喘息・COPDのための多剤併用療法の進歩<br>Advances in Combination Therapy for Asthma and COPD

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喘息・COPDのための多剤併用療法の進歩
Advances in Combination Therapy for Asthma and COPD

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  • 製本 Hardcover:ハードカバー版/ページ数 350 p.
  • 言語 ENG
  • 商品コード 9780470727027
  • DDC分類 616.23061

Full Description


Aimed at specialists in respiratory medicine, this new book comprehensively reviews the variety of agents currently available for treatment of asthma, COPD, and other airway diseases and covers practical guidelines as well as challenges and complications in their use. Advances in Combination Therapy for Asthma and COPD is the first book to address the complexity of multi-agent therapy and deal with management issues in an integrated fashion. A review of currently available agents and their applications, as well as new therapies soon to become available are outlined. Advantages of combined therapies and additional considerations that arise from multi-agent programs are highlighted.

Table of Contents

Contributors                                       xi
Preface xiii
1 Similarities and differences in the 1 (15)
pathophysiology of asthma and COPD
J. Christian Virchow
1.1 Introduction 1 (2)
1.2 Pulmonary function abnormalities in 3 (2)
asthma and COPD
1.3 Risk factors for asthma and COPD 5 (3)
1.4 Cellular inflammation in asthma and COPD 8 (1)
1.5 Distribution and consequences of 9 (1)
inflammation in asthma and COPD
1.6 Patterns of epithelial injury in asthma 10 (1)
and COPD
1.7 Airway hyperresponsiveness 10 (1)
1.8 Beta-receptor blockers 10 (1)
1.9 Differential diagnosis of asthma and 11 (1)
COPD
1.10 Overlap syndrome 12 (1)
1.11 Conclusion 12 (1)
References 13 (3)
2 Glucocorticoids: pharmacology and mechanisms 16 (22)
Peter J. Barnes
2.1 Introduction 16 (1)
2.2 Chemical structures 16 (1)
2.3 The molecular basis of inflammation 17 (2)
2.4 Cellular effects of glucocorticoids 19 (1)
2.5 Glucocorticoid receptors 20 (2)
2.6 Glucocorticoid activation of gene 22 (1)
transcription
2.7 Suppression of inflammatory genes 23 (6)
2.8 Steroid resistance 29 (3)
2.9 Interaction with β2-adrenergic 32 (1)
receptors
2.10 Conclusions 33 (1)
References 33 (5)
3 Inhaled corticosteroids: clinical effects in 38 (15)
asthma and COPD
Paul M. O'Byrne
Desmond M. Murphy
3.1 Introduction 38 (1)
3.2 Anti-inflammatory activity of 38 (1)
corticosteroids
3.3 Routes of administration 39 (2)
3.4 Absorption and fate of corticosteroids 41 (1)
3.5 Currently available inhaled 41 (2)
corticosteroids
3.6 Efficacy in asthma 43 (1)
3.7 Efficacy in COPD 44 (2)
3.8 Side effects of ICS 46 (3)
3.9 Conclusions 49 (1)
References 49 (4)
4 LABAs: pharmacology, mechanisms and 53 (28)
interaction with anti-inflammatory treatments
Gary P. Anderson
4.1 Galenical forms of LABAs: formulations, 55 (1)
isomers, enantiomers, diasteriomers and
salts
4.2 Absolute and functional 56 (2)
β2-adrenoceptor selectivity
4.3 Cellular organization of receptor 58 (2)
clusters: functional structure of the
β2-adrenoceptor and mode of signalling
4.4 Dimers and oligomers: homo- and 60 (1)
heterodimerism/oligoism
4.5 Pharmacogenomics of the 61 (1)
β2-adrenoceptor and adenylate cyclase
polymorphism in relation to LABAs
4.6 Understanding the 'reassertion' 61 (2)
paradox, 'exosites' and relative speed of
onset: the membrane diffusion microkinetic
model of LABA action
4.7 Regulation and desensitization 63 (1)
4.8 Full versus partial agonism 64 (3)
(pharmacological efficacy)
4.9 Beta-blockers not LABAs? 67 (1)
4.10 Non-receptor-mediated effects? 68 (1)
4.11 Biochemical basis of functional 68 (1)
antagonism and its critical role in LABA
action in disease and exacerbations
4.12 Molecular cooperativity between LABAs 69 (4)
and steroids
4.13 Perspective 73 (1)
References 73 (8)
5 Long- and ultra-long-acting β2-agonists 81 (21)
Mario Cazzola
Maria Gabriella Matera
5.1 Introduction 81 (1)
5.2 Long-acting β2-agonists 82 (4)
5.3 Novel ultra-long-acting β2-agonists 86 (9)
5.4 Conclusion 95 (1)
References 95 (7)
6 The safety of long-acting beta-agonists and 102 (33)
the development of combination therapies for
asthma and COPD
Victor E. Ortega
Eugene R. Bleecker
6.1 Introduction 102 (1)
6.2 Asthma-related mortality and 103 (2)
beta-agonist exposure
6.3 Long-acting beta-agonists and increased 105 (2)
asthma-related mortality
6.4 Safety and efficacy of LABA therapy in 107 (3)
asthma: retrospective analyses
6.5 Efficacy of LABA therapy as a component 110 (3)
of combination therapy with ICS for the
management of asthma
6.6 Scientific basis of the beneficial and 113 (1)
adverse effects of beta-agonist therapy: in
vitro data and the beta-agonist paradox
6.7 Conclusions regarding the safety of 114 (1)
LABA therapy as a component of combination
therapy with ICS for the management of
asthma
6.8 Beta-agonist therapy and adverse events 115 (1)
in COPD
6.9 Safety and efficacy of LABA therapy in 116 (1)
the management of COPD: the clinical
evidence
6.10 Role of LABA therapy as a component of 117 (3)
combination therapy with ICS for the
management of COPD
6.11 Conclusions regarding the safety of 120 (1)
LABA therapy as a component of combination
therapy for the management of COPD
6.12 Pharmacogenetics of LABAs and 120 (6)
combination therapy
6.13 Safety and efficacy of LABA therapy 126 (1)
and the development of combination
therapies for the management of asthma and
COPD
6.14 Summary and future directions 127 (1)
Acknowledgement 128 (1)
References 128 (7)
7 Inhaled combination therapy with 135 (19)
glucocorticoids and long-acting
β2-agonists in asthma and COPD, current
and future perspectives
Jan L vall
7.1 Pharmacological management guidelines 135 (1)
of asthma and COPD
7.2 Steroid treatment in asthma 136 (1)
7.3 Effects of adding LABA to inhaled 137 (3)
glucocorticoids in asthma
7.4 Steroid treatment in COPD 140 (1)
7.5 Effects of LABAs in COPD 140 (1)
7.6 Combination inhalers versus two 141 (2)
separate inhalers for inhaled GCS and LABAs
7.7 Regular treatment alone versus 143 (2)
additional formoterol-containing
combinations as reliever therapy
7.8 Currently available combination inhalers 145 (1)
7.9 Upcoming and alternative combinations 146 (2)
of inhaled GCS and LABAs
7.10 Future of combined inhalation therapy 148 (1)
in respiratory disease
References 149 (5)
8 Novel anti-inflammatory treatments for asthma 154 (49)
and COPD
Paul A. Kirkham
Gaetano Caramori
K. Fan Chung
Ian M. Adcock
8.1 Introduction 154 (4)
8.2 Current asthma and COPD therapies 158 (2)
8.3 The need for new therapies 160 (2)
8.4 Improving current therapies 162 (4)
8.5 Targeting chemokines and their 166 (3)
receptors in asthma and COPD
8.6 Targeting T-cell-derived and 169 (3)
proinflammatory cytokines in asthma and COPD
8.7 Targeting adhesion molecules in asthma 172 (1)
and COPD
8.8 Growth factor blockers in asthma and 173 (1)
COPD
8.9 Mucous cells, submucosal glands and 173 (1)
mucus production in asthma and COPD
8.10 Infections in asthma and COPD 174 (1)
8.11 Intracellular signalling pathways 175 (3)
8.12 Inhibition of transcription factors in 178 (3)
asthma and COPD
8.13 Antioxidants in asthma and COPD 181 (1)
8.14 Immunomodulation and anti-allergy 182 (3)
treatments in asthma and COPD
8.15 Conclusions 185 (1)
Acknowledgements 186 (1)
References 186 (17)
9 Novel biologicals alone and in combination in 203 (29)
asthma and allergy
Sharmilee M. Nyenhuis
William W. Busse
9.1 Introduction 203 (1)
9.2 Targets of therapy 204 (1)
9.3 Interleukin-4 204 (3)
9.4 Interleukin-5 207 (4)
9.5 Interleukin-13 211 (1)
9.6 Tumor necrosis factor-α 212 (3)
9.7 Immunoglobulin E 215 (5)
9.8 DNA vaccines 220 (2)
9.9 Future directions 222 (2)
9.10 Conclusion 224 (1)
References 225 (7)
10 Anti-infective treatments in asthma and COPD 232 (36)
Jonathan D.R. Macintyre
Sebastian L. Johnston
10.1 Introduction 232 (2)
10.2 Current guidelines 234 (2)
10.3 Acute exacerbations of asthma 236 (1)
10.4 Increased susceptibility to infection 236 (1)
in asthmatics
10.5 Role of atypical bacteria in asthma 237 (7)
10.6 Role of viruses in asthma exacerbations 244 (6)
10.7 Anti-infectives in COPD exacerbations 250 (6)
10.8 Use of antibiotics in stable COPD 256 (1)
10.9 Role of vaccination 257 (2)
10.10 Conclusion 259 (1)
References 260 (8)
11 Long-acting muscarinic antagonists in asthma 268 (28)
and COPD
M. Diane Lougheed
Josuel Ora
Denis E. O'Donnell
11.1 Introduction 268 (1)
11.2 Innervation of the airways 268 (2)
11.3 Cholinergic mechanisms in asthma and 270 (1)
COPD
11.4 Role of long-acting anticholinergic 271 (16)
bronchodilators in obstructive lung disease
11.5 Summary 287 (1)
References 288 (8)
12 Phosphodiesterase inhibitors in obstructive 296 (15)
lung disease
Jan L vall
Bo Lundb臘k
12.1 Introduction 296 (1)
12.2 Phosphodiesterase enzymes 297 (1)
12.3 Different pharmacological agents 298 (2)
blocking PDE4
12.4 Biological effects of PDE4 inhibition, 300 (2)
preclinical information
12.5 Clinical effects of PDE4 inhibition in 302 (2)
COPD
12.6 Effects of PDE4 inhibitors on systemic 304 (1)
processes in COPD
12.7 Side effects of PDE4 inhibitors 304 (1)
12.8 PDE4 inhibitors in COPD management 305 (1)
plans
12.9 Future prospects with PDE4 inhibitors 305 (1)
in obstructive airways disease
12.10 Summary 306 (1)
References 306 (5)
13 Biological therapies in development for COPD 311 (22)
J. Morjaria
R. Polosa
13.1 Introduction 311 (1)
13.2 Inflammatory cells involved in the 312 (3)
pathogenesis of COPD
13.3 Cytokines and chemokines in COPD 315 (5)
13.4 Development of biological agents in 320 (3)
COPD
13.5 Conclusions 323 (1)
References 323 (10)
14 'Triple therapy' in the management of COPD: 333 (10)
inhaled steroid, long-acting anticholinergic
and long-acting β2-agonist
Ronald Dahl
14.1 Introduction 333 (1)
14.2 Long-acting inhaled anticholinergic 333 (1)
(LAMA) and β2-agonist (LABA)
bronchodilators
14.3 Treatment strategies for COPD 334 (1)
14.4 Inhaled corticosteroids and COPD 334 (1)
14.5 Combination treatment with ICS, LAMA 335 (2)
and LABA: 'triple therapy'
14.6 Extracted data from TORCH and UPLIFT 337 (3)
studies
14.7 Conclusions 340 (1)
References 341 (2)
Index 343