Allergy Frontiers:Therapy and Prevention (eBook)

Prof. Stephen Holgate MRC Clinical Professor of Immunopharmacology Division of Respiratory Cell and Molecular Biology University of Southhampton School of Medicine Applying basic science to the clinical interface in allergy and asthma has been the guiding principle of Prof. Stephen Holgate's career. This has involved him in environmental and genetic epidemiology, physiology, cell and molecular biology of disease processes as they occur in humans. An AAAAI member since 1986 and Fellow from 1993, Professor Holgate has been active in the field of allergy and immunology both in the United Kingdom and overseas and in 2001 received the Academy's Honorary Fellow Award. He was President of the British Society of Allergy and Clinical Immunology (BSACI) from 1990-1993 and the Robert Cook Memorial Lecturer in 1995 and 2000. He received the RCP London Graham Bull Prize for research and was elected an honorary member of the Association of Physicians in UK and Ireland following the delivery of the Sir William Osler Lecture in 2003. He has been an active contributor to the Collegium Internationale Allergologicum since 1990. Professor Holgate is a member of the Infection, Inflammation and Repair Division in the School of Medicine, University of Southampton at Southampton General Hospital, UK and since 1987 has held a Medical Research Council (MRC) Clinical Professorship. He received his undergraduate medical training at Charing Cross Hospital, London and specialised in respiratory medicine and allergy. He holds Fellowships from the Royal Colleges of Physicians, Pathologists, Institute of Biology and Academy of Medical Sciences. He is a member of the Royal Commission on Environmental Pollution and has been a censor of the Royal College of Physicians. He has served on a number of Government Committees including the Sub-committee for Efficacy and Adverse Drug Reactions of the CSM (SEAR), MRC Project Grant Committee, Systems Board, Cross Board Group and most recently Councils Subcommittee on Corporate Policy and Evaluation (SCoPE), its Clinical Research Oversight Group (CROG) and is Chairman of Councils new Subcommittee on Evaluation (SOE). He has been Chairman of the UK Department of Health Committee on the Medical Effects of Air Pollution and has been appointed as Chairman of the UK Government (DEFA) Expert Panel on Air Quality Standards and Chairman of the Science Council's Science in Health Group. He has been a member of the Royal Commission of Environmental Pollution since 2002. He serves as a member of the Board of Directors for the World Allergy Organization (WAO). Professor Holgate is co-editor of Clinical and Experimental Allergy and has served on the editorial board of the Journal of Allergy and Clinical Immunology. He has edited several textbooks on allergy including Asthma and Rhinitis and Allergy, with release of 2nd editions in 2000 and is one of the co-editors of Allergy: Principles and Practice. He has published over 800 papers in peer reviewed journals. His work has been recognised with a Scientific Achievement Award of the IAACI in 1994, the Rhone-Poulenc Rorer World Health Award in 1995, the King Faisal International Prize in Medicine in 1999 and Doctorates Hon Causa at University of Ferrara, Italy and Jagellonian University, Krakow, Poland in 1997 and 1999 respectively. He was elected to the Polish Academy of Arts and Science in 2001, received the Royal Society of Medicine Ellison Cliffe Medal in 2003 and the University of Ghent Gold Medal for Achievement in Clinical Science in 2004. According to the ISI Prof. Holgate was 8th most frequently cited author between 1990-2000 in the field of Biomedical Sciences in the United Kingdom and in 2002 became a member of ISI's most highly cited researcher database. Prof. Ruby Pawankar Rhinology and Allergy, Nippon Medical School, Tokyo, Japan Guest Professor, Kyung Hee University School of Medicine, Seoul Korea Prof. Pawankar MD., Ph.D is the Treasurer of the World Allergy Organization (WAO) and has served on the Board of Directors since 2000, is an Executive and Scientific Committee Member of the WHO's ARIA Initiative and Chair of its Asia-Pacific Affiliate. She has served on several boards/ committeees like Vice-Chair of the Rhinitis Committee of the American Academy of Allergy Asthma and Immunology, Vice-Chair Asia Pacific Committee, and International Commiittee American College of Allergy Asthma and Immunology. She has been the President of the Trans-Pacific Allergy and Immunology Society and Asian Rhinology Symposium, is the Founder President of the International Symposium on Asthma and Allergic Rhinitis (ISBAAR) and Director, Asian Allergy and Asthma Foundation and has served as a Committee Member/ Faculty at several International Congresses as well as government initiatives in the field of Rhinology, Allergy and Asthma. Prof. Pawankar's research interest is in the pathomechanisms, epidemiology and risk factors of allergy, asthma, air pollution, immune and molecular mechanisms in allerigc airway disease. new strategies in managing respiratory allergy, rhinosinusitis and nasal polyps, focussing on translational research in allergy, asthma and clinical immunology. Most important amongst her original works is the role of masts cells and gamma delta T cells in allergic airway disease. She is an Editor/Editorial Board Member of several academic journals like Clinical and Experimental Allergy, International Archives Allergy and Immunology, Current Opinion in Allergy and Clinical Immunology, Current Allergy Asthma Reports, Journal of the World Allergy Organization, Am J Rhinology and several more. Prof. Pawankar has received several prestigious academic awards and orations, has published more than 300 original papers and invited reviews and books including the J Clinical Investigation and Am J Crit Care Medicine. She is a member of several academic organizations like the Collegium International Allergolicum and honorary Fellow/ Member of several academic societies. She has been Visiting Professor to many universities including the Dept. of Pediatrics, Showa Univ School of Medicine. She is also an educator conducting courses and symposia and vivid campaigner to increase public awareness on allergy within the Asian region. Prof. Lanny J. Rosenwasser Dee Lyons/Missouri Chair in Pediatric Immunology Research Children's Mercy, Kansas City, USA Professor of Pediatrics Allergy/Asthma/Immunology Medical Research Prof. Rosenwasser, MD, Ph.D has been named the first Dee Lyons/Missouri Endowed Chair in Pediatric Immunology Research at Children's Mercy Hospitals and Clinics. Prof. Rosenwasser comes to Children's Mercy from the National Jewish Center for Immunology and Respiratory Medicine and the University of Colorado Health Sciences Center where he was a professor of medicine and the co-director of the Division of Allergy and Clinical Immunology. Dr. Rosenwasser is board certified in Internal Medicine and Allergy and Immunology, with additional certification in Diagnostic Laboratory Immunology. Prof. Rosenwasser's research interests include the molecular, cellular and genetic regulation of cytokines, the genetics of atopy and asthma, the role of cytokines in asthma, and vasculitis. Research-Cellular and Molecular Immunology. Allergen structure and recognition by T cells. Clinical-Asthma, Vasculitis, Drug Allergy, Insulin Allergy, New Therapies for Asthma and Allergy. He was a former President of the American Academy of Allergy, Asthma and Immunology. He has also served as Editor-in-Chief of the Yearbook of Allergy, Asthma and Clinical Immunology published by Elsevier since 1994. He has published over 110 original publications as well as invited reviews and book such as the New England Journal of Medicine and the Journal of Experimental Medicine. He has also served on a number of government and foundation committees for grant review, including the National Institute of Allergy and Infectious Diseases AIDS Research Center, the National Institute of Health Immunological Sciences Study, the Arthritis Foundation, the American Heart Association and the American Lung Association. In 1997, he received the Solomon A Berson Alumni Achievement Award for research in clinical science from New York University. He serves as a member of the Board of Directors for the World Allergy Organization (WAO).

Foreword 5
Preface 11
Contents 13
Contributors 17
Part I: Therapy and Prevention of Allergies 24
Chapter 1 25
Allergen Avoidance and Prevention of Allergy 25
Introduction 25
Definitions 25
Risk Factors 26
At Risk Population 26
Early Critical Period 26
Allergen Exposure 27
Exposure and Disease 27
Primary Prevention 28
Food Allergen Avoidance 28
Breast Feeding 28
During Pregnancy 29
Late Introduction of Solid Foods 30
Hydrolyzed Milk Formulae 30
Aeroallergens 31
House Dust Mite Allergen Avoidance 31
Other Aeroallergens 33
Combined Approach 34
Secondary Prevention 34
Occupational Allergens 35
Food Allergens 35
Aeroallergens 35
Summary 36
References 37
Chapter 2 41
Pharmacotherapy of Allergic Rhinitis 41
Introduction 41
Oral H1 -Antihistamines 41
First Generation H1 -Antihistamines 42
Second Generation H1 -Antihistamines 42
Cetirizine 43
Levocetirizine 44
Loratadine 44
Desloratadine 44
Fexofenadine 45
Intranasal H1 -Antihistamines 45
Azelastine 45
Olopatadine 46
Intranasal Corticosteroids 46
INS Compared with Placebo 47
Comparison of Individual INS 47
INS Compared with Oral H1 Antihistamines 48
Adverse Effects of INS 48
Leukotriene Modifying Agents 50
Local Chromones 51
Local Anticholinergics 51
Decongestants 51
Summary 52
References 53
Chapter 3 59
Antihistamines in Rhinitis and Asthma 59
Histamine: Role in Health and Disease 59
Histamine Receptors and Agonists: Diversity of Action 60
Classifications of Allergic Rhinitis and Implications for Treatment 63
Antihistamines in the Treatment of Allergic Rhinitis: Beyond the Histamine Effects 64
Antihistamines in Asthma: Same Airway Disease, but Dramatically Different 67
Antihistamines in Children, Elderly and Pregnant Women with Rhinitis 68
The Ideal Antihistamine: Basis for Comparison of all Existing Preparations 69
References 70
Chapter 4 73
Antiallergic and Vasoactive Drugs for Allergic Rhinitis 73
Introduction 73
Guidelines for the Treatment of AR 74
Cornerstones of Rhinitis Treatment 74
Oral H1 -Receptor Antagonists 75
Topical Nasal H1 -Receptor Antagonists 76
Topical Nasal Corticosteroids 76
Systemic Corticosteroids 77
Antileukotrienes 77
Sodium Cromoglicate 78
Anti-IgE 78
Intranasal Decongestants 78
Oral Decongestants 79
Conclusion 79
References 79
Chapter 5 84
Antileukotrienes in Asthma and Rhinitis 84
Introduction 84
The Leukotriene Biosynthetic Pathway 84
Cellular Sources of Leukotrienes 86
Cysteinyl-Leukotriene Receptors 86
Actions of cys-LTS in Asthma and Rhinitis 88
Bronchoconstriction 88
Vascular Effects 88
Leukocyte Recruitment 89
Other Inflammatory Actions 90
Airway Remodeling 90
Leukotrienes in Biological Fluids 91
Classes of Oral Antileukotriene Drug 91
Antileukotriene Drugs in Provocation Studies 93
Allergen Bronchoprovocation 93
Exercise and Cold Air Challenges 93
Aspirin Challenge 94
Efficacy of Antileukotriene Drugs in Asthma 94
Acute Asthma 94
Chronic Asthma 95
Anti-Inflammatory and Remodeling Effects 95
Comparison with Other Asthma Therapies 96
Add-on Therapy and Steroid-Tapering Trials 98
Efficacy of Antileukotriene Drugs in Allergic Rhinitis 100
Monotherapy 100
Combination Therapy 100
Safety, Compliance, and Adherence 101
Variability in Clinical Response 102
Summary 102
References 103
Chapter 6 112
Mechanisms of Action of beta2 Adrenoceptor Agonists 112
Introduction 112
Adrenoceptor Populations in the Airways 112
Molecular Genetics of the Human beta2 Adrenoceptor 113
Structure–Function Relationships of the beta2 Adrenoceptor 113
Distribution of beta2 Adrenoceptor Expression 115
Regulation of beta2 Adrenoceptor Expression 116
Pharmacology of beta Adrenoceptor Agonists 117
Clinical Pharmacology of SABAs and LABAs 118
Clinical Effects 118
Safety of SABAs and LABAs 119
Summary 121
References 121
Chapter 7 125
Alkylxanthines and Phosphodiesterase 4 Inhibitors for Allergic Diseases 125
Introduction 125
Generic Properties and Characteristics of Cyclic Nucleotide PDEs 126
Phosphodiesterase 4 131
Therapeutic Indications of PDE4 Inhibitors 131
Anti-inflammatory Effects of PDE Inhibitors In Vivo 132
IgE-Mediated Processes 133
Proinflammatory Cell Infiltration 133
Microvascular Leakage and Edema 134
Clinical Trials of Theophylline in Asthma 135
Clinical Trials of PDE4 Inhibitors in Asthma and Rhinitis 135
Asthma 135
Clinical Trials of PDE4 Inhibitors in Psoriasis and Atopic/Contact Dermatitis 137
Rolipram and Rolipram Analogues 137
Xanthines 138
Thalidomide Derivatives 139
Safety, Tolerability, Drug Metabolism and Pharmacokinetics of Theophylline and PDE4 Inhibitors: A Comparison 139
Adverse Events of Theophylline and PDE4 Inhibitors 140
Theophylline 140
PDE4 Inhibitors 142
Concluding Remarks 143
References 144
Chapter 8 153
Glucocorticoid Insensitive Asthma 153
Definition of GC Insensitive Asthma 154
Abnormal Activation of the GC Receptor and its Nuclear Inhibitory Effects 154
GC Insensitivity Due to the Presence of a “Different” Inflammatory Process 158
GC Insensitivity Due to the Lack of Any Inflammatory Process 158
GC Insensitivity Due to the Presence of an Inflammatory Process in a Region of the Lung Poorly Accessible to Inhaled CS Therapy 159
Approaches to Therapy in GC Insensitive Patients 160
Conclusions 161
References 161
Chapter 9 165
Recalcitrant Asthma 165
Introduction 165
Definitions of Severe Asthma 165
Risk Factors for Severe Asthma 169
Genetic Risk Factors 171
Environmental Risk Factors 173
Infections 173
Smoking 177
Obesity 177
Gastroesophageal Reflux Disease (GERD) 178
Adherence 178
Histological Features of Severe Asthma 179
Management of Severe Asthma 182
New Approaches to Treatment of Severe Asthma 185
Conclusion 186
References 187
Chapter 10 191
Mechanisms and Management of Exercise-Induced Bronchoconstriction 191
Introduction 191
Epidemiology 191
Pathogenesis 192
Clinical Manifestations 194
Diagnosis 194
Differential Diagnosis 195
Management 196
Pharmacological 196
Beta 2 Agonists 196
Cromoglycates 197
Inhaled Corticosteroids 198
Leukotriene-Modifying Agents 199
Histamine (H 1 ) Antagonists 200
Dietary Modification 200
Other Therapies 201
Nonpharmacological 201
Conclusion 201
References 202
Chapter 11 207
Use of Theophylline and Sodium Cromoglycate in Adult Asthma 207
Introduction 207
Properties of Sustained-Release Theophylline 208
Pharmacological Properties of Theophylline 208
Anti-Inflammatory Effects of Theophylline 209
Safety of Theophylline 210
Evidence Supporting the Effectiveness of Theophylline for the Long-Term Management of Asthma 211
Evidence Supporting the Concurrent Use of Theophylline and Inhaled Corticosteroids 211
Evidence Supporting the Effectiveness of Theophylline for Severe Asthma 212
References 213
Chapter 12 215
New Insights into Allergen-Specific Immunotherapy in Rhinitis and Asthma 215
Historical Context 215
Injection Immunotherapy 216
Efficacy and Safety 216
Mechanisms 217
Long-Lasting Effect and Prevention 218
Sublingual Immunotherapy 219
Efficacy and Safety 219
Mechanisms 221
Aspects Currently Under Investigation 222
Future Developments 223
Novel Formulations and Routes of Administration 223
Immunotherapy with Adjuvants 224
Immunotherapy with Bacterial Adjuvants 225
DNA-Adjuvanted Immunotherapy 225
Immunotherapy with Peptides 226
Recombinant and Engineered Allergens 226
Concluding Remarks 227
References 227
Chapter 13 236
Sublingual Immunotherapy in Allergic Rhinitis and Asthma 236
Introduction 236
Mechanisms 237
Clinical Evidence of Efficacy 240
New Dosing Regimes 241
Economic Evaluation 241
Safety 242
Psychological Stress and Response to SLIT 242
Future Directions 242
References 243
Chapter 14 246
Anti-IgE in Allergic Airway Diseases: Indications and Applications 246
Introduction: Role of IgE and Anti-IgE Molecules 246
Proof of Concept of Omalizumab Actions in Asthma 249
Clinical Efficacy in Allergic Asthma 249
Design of Studies 250
Asthma Exacerbations 250
Inhaled Corticosteroids 250
The Effect of Omalizumab on Other Medication Use, Including Beta-2 Agonists and Oral Corticosteroids 251
Lung Function 251
Quality of Life 251
Severe Asthma 252
Children 252
Predictors of Response to Omalizumab 252
Asthma Guidelines 253
Allergic Rhinitis 253
Mechanism of Action of Anti-IgE 255
Pharmacokinetics of Omalizumab 256
Safety of Omalizumab 257
Neoplasms 258
Immune Complex and Antibodies 259
Helminth Infection 259
Thrombocytopenia 259
Summary 260
References 260
Chapter 15 263
Drug Delivery Devices and Propellants 263
Introduction 263
Aerosol Characteristics 263
Aerosol Devices 265
Inhalers 265
Dry Powder Inhalers (DPI) 265
Pressurized Metered Dose Inhalers (pMDI) 266
Breath Activated pMDI 267
Venturi Type Jet Nebulizers (JN) 268
Breath Activated Nebulizers 268
Large Volume Nebulizers (LVN) 268
Ultrasonic Nebulization 269
Vibrating Mesh Nebulizers (VM) 269
Other New Nebulizer Technologies 269
Accessory Devices 270
Spacers 270
Valved Holding Chambers (VHC) 270
Masks 271
Activation Enablers 271
Special Uses 271
Neonatal and Pediatric Aerosol Therapy 271
Emergency Department Aerosol Delivery for Acute Asthma 272
Care of Devices 273
Jet Nebulizer Maintenance 273
VHC Maintenance 273
DPI and pMDI Maintenance 274
Patient Education 274
References 274
Chapter 16 277
Update on the Management of AtopicDermatitis/Eczema 277
Introduction 277
Basic Approach to Therapy 278
Avoidance of Exacerbating Factors 278
Topical Treatments 280
Emollients 280
Topical Steroids 282
Topical Calcineurin Inhibitors 283
Infection and Antimicrobial Treatments 284
Bacterial Infections 284
Viral Infections 285
Fungal Infections 286
Antimicrobial Peptides 286
Anti-Itch Treatment 287
Systemic Immunosuppressive Therapy 288
Systemic Steroids 289
Methotrexate 289
Oral Calcineurin Inhibitors 290
Mycophenolate Mofetil 291
Azathioprine 292
Biologics 292
Interferon- gamma (rIFN- gamma) 293
Intravenous Immunoglobulin (IVIg) 293
Tumor Necrosis Factor (TNF) alpha inhibitors (Etanercept – Enbrel®,Amgen Infliximab – Remicade®, Centocor
Anti-LFA agents (Efalizumab – Raptiva®, Genentech-Xoma) 295
Anti IgE Agents (Omalizumab – Xolair®, Genentech) 295
Alternative Approaches 296
Probiotics 296
Gamma linoleic Acid (GLA) 297
Psychological Interventions 297
Conclusions 297
References 298
Chapter 17 309
Immunosuppressants as Treatment for Atopic Dermatitis 309
Introduction 309
Glucocorticosteroids 309
GCS Signaling 310
GCS and the Th1/Th2 Balance 310
GCS and Antigen Presentation 311
GCS and Leucocyte Migration 312
GSC and Cell Viability/Skin Barrier 312
GSC and Mast Cells/Eosinophils 313
Cyclosporine 314
CsA and Keratinocytes 314
CSA and Leukocyte Migration 315
CsA and IgE Autoreactivity 315
Calcineurine Inhibitors 316
CNI and T cells 316
CNI and Antigen Presentation 317
CNI and Eosinophils 318
CNI and Effector Cells 318
CNI and Keratinocytes 318
Mycophenolate Mofetil 319
Methotrexate 319
Intravenous Immunoglobulines 320
Biologicals 320
Conclusion 321
References 321
Chapter 18 329
Management of Anaphylaxis 329
The Prevention of Anaphylactic Episodes 329
General Preventive Measures 329
Preventive Measures for Patients at Risk 330
Management of the Acute Event 331
Treatment Administered in a Medical Facility 331
Immediate Measures 334
Measures Initiated After Further Evaluation 335
Treatment in the Field by the Patient 337
The Observation Period After Resolution of Symptoms 338
Fatalities 339
References 340
Chapter 19 342
Anaphylaxis: Are Regulatory T Cells the Targetof Venom Immunotherapy? 342
Abbreviations 342
Introduction 342
Types of TReg Cells and Allergic Responses to Insect Venoms 344
Role of T Reg Cells During Natural Tolerance and Venom SIT 345
Conclusion 348
References 348
Chapter 20 352
Food Allergy: Opportunities and Challenges in the Clinical Practice of Allergy and Immunology 352
Introduction 352
Allergen-Specific Immunotherapy 353
Allergen Immunotherapy 353
Subcutaneous Immunotherapy (SCIT) 353
Oral Immunotherapy (Specific Oral Tolerance Induction, SOTI) 354
Sublingual Immunotherapy (SLIT) 356
Modified Recombinant Vaccines 357
Peptide Immunotherapy 358
Immunostimulatory Sequence-Conjugated Protein Immunotherapy 358
Plasmid DNA Immunotherapy 359
Allergen Non-Specific Immunotherapy 359
Anti-IgE 359
Herbal Medicine 359
Summary and Conclusions 360
References 360
Chapter 21 364
Early Immunological Influences on Asthma Development: Opportunities for Early Intervention 364
Introduction 364
Postnatal Development of Immune Competence 365
Recent Thymic Emigrants (RTE) and the Conundrum of Intrauterine Sensitisation to Allergens 367
Immune Maturation and Genetic Risk for Atopic Disease 367
Pathways Leading to Development of Wheeze in Childhood: Towards a Rational Basis for Development of Effective Prevention Strategies 368
Strategies for Primary and Secondary Prevention of Persistent Atopic Asthma: Current and Future Options 370
Rational for Early Intervention Strategies for Asthma Prevention 370
Targeting Postnatal Maturation of Immune Competence 371
Protection against the Induction and Persistence of Allergic Sensitization 372
Early Treatment with Anti-Inflammatory Drugs to Blunt the Asthma-Promoting Effects of Airway Inflammation in Children 373
Protection Against Early Respiratory Viral Infections: The Ultimate Challenge 373
Conclusions 374
References 375
Chapter 22 381
Asthma and Allergy in Childhood: Predictionand Early Diagnosis 381
Why Should We Predict Disease? 381
Some Definitions and Considerations 382
Prediction Versus Risk Factors 383
Tools for Prediction 385
Early Diagnosis 389
References 390
Chapter 23 394
Early Interventions in Allergic Diseases 394
Introduction 394
Risk Factors for Allergies and Asthma 395
Respiratory Viruses, Wheezing, Allergen Sensitization and Asthma 395
Breast Feeding 398
Endotoxin 398
Pet Ownership 399
Tobacco Smoke 400
Therapeutic and Preventive Strategies 401
Perspectives of Treatment and Prevention of Respiratory Viral Infections 401
Environmental Interventions in Genetically Predisposed Infants 402
Pharmacological Treatment 403
Allergen-Specific Immunotherapy 404
Conclusions 404
References 406
Chapter 24 411
Birth Cohort Studies for the Prevention of Allergy: New Perspectives—Where Do We Go from Now? 411
Introduction 411
Study Design 411
Cross-Sectional Studies 412
Cohort Studies 412
Observational Birth Cohort Studies 412
Interventional Birth Cohort Studies 413
Defining Allergies 413
Natural Course of Allergic Illnesses 414
Risk Factors and Protective Exposures 415
Nutrition 415
Maternal Diet 415
Breastfeeding 415
Hypoallergenic Infant Formula 416
Infantile Diet 416
Probiotics 417
Environmental Factors 418
Environmental Tobacco Smoke 418
Traffic Related Pollution 418
Inhaled Allergens 418
Pets 419
Family Size/Day Care 420
Infections 421
Microbial Exposures in the Environment 421
Antibiotics/Vaccinations/Paracetamol 421
Multifaceted Interventional Studies 422
Secondary and Tertiary Prevention in Cohort Studies 423
Conclusion 423
Where do we go from now? 424
References 424
Chapter 25 430
Novel Immunomodulatory Strategies for the Prevention of Atopy and Asthma 430
Introduction 430
The Need for Early Interventions for Allergy Prevention 431
Limitations of Current Strategies 432
Identifying Target Populations for PreventionStrategies - the Need for Better Allergy Predictors 432
Novel Non-Invasive Strategies Using Dietary Nutrients to Prevent Disease 434
Novel Strategies using other Microbial Products 438
The Role of Allergen Immunotherapy 440
Future Directions 440
References 441
Chapter 26 446
Recombinant Allergens for Therapy and Prevention: Molecular Design and Delivery of Allergy Vaccines 446
Introduction 446
Recombinant Allergens 447
Recombinant Allergy Vaccines 448
Molecular Design of Allergy Vaccines 449
Delivery of Allergy Vaccines 451
Cytokines 452
CpG DNA 453
Live Bacillus Calmette-Guerin BCG 453
Live Vectors 454
Nanoparticles 454
Future of Immunotherapy 455
Concluding Remarks 455
References 456
Chapter 27 460
Prevention of Allergic Diseases 460
Introduction 460
Factors in the Environment that May Confer Protection 461
Farm Milk Consumption 461
Raw Vegetable and Fresh Fruit Consumption 462
Natural Water Consumption 462
Tolerance 463
Definition of Tolerance 463
Mechanisms Involved in the Development of Tolerance 464
Bell-Shaped Curve 464
Toll-Like Receptors in the Development of Tolerance 465
Healthy Immune Response vs. Allergic Immune Response 467
Can Tolerance Be Restored in Atopic Individuals? 468
Primary Prevention 468
The Finnish Allergy Programme 2008–2018 Launched 470
Goals and Focus 471
Conclusion 471
References 472
Chapter 28 478
Emerging Nonsteroidal Anti-Inflammatory Therapies Targeting Specific Mechanisms in Asthma and Allergy 478
Introduction 478
Anti-Leukotrienes 478
Anti-Prostanoids 479
Nonsteroidal Therapy in Asthma & Allergy 467act also as a CRTH2 receptor antagonist. Modest, though beneficial effects havebeen reported when applied in allergic rhinitis and asthma, the drug has been registeredin Japan as a controller of allergy [18]. Pres
Anti-IgE 480
Allergen Specific Immunotherapy 481
Anti-Cytokine Therapy 481
Anti-TNF- alpha 483
Anti-IL-5 483
Anti-IL-4 and Anti-IL-13 484
Anti-IL-13 485
Anti-IL-9 485
IL-10 485
Recombinant IL-12 486
Conclusion Anti-Cytokine Therapy 486
Probiotics 487
Heparins 487
Other Potential Anti-Asthma Targets 488
Conclusion 489
References 489
Part II: Special Consideration in Children, Elderly and Pregnancy 496
Chapter 29 497
Asthma and Rhinitis in Pregnancy 497
Introduction 497
Asthma During Pregnancy 497
Asthma Control 497
Asthma Exacerbations 498
Lung Function During Pregnancy 499
Rhinitis During Pregnancy 499
Allergic Rhinitis 500
Pregnancy Rhinitis 500
Snoring and Rhinitis in Pregnancy 501
Maternal and Fetal Complications of Asthma in Pregnancy 501
Low Birth Weight 501
Preterm Birth 502
Pre-eclampsia and Pregnancy induced hypertension 502
Congenital Malformations 502
Perinatal Mortality 502
Management of Asthma and Rhinitis During Pregnancy 503
Managing Asthma and Rhinitis 503
Treatment of Asthma Exacerbations During Pregnancy 503
Safety of Drug Treatments for Asthma and Rhinitis 504
beta2 -Agonists 504
Inhaled Corticosteroids 505
Intranasal Corticosteroids 505
Oral Corticosteroids 505
Leukotriene Receptor Antagonists 506
Antihistamines 506
Nasal Decongestants 506
Conclusions 506
References 507
Chapter 30 510
Asthma in the Elderly 510
Introduction 510
Diagnosis 510
Onset and Prevalence 512
Course 512
Death 513
Management and Treatment 513
Irreversibility 515
Summary and Conclusions 518
References 519
Chapter 31 522
The Natural History of Childhood Asthma 522
Introduction 522
Definition of Asthma 522
When does Asthma begin? 524
Who gets Asthma? 525
Natural History of Early Childhood Asthma 527
Can the Natural History of Asthma be Altered? 535
Other Asthma Phenotypes in Childhood 535
Summary 537
References 537
Chapter 32 542
The Wheezing Infant and Young Child 542
Interpretation of Wheeze 543
Infant Wheeze 543
Early Wheezing and Prematurity 544
Wheezing after RSV Bronchiolitis 544
Recurrent Symptoms Beyond Infancy 545
Atopic Asthma 545
Viral Associated Wheeze 545
Cough 546
Major Environmental Factors 547
Airway Inflammation and Remodelling 547
Persistence and Resolution 548
Implications for Therapy 549
Conclusions 549
References 550
Chapter 33 554
Acute Severe Asthma in Children 554
Definition 554
Epidemiology of Severe Acute Asthma in Children 555
Recognition and Treatment of Severe Acute Asthma 556
Assessment in the Emergency Department or Acute Care Facility 557
First Line Care in the ED 558
The History and Physical Examination 560
Ongoing ED Care 561
Monitoring Response to Therapy 563
Consideration of Hospital Based Therapy 563
Respiratory Failure 563
Prevention and Discharge Planning 564
Summary 567
References 567
Chapter 34 575
Best Estimates of Asthma Control in Children 575
Asthma Severity Versus Asthma Control 575
Assessment of Asthma Control Using Subjective Measures 577
Symptom Assessments 577
Quality of Life Measures 578
Healthcare Utilization 579
Assessment of Asthma Control Using Objective Measures 580
Monitoring the Peak Expiratory Flow Rate 580
Forced Expiratory Spirometry 581
Sputum Eosinophil Counts 581
Measurement of Exhaled Nitric Oxide 582
Is Asthma Control Possible? 582
Achieving Asthma Control 583
Improving Asthma Control 583
References 584
Chapter 35 587
Risk-Benefit of Asthma Therapy in Children: Topical Corticosteroids 587
Characteristics of Inhaled Corticosteroids 588
Effects of Inhaled Corticosteroids 588
Similarities and Differences in Inhaled Corticosteroids 588
Benefits of Inhaled Corticosteroids in Children 590
Overview of Efficacy of Inhaled Corticosteroids 590
Early Intervention with Inhaled Corticosteroids 590
Failure to Respond to Inhaled Corticosteroids 591
Risks of Inhaled Corticosteroids in Children 591
Effect of ICS on Linear Growth and Bone Metabolism 591
Effect of ICS on the HPA Axis 593
Other Potential Adverse Effects of ICS 593
Maximizing the Benefits and Minimizing the Risks 594
Inhaled Corticosteroids in Infants 594
Combining Inhaled Corticosteroids with Long-Acting Beta-Agonists in Children 595
Conclusion: Treatment with ICS in Asthmatic Children: Risk or Benefit? 595
References 596
Chapter 36 602
Risk-Benefit of Asthma Therapy in Children: Nonsteroidal Anti-Inflammatory Drugs 602
Introduction 602
General Principles 602
Cromolyn Sodium and Nedocromil 604
Mechanism of Action 604
Benefits and Place in Therapy 606
Risks and Drawbacks 607
Ketotifen 607
Mechanism of Action 607
Benefits and Place in Therapy 607
Risks and Drawbacks 608
Theophylline 608
Mechanism of Action 608
Benefits and Place in Therapy 608
Risks and Drawbacks 609
Leukotriene Modifiers 609
Mechanism of Action 609
Benefits and Place in Therapy 610
Risks and Drawbacks 612
Omalizumab 613
Mechanism of Action 613
Benefits and Place in Therapy 613
Risks and Drawbacks 613
Conclusions 614
References 614
Chapter 37 619
The Role of Influenza Vaccination in Asthmatic Children 619
Introduction 619
Influenza: Incidence and Clinical Impact 620
Availability and Immunogenicity of Vaccines 621
Adverse Effects of Influenza Vaccination 622
Effectiveness 622
Vaccine Uptake in Children with Asthma 624
Cost Effectiveness of Influenza Vaccination 624
Conclusion 625
References 625
Chapter 38 628
Treatment of Infants with Atopic Dermatitis 628
Genetic and Other Risk Factors for AD 628
Pathophysiology 629
Triggers of AD 630
Allergens 630
Microorganisms 630
Irritant Factors 631
Diagnostic Work-Up 631
Food 631
Treatment 632
Basic Treatment 632
Topical Treatment 633
Emollients 633
Topical Glucocorticosteroids 633
Topical Calcineurin Inhibitors (TCIs) 634
Wet-Wrap Therapy 634
Topical Antimicrobial Therapy 635
Systemic Treatment 635
Antimicrobial Treatment 635
Systemic Corticosteroids 636
Cyclosporin A 636
Antihistamines 637
Diet 637
Education 637
References 638
Chapter 39 642
Diagnosing Food Allergy in Children 642
Introduction 642
Features of IgE-Mediated Food Allergy 642
Features of NonIgE-Mediated Food Allergy 644
Evaluation of the Food Allergic Child 645
History 645
Physical Examination 647
Skin Testing 648
Atopy Patch Testing 649
Laboratory Testing 650
Elimination Diets 651
Food Challenges 651
Management of the Food Allergic Child 653
Future Directions 655
References 656
Chapter 40 660
Diagnosis and Treatment of Latex Allergy 660
Introduction 660
Latex Allergens 661
Functional Properties of Latex Allergens 663
Biological Properties 663
Polyisoprene Elongation 664
Plant Defense Functions 664
Common Enzymes and Structural Proteins 665
Immunologic Properties 665
Immune Responses to Rubber Biosynthesis Proteins 665
Immune Responses to Defense-Related proteins 666
Hev b 8 (Profilin) 668
Hev b 9 (Enolase) 668
Hev b 10 (Manganese Superoxide Dismutase ) 668
Hev b 11 (Endochitinase) 669
Hev b 12 (Lipid Transfer Protein) 669
Hev b 13 (Latex Esterase) 669
Diagnosis of Latex Allergy 669
In Vitro Testing for Latex Allergy 671
In Vivo Provocation Testing 672
Prevention and Treatment of the Patient with Latex Allergy 673
Summary 675
References 675
Chapter 41 682
New Aspects of Peanut and Tree Nut Allergy 682
Introduction 682
Environmental and Genetic Factors 683
Genetics 684
Linkage Analyses 684
HLA 685
SPINK5 686
Peanut and Tree Nut Allergens 686
Peanut 687
Hazelnut 687
Walnut 688
Almond, Cashew and Brazil Nut 688
Cross-Reactivity 689
Tree Nut Allergy 690
Diagnosis 690
Skin Testing 690
IgE Levels 691
Possibilities for Remission 691
Avoidance 692
Treatments 692
Immunotherapy 692
Anti-IgE 694
Herbal Treatments 694
Conclusions 695
References 695
Chapter 42 701
Allergic Fungal Sinusitis: Controversy and Evolution of Understanding with Therapeutic Implications 701
Introduction 701
Historical Aspects 703
Confusion and Controversy over the Diagnosis of AFS Categorization 703
Epidemiology and Geography 704
Pathophysiology Similarities and Differences of AFS to ABPFD 705
Proteases and Fungal Sinus Disease 706
Superantigen and Genetic Predisposition 707
IgE Levels and Associated Fungal Findings 708
Fungal Culture 709
Clinical Presentation 709
Radiological Findings 710
Treatment 711
Surgical Management 711
Medical Management 712
Antifungal Therapy 712
Immunotherapy 714
Anti-IgE 714
Other Modalities 714
Discussion 715
References 715
Chapter 43 718
Immunomodulatory Role of Bacillus Calmette-Guérin in the Prevention and Therapy of Allergy and Asthma 718
Abbreviations 718
Introduction 718
Hygiene Hypothesis 719
Bacillus Calmette-Guérin 719
Therapeutic Effects of BCG 719
BCG in Allergy and Asthma 720
Factors Regulating Efficacy of BCG as an Anti-Asthma Therapy 720
BCG-Induced Immunoregulation and Airway Remodeling 721
T H 1/T H 2 Concept 721
Growing Skepticism on the T H 1/T H 2 Concept 722
Role of Other Immunoregulatory Cells 722
T reg Cells 722
CD8 + T-Cells 723
gamma delta -T Cells 724
NKT Cells 725
Antigen Presenting Cells 725
Role of NRAMP and TLRs 725
NRAMP1 725
Toll-Like Receptors 726
Conclusion 726
References 727
Chapter 44 732
Use of Theophylline and Sodium Cromoglycate in Pediatric Asthma 732
Introduction 732
Theophylline 732
Pharmacological Properties 732
Physiological Effects 732
Anti-Inflammatory Effects 733
Molecular Mechanisms of Theophylline Effects 733
PDE Inhibition 733
Adenosine Receptor Antagonism 733
Other Effects 734
Therapeutic Use 734
Epigenetics 735
Sodium Cromoglycate 735
Introduction 735
Pharmacological Properties 736
Pharmacologic Effects 737
Absorption, Fate and Excretion 737
Toxicity 737
Therapeutic Use 738
References 738
Chapter 45 741
Antibody Deficiency Syndromes (Including Diagnosis and Treatment) 741
Introduction 741
Antibody-Mediated Immunity 741
Clinical Aspects of Antibody Deficiency 743
General Evaluation of Antibody-Mediated Immunity 744
Antibody Deficiency Syndromes 746
Agammaglobulinemia 746
Hyper-IgM Syndrome 747
Common Variable Immunodeficiency Disease (CVID) 747
Transient Hypogammaglobulinemia of Infancy 749
Selective IgA Deficiency 749
IgG Subclass Deficiencies 750
IgG1 Subclass Deficiency 751
IgG2 Subclass Deficiency 751
IgG3 Subclass Deficiency 751
IgG4 Subclass Deficiency 751
Specific Antibody Deficiency with Normal Immunoglobulins 751
Selective Anti-Pure (Non-Conjugated) Polysaccharide Antibody Deficiency 752
Treatment of Antibody Deficiencies 753
Clinical Staging of Complications 754
Summary 754
References 754
Index 758