Inhaled steroids in asthma: optimizing effects in the airways
Saved in:
| Format: | Book |
|---|---|
| Language: | English |
| Published: |
New York [u.a.]
Dekker
2002
|
| Series: | Lung biology in health and disease
163 |
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XXII, 713 S. Ill., graph. Darst. |
| ISBN: | 0824705858 |
Staff View
MARC
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Record in the Search Index
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| adam_text | CONTENTS
Introduction Claude Lenfant Hi
Preface v
Contributors vii
Part One INTRODUCTION
1. Drug Development of Inhaled Steroids: A Pharmacologist s
View Based on Experiences from the Budesonide Project 3
Ralph Brattsand
I. Introduction 3
II. Skin Steroids: The Forerunners of IS 4
III. Early Failures and Successes of IS Therapy 5
IV. The Budesonide Project 8
V. The Difficulty of Forecasting a Market Potential 16
VI. Budesonide as a Tool for Elucidating Mechanisms Behind
Airways/Lung Selectivity of IS: Personal Views 17
xiii
V(v Contents
VII. Remaining Pharmacological Questions About IS Efficacy
and Selectivity 23
VIII. Comments on the Animal Models Used in the
Preclinical Selection and Documentation of BUD 23
References 27
Discussion 33
Part Two USE OF INHALED STEROIDS
2. How Inhaled Corticosteroids Changed Asthma Therapy 37
William W. Busse
I. Introduction 37
II. Early Trials with Inhaled Corticosteroids 38
III. The Benefits of Inhaled Corticosteroids
for Asthma Complications 41
IV. Benefit of the Addition of Inhaled Corticosteroids 43
V. Inhaled Corticosteroids as Research Tools
for Mechanisms of Asthma 43
VI. Summary 46
References 46
Discussion 48
3. Side Effects of Inhaled Corticosteroids 49
Paul M. O Byrne and Dilini Vethanayagam
I. Introduction 49
II. Inhaled Corticosteroid Preparations 50
III. Side Effects of Corticosteroids 50
IV. Conclusions 57
References 58
Discussion 61
Part Three MOLECULAR ASPECTS OF STEROID ACTION
4. Mechanisms of Gene Regulation by the Glucocorticoid Receptor 67
Gary B. Faulds, Nanthakumar Subramaniam, Johan Liden,
and Sam Okret
I. Introduction 67
II. The Nuclear Receptor Superfamily 68
III. The Glucocorticoid Receptor 69
IV. Gene Regulation by Glucocorticoid Receptor 72
Contents ^
V. Glucocorticoid Receptor and Inflammation 80
VI. Summary g2
References 83
Discussion 92
5. Relationship of Dose and Time Dependent
Corticosteroid Responses to Receptor Turnover 95
William J. Jusko
I. Introduction 95
II. Dynamics of Rapid Steroid Effects 96
III. Role of Administration Rate 97
IV. Liposomal Methylprednisolone 97
V. Drug Interactions 99
VI. Dynamics of Receptor Gene Mediated Processes 101
VII. Pharmacodynamic Studies 104
VIII. Dosage Regimen Simulations 106
References 109
Discussion 112
6. Blockade of Chemokine Production/Function as an Example
of Glucocorticoid Anti inflammatory Actions 113
Cristiana Stellato
I. Overview of the Chemokine/Chemokine
Receptor Superfamilies 113
II. The Role of Chemokines in Airway Allergic
Inflammatory Diseases 117
III. Chemokine Expression as a Target
of Glucocorticoid Action 121
IV. Concluding Remarks 126
References 126
Discussion 134
7. Newly Recognized Glucocorticoid Targets 137
Nicola M. Heller and Robert P. Schleimer
I. Introduction 137
II. Glucocorticoids and Regulation of Gene Expression 138
III. Regulation of Immune and Inflammatory
Responses by Glucocorticoids 144
IV. Effects of Glucocorticoids on Fluid Dynamics in the
Airways 147
V. Glucocorticoid Effects on Bone 150
xvi Contents
VI. Somatostatin 150
VII. Miscellaneous Targets 151
VIII. Conclusions 151
References 152
Discussion 165
Part Four DETERMINANTS OF AIRWAY LUNG
SELECTIVITY
8. Aerosol Delivery Devices and Airways/Lung Deposition 169
Myrna B. Dolovich
I. Introduction 169
II. Aerosol Delivery Systems 170
III. Characterization of an Aerosol Dose from a
Delivery System 178
IV. Effect of Particle Size and Inspiratory Flow Rate
on the Emitted Dose 191
V. Measuring Aerosol Lung Dose and Distribution 192
VI. Considerations for Future Investigations 195
References 200
Discussion 211
9. Uptake, Retention, and Biotransformation of Corticosteroids
in the Lung and Airways 213
Staffan Edsbdcker
I. Introduction 213
II. Site of Deposition 214
III. Rate of Dissolution and Absorption 215
IV. Mucociliary Clearance 216
V. Airway and Lung Uptake and Retention 219
VI. Corticosteroid Esterification 222
VII. Biotransformation of CSs, Other Than
Esterification, in Airways and Lung 227
VIII. Kinetics of Receptor Binding and Cellular Response 229
IX. Clinical Implications 232
X. Some Unanswered Questions 235
XI. Conclusion 236
References 236
Discussion 245
Contents xva
10. Systemic Disposition and Effects of Inhaled Corticosteroids 247
Hartmut Derendorf, Sriram Krishnaswami,
Gunther Hochhaus, and Helmut Mollmann
I. Introduction 247
II. PK/PD Properties of Inhaled Corticosteroids 248
III. PK/PD Modeling of Cortisol Suppression 256
IV. Conclusions 265
References 266
Discussion 271
11. Extrapulmonary Effects of Inhaled Corticosteroids 273
Judah A. Denburg, Mark D. Inman, Roma Sehmi,
Lorna J. Wood, Gail M. Gauvreau, and Paul M. O Byrne
I. Introduction 273
II. Evidence for a Systemic Allergic Airways
Inflammatory Disease 274
III. Effects of IS In Vivo on Progenitors in Asthma
and Rhinitis 274
IV. The Effects of IS In Vitro and Ex Vivo on
Hemopoietic Responses 277
V. Mechanisms of IS Effects on Hemopoietic Processes 278
References 279
Discussion 282
12. Factors Involved in the Pulmonary Targeting of Inhaled
Glucocorticoids: The Use of Pharmacokinetic/
Dynamic Simulations 283
Gunther Hochhaus, Hartmut Derendorf,
Helmut Mollmann, and James Talton
I. Introduction 283
II. Assessment of Pulmonary Selectivity 284
III. Conclusion 301
References 301
Discussion 306
13. Reversible Glucocorticoid Esterification 309
Magnus Jendbro and Carl Johan Johansson
I. Introduction 309
II. General Models for Lung Selectivity 310
xviii Contents
III. Pharmacokinetic Modeling of BUD in the Rat 318
IV. Concluding Remarks 326
References 327
Discussion 329
Part Five AIRWAY LUNG SELECTIVITY OF CURRENT
INHALED STEROIDS
14. Airway Selectivity of Current Inhaled Corticosteroids
in Properly Designed Studies 333
J. Paul Seale and Paul M. O Byrne
I. Methodology of Well Designed Clinical Studies 333
II. Do Studies in Normal Subjects Accurately Predict
Drug Behavior in Asthmatic Patients? 336
III. Variability in Systemic Bioavailability Between Subjects 340
IV. Comparative Clinical Studies 341
V. Systemic Unwanted Effects 342
VI. Summary 344
References 345
Discussion 349
15. Childhood Asthma and Growth 353
S0ren Pedersen
I. Introduction 353
II. Definitions and Study Designs 354
III. Growth 359
IV. Summary 377
References 377
Discussion 386
16. Evaluation and Comparison of Inhaled Steroids 389
Stanley J. Szefler and Richard J. Martin
I. Introduction 389
II. Why Compare Inhaled Steroids? 391
III. Where Are We Now? 400
IV. What Would We Like to Know in Order to
Advance Inhaled Glucocorticoid Therapy? 402
V. How Do We Get the Necessary Information? 402
VI. The Approach of the National Heart, Lung and
Blood Institute s Asthma Clinical Research Network 402
Contents xjx
VII. What Is the Best Way to Select Inhaled Glucocorticoids? 410
VIII. Prospectus 412
References 413
Discussion 417
Part Six IN VIVO RESEARCH ON AIRWAY LUNG
SELECTIVITY
17. The Role of Direct Assessment of Airway Inflammation
in Evaluating Inhaled Glucocorticosteroid Efficacy
and in Managing the Asthmatic Patient 421
Mark D. Inman
I. Introduction 421
II. Direct Measurement of Airway Inflammation to
Assess the Efficacy of Inhaled Glucocorticosteroids 422
III. Measurement of Airway Inflammation as a Guide for
Treatment Decisions 427
IV. Summary 432
References 433
Discussion 436
18. Use of Exhaled Nitric Oxide as Readout for Inhaled
Corticosteroid Efficacy 441
Sergei A. Kharitonov and Peter J. Barnes
I. Introduction 441
II. General Principles of Exhaled Nitric Oxide Measurements 442
III. Origin of Nitric Oxide in Exhaled Air 443
IV. Clinical Relevances of Exhaled Nitric Oxide in Asthma 444
V. Future Directions 454
References 455
Discussion 461
19. Markers of Systemic Actions of Corticosteroids 465
Louis Philippe Boulet
I. Introduction 465
II. Pharmacokinetics of Glucocorticosteroids 467
III. Markers of Systemic Effects 468
IV. Which Is the Best Marker of Systemic Effects of ICS? 479
V. Comparison of Systemic Effects of Different ICS:
Some Methodological Aspects 480
xx Contents
VI. Clinical Significance of Changes in Markers
of Systemic Effects 481
VII. How to Reduce Systemic Effects 481
VIII. Conclusion 482
References 483
Discussion 489
20. Patient Adherence to Inhaled Corticosteroid Therapy 491
Cynthia S. Rand and Kathleen Weeks Schiller
I. Inhaled Steroid Adherence and Asthma Morbidity 492
II. Rates of Adherence with ICS and/or Other
Preventive Asthma Drugs 493
III. Forms of Nonadherence 497
IV. Factors Associated with ICS/Other Adherence 499
V. Adherence Issues in Special Populations 504
VI. Intervention Strategies to Improve Patient
Adherence to ICS Therapy 507
VII. Summary and Recommendations 510
References 510
Discussion 515
Part Seven FUTURE CHALLENGES
Drug Development
21. Prospects for Developing Inhaled Steroids with Extrahepatic
Metabolism: Soft Steroids 521
Arne Thalen, Paul H. Andersson, Per T. Andersson,
Bengt Axelsson, Staffan Edsbdcker, and Ralph Brattsand
I. Introduction 521
II. Astra Soft Steroid Project 525
III. GlaxoWellcome Soft Steroid Project 532
IV Current Status of Soft Steroids 533
References 534
Discussion 538
22. Design and Development of a Soft Corticosteroid,
Loteprednol Etabonate 541
Nicholas Bodor and Peter Buchwald
I. Introduction 541
II. Soft Drugs 543
Contents xxj
III. Loteprednol Etabonate 545
IV. Effect of Loteprednol Etabonate on Airway Activity 552
V. Conclusions 558
References 558
23. Development of Inhaled Steroids Based Upon Prodrugs
with Prolonged Intraluminal Retention Time 565
Bengt Axelsson, Per Backman, Per Strandberg,
and Ralph Brattsand
I. Introduction 565
II. Aim of Astra Project 566
III. Lipid Formulation for Attaining Bioavailability of D5522 567
IV. Pharmacological Testing 568
V. Deposition, Luminal Spreading, and Uptake
Mechanisms of D5522L 570
VI. Conclusion and Prospects 575
References 575
24. Transcription Factors AP 1 and NF kB as Targets
for Development of Anti inflammatory Drugs 577
Michael Karin
I. Introduction 577
II. Mechanisms of AP 1 and NF kB Activation 578
III. Involvement of AP 1 and NF kB in Inflammatory Responses 580
IV. Physiological Inhibitors of Inflammation, AP 1 and NF kB 581
V. Development of AP 1 and NF kB Inhibitors 583
References 585
Discussion 589
Medical Documentation
25. Remodeling and the Effects of Steroids in Asthma 593
Peter K. Jeffery
I. Introduction 593
II. Surface Epithelium 597
III. Reticular Basement Membrane 601
IV. Interstitial Collagen and Elastic Tissue 605
V. Airway Vessels 606
VI. Bronchial Smooth Muscle 607
VII. Airway Wall Nerves 611
VIII. Remodeling and Airflow Limitation 611
xxii Contents
IX. Summary and Conclusion 612
References 612
Discussion 619
26. Inhaled Corticosteroids and the Natural History of Asthma 623
Fernando D. Martinez
I. Asthma and Airway Inflammation 623
II. Challenging the Inflammatory Theory of Asthma 625
III. Natural History of Asthma Symptoms During
Childhood and Early Adult Life 626
IV. A Developmental Approach to Asthma Treatment 629
V. Recognizing Early Asthma 630
References 631
27. Combination Therapies Using Inhaled Corticosteroids 635
Romain A. Pauwels and OlofSelroos
I. Introduction 635
II. Inhaled Corticosteroids Plus Long Acting
Inhaled (5: Agonists 637
III. Inhaled Corticosteroids Plus Theophylline 640
IV. Inhaled Corticosteroids Plus Leukotriene
Receptor Antagonists 640
V. Trials Comparing Combination Treatments 642
VI. Conclusions 643
References 644
Discussion 647
Author Index 649
Subject Index 705
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| series | Lung biology in health and disease |
| series2 | Lung biology in health and disease |
| spelling | Inhaled steroids in asthma optimizing effects in the airways ed. by Robert P. Schleimer ... New York [u.a.] Dekker 2002 XXII, 713 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Lung biology in health and disease 163 Asthme - Chimiothérapie Asthme - Chimiothérapie ram Glucocorticoïdes - Emploi en thérapeutique Glucocorticoïdes - Emploi en thérapeutique ram Traitement respiratoire Asthma Chemotherapy Asthma drug therapy Glucocorticoids Therapeutic use Glucocorticoids therapeutic use Respiratory Therapy methods Steroide (DE-588)4057379-5 gnd rswk-swf Inhalationstherapie (DE-588)4161728-9 gnd rswk-swf Corticosteroide (DE-588)4070120-7 gnd rswk-swf Aerosoltherapie (DE-588)4211529-2 gnd rswk-swf Bronchialasthma (DE-588)4069674-1 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Bronchialasthma (DE-588)4069674-1 s Steroide (DE-588)4057379-5 s Inhalationstherapie (DE-588)4161728-9 s DE-604 Corticosteroide (DE-588)4070120-7 s Aerosoltherapie (DE-588)4211529-2 s Schleimer, Robert P. Sonstige oth Lung biology in health and disease 163 (DE-604)BV000008326 163 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009714047&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Inhaled steroids in asthma optimizing effects in the airways Lung biology in health and disease Asthme - Chimiothérapie Asthme - Chimiothérapie ram Glucocorticoïdes - Emploi en thérapeutique Glucocorticoïdes - Emploi en thérapeutique ram Traitement respiratoire Asthma Chemotherapy Asthma drug therapy Glucocorticoids Therapeutic use Glucocorticoids therapeutic use Respiratory Therapy methods Steroide (DE-588)4057379-5 gnd Inhalationstherapie (DE-588)4161728-9 gnd Corticosteroide (DE-588)4070120-7 gnd Aerosoltherapie (DE-588)4211529-2 gnd Bronchialasthma (DE-588)4069674-1 gnd |
| subject_GND | (DE-588)4057379-5 (DE-588)4161728-9 (DE-588)4070120-7 (DE-588)4211529-2 (DE-588)4069674-1 (DE-588)4143413-4 |
| title | Inhaled steroids in asthma optimizing effects in the airways |
| title_auth | Inhaled steroids in asthma optimizing effects in the airways |
| title_exact_search | Inhaled steroids in asthma optimizing effects in the airways |
| title_full | Inhaled steroids in asthma optimizing effects in the airways ed. by Robert P. Schleimer ... |
| title_fullStr | Inhaled steroids in asthma optimizing effects in the airways ed. by Robert P. Schleimer ... |
| title_full_unstemmed | Inhaled steroids in asthma optimizing effects in the airways ed. by Robert P. Schleimer ... |
| title_short | Inhaled steroids in asthma |
| title_sort | inhaled steroids in asthma optimizing effects in the airways |
| title_sub | optimizing effects in the airways |
| topic | Asthme - Chimiothérapie Asthme - Chimiothérapie ram Glucocorticoïdes - Emploi en thérapeutique Glucocorticoïdes - Emploi en thérapeutique ram Traitement respiratoire Asthma Chemotherapy Asthma drug therapy Glucocorticoids Therapeutic use Glucocorticoids therapeutic use Respiratory Therapy methods Steroide (DE-588)4057379-5 gnd Inhalationstherapie (DE-588)4161728-9 gnd Corticosteroide (DE-588)4070120-7 gnd Aerosoltherapie (DE-588)4211529-2 gnd Bronchialasthma (DE-588)4069674-1 gnd |
| topic_facet | Asthme - Chimiothérapie Glucocorticoïdes - Emploi en thérapeutique Traitement respiratoire Asthma Chemotherapy Asthma drug therapy Glucocorticoids Therapeutic use Glucocorticoids therapeutic use Respiratory Therapy methods Steroide Inhalationstherapie Corticosteroide Aerosoltherapie Bronchialasthma Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009714047&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV000008326 |
| work_keys_str_mv | AT schleimerrobertp inhaledsteroidsinasthmaoptimizingeffectsintheairways |