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Book Details
Abstract
This issue of Clinics in Chest Medicine is Guest Edited by Peter J. Barnes FRS, FMedSci from Imperial College London and will fosus on COPD. Article topics include epidemiology, pathophysiology, cellular and molecular mechanisms and comorbidities of COPD, diagnosis and phenotype of COPD, pulmonary rehabilitation, asthma and COPD, biomarkers, bronchodilators, non invasive ventialtion, and new drug therapies.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Title page\r | i | ||
| Copyright page\r | ii | ||
| Contributors | iii | ||
| Editor | iii | ||
| Authors | iii | ||
| Contents | vii | ||
| Chronic Obstructive Pulmonary Disease | xiii | ||
| COPD | 1 | ||
| Key points | 1 | ||
| Definition | 1 | ||
| Diagnostic criteria | 2 | ||
| ATS 1995 | 1 | ||
| ERS 1995 | 1 | ||
| Considerations for future diagnostic criteria | 3 | ||
| COPD phenotypes | 4 | ||
| Specific COPD phenotypes | 4 | ||
| References | 5 | ||
| Epidemiology and Prevalence of Chronic Obstructive Pulmonary Disease | 7 | ||
| Key points | 7 | ||
| Introduction | 7 | ||
| Definition of COPD | 7 | ||
| Measures of Airflow Limitation and Reversibility | 8 | ||
| Clinical Features and Overlap Syndromes | 8 | ||
| Risk factors | 8 | ||
| Active and Passive Cigarette Smoking | 8 | ||
| Occupational Risk Factors | 9 | ||
| Air Pollution | 9 | ||
| Genetic Factors | 9 | ||
| Prevalence of COPD | 9 | ||
| Criteria and Impact on Disease Prevalence | 9 | ||
| Prevalence Estimates | 10 | ||
| Prevalence of COPD and Gender Differences | 11 | ||
| Burden of COPD and mortality | 11 | ||
| Summary | 14 | ||
| References | 14 | ||
| Tobacco Smoking and Environmental Risk Factors for Chronic Obstructive Pulmonary Disease | 17 | ||
| Key points | 17 | ||
| Introduction | 17 | ||
| Tobacco smoking | 18 | ||
| Second-hand smoke or environmental tobacco smoke | 19 | ||
| Exposure to indoor biomass fuel smoke | 20 | ||
| Other indoor air pollutants | 21 | ||
| Occupational COPD | 22 | ||
| Farming | 22 | ||
| Other Occupations Associated with COPD | 23 | ||
| Outdoor air pollution | 24 | ||
| Summary | 24 | ||
| References | 25 | ||
| Genetic Susceptibility | 29 | ||
| Key points | 29 | ||
| Introduction | 29 | ||
| Unbiased approaches | 30 | ||
| Candidate gene approaches | 30 | ||
| The Extracellular Matrix | 30 | ||
| Protease-Antiprotease Balance | 31 | ||
| Reactive Oxygen Species | 32 | ||
| Inflammation | 33 | ||
| Summary | 34 | ||
| References | 34 | ||
| Alpha1-antitrypsin Review | 39 | ||
| Key points | 39 | ||
| Prevalence | 39 | ||
| Clinical impact | 40 | ||
| Pathophysiology | 41 | ||
| Susceptibility of Other Phenotypes | 42 | ||
| Augmentation | 43 | ||
| New treatments | 46 | ||
| Recombinant A1AT | 46 | ||
| Secretion Strategies | 46 | ||
| Gene Therapies | 46 | ||
| Drugs | 46 | ||
| Biomarkers | 46 | ||
| Summary | 47 | ||
| References | 47 | ||
| Chronic Obstructive Pulmonary Disease | 51 | ||
| Key points | 51 | ||
| Introduction | 51 | ||
| Mild COPD | 51 | ||
| Clinical Relevance | 51 | ||
| Resting Physiologic Abnormalities in Mild COPD | 52 | ||
| Small airways dysfunction | 52 | ||
| Ventilation-perfusion abnormalities | 53 | ||
| Responses to Exercise in Mild COPD | 54 | ||
| High ventilatory requirements | 54 | ||
| Impairment of dynamic respiratory mechanics | 54 | ||
| Cardiocirculatory impairment | 54 | ||
| Skeletal muscle dysfunction | 56 | ||
| Moderate-to-severe COPD | 56 | ||
| Resting Physiologic Abnormalities in Moderate-to-Severe COPD | 56 | ||
| Progression of resting lung hyperinflation | 56 | ||
| Pulmonary gas exchange abnormalities | 57 | ||
| Responses to Exercise in Moderate-to-Severe COPD | 57 | ||
| Increased central respiratory drive | 57 | ||
| Dynamic respiratory mechanics across the continuum of COPD | 58 | ||
| Cardiocirculatory impairment | 59 | ||
| Skeletal muscle dysfunction | 61 | ||
| Physiologic mechanisms of dyspnea in COPD | 61 | ||
| Summary | 62 | ||
| References | 63 | ||
| Cellular and Molecular Mechanisms of Chronic Obstructive Pulmonary Disease | 71 | ||
| Key points | 71 | ||
| Introduction | 71 | ||
| Pathology | 71 | ||
| COPD as an inflammatory disease | 72 | ||
| Inflammatory cells | 72 | ||
| Epithelial cells | 72 | ||
| Macrophages | 72 | ||
| Neutrophils | 74 | ||
| Eosinophils | 74 | ||
| Dendritic cells | 74 | ||
| T lymphocytes | 75 | ||
| Mediators of inflammation | 75 | ||
| Lipid Mediators | 75 | ||
| Cytokines | 75 | ||
| Chemokines | 76 | ||
| Growth Factors | 76 | ||
| Proteases | 76 | ||
| Oxidative stress | 77 | ||
| Systemic inflammation in COPD | 78 | ||
| Acute Phase Proteins | 79 | ||
| Cytokines | 79 | ||
| Defective resolution of inflammation and repair | 79 | ||
| Proresolving Lipid Mediators | 80 | ||
| Accelerated Aging | 80 | ||
| Airway Fibrosis | 80 | ||
| Implications for future therapy | 80 | ||
| Reversal of Corticosteroid Resistance | 80 | ||
| New Antiinflammatory Therapies | 81 | ||
| New Pathways | 81 | ||
| The Need for Biomarkers | 81 | ||
| Disease Phenotypes | 81 | ||
| Treating Acute Exacerbations | 82 | ||
| References | 82 | ||
| Role of Infections | 87 | ||
| Key points | 87 | ||
| Introduction | 87 | ||
| Acute infection | 88 | ||
| Causes of Exacerbations | 88 | ||
| Virus | 88 | ||
| Bacteria | 89 | ||
| Coinfection with virus and bacteria | 91 | ||
| Community-acquired Pneumonia | 91 | ||
| Epidemiology | 91 | ||
| Causes of CAP in COPD | 91 | ||
| Role of inhaled corticosteroids | 91 | ||
| Antimicrobial therapy in COPD and CAP | 92 | ||
| Chronic infection | 92 | ||
| Vicious-circle Hypothesis | 92 | ||
| Evidence to Support Chronic Infection | 93 | ||
| Mechanism of Increased Susceptibility to Infection in COPD | 94 | ||
| Host Defects: Innate Immunity | 94 | ||
| Mucociliary clearance | 94 | ||
| Immunoglobulin A | 94 | ||
| Antimicrobial peptides | 94 | ||
| Macrophage function | 95 | ||
| Pathogen Mechanisms | 96 | ||
| Tissue invasion | 96 | ||
| Biofilm formation | 96 | ||
| Antigenic alteration | 96 | ||
| Future directions | 96 | ||
| References | 96 | ||
| Comorbidities and Systemic Effects of Chronic Obstructive Pulmonary Disease | 101 | ||
| Key points | 101 | ||
| Introduction | 101 | ||
| Classification | 101 | ||
| Cardiovascular disease | 101 | ||
| Prevalence | 102 | ||
| Pathogenesis | 102 | ||
| Inflammation | 102 | ||
| Hypoxia | 104 | ||
| Effect of cigarette smoking | 104 | ||
| Polycythemia | 104 | ||
| Hypercapnic acidosis | 104 | ||
| Abnormalities in vascular endothelial function/vessel wall | 105 | ||
| Common Cardiovascular Complications | 105 | ||
| Interventions to Reduce Cardiovascular Complications | 106 | ||
| Smoking cessation | 106 | ||
| Effective management of COPD | 106 | ||
| Cardiovascular drugs | 106 | ||
| Skeletal muscle effects | 107 | ||
| Prevalence | 107 | ||
| Pathophysiologic Changes Associated with Muscle Dysfunction/Wasting | 107 | ||
| Factors Contributing to Muscle Dysfunction | 107 | ||
| Interventions to Improve Skeletal Muscle Dysfunction | 109 | ||
| Osteoporosis | 109 | ||
| Prevalence of Osteoporosis in COPD | 110 | ||
| Potential Contributors to Osteoporosis in COPD | 110 | ||
| Corticosteroids | 110 | ||
| Inflammation | 110 | ||
| Calcification paradox | 111 | ||
| Therapeutic Interventions | 111 | ||
| Nonpharmacologic measures | 111 | ||
| Pharmacologic measures | 111 | ||
| Nutritional effects in COPD | 111 | ||
| Prevalence and Implications | 111 | ||
| Factors Contributing to Nutritional Depletion | 112 | ||
| Therapeutic Interventions | 112 | ||
| Obesity and obstructive sleep apnea in COPD | 112 | ||
| Management of OSA and COPD | 113 | ||
| Anemia in COPD | 113 | ||
| Prevalence | 113 | ||
| Pathogenesis | 113 | ||
| Management | 115 | ||
| Autonomic Dysfunction | 115 | ||
| Prevalence and Clinical Implications | 115 | ||
| Lung Cancer and COPD | 115 | ||
| Prevalence | 115 | ||
| Pathogenesis and Clinical Implications of Lung Cancer in COPD | 116 | ||
| Psychological effects in COPD | 117 | ||
| Prevalence | 117 | ||
| Clinical Implications | 117 | ||
| Diabetes and metabolic syndrome in COPD | 117 | ||
| Prevalence and Pathogenesis | 117 | ||
| Management and Clinical Implications | 117 | ||
| Systemic inflammation in COPD | 118 | ||
| Summary | 121 | ||
| References | 121 | ||
| Biomarkers in COPD | 131 | ||
| Key points | 131 | ||
| Introduction | 131 | ||
| Markers and outcomes: general concepts | 131 | ||
| Biomarkers: definition and requirements | 133 | ||
| Biomarkers in COPD: where are we now? | 133 | ||
| Fibrinogen: the Most Promising Biomarker | 133 | ||
| Other Acute Phase Reactants Regulated by IL-6 | 135 | ||
| Emerging Biomarkers | 136 | ||
| Pneumoproteins | 136 | ||
| Other Biomarkers | 137 | ||
| Biomarkers of Therapeutic Responses | 137 | ||
| A Network Approach to Inflammation: the Systemic Inflammome | 137 | ||
| How can we progress in the field? | 138 | ||
| Summary | 139 | ||
| References | 139 | ||
| Asthma and Chronic Obstructive Pulmonary Disease | 143 | ||
| Key points | 143 | ||
| Introduction | 143 | ||
| Definitions | 144 | ||
| Clinical features | 144 | ||
| Symptoms | 144 | ||
| Airway Obstruction and Reversibility | 145 | ||
| Atopy | 146 | ||
| Airway Hyperresponsiveness | 146 | ||
| The Overlap Phenotype | 147 | ||
| Genetics and environment | 148 | ||
| Overlap of Asthma and COPD | 149 | ||
| Inflammation and remodeling | 150 | ||
| Pharmacologic responses | 151 | ||
| Summary | 152 | ||
| References | 153 | ||
| Acute COPD Exacerbations | 157 | ||
| Key points | 157 | ||
| Impact of COPD exacerbations | 157 | ||
| Definition of exacerbations | 157 | ||
| Causes and pathogenesis of exacerbation | 158 | ||
| The frequent exacerbator phenotype | 159 | ||
| Exacerbation prevention | 159 | ||
| Vaccines | 159 | ||
| Inhaled Corticosteroids and Long-acting Bronchodilators | 159 | ||
| Dual Bronchodilators | 160 | ||
| Phosphodiesterase Inhibitors | 161 | ||
| Long-term Antibiotics | 161 | ||
| Pulmonary Rehabilitation, Home Oxygen, and Ventilatory Support | 161 | ||
| Management of the acute exacerbation | 161 | ||
| References | 162 | ||
| Smoking Cessation | 165 | ||
| Key points | 165 | ||
| Introduction | 165 | ||
| Physiology of smoking | 165 | ||
| Approach to a quit attempt | 167 | ||
| Strategy for the quit attempt | 168 | ||
| Pharmacotherapy | 169 | ||
| NRT | 169 | ||
| Nicotine polacrilex gum | 170 | ||
| Nicotine polacrilex lozenge | 170 | ||
| Transdermal nicotine | 170 | ||
| Nicotine inhaler | 170 | ||
| Nicotine nasal spray | 171 | ||
| Combinations of NRT | 171 | ||
| Bupropion | 171 | ||
| Varenicline | 171 | ||
| Off-label agents | 172 | ||
| Harm reduction | 172 | ||
| Summary | 173 | ||
| References | 173 | ||
| Current Drug Treatment, Chronic and Acute | 177 | ||
| Key points | 177 | ||
| Introduction | 177 | ||
| Drug treatment in acute exacerbations | 177 | ||
| Drug treatment in chronic management | 179 | ||
| ICS and COPD | 179 | ||
| Evidence-based therapy | 182 | ||
| Evaluating patients | 182 | ||
| Initial drug therapy | 183 | ||
| Alternative therapies | 183 | ||
| Emerging issues | 184 | ||
| Summary | 185 | ||
| References | 185 | ||
| Bronchodilators | 191 | ||
| Key points | 191 | ||
| The importance of bronchodilation in COPD | 191 | ||
| Classes of bronchodilators | 192 | ||
| β2-Agonists | 192 | ||
| Antimuscarinic Agents | 192 | ||
| Methylxanthines | 193 | ||
| The choice of bronchodilators in stable COPD | 193 | ||
| When Starting Treatment with Bronchodilators | 193 | ||
| Choice of Treatment Based on Effectiveness | 193 | ||
| Choice of Treatment Based on Safety | 194 | ||
| When Combining Two Bronchodilators with Different Mechanisms of Action | 194 | ||
| Future developments | 195 | ||
| Novel Classes | 195 | ||
| New Traditional Bronchodilators | 196 | ||
| References | 198 | ||
| How Phosphodiesterase 4 Inhibitors Work in Patients with Chronic Obstructive Pulmonary Disease of the Severe, Bronchitic, F ... | 203 | ||
| Key points | 203 | ||
| Introduction | 203 | ||
| PDE4 inhibitors and COPD | 204 | ||
| A triple combination therapy? | 205 | ||
| Scientific rationale for adding on a PDE4 inhibitor to an ICS/LABA combination therapy: a case for gene transactivation | 205 | ||
| Why ICS/LABA combination therapies are not enough | 207 | ||
| Candidate antiinflammatory genes | 209 | ||
| Mitogen-activated Protein Kinase Phosphatase 1 | 209 | ||
| Glucocorticoid-induced Leucine Zipper | 209 | ||
| Regulator of G-protein Signaling 2 | 210 | ||
| Cluster of Differentiation 200 | 210 | ||
| Cysteine-rich Secretory Protein Limulus Clotting Factor C, Cochlin, Lgl1 Domain-containing 2 | 210 | ||
| p57kip2 | 211 | ||
| Suppressor of Cytokine Signaling 3 | 211 | ||
| Cylindromatosis | 211 | ||
| Tristetraprolin | 211 | ||
| Gene transactivation and glucocorticoid resistance | 212 | ||
| A note on cAMP-induced, adverse-effect genes | 212 | ||
| Summary and future directions | 212 | ||
| Acknowledgments | 213 | ||
| References | 213 | ||
| New Drug Therapies for COPD | 219 | ||
| Key points | 219 | ||
| Introduction | 219 | ||
| Drugs to aid smoking cessation | 221 | ||
| Inhaled bronchodilators and corticosteroids | 222 | ||
| Inhaled Bronchodilators | 222 | ||
| ICS | 222 | ||
| Steroid Resistance | 223 | ||
| Antiinfective and antiinflammatory agents | 223 | ||
| Antibiotics | 223 | ||
| Antivirals | 225 | ||
| Agents Acting on Innate Immunity | 225 | ||
| Chemokine Receptor Antagonists | 226 | ||
| Chemoattractant Receptor-homologous Receptor Antagonism | 226 | ||
| LTB4 Receptor Antagonists | 226 | ||
| Selectin Antagonism | 226 | ||
| Phosphodiesterase Inhibitors | 226 | ||
| Kinase Inhibitors | 227 | ||
| Statins | 227 | ||
| Miscellaneous additional classes of new drugs | 228 | ||
| Antioxidants | 228 | ||
| Mucoactive Drugs | 229 | ||
| Proteases | 229 | ||
| Fibrosis and Remodeling | 229 | ||
| Biologics: MoABs | 230 | ||
| Aging and Autoimmunity | 230 | ||
| Lung Regeneration | 230 | ||
| Summary | 231 | ||
| References | 231 | ||
| Pulmonary Rehabilitation | 241 | ||
| Key points | 241 | ||
| Outline | 241 | ||
| Definition | 241 | ||
| The evidence base for pulmonary rehabilitation | 242 | ||
| Where can pulmonary rehabilitation be organized | 243 | ||
| A comprehensive intervention: program content | 243 | ||
| Patient screening and selection | 245 | ||
| Screening for the Extrapulmonary Consequences of COPD | 246 | ||
| Symptoms | 247 | ||
| Physical Activity | 247 | ||
| Severe Exacerbations | 247 | ||
| Maintaining the effects of pulmonary rehabilitation | 247 | ||
| Summary | 248 | ||
| References | 248 | ||
| Noninvasive Ventilation and Lung Volume Reduction | 251 | ||
| Key points | 251 | ||
| Introduction | 251 | ||
| NIV | 251 | ||
| NIV during acute hypercapnic respiratory failure | 252 | ||
| Indications | 252 | ||
| Predictors of Treatment Success and Treatment Failure | 252 | ||
| Ventilator Mode and Setup | 253 | ||
| Domiciliary NIV for chronic hypercapnic respiratory failure | 253 | ||
| Physiologic Basis | 253 | ||
| Respiratory Drive | 253 | ||
| Respiratory load | 254 | ||
| Respiratory muscle capacity | 254 | ||
| Early Trials | 254 | ||
| Current Data and Practice | 254 | ||
| Could Technical Factors Explain the Failure to Show a Benefit with NIV? | 255 | ||
| Summaries | 255 | ||
| LVR for the treatment of emphysema | 255 | ||
| Physiologic Basis | 255 | ||
| Surgical LVR | 256 | ||
| Bullectomy | 256 | ||
| LVRS | 256 | ||
| Bronchoscopic LVR | 260 | ||
| Endobronchial airway valves | 260 | ||
| Biologic LVR | 261 | ||
| Bronchoscopic thermal vapor ablation (steam) | 262 | ||
| RePneu LVR coils | 262 | ||
| Airways bypass stents | 263 | ||
| Summary | 265 | ||
| References | 265 | ||
| Index | 271 | ||
| A | 271 | ||
| B | 271 | ||
| C | 272 | ||
| D | 274 | ||
| E | 274 | ||
| F | 274 | ||
| G | 274 | ||
| H | 275 | ||
| I | 275 | ||
| K | 275 | ||
| L | 275 | ||
| M | 276 | ||
| N | 276 | ||
| O | 276 | ||
| P | 276 | ||
| Q | 277 | ||
| R | 277 | ||
| S | 277 | ||
| T | 277 | ||
| V | 278 |