Advances in Combination Therapy for Asthma and COPD

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
• Preface

1. Similarities and differences in the pathophysiology of asthma and COPD, J. Christian Virchow
1. Introduction
2. Pulmonary function abnormalities in asthma and COPD
3. Risk factors for asthma and COPD
4. Cellular inflammation in asthma and COPD
5. Distribution and consequences of inflammation in asthma and COPD
6. Patterns of epithelial injury in asthma and COPD
7. Airway hyperresponsiveness
8. Beta-receptor blockers
9. Differential diagnosis of asthma and COPD
10. Overlap syndrome
11. Conclusion
12. References
2. Glucocorticoids: pharmacology and mechanisms, Peter J. Barnes
1. Introduction
2. Chemical structures
3. The molecular basis of inflammation
4. Cellular effects of glucocorticoids
5. Glucocorticoid receptors
6. Glucocorticoid activation of gene transcription
7. Suppression of inflammatory genes
8. Steroid resistance
9. Interaction with 2-adrenergic receptors
10. Conclusions
11. References
3. Inhaled corticosteroids: clinical effects in asthma and COPD, Paul M. O’Byrne and Desmond M. Murphy
1. Introduction
2. Anti-inflammatory activity of corticosteroids
3. Routes of administration
4. Absorption and fate of corticosteroids
5. Currently available inhaled corticosteroids
6. Efficacy in asthma
7. Efficacy in COPD
8. Side effects of ICS
9. Conclusions
10. References
4. LABAs: pharmacology, mechanisms and interaction with anti-inflammatory treatments
1. Gary P. Anderson
2. Galenical forms of LABAs: formulations, isomers, enantiomers, diasteriomers and salts
3. Absolute and functional 2-adrenoceptor selectivity
4. Cellular organization of receptor clusters: functional structure of the 2-adrenoceptor and mode of signalling
5. Dimers and oligomers: homo- and heterodimerism/oligoism
6. Pharmacogenomics of the 2-adrenoceptor and adenylate cyclase polymorphism in relation to LABAs
7. Understanding the ‘reassertion’ paradox, ‘exosites’ and relative speed of onset: the membrane diffusion microkinetic model of LABA action
8. Regulation and desensitization
9. Full versus partial agonism (pharmacological efficacy)
10. Beta-blockers not LABAs?
11. Non-receptor-mediated effects?
12. Biochemical basis of functional antagonism and its critical role in LABA action in disease and exacerbations
13. Molecular cooperativity between LABAs and steroids
14. Perspective
15. References
5. Long- and ultra-long-acting 2-agonists
1. Mario Cazzola and Maria Gabriella Matera
2. Introduction
3. Long-acting 2-agonists
4. Novel ultra-long-acting 2-agonists
5. Conclusion
6. References
6. The safety of long-acting beta-agonists and the development of combination therapies for asthma and COPD, Victor E. Ortega and Eugene R. Bleecker
1. Introduction
2. Asthma-related mortality and beta-agonist exposure
3. Long-acting beta-agonists and increased asthma-related mortality
4. Safety and efficacy of LABA therapy in asthma: retrospective analyses
5. Efficacy of LABA therapy as a component of combination therapy with ICS for the management of asthma 110
6. Scientific basis of the beneficial and adverse effects of beta-agonist therapy: in vitro data and the beta-agonist paradox
7. Conclusions regarding the safety of LABA therapy as a component of combination therapy with ICS for the management of asthma
8. Beta-agonist therapy and adverse events in COPD
9. Safety and efficacy of LABA therapy in the management of COPD: the clinical evidence
10. Role of LABA therapy as a component of combination therapy with ICS for the management of COPD
11. Conclusions regarding the safety of LABA therapy as a component of combination therapy for the management of COPD
12. Pharmacogenetics of LABAs and combination therapy
13. Safety and efficacy of LABA therapy and the development of combination therapies for the management of asthma and COPD
14. Summary and future directions
15. Acknowledgement
16. References
7. Inhaled combination therapy with glucocorticoids and long-acting 2-agonists in asthma and COPD, current and future perspectives, Jan Lötvall
1. Pharmacological management guidelines of asthma and COPD
2. Steroid treatment in asthma
3. Effects of adding LABA to inhaled glucocorticoids in asthma
4. Steroid treatment in COPD
5. Effects of LABAs in COPD
6. Combination inhalers versus two separate inhalers for inhaled GCS and LABAs
7. Regular treatment alone versus additional formoterol-containing combinations as reliever therapy
8. Currently available combination inhalers
9. Upcoming and alternative combinations of inhaled GCS and LABAs
10. Future of combined inhalation therapy in respiratory disease
11. References
8. Novel anti-inflammatory treatments for asthma and COPD, Paul A. Kirkham, Gaetano Caramori, K. Fan Chung and Ian M. Adcock
1. Introduction
2. Current asthma and COPD therapies
3. The need for new therapies
4. Improving current therapies
5. Targeting chemokines and their receptors in asthma and COPD
6. Targeting T-cell-derived and proinflammatory cytokines in asthma and COPD
7. Targeting adhesion molecules in asthma and COPD
8. Growth factor blockers in asthma and COPD
9. Mucous cells, submucosal glands and mucus production in asthma and COPD
10. Infections in asthma and COPD
11. Intracellular signalling pathways
12. Inhibition of transcription factors in asthma and COPD
13. Antioxidants in asthma and COPD
14. Immunomodulation and anti-allergy treatments in asthma and COPD
15. Conclusions
16. Acknowledgements
17. References
9. Novel biologicals alone and in combination in asthma and allergy, Sharmilee M. Nyenhuis and William W. Busse
1. Introduction
2. Targets of therapy
3. Interleukin-4
4. Interleukin-5
5. Interleukin-13
6. Tumor necrosis factor-12
7. Immunoglobulin E
8. DNA vaccines
9. Future directions
10. Conclusion
11. References
10. Anti-infective treatments in asthma and COPD, Jonathan D.R. Macintyre and Sebastian L. Johnston
1. Introduction
2. Current guidelines
3. Acute exacerbations of asthma
4. Increased susceptibility to infection in asthmatics
5. Role of atypical bacteria in asthma
6. Role of viruses in asthma exacerbations
7. Anti-infectives in COPD exacerbations
8. Use of antibiotics in stable COPD
9. Role of vaccination
10. Conclusion
11. References
11. Long-acting muscarinic antagonists in asthma and COPD , M. Diane Lougheed, Josuel Ora and Denis E. O’Donnell
1. Introduction
2. Innervation of the airways
3. Cholinergic mechanisms in asthma and COPD
4. Role of long-acting anticholinergic bronchodilators in obstructive lung disease
5. Summary
6. References
12. Phosphodiesterase inhibitors in obstructive lung disease , Jan Lötvall and Bo Lundbä ck
1. ntroduction
2. Phosphodiesterase enzymes
3. Different pharmacological agents blocking PDE4
4. Biological effects of PDE4 inhibition, preclinical information
5. Clinical effects of PDE4 inhibition in COPD
6. Effects of PDE4 inhibitors on systemic processes in COPD
7. Side effects of PDE4 inhibitors
8. PDE4 inhibitors in COPD management plans
9. Future prospects with PDE4 inhibitors in obstructive airways disease
10. Summary
11. References
13. Biological therapies in development for COPD, J. Morjaria and R. Polosa
1. Introduction
2. Inflammatory cells involved in the pathogenesis of COPD
3. Cytokines and chemokines in COPD
4. Development of biological agents in COPD
5. Conclusions
6. References
14. ‘Triple therapy’ in the management of COPD: inhaled steroid, long-acting anticholinergic and long-acting 2-agonist, Ronald Dahl
1. Introduction
2. Long-acting inhaled anticholinergic (LAMA) and 2-agonist (LABA) bronchodilators
3. Treatment strategies for COPD
4. Inhaled corticosteroids and COPD
5. Combination treatment with ICS, LAMA and LABA: ‘triple therapy’
6. Extracted data from TORCH and UPLIFT studies
7. Conclusions

• References
• Index