Inhaled Steroids in Asthma

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.

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.