This book presents state of the art knowledge on severe asthma with the aim of providing readers with a clear understanding of, first, the heterogeneity of the condition and of patients’ symptom profiles and responses to therapy and, second, the future implications of this heterogeneity for individualized patient care. After an opening section that offers an overview of severe asthma, including its clinical significance, the pathogenesis, available diagnostic approaches, and treatment options are described in detail. The sections on diagnosis and treatment cover the role of biomarkers, the use of radiologic diagnostic modalities, and both pharmacologic and non-pharmacologic therapies, including emerging options that will address hitherto unmet needs of patients. The outcomes of cutting-edge preclinical and clinical research are carefully documented and numerous useful tips provided on patient management. The inclusion of many informative schematic figures will assist readers in grasping the contents easily. The book will be of high value for medical students, researchers, general physicians, specialists, and paramedical staff.

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zlib/Medicine/Yong Chul Lee,So Ri Kim,Seong Ho Cho (eds.)/Severe Asthma: Toward Personalized Patient Management_3396392.pdf

Lee, Yong Chul; Kim, So Ri; Cho, Seong Ho

Yong Chul Lee; So Ri Kim; Seong Ho Cho

Adobe InDesign CC 2017 (Windows)

P. Zambrano-Robledo

Springer Science + Business Media Singapore Pte Ltd

Springer Nature Singapore

Springer London, Limited

Springer Nature, Singapore, 2018

1st ed. 2018, PS, 2017

Singapore, Singapore

Nov 01, 2017

2, 20171030

sm66846227

producers:
Adobe PDF Library 15.0

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Source title: Severe Asthma: Toward Personalized Patient Management

Preface 5
Contents 6
List of Contributors 7
Part I: Overview of Severe Asthma 8
1: Basics of Severe Asthma in Clinical Practice 9
1.1 Definition of Severe Asthma 9
1.2 Epidemiology and Clinical Significance of Severe Asthma 11
1.3 Specific Considerations in Severe Asthma 14
1.3.1 Fungal Sensitization/Allergy- 14
1.4 Conditions Mimicking Severe Asthma 15
References 16
2: Heterogeneity in Severe Asthma 19
2.1 Asthma-COPD Overlap Syndrome and Smoking Asthmatics in Severe Asthma 19
2.1.1 Definition 19
2.1.2 Prevalence 20
2.1.3 Influence of Tobacco Smoking in Asthma 21
2.1.4 Management and Future of ACOS 21
2.2 Comorbid Conditions of Severe Asthma 22
2.2.1 Respiratory Infections 23
2.2.2 Rhinitis and Rhinosinusitis 23
2.2.3 Gastroesophageal Reflux Disease (GERD) 24
2.2.4 Obesity and Obstructive Sleep Apnea (OSA) 24
2.2.5 Psychopathologies and Breathing Dysfunction 25
2.3 Allergic Bronchopulmonary Aspergillosis and Severe Asthma 25
2.3.1 Prevalence 26
2.3.2 Historical Preview 26
2.3.3 Aspergillus and Relationship with Asthma 26
2.3.4 Pathophysiology 26
2.3.5 Clinical Features and Diagnosis 27
2.3.6 Radiologic Findings 28
2.3.7 Histopathologic Findings 28
2.3.8 Treatment 29
2.3.8.1 Glucocorticosteroids (GCs) 29
2.3.8.2 Antifungal Agents 29
2.3.8.3 Biologics 29
2.4 Aspirin-Exacerbated Respiratory Disease and Severe Asthma 30
2.4.1 Historical Preview 30
2.4.2 Prevalence and Presentations 30
2.4.3 Diagnosis 30
2.4.4 Pathogenesis 31
2.4.5 Management and Medications 32
2.4.6 Aspirin Desensitization 32
2.4.7 Surgery 33
References 33
Part II: Pathobiology of Severe Asthma 41
3: Pathogenesis of Severe Asthma 42
3.1 Structural Abnormalities and Airway Remodeling 42
3.1.1 Alterations of Bronchial Epithelium 42
3.1.2 Proliferation and Hypertrophy of Airway Smooth Muscle (ASM) 43
3.1.3 Fibrosis, Subepithelial Thickening, and Alternation of ECM 44
3.1.4 Vascularity and Vascular Permeability 45
3.2 Corticosteroid Resistance and Its Molecular Mechanisms 46
3.2.1 Genetic Association 46
3.2.2 Functional Changes of GRs 46
3.2.3 GR Isoform Identity and Expression 46
3.2.4 Pro-inflammatory Transcription Factor Activation 46
3.2.5 Defective Histone Acetylation 47
3.2.6 Immune Mechanisms 47
3.3 Type 2 Inflammation 47
3.3.1 T Helper Type 2 (Th2) Cell- 47
3.3.2 Innate Lymphoid Type 2 Cell-Associated Inflammation 48
3.4 Non-type 2 Inflammation 48
3.4.1 Inflammasome 49
3.4.2 TNF-α 49
3.4.3 Th17 Cell-Dependent Inflammation 50
3.4.4 Infection and IFN-γ 50
3.5 Subcellular Organelles 51
3.5.1 Endoplasmic Reticulum (ER) 51
3.5.2 Mitochondrial Dysfunction 52
References 52
Part III: Diagnostic Approaches to Severe Asthma 62
4: Biomarkers in Severe Asthma 63
4.1 Diagnostic Significance of Pulmonary Function Testing in Severe Asthma 63
4.2 Exhaled Breath Including FeNO 65
4.2.1 FeNO 65
4.2.2 Exhaled Breath Condensate (EBC) 68
4.2.3 Exhaled Breath Temperature (EBT) 69
4.2.4 pH 69
4.2.5 Biomarkers of Oxidative Stress 69
4.2.5.1 H2O2 69
4.2.5.2 8-Isoprostane 70
4.2.5.3 Nitrite/Nitrate 71
4.2.5.4 ADMA 71
4.2.6 Arachidonic Acid Metabolites 71
4.2.6.1 Prostanoids Prostaglandins, Prostacyclin, and Thromboxanes 71
4.2.6.2 Leukotrienes 71
4.2.7 Cytokines and Chemokines 71
4.2.8 Other Molecules 72
4.3 Blood 72
4.3.1 IgE 72
4.3.2 Blood Eosinophils 73
4.3.3 Periostin 73
4.3.4 Other Biomarkers 74
4.4 Bronchial Specimens 74
4.4.1 Biomarkers in Induced Sputum 74
4.4.2 Sputum Eosinophil and Neutrophil Counts 75
4.4.3 Other Biomarkers 76
4.4.4 Bronchoalveolar Lavage, Bronchial Wash, and Bronchial Biopsy 77
4.5 Others 77
References 78
5: Radiologic Diagnostic Modalities in Severe Asthma 93
References 98
Part IV: Current and Future Therapies for Severe Asthma 100
6: Pharmacologic Therapies for Severe Asthma 101
6.1 Improved Current Medications: Inhaled Corticosteroids (ICS) and Bronchodilators 101
6.1.1 Corticosteroids 101
6.1.1.1 High Dose of ICS or OCS 101
6.1.1.2 New ICSs 101
6.1.2 LABA 102
6.1.3 Long-Acting Muscarinic Antagonists (LAMA) 103
6.2 Broad Inflammatory Therapeutic Modalities to Overcome Steroid Resistance 104
6.2.1 Kinase Inhibitors 104
6.2.2 Antioxidants and Selective Mitochondria-Targeting Antioxidants 105
6.2.3 Phosphodiesterase-4 (PDE4) Inhibitors 105
6.2.4 ER Stress Modulator 106
6.3 Endotype-Based Therapeutic Strategies 106
6.3.1 Type 2 Related Inflammation- 106
6.3.1.1 Anti-IgE Approach 106
6.3.1.2 Inhibition of Cytokines: Targeting IL-4/IL-13 and IL-5, TSLP 107
6.3.2 Blockade of Lipid Mediators 109
6.3.3 Chemokine Receptor Antagonists: CCR3 and CCR4 110
6.4 Non-type 2-Related Inflammation-Targeting Therapies 111
6.4.1 Anti-tumor Necrosis Factor α (TNF-α) 111
6.4.2 Anti-interleukins: IL-17 111
6.4.3 Inflammasome Inhibitor 111
6.4.4 Chemokine Receptor Antagonists: CXCR2 112
6.5 Clinical Comorbidities-Based Therapeutic Modalities 112
6.5.1 Antifungal Agents: Allergic Bronchopulmonary Aspergillosis (ABPA) and Severe Asthma with Fungal Sensitization (SAFS) 112
6.5.2 Macrolides: Infections and Bronchiectasis 113
6.5.3 Intranasal Spray and Intranasal Inhalation of Corticosteroids: Allergic Rhinitis (AR) 113
6.5.4 IFN-β: Viral Infection-­Associated Asthma Exacerbation 113
References 114
7: Non-pharmacologic Therapies for Severe Asthma 125
7.1 Education, Partnership, and Action Plan 125
7.2 Environmental Control 126
7.3 Comorbid Conditions of Severe Asthma 127
7.4 Other Non-pharmacologic Therapies 128
7.5 Future Directions 129
References 130
Index 132

Front Matter ....Pages i-ix
Front Matter ....Pages 1-1
Basics of Severe Asthma in Clinical Practice (Jae Seok Jeong, Yong Chul Lee)....Pages 3-12
Heterogeneity in Severe Asthma (Chen Hsing Lin, Sultan Alandijani, Seong H. Cho)....Pages 13-34
Front Matter ....Pages 35-35
Pathogenesis of Severe Asthma (So Ri Kim)....Pages 37-56
Front Matter ....Pages 57-57
Biomarkers in Severe Asthma (Wenjing Li, Mark C. Glaum)....Pages 59-88
Radiologic Diagnostic Modalities in Severe Asthma (Gong Yong Jin)....Pages 89-95
Front Matter ....Pages 97-97
Pharmacologic Therapies for Severe Asthma (So Ri Kim)....Pages 99-122
Non-pharmacologic Therapies for Severe Asthma (Yoon-Seok Chang)....Pages 123-129
Back Matter ....Pages 131-134

2017-11-21