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.

• INTRODUCTONDrug Development of Inhaled Steroids: A Pharmacologist's View Based on Experiences from the Budesonide ProjectRalph BrattsandPart Two USE OF INHALED STEROIDSHow Inhaled Corticosteroids Changed Asthma TherapyWilliam W. BusseSide Effects of Inhaled CorticosteroidsPaul M. O'Byrne and Dilini VethanayagamPart Three MOLECULAR ASPECTS OF STEROID ACTIONMechanisms of Gene Regulation by the Glucocorticoid ReceptorGary B. Faulds, Nanthakumar Subramaniam, Johan Lidén, and Sam OkretRelationship of Dose- and Time-Dependent Corticosteroid Responses to Receptor TurnoverWilliam J. JuskoBlockade of Chemokine Production/Function as an Example of Glucocorticoid Anti-inflammatory ActionsCristiana StellatoNewly Recognized Glucocorticoid TargetsNicola M. Heller and Robert P. SchleimerPart Four DETERMINANT S OF AIRWAY-LUNG SELECTIVITYAerosol Delivery Devices and Airways/Lung DepositionMyrna B. DolovichUptake, Retention, and Biotransformation of Corticosteroids in the Lung and AirwaysStaffan EdsbäckerSystemic Disposition and Effects of Inhaled CorticosteroidsHartmut Derendorf, Sriram Krishnaswami, Gunther Hochhaus, and Helmut MöllmannExtrapulmonary Effects of Inhaled CorticosteroidsJudah A. Denburg, Mark D. Inman, Roma Sehmi, Lorna J. Wood, Gail M. Gauvreau, and Paul M. O'ByrneFactors Involved in the Pulmonary Targeting of Inhaled Glucocorticoids: The Use of Pharmacokinetic/Dynamic SimulationsGunther Hochhaus, Hartmut Derendorf, Helmut Möllmann, and James TaltonReversible Glucocorticoid EsterificationMagnus Jendbro and Carl-Johan JohanssonPart Five AIRWAY-LUNG SELECTIVITY OF CURRENT INHALED STEROIDSAirway Selectivity of Current Inhaled Corticosteroids in Properly Designed StudiesJ. Paul Seale and Paul M. O'ByrneChildhood Asthma and GrowthSøren PedersenEvaluation and Comparison of Inhaled SteroidsStanley J. Szefler and Richard J. MartinPart Six IN VIVO RESEARCH ON AIRWAY-LUNG SELECTIVITYThe Role of Direct Assessment of Airway Inflammation in Evaluating Inhaled Glucocorticosteroid Efficacy and in Managing the Asthmatic PatientMark D. InmanUse of Exhaled Nitric Oxide as Readout for Inhaled Corticosteroid EfficacySergei A. Kharitonov and Peter J. BarnesMarkers of Systemic Actions of CorticosteroidsLouis-Philippe BouletPatient Adherence to Inhaled Corticosteroid TherapyCynthia S. Rand and Kathleen Weeks SchillerPart Seven FUTURE CHALLENGESDrug 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 BrattsandDesign and Development of a Soft Corticosteroid, Loteprednol EtabonateNicholas Bodor and Peter Buchwald Development of Inhaled Steroids Based Upon Prodrugs with Prolonged Intraluminal Retention TimeBengt Axelsson, Per Bäckman, Per Strandberg, and Ralph BrattsandTranscription Factors AP-1 and NF-kB as Targets for Development of Anti-inflammatory DrugsMichael KarinMedical Documentation Remodeling and the Effects of Steroids in AsthmaPeter K. JefferyInhaled Corticosteroids and the Natural History of Asthma Fernando D. MartinezCombination Therapies Using Inhaled CorticosteroidsRomain A. Pauwels and Olof SelroosAuthor IndexSubject IndexThis 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 Asthmadescribes 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.