Inhaled Steroids in Asthma

INTRODUCTON Drug Development of Inhaled Steroids: A Pharmacologist's View Based on Experiences from the Budesonide Project Ralph Brattsand Part Two USE OF INHALED STEROIDS How Inhaled Corticosteroids Changed Asthma Therapy William W. Busse Side Effects of Inhaled Corticosteroids Paul M. O'Byrne and Dilini Vethanayagam Part Three MOLECULAR ASPECTS OF STEROID ACTION Mechanisms of Gene Regulation by the Glucocorticoid Receptor Gary B. Faulds, Nanthakumar Subramaniam, Johan Lidén, and Sam Okret Relationship of Dose- and Time-Dependent Corticosteroid Responses to Receptor Turnover William J. Jusko Blockade of Chemokine Production/Function as an Example of Glucocorticoid Anti-inflammatory Actions Cristiana Stellato Newly Recognized Glucocorticoid Targets Nicola M. Heller and Robert P. Schleimer Part Four DETERMINANT S OF AIRWAY-LUNG SELECTIVITY Aerosol Delivery Devices and Airways/Lung Deposition Myrna B. Dolovich Uptake, Retention, and Biotransformation of Corticosteroids in the Lung and Airways Staffan Edsbäcker Systemic Disposition and Effects of Inhaled Corticosteroids Hartmut Derendorf, Sriram Krishnaswami, Gunther Hochhaus, and Helmut Möllmann Extrapulmonary Effects of Inhaled Corticosteroids Judah A. Denburg, Mark D. Inman, Roma Sehmi, Lorna J. Wood, Gail M. Gauvreau, and Paul M. O'Byrne Factors Involved in the Pulmonary Targeting of Inhaled Glucocorticoids: The Use of Pharmacokinetic/Dynamic Simulations Gunther Hochhaus, Hartmut Derendorf, Helmut Möllmann, and James Talton Reversible Glucocorticoid Esterification Magnus Jendbro and Carl-Johan Johansson Part Five AIRWAY-LUNG SELECTIVITY OF CURRENT INHALED STEROIDS Airway Selectivity of Current Inhaled Corticosteroids in Properly Designed Studies J. Paul Seale and Paul M. O'Byrne Childhood Asthma and Growth Søren Pedersen Evaluation and Comparison of Inhaled Steroids Stanley J. Szefler and Richard J. Martin Part Six IN VIVO RESEARCH ON AIRWAY-LUNG SELECTIVITY The Role of Direct Assessment of Airway Inflammation in Evaluating Inhaled Glucocorticosteroid Efficacy and in Managing the Asthmatic Patient Mark D. Inman Use of Exhaled Nitric Oxide as Readout for Inhaled Corticosteroid Efficacy Sergei A. Kharitonov and Peter J. Barnes Markers of Systemic Actions of Corticosteroids Louis-Philippe Boulet Patient Adherence to Inhaled Corticosteroid Therapy Cynthia S. Rand and Kathleen Weeks Schiller Part Seven FUTURE CHALLENGES Drug Development Prospects for Developing Inhaled Steroids with Extrahepatic Metabolism: Soft Steroids Arne Thalén, Paul H. Andersson, Per T. Andersson, Bengt Axelsson, Staffan Edsbäcker, and Ralph Brattsand Design and Development of a Soft Corticosteroid, Loteprednol Etabonate Nicholas Bodor and Peter Buchwald Development of Inhaled Steroids Based Upon Prodrugs with Prolonged Intraluminal Retention Time Bengt Axelsson, Per Bäckman, Per Strandberg, and Ralph Brattsand Transcription Factors AP-1 and NF-kB as Targets for Development of Anti-inflammatory Drugs Michael Karin Medical Documentation Remodeling and the Effects of Steroids in Asthma Peter K. Jeffery Inhaled Corticosteroids and the Natural History of Asthma Fernando D. Martinez Combination Therapies Using Inhaled Corticosteroids Romain A. Pauwels and Olof Selroos Author Index Subject Index 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 pharmacology, impact of new simulation models, newly recognized molecular targets, and therapeutic outcomes of short- and long-term steroid inhalation therapy! Containing more than 1600 works cited, drawings, tables, equations, and micrographs, Inhaled Steroids in Asthma describes the developmental history of inhaled steroids and provides general models for lung selectivity considers the best way to select inhaled steroids clarifies local metabolism, airway and lung uptake and retention, and other determinants of once-daily usage addresses variations in lung deposition and total bioavailability among available steroids and formulations surveys the dynamics of receptor gene-mediated processes analyzes the role of chemokines in airway allergic inflammatory diseases discusses the effects of inhaled steroids in vivo on cell progenitors in asthma and rhinitis details measuring airway inflammation as a guide for treatment decisions outlines the clinical relevancy of exhaled nitric oxide in asthma covers optimal trial design for judging antiasthmatic potency and efficacy evaluates the safety of inhaled steroids Written by more than 40 of the world's leading authorities and investigators, Inhaled Steroids in Asthma is an authoritative reference for pulmonologists and pulmonary disease specialists; physiologists; allergists; immunologists; molecular, cell, and lung biologists; pediatricians; pharmaceutical scientists and pharmacologists; and medical school and upper-level undergraduate, graduate, and medical school students in these disciplines.