uptake, Retention, and Biotransformation of Corticosteroids in the Lung and Airways 10. Systemic Disposition and Effects of Inhaled Corticosteroids 11. Extrapulmonary Effects of Inhaled Corticosteroids 12. Factors Involved in the Pulmonary Targeting of Inhaled Glucocorticoids: The Use of Pharmacokinetic 13. Reversible Glucocorticoid Esterification Part Five AIRWAY-LUNG SELECTIVITY OF CURRENT INHALED STEROIDS 14. Airway Selectivity of Current Inhaled Corticosteroids in Properly Designed Studies 15. Childhood Asthma and Growth 16. Evaluation and Comparison of Inhaled Steroids Part Six IN VIVO RESEARCH ON AIRWAY-LUNG SELECTIVITY17. The Role of Direct Assessment of Airway Inflammation in Evaluating Inhaled Glucocorticosteroid Efficacy 18. Use of Exhaled Nitric Oxide as Readout for Inhaled Corticosteroid Efficacy 19. Markers of Systemic Actions of Corticosteroids 20. Patient Adherence to Inhaled Corticosteroid Therapy Part Seven FUTURE CHALLENGES 21. Prospects for Developing Inhaled Steroids with Extrahepatic Metabolism: "Soft Steroids" 22. Design and Development of a Soft Corticosteroid, Loteprednol Etabonate 23. Development of Inhaled Steroids Based Upon Prodrugs with Prolonged Intraluminal Retention Time 24. Transcription Factors AP-1 and NF-B as Targets for Development of Anti-inflammatory Drugs 25. Remodeling and the Effects of Steroids in Asthma 26. Inhaled Corticosteroids and the Natural History of Asthma 27. Combination Therapies Using Inhaled Corticosteroids