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Middleton's Allergy: Principles and Practice E-Book

Middleton's Allergy: Principles and Practice E-Book

N. Franklin Adkinson Jr. | William W Busse | Bruce S Bochner | Stephen T. Holgate | F. Estelle R. Simons | Robert F Lemanske

(2008)

Additional Information

Book Details

Abstract

This best-selling resource has a worldwide reputation as the leader in its field. Focusing on human immunology and biology, while also reporting on scientific experimentation and advancement, it provides comprehensive coverage of state-of-the-art basic science as well as authoritative guidance on the practical aspects of day-to-day diagnosis and management. This new edition includes 700 full-color illustrations and a new, more accessible format to make finding information a snap for the busy practitioner. And this Expert Consult Edition offers online access to the complete contents of the 2-volume set, fully searchable, and much more.

  • Includes a glossary of allergy and immunology for quick and easy reference.
  • Contains keypoints and clinical pearls highlighted to find important information quickly.
  • links to useful online resources both for you and for your patients.
  • Offers contributions from hundreds of international authorities for world-class expertise in overcoming any clinical challenge.
  • Contains 400 new illustrations, 700 in all, to better illustrate complex immunology.
  • Covers the very latest in the field, including hot topics such as food allergy and immunotherapy.
  • Includes the latest guidelines from The National Asthma Education and Prevention Program (NAEPP).
  • Utilizes a new, more user-friendly full-color format for easier reference.
  • Includes online access to the entire contents of the book, fully searchable, with links to MEDLINE abstracts for all of the references.

Table of Contents

Section Title Page Action Price
e9780323056595v1 1
Front Cover 1
Middleton’s Allergy Seventh edition Principles & Practice 4
Copyright Page 5
Contents 6
Preface 14
Preface to the first edition 16
Contributors 18
Section A - IMMUNOLOGY 33
Chapter 1 - The Immune System: an Overview 35
INTRODUCTION 35
COMPONENTS OF THE IMMUNE SYSTEM 36
THE IMMUNE RESPONSE 43
IMMUNOPATHOLOGY - MECHANISMS OF IMMUNE-MEDIATED DISEASES 45
CONCLUSION 48
References 48
Chapter 2 - Innate Immunity 51
INTRODUCTION 51
MICROBIAL PATTERN RECOGNITION BY THE INNATE IMMUNE SYSTEM 52
PATTERN RECOGNITION RECEPTORS 52
RESIDENT CELLULAR RESPONSES OF INNATE IMMUNITY 57
INFILTRATIVE CELLULAR RESPONSES OF INNATE IMMUNITY 58
INNATE INSTRUCTION OF ADAPTIVE IMMUNE RESPONSES 59
HOMEOSTASIS IN THE INNATE IMMUNE SYSTEM 59
INNATE IMMUNITY AND ALLERGY 62
References 64
Chapter 3 - Molecular Biology and Genetic Engineering 69
ANATOMY OF THE GENE 69
RNA AND PROTEIN SYNTHESIS 70
DNA REPAIR 73
DNA REPLICATION 73
CONTROL OF GENE EXPRESSION 74
DNA REARRANGEMENT (GENETIC RECOMBINATION) 75
RECOMBINANT DNA TECHNOLOGY 76
FRAGMENTATION, SEPARATION, SEQUENCING, AND IDENTIFICATION OF DNA 76
NUCLEIC ACID HYBRIDIZATION 78
GENE CLONING 80
ISOLATION OF GENE 83
GENE MAPPING 84
DNA ENGINEERING 85
GENOMICS AND PROTEOMICS 85
RNA INTERFERENCE/RNA SILENCING 87
EPIGENETICS 87
SUMMARY 89
References 89
Chapter 4 - Principles of Genetics in Allergic Diseases and Asthma 91
INTRODUCTION 91
PHENOTYPE DEFINITION 92
EVIDENCE FOR A GENETIC COMPONENT IN ASTHMA 92
CURRENT KNOWLEDGE ON GENES ASSOCIATED WITH ASTHMA 93
GENOME-WIDE LINKAGE STUDIES 93
CANDIDATE GENE APPROACH 95
CANDIDATE GENE ASSOCIATION STUDIES FOR ASTHMA-RELATED PHENOTYPES 96
GENE BY GENE INTERACTION 97
GENE–ENVIRONMENT INTERACTION IN ASTHMA 97
PHARMACOGENOMICS OF ASTHMA 99
NEW APPROACHES TO ASTHMA GENETICS 100
GENOME-WIDE ASSOCIATION STUDIES 101
References 103
Chapter 5 - Immunoglobulin Structure and Function 105
INTRODUCTION 105
B LYMPHOCYTES AND THE ­HUMORAL IMMUNE RESPONSE 105
IMMUNOGLOBULIN STRUCTURE AND FUNCTION 108
IMMUNOGLOBULIN GENES: ­GENERATION OF DIVERSITY AND CLASS SWITCH 114
THERAPEUTIC APPLICATIONS OF IMMUNOGLOBULINS 116
SUMMARY 118
References 118
Chapter 6 - The Complement System 121
OVERVIEW 121
INTRODUCTION TO THE COMPLEMENT SYSTEM 122
THE CLASSICAL PATHWAY 123
THE ALTERNATIVE PATHWAY 124
THE LECTIN ACTIVATION PATHWAY 125
THE MEMBRANE ATTACK COMPLEX 125
RECEPTORS AND BIOLOGICAL FUNCTIONS 126
REGULATION OF COMPLEMENT ­ACTIVATION 128
DISORDERS ASSOCIATEDWITH COMPLEMENT ACTIVATION 131
DISORDERS ASSOCIATED WITH COMPLEMENT DEFICIENCY 133
MANAGEMENT OF COMPLEMENT DEFICIENCIES 140
LABORATORY ASSESSMENT OF COMPLEMENT 141
References 142
Chapter 7 - Immunobiology of IgE 147
INDUCTION OF IgE SYNTHESIS: CELL–CELL INTERACTIONS 147
MOLECULAR EVENTS IN THE INDUCTION OF IgE SYNTHESIS 150
IgE REGULATION AND THE ENVIRONMENT 155
ISOTYPE SWITCHING IN TISSUES 156
IgE REGULATION: BENCH TO BEDSIDE 157
THE GENETIC REGULATION OF IgE RESPONSES 158
References 159
Chapter 8 - Signal Transduction 161
introduction 161
GENERAL PRINCIPLES 162
CELL STRUCTURES 162
GENERAL FEATURES OF ­RECEPTORS AND SIGNALING 162
MECHANISMS MEDIATING ­INTRACELLULAR SIGNALING 164
SELECTED SIGNALING SYSTEMS RELEVANT TO ALLERGY 175
ADDITIONAL THERAPEUTIC CONSIDERATIONS 178
References 178
Chapter 9 - Cellular Adhesion in Inflammation 181
INTRODUCTION 181
SELECTINS AND SELECTIN LIGANDS 182
INTEGRINS 184
IMMUNOGLOBULIN GENE SUPERFAMILY 186
GALECTINS, CADHERINS, AND CD44 188
LEUKOCYTE ADHESION TO AND ACROSS THE ENDOTHELIUM 189
REGULATION OF ADHESION ­MOLECULE EXPRESSION 192
HUMAN DISEASE ASSOCIATED WITH ADHESION MOLECULE DEFICIENCY 193
ADHESION MOLECULES IN HUMAN ALLERGIC INFLAMMATION 193
POTENTIAL SIDE EFFECTS OF ADHESION-BASED THERAPY 194
SUMMARY 194
References 194
Chapter 10 - Cytokines in Allergic Inflammation 197
INTRODUCTION: DEFINITION, -EVOLUTION OF CYTOKINE BIOLOGY, AND NOMENCLATURE 197
Cytokine production by antigen-presenting cells 198
CYTOTOXIC IMMUNITY 200
HUMORAL IMMUNITY 200
CELLULAR IMMUNITY 200
ALLERGIC IMMUNITY 201
Antiinflammatory cytokines 203
T helper lymphocyte families 210
CYTOKINES AND IMMUNE RESPONSES TO ALLERGENS 208
SUMMARY 208
References 209
Chapter 11 - Chemokines in Cell Movement and Allergic Inflammation 213
INTRODUCTION 213
CHEMOKINES 213
CHEMOKINE RECEPTORS AND SIGNALING 214
REGULATORY MECHANISMS FOR THE CHEMOKINE RESPONSE 218
BIOLOGICAL ROLE OF CHEMOKINE–CHEMOKINE RECEPTOR INTERACTIONS 222
ROLE IN HUMAN DISEASE 224
CLINICAL MANIFESTATIONS OF GENE MUTATIONS AFFECTING THE CHEMOKINE SYSTEM 230
CONCLUSION 231
References 231
Chapter 12 - Lipid Mediators of Hypersensitivity and Inflammation 235
INTRODUCTION 235
GENERATION OF LIPID MEDIATOR PRECURSORS BY PHOSPHOLIPASE A2 235
EICOSANOID FORMATION 236
INDIVIDUAL PROSTANOIDS 238
LIPOXYGENASE PATHWAY 244
ISOPROSTANES 248
SPHINGOSINE-1-PHOSPHATE 249
SUMMARY 250
References 250
Chapter 13 - Neuronal Control of Airway Function in Allergy 255
INTRODUCTION 255
LOWER AIRWAY INNERVATION 256
AIRWAY NEUROPHYSIOLOGY AND THE ALLERGIC REACTION 260
CONCLUSIONS 264
References 264
Chapter 14 - Biochemical Events in Basophil/Mast Cell Activation and Mediator Release 267
INTRODUCTION 267
IgE-MEDIATED SIGNALING: THE AGGREGATION REACTION 268
IgE RECEPTOR STRUCTURE 269
BRIEF OVERVIEW OF THE EARLY STAGES OF FcεRI-MEDIATED SIGNALING 269
References 288
Chapter 15 - Stem Cells: What Are They and Why Do We Need Them? 291
STEM CELLS: DEFINITION AND GENERAL CHARACTERISTICS 291
EMBRYONIC AND ADULT STEM CELLS 291
ADULT STEM CELLS (ASC) 292
HEMATOPOIETIC STEM CELLS 294
THE STEM CELL NICHE 296
STEM CELL CLINICAL APPLICATIONS 299
FUTURE DIRECTIONS 300
References 301
Chapter 16 - Biology of Lymphocytes 303
INTRODUCTION 303
T LYMPHOCYTES 303
B LYMPHOCYTES 308
LYMPHOCYTES IN ASTHMA 309
References 312
Chapter 17 - Biology of Neutrophils 315
INTRODUCTION 315
NEUTROPHIL MIGRATION 315
MEDIATORS RELEASED BY ­ACTIVATED NEUTROPHILS 318
NEUTROPHIL CLEARANCE AND DEATH 319
NEUTROPHILS IN ASTHMA 320
CONCLUSION 325
References 325
Chapter 18 - Biology of Eosinophils 327
INTRODUCTION 327
EOSINOPHIL DIFFERENTIATION AND TISSUE RECRUITMENT 327
SURFACE MARKERS IN ­EOSINOPHILS 330
EOSINOPHIL-DERIVED ­MEDIATORS 331
EOSINOPHIL AS EFFECTOR CELLS IN WORM INFECTIONS 339
CONCLUSIONS 340
References 340
Chapter 19 - Biology of Mast Cells and their Mediators 343
INTRODUCTION 343
HISTOLOGIC IDENTIFICATION OF MAST CELLS 343
MORPHOLOGY OF MAST CELLS 344
MAST CELL GROWTH AND DEVELOPMENT 347
ACTIVATING AND INHIBITORY RECEPTORS OF MAST CELLS 350
MAST CELL-DERIVED MEDIATORS 351
MAST CELL PATHOBIOLOGY 355
SUMMARY 357
References 357
Chapter 20 - Biology of Basophils 361
INTRODUCTION 361
DEVELOPMENT AND MORPHOLOGY 361
FUNCTIONAL AND PHENOTYPIC MARKERS 362
INFLAMMATORY MEDIATORS 364
BASOPHIL ACTIVATION 365
PHARMACOLOGICAL MODULATION OF SECRETION 368
BASOPHIL INVOLVEMENT IN DISEASE 369
SUMMARY 370
References 371
Chapter 21 - Antigen-Presenting Dendritic Cells 373
INTRODUCTION 373
DENDRITIC CELL TERMINOLOGY AND HETEROGENEITY 373
ANTIGEN UPTAKE 374
ANTIGEN PRESENTATION 374
INTEGRATED FUNCTION OF DENDRITIC CELLS IN THE IMMUNE RESPONSE 376
ROLE FOR DENDRITIC CELLS IN ALLERGIC SENSITIZATION IN HUMANS 382
DENDRITIC CELLS IN ALLERGIC ASTHMA 382
DENDRITIC CELLS IN ATOpIC DERMATITIS 384
ROLE Of DENDRITIC CELLS IN ALLERGIC RHINITIS 384
DENDRITIC CELLS AS DRUG TARGETS IN ALLERGIC DISEASES 384
CONCLUSION 385
References 385
Chapter 22 - The Biology of Monocytes and Macrophages 387
INTRODUCTION 387
MACROPHAGES AND AFFERENT ARM IMMUNE FUNCTION 388
MACROPHAGES AND EFFERENT ARM IMMUNE FUNCTION – GENERAL CONCEPTS 396
MACROPHAGES IN ASTHMA 397
SUMMARY 401
References 401
Chapter 23 - Biology of Epithelial Cells 405
EPITHELIAL ANATOMY AND PHENOTYPE 405
CELL–CELL ADHESION AND COMMUNICATION 406
EPITHELIAL CHANGES IN ASTHMA 408
EPITHELIAL CELLS AND AIRWAY INFLAMMATION 408
LEUKOCYTE–EPITHELIAL INTERACTIONS 411
EPITHELIAL CELLS AND AIRWAY REMODELING 411
EPITHELIAL CELLS AND HOST DEFENSE 412
EPITHELIUM AND INNATE IMMUNITY 413
SUMMARY 416
References 416
Chapter 24 - Biology of Endothelial Cells 419
INTRODUCTION 419
THE ENDOTHELIUM AND REGULATION OF THE INFLAMMATORY RESPONSE 419
ENDOTHELIAL CELL INJURY DURING ACUTE INFLAMMATION 422
ENDOTHELIAL CELLS IN ALLERGY AND ASTHMA 427
CONCLUSIONS 429
References 429
Chapter 25 - Biology of Airway Smooth ­Muscle Cells 431
INTRODUCTION 431
ASM CONTRACTION AND AIRWAY HYPERRESPONSIVENESS 432
CELLULAR AND MOLECULAR MECHANISMS REGULATING AIRWAY SMOOTH MUSCLE CELL GROWTH 433
SYNTHETIC FUNCTION OF ASM 437
SUMMARY 440
References 440
Chapter 26 - Regulation of Cell Survival 445
INTRODUCTION 445
KEY REGULATORS OF CELL ­SURVIVAL 445
MAST CELLS 447
EOSINOPHILS 448
T CELLS 449
DENDRITIC CELLS 450
RESOLUTION OF INFLAMMATION 450
CONCLUSIONS 451
References 451
Chapter 27 - Protease-Activated Pathways of Inflammation 455
INTRODUCTION 455
STRUCTURE AND INTRACELLULAR SIGNALING OF PROTEASE-ACTIVATED RECEPTORS 456
PROTEASES THAT ACTIVATE PARs 458
FUNCTIONS OF PARs AND PROTEASES IN INDIVIDUAL CELL TYPES 460
PROTEASE INHIBITORS 460
DISEASE CORRELATIONS 463
MODULATION OF PAR FUNCTIONS AS A POTENTIAL TREATMENT 465
CONCLUSION 465
References 466
Chapter 28 - Animal Models of Allergen-­Induced Asthma 469
INTRODUCTION 469
CHARACTERISTICS OF ANIMAL MODELS OF ALLERGIC ASTHMA 470
CHARACTERISTICS AND ASSESSMENT OF THE ALLERGIC ASTHMA PHENOTYPE 472
DISSECTING MECHANISMS IN ANIMAL MODELS OF ALLERGIC ASTHMA 474
EXAMINING THE KINETICS OF THE ASTHMATIC RESPONSE 475
USING ANIMAL MODELS TO IDENTIFY NOVEL ASTHMA SUSCEPTIBILITY GENES 475
T-CELL MEDIATORS OF ALLERGIC ASTHMA 477
INNATE IMMUNE RESPONSES IN ASTHMA 481
CONCLUSION 482
References 482
Chapter 29 - Pathophysiology of Allergic Inflammation 487
INTRODUCTION 487
INFLAMMATORY CELLS 488
INFLAMMATORY MEDIATORS 491
EFFECTS OF INFLAMMATION 494
TRANSCRIPTION FACTORS 498
ANTIINFLAMMATORY MECHANISMS IN ALLERGY 499
FUTURE DIRECTIONS 500
References 501
Chapter 30 - Immunopathology of Allergic Airway Inflammation 505
INTRODUCTION 505
IMMUNOGLOBULIN E AND RECEPTORS 505
KEY INFLAMMATORY CELLS IN HUMAN ALLERGIC AIRWAYS DISEASE 507
Th2 CYTOKINE EXPRESSION IN HUMAN ALLERGIC AIRWAYS DISEASE 512
CHEMOKINES IN ALLERGIC AIRWAYS INFLAMMATION 517
TRANSCRIPTION FACTORS 520
SUMMARY 522
References 522
Section B - AEROBIOLOGY AND ALLERGENS 525
Chapter 31 - Air Pollution: Indoor and ­Outdoor 527
INTRODUCTION 527
NATURE OF AIRBORNE ­CONTAMINANTS 527
BIOLOGICAL EFFECTS OF SPECIFIC AIR POLLUTANTS 531
GAS PHASE AIR POLLUTANTS 534
OXIDANT BIOLOGY AND EVIDENCE FOR GENETIC INFLUENCES ON THE RESPONSE TO POLLUTANTS 535
INTERVENTIONS FOR THE ­EFFECTS OF POLLUTANTS ON AIRWAY ­PHYSIOLOGY 537
SUMMARY 538
References 538
Chapter 32 - Aerobiology of Outdoor Allergens 541
AEROALLERGENS AND SOURCES 541
FACTORS INFLUENCING CLINICAL SIGNIFICANCE OF AEROALLERGENS 541
DETECTION OF AEROALLERGENS 542
POLLEN AEROALLERGENS 544
FUNGI AS AEROALLERGENS 554
OTHER PLANT AND MICROBIAL PARTICLES AS ALLERGEN SOURCES 567
References 568
Chapter 33 - Indoor Allergens 571
INTRODUCTION 571
HISTORY 571
RELEVANCE TO ALLERGIC DISEASES 573
SOURCES OF INDOOR ALLERGENS 573
MOLECULAR BIOLOGY 578
INDOOR ALLERGEN EXPOSURE AND SENSITIZATION OR DISEASE 578
AIR-BORNE INDOOR ALLERGENS 579
AVOIDANCE MEASURES FOR INDOOR ALLERGENS 581
IMMUNE RESPONSES TO ALLERGENS FROM DIFFERENT SOURCES 583
CONCLUSIONS 584
References 584
Chapter 34 - Preparation and Standardization of Allergen Extracts 589
INTRODUCTION 589
SOURCE MATERIALS 590
MANUFACTURE OF ALLERGEN EXTRACTS 593
STABILITY OF ALLERGEN EXTRACTS 595
US STANDARDIZATION OF EXTRACTS 595
ALLERGEN EXTRACTS IN EUROPE 599
SUMMARY 599
References 599
Chapter 35 - The Structure and Function of Allergens 601
INTRODUCTION 601
ALLERGEN NOMENCLATURE 602
ALLERGENS AND ALLERGEN SOURCES 602
AEROALLERGENS – POLLENS 602
AEROALLERGENS – FUNGI 608
AEROALLERGENS – ANIMAL-DERIVED 613
AEROALLERGENS – ARTHROPOD-DERIVED 615
AEROALLERGENS – OCCUPATIONAL 617
INGESTED ALLERGENS 622
INJECTED INSECT ALLERGENS 623
PATHOGEN-DERIVED ALLERGENS AND AUTOALLERGENS 627
THREE-DIMENSIONAL ­STRUCTURES OF ALLERGENS 629
ALLERGEN BIOCHEMISTRY, IMMUNOGENICITY, AND INFLAMMATION 631
CONCLUSIONS 639
References 639
Section C - PHYSIOLOGY 641
Chapter 36 - Structural and Functional Cutaneous Immunology 643
INTRODUCTION 643
CELLS AND STRUCTURE OF THE SKIN 643
CUTANEOUS IMMUNOLOGY 652
SUMMARY 660
References 662
Chapter 37 - Airway Smooth Muscle and ­Related Extracellular Matrix in Normal and Asthmatic Lung 665
INTRODUCTION 665
STRUCTURE AND FUNCTION OF AIRWAY SMOOTH MUSCLE 666
DETERMINANTS OF AIRWAY NARROWING 668
CYTOSKELETAL ELEMENTS OF AIRWAYS MODULATE MUSCLE ­CONTRACTION 669
ROLE OF EXTRACELLULAR MATRIX IN AIRWAY REMODELING IN ASTHMA 670
ASTHMATIC AIRWAY SMOOTH MUSCLE MORPHOLOGY AND ­MECHANICAL PROPERTIES 671
IMPLICATIONS REGARDING THERAPY FOR ASTHMA 672
UNIFYING HYPOTHESIS: ­ALTERED MECHANICAL RESTRAINTS AND ­MUSCLE PLASTICITY INDUCE ­EXCESSIVE AIRWAY SMOOTH ­MUSCLE SHORTENING IN ASTHMA 673
References 673
Chapter 38 - Development, Structure, and Physiology in Normal Lung and in Asthma 677
INTRODUCTION 677
LUNG DEVELOPMENT 677
AIRWAY REMODELING 678
AIRFLOW LIMITATION 678
AIRWAY HYPER-RESPONSIVENESS 683
LUNG PARENCHYMA 683
AIRWAY CLOSURE 685
PFT INTERPRETATION 685
INTERPRETATION SUMMARY 689
References 689
Chapter 39 - Airway Mucus and the Mucociliary System 691
INTRODUCTION 691
CONSTITUENTS OF AIRWAY MUCUS 692
CELLULAR REGULATION OF MUCOCILIARY CLEARANCE AND SECRETION' 694
MUCIN PACKAGING AND DISCHARGE FROM AIRWAY SECRETORY CELLS 696
MUCOCILIARY CLEARANCE 696
CLINICAL IMPORTANCE AND CELLULAR CHARACTERISTICS OF MUCUS HYPERSECRETION IN ASTHMA 696
PATHOPHYSIOLOGY OF MUCUS HYPERSECRETION IN ASTHMA 699
TREATMENT OF MUCUS HYPERSECRETION IN ASTHMA 703
SUMMARY 706
References 706
Chapter 40 - Aerosols and Aerosol Drug Delivery Systems 711
INTRODUCTION 711
DEFINITION AND TYPES OF AEROSOLS 712
AEROSOLS FOR THERAPY 712
AEROSOL DEPOSITION MECHANISMS 714
NOMENCLATURE FOR INDICATORS\r\nOF DRUG DELIVERY DEVICE\r\nPERFORMANCE 716
AEROSOL DRUG DELIVERY DEVICES 718
INHALER SELECTION FOR THERAPY 728
SUMMARY 729
Chapter 41 - Anatomy and Physiology of the Nose and Control of Nasal Airflow 733
FUNCTIONS OF THE NOSE 733
EMBRYOLOGY AND ANATOMY OF THE NOSE 734
NASAL AIRFLOW 738
References 743
e9780323056595v2 745
Front Cover 745
Middleton’s Allergy Seventh edition Principles & Practice 748
Copyright Page 749
Contents 750
Preface 758
Preface to the first edition 760
Contributors 762
Section D - CLINICAL SCIENCE 777
Chapter 42 - Epidemiology of Asthma and Allergic Diseases 779
THE OCCURRENCE OF ASTHMA 779
EPIDEMIOLOGY OF ASTHMA 779
RISK FACTORS FOR ASTHMA 799
NATURAL HISTORY OF ASTHMA 814
SUMMARY OF ASTHMA EPIDEMIOLOGY 820
ALLERGIC DISEASES 820
References 824
Chapter 43 - Factors Underlying the Increasing Incidence and Prevalence of Allergic Diseases 833
INTRODUCTION 833
THE HYGIENE HYPOTHESIS 834
OTHER CHANGING EXPOSURES 838
CONCLUSION 841
References 841
Chapter 44 - Development and Prevention of Atopic Disease in Childhood 843
INTRODUCTION 843
NATURAL HISTORY OF ­SENSITIZATION AND ATOPIC ­MANIFESTATIONS 843
DETERMINANTS OF DISEASE ­DEVELOPMENT IN CHILDHOOD 844
PRIMARY PREVENTION 848
PERSPECTIVES 848
References 849
Chapter 45 - Immune Complexes and ­Allergic Disease 851
INTRODUCTION 851
IMMUNOCHEMICAL FACTORS IN IMMUNE COMPLEX BIOACTIVITY 852
CLEARANCE OF IMMUNE ­COMPLEXES 852
IMMUNE COMPLEX -INTERACTION WITH Fcγ-RECEPTOR-BEARING CELLS 853
IMMUNE COMPLEXES AND ­INDUCTION OF THE IMMUNE ­RESPONSE 854
ENDOTHELIAL CELLS, CELL ­ADHESION MOLECULES, AND ­CYTOKINES 855
ANIMAL MODELS OF ANTIBODY-MEDIATED AND ­IMMUNE COMPLEX-MEDIATED TISSUE ­DAMAGE 855
METHODS OF ­DETECTING ­CIRCULATING IMMUNE ­COMPLEXES 857
DISEASES MEDIATED BY ­CIRCULATING IMMUNE ­COMPLEXES 858
LABORATORY FINDINGS 861
TREATMENT 862
References 862
Chapter 46 - Primary Immunodeficiency Diseases 865
INTRODUCTION 865
X-LINKED DEFECTS 868
DEFECTS OF INNATE IMMUNITY 883
AUTOSOMAL DEFECTS FOR WHICH THE MOLECULAR BASIS IS NOT KNOWN 885
INTRAUTERINE DIAGNOSIS AND CARRIER DETECTION OF PRIMARY IMMUNODEFICIENCY DISEASES 890
TREATMENT 890
References 891
Chapter 47 - Human Immunodeficiency Virus and Allergic Disease 895
INTRODUCTION 895
PATHOPHYSIOLOGY AND IMMUNOLOGIC CHANGES 895
PATHOGENESIS 897
CLINICAL FEATURES OF HIV INFECTION 900
DISEASE PROGRESSION 902
CLINICAL HIV MANIFESTATIONS SUGGESTING ALLERGIC DISEASE 903
CONCLUSION 906
References 907
Chapter 48 - Clinical Significance of Immunoglobulin E 909
INTRODUCTION 909
NORMAL IgE PRODUCTION 910
IgE IN ALLERGIC DISEASE 911
IgE IN INFECTIOUS AND PARASITIC DISEASE 915
IgE IN NON-ATOPIC DISEASES 917
ENVIRONMENTAL EXPOSURES AND IgE 918
References 918
Chapter 49 - Eosinophilia and Eosinophil-Related Disorders 923
INTRODUCTION 923
ALLERGIC DISORDERS 924
INFECTIOUS DISEASES 926
HEMATOLOGIC AND NEOPLASTIC DISORDERS 928
DISEASES WITH SPECIFIC ORGAN INVOLVEMENT 931
IMMUNOLOGIC REACTIONS 939
ENDOCRINE 939
OTHER 939
References 939
Chapter 50 - Eosinophilic Gastroenteropathies 943
OVERVIEW OF EGID 943
EOSINOPHILIC ESOPHAGITIS 948
EOSINOPHILIC GASTRITIS AND GASTROENTERITIS 950
EOSINOPHILIC COLITIS 951
CONCLUSION 952
References 953
Chapter 51 - Asthma Pathogenesis 957
INTRODUCTION 957
PREVALENCE 957
PATHOLOGY 958
ORIGINS OF ASTHMA: RISK FACTORS FOR DISEASE 962
PROVOCATEURS OF ASTHMA AND THEIR MECHANISMS OF ACTION 965
CELLULAR INFLAMMATION AND ITS REGULATION 969
AIRWAY HYPER-­RESPONSIVENESS 973
AIRFLOW OBSTRUCTION 974
AIRWAY REMODELING 975
CONCLUSIONS 979
References 979
Chapter 52 - Pathology of Asthma Compared with Chronic Obstructive Pulmonary Disease 985
OVERVIEW OF ASTHMA AND COPD 985
REMODELING AND INFLAMMATION 987
SPUTUM AND BRONCHOALVEOLAR LAVAGE FLUID 987
AIRWAY PLUGGING 988
STRUCTURAL CHANGES (REMODELING) 988
INFLAMMATION IN ASTHMA 994
COMPARISON OF INFLAMMATION IN MILD ASTHMA AND COPD 997
SEVERE CHRONIC DISEASE 998
EXACERBATIONS 998
CHILDHOOD AND INFANT ‘ASTHMA’ 999
CONCLUSION 999
References 1000
Chapter 53 - Occupational Asthma 1003
AGENTS THAT CAUSE OCCUPATIONAL ASTHMA 1004
PHYSIOPATHOLOGY 1004
EXPOSURE AND HOST FACTORS 1008
NATURAL HISTORY 1011
CLINICAL ASPECTS 1011
MEDICOLEGAL ASPECTS, SOCIAL IMPACT, AND SURVEILLANCE 1014
PREVENTION 1014
OCCUPATIONAL ASTHMA AS A SATISFACTORY MODEL FOR ­ENVIRONMENTAL ASTHMA 1015
SPECIFIC AGENTS CAUSING OCCUPATIONAL ASTHMA 1015
CONCLUSIONS 1017
References 1017
Chapter 54 - Immunologic Non-Asthmatic Diseases of the Lung 1021
INTRODUCTION 1021
WEGENER’S GRANULOMATOSIS 1021
MICROSCOPIC POLYANGIITIS 1026
CHURG-STRAUSS SYNDROME 1027
SARCOIDOSIS 1028
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS 1031
GOODPASTURE’S DISEASE 1032
References 1033
Chapter 55 - Allergic and Non-Allergic Rhinitis 1037
INTRODUCTION 1037
NASAL ANATOMY AND ­PHYSIOLOGY 1038
EPIDEMIOLOGY 1039
ALLERGIC RHINITIS 1040
NON-ALLERGIC RHINITIS 1041
PERSONAL BURDEN AND ­SOCIOECONOMIC IMPACT 1043
MECHANISM OF ALLERGIC ­RHINITIS 1044
DIAGNOSIS 1046
COMORBIDITY 1048
TREATMENT OF RHINITIS 1048
RHINITIS IN PREGNANCY 1050
CONCLUSION 1051
References 1051
Chapter 56 - Nasal Polyps and Rhinosinusitis 1055
GENERAL REMARKS 1055
NASAL POLYPS 1055
ACUTE AND CHRONIC ­RHINOSINUSITIS 1062
References 1067
Chapter 57 - Insect Allergy 1069
STINGING INSECT ALLERGY 1069
BITING INSECT ALLERGY 1079
INHALANT INSECT ALLERGY 1079
References 1079
Chapter 58 - Natural Rubber Latex Allergy 1083
BACKGROUND 1083
LATEX ALLERGENS 1084
EPIDEMIOLOGY 1085
CLINICAL MANIFESTATIONS 1086
DIAGNOSIS 1086
MANAGEMENT 1086
LONG-TERM FOLLOW-UP ­STUDIES 1088
CONCLUSION 1089
References 1089
Chapter 59 - Anaphylaxis 1091
TERMINOLOGY 1091
INCIDENCE AND CAUSATIVE AGENTS 1091
PATHOLOGY 1095
PATHOPHYSIOLOGY 1096
BASOPHIL AND MAST CELL ­DEGRANULATION SYNDROMES 1097
MECHANISMS INVOLVED IN THE PRODUCTION OF ANAPHYLACTIC SHOCK 1099
SIGNS AND SYMPTOMS 1100
DIFFERENTIAL DIAGNOSIS 1102
THE LABORATORY IN THE ­DIFFERENTIAL DIAGNOSIS 1104
PREVENTION AND MANAGEMENT 1105
FATALITIES 1110
References 1111
Chapter 60 - Mastocytosis 1115
INTRODUCTION 1115
ETIOLOGY AND PATHOGENESIS 1115
CLINICAL FEATURES 1117
DIAGNOSIS AND EVALUATION 1122
TREATMENT 1124
PROGNOSIS 1125
References 1125
Chapter 61 - Urticaria and Angioedema 1127
INTRODUCTION 1127
MEDIATOR PATHWAYS 1127
GENERAL CONSIDERATIONS OF ETIOLOGY, PATHOGENESIS, AND TREATMENT 1129
PHYSICAL URTICARIA AND ­ANGIOEDEMA 1131
HEREDITARY FORMS OF ­URTICARIA AND ANGIOEDEMA 1137
CHRONIC IDIOPATHIC URTICARIA AND IDIOPATHIC ANGIOEDEMA 1139
References 1143
Chapter 62 - Atopic Dermatitis 1147
INTRODUCTION 1147
CLINICAL ASPECTS 1147
ROLE OF THE EPIDERMAL BARRIER 1151
ROLE OF ALLERGENS 1151
IMMUNOLOGY 1152
MANAGEMENT 1156
CONCLUSION 1163
References 1163
Chapter 63 - Contact Dermatitis 1169
INTRODUCTION 1169
EPIDERMAL CELLS 1172
LYMPHOCYTES 1175
CONCLUSIONS 1177
References 1178
Chapter 64 - Allergic and Immunologic ­Diseases of the Eye 1181
INTRODUCTION 1181
ANATOMY AND PHYSIOLOGY OF THE EYE 1181
ALLERGIC DISEASES OF THE EYE 1183
CONJUNCTIVAL PROVOCATION TESTING 1190
GENERAL PRINCIPLES OF TREATMENT FOR ALLERGIC EYE DISEASE 1190
CONTACT DERMATITIS 1194
IMMUNOLOGIC DISEASES OF THE EYE 1195
SUMMARY 1199
References 1199
Chpter 65 - Adverse Reactions to Foods 1203
BACKGROUND AND DEFINITIONS 1203
PREVALENCE OF FOOD HYPERSENSITIVITY 1204
ANTIGEN HANDLING BY THE GASTROINTESTINAL TRACT 1205
FOOD ALLERGENS 1207
PATHOPHYSIOLOGIC MECHANISMS 1211
CLINICAL MANIFESTATIONS OF FOOD HYPERSENSITIVITY 1212
DIAGNOSING ADVERSE FOOD ­REACTIONS 1221
THERAPY OF FOOD ALLERGIC DISORDERS 1223
NATURAL HISTORY OF FOOD HYPERSENSITIVITY 1226
PROPHYLAXIS OF FOOD ­HYPERSENSITIVITY 1227
SUMMARY 1227
References 1227
Chapter 66 - Adverse Reactions to Food and Drug Additives 1233
INTRODUCTION 1233
LABELING OF FOOD AND DRUG ADDITIVES 1233
CLINICAL AND DIAGNOSTIC APPROACHES TO ADVERSE REACTIONS TO FOOD AND DRUG ADDITIVES 1234
FOOD AND DRUG ADDITIVES KNOWN OR SUSPECTED TO CAUSE ADVERSE REACTIONS n 1239
References 1249
Chapter 67 - Adverse Reactions to Vaccines for Infectious Diseases 1253
PUTTING ADVERSE REACTIONS TO VACCINES IN PERSPECTIVE n 1253
CHANGES IN US VACCINE RECOMMENDATIONS RELATED TO ADVERSE REACTIONS n 1255
IgE-MEDIATED REACTIONS TO VACCINES n 1255
NON-IgE-MEDIATED REACTIONS TO VACCINES n 1260
ADVERSE REACTIONS TO VACCINES FOR BIOLOGICAL AGENTS USED AS WEAPONS n 1262
CONTROVERSIES REGARDING LONG-TERM CONSEQUENCES OF VACCINATION n 1263
VACCINATION RELATIVE TO IMMUNOCOMPROMISE AND IMMUNOGLOBULIN ­PREPARATIONS n 1264
SUMMARY 1264
References 1265
Chapter 68 - Drug Allergy 1269
INTRODUCTION 1269
EPIDEMIOLOGY AND BURDEN OF DRUG HYPERSENSITIVITY 1270
HOW DRUGS ARE RECOGNIZED BY THE IMMUNE SYSTEM 1270
FACTORS INFLUENCING DRUG IMMUNOGENICITY 1274
SPECIFICITY OF DRUG-INDUCED IMMUNE RESPONSES 1275
IMMUNOPATHOLOGIC FEATURES OF DRUG ALLERGY 1276
RISK FACTORS FOR DRUG ­HYPERSENSITIVITY 1277
NON-ALLERGIC DRUG ­HYPERSENSITIVITY (PSEUDOALLERGIC) REACTIONS 1279
DIAGNOSIS OF DRUG ALLERGY 1280
MANAGEMENT OF DRUG ­ALLERGY 1284
SUMMARY 1287
References 1287
Chapter 69 - Hypersensitivity to Aspirin and Non-Steroidal Antiinflammatory Drugs 1291
INTRODUCTION 1291
HISTORICAL NOTE 1291
CLASSIFICATION 1292
ASPIRIN-INDUCED ASTHMA 1292
ASTHMA IMPROVED BY ASPIRIN 1301
ASPIRIN-SENSITIVE URTICARIA/ANGIOEDEMA 1301
ALLERGIC REACTIONS TO NSAIDs 1303
References 1304
Section E - DIAGNOSIS AND APPROACH TO THE PATIENT 1309
Chapter 70 - Laboratory tests for allergic and Immunodeficiency diseases: principles and interpretations 1311
TERMINOLOGY 1312
HUMORAL IMMUNE RESPONSES OF IMPORTANCE TO ALLERGIC AND IMMUNODEFICIENCY DISEASE 1312
ALLERGENS 1314
IMMUNOCHEMICAL METHODS FOR MEASUREMENT Of IGE PROTEIN 1319
IMMUNOCHEMICAL METHODS FOR MEASUREMENT OF IgE ANTIBODIES OF DEFINED ALLERGEN SPECIFICITY 1319
QUALITY ASSURANCE 1322
SERUM TRYPTASE 1324
OTHER ANALYTES OF INTEREST IN ALLERGIC DISORDERS AND ASTHMA 1324
ASSESSMENT OF ENVIRONMENTAL ALLERGENS 1325
LABORATORY METHODS IN CELLULAR IMMUNOLOGY 1326
CONCLUSION 1328
References 1328
Chapter 71 - In Vivo Methods for the Study of Allergy 1331
PATHOPHYSIOLOGY OF THE SKIN RESPONSE 1331
TECHNIQUES OF SKIN TESTING 1332
FACTORS AFFECTING SKIN TESTS 1336
INTERPRETATION OF SKIN TESTS 1339
SKIN TESTS USED FOR NON-DIAGNOSTIC PURPOSES 1341
CONCLUSIONS 1342
References 1342
Chapter 72 - Nasal Provocation Testing 1345
INTRODUCTION 1345
NASAL ALLERGEN PROVOCATION 1345
METHODS OF NASAL PROVOCATION 1347
NASAL PROVOCATION WITH PHYSICAL, CHEMICAL, AND BIOCHEMICAL STIMULI 1350
OUTCOMES OF NASAL PROVOCATION 1351
References 1356
Chapter 73 - Bronchial Challenge Testing 1359
AIRWAY HYPERRESPONSIVENESS AND ITS MEASUREMENT 1359
HISTAMINE AND METHACHOLINE CHALLENGES 1360
INDIRECT AIRWAY HYPERRESPONSIVENESS 1362
NON-SELECTIVE CHALLENGES: CLINICAL UTILITY 1363
ALLERGEN CHALLENGE 1365
OCCUPATIONAL CHALLENGES 1369
SUMMARY 1369
References 1370
Chapter 74 - Oral Food Challenge Testing 1373
INTRODUCTION 1373
INDICATIONS FOR ORAL CHALLENGE TESTING 1373
METHODOLOGY 1374
RISK AND TREATMENT OF ORAL FOOD CHALLENGES 1378
References 1380
Chapter 75 - Approach to Infants and Children with Asthma 1383
INTRODUCTION 1383
EPIDEMIOLOGY 1383
PATHOPHYSIOLOGY 1387
GENETICS 1387
DIAGNOSIS AND EVALUATION 1388
COEXISTING ISSUES IN PEDIATRIC ASTHMA 1392
MANAGEMENT OF ASTHMA 1393
MANAGING EXACERBATIONS 1398
PREVENTION 1403
PROGNOSIS 1403
References 1404
Chapter 76 - Approach to Adults with Asthma 1409
INTRODUCTION 1410
DEFINITION 1410
PREVALENCE OF ASTHMA, AND ASSOCIATED MORBIDITY AND ­MORTALITY 1410
NATURAL HISTORY OF THE DISEASE 1410
FACTORS PREDISPOSING TO ASTHMA: ENVIRONMENT, GENETICS, AND OTHERS 1410
PATHOPHYSIOLOGY OF ASTHMA: TARGETS FOR THERAPY 1411
DIAGNOSIS 1412
MANAGEMENT OF ASTHMA 1413
EVALUATION OF ASTHMA 1413
ASSESSMENT OF CONTROL 1414
ASTHMA SEVERITY 1415
ASSESSMENT OF ALLERGIC ­STATUS 1416
TRIGGERS AND INDUCERS 1416
ASTHMA TREATMENT PLAN 1417
ENVIRONMENTAL CONTROL AND AVOIDANCE OF TRIGGERS n 1419
PHARMACOTHERAPY 1420
RESCUE MEDICATION 1420
CONTROLLERS 1420
OTHER MEDICATIONS 1423
IMMUNOTHERAPY 1423
ASTHMA MANAGEMENT PLAN 1423
COMORBIDITES 1424
OTHER MEASURES 1424
ASTHMA AND DIABETES 1426
ASTHMA AND SURGERY/­ANESTHESIA 1426
THE TRAVELING ASTHMATIC ­PATIENT 1426
FUTURE DEVELOPMENTS 1427
References 1427
Chapter 77 - Emergency Treatment and ­Approach to the Patient with Acute Asthma 1431
INTRODUCTION 1431
EVALUATION 1432
TREATMENT 1432
OTHER ISSUES 1443
CONCLUSION 1446
References 1446
Chapter 78 - Approach to the Patient with Exercise-Induced Airway Narrowing* 1449
INTRODUCTION 1449
PATHOGENESIS 1450
CLINICAL PHYSIOLOGIC FEATURES 1453
REFRACTORY PERIOD 1454
LATE REACTIONS 1454
EXERCISE-INDUCED ASTHMA AND BRONCHIAL REACTIVITY 1454
DIAGNOSIS 1454
THERAPY 1455
References 1456
Chapter 79 - Approach to the Patient with Chronic Cough 1459
INTRODUCTION 1459
PATHOPHYSIOLOGY OF COUGH 1459
DIAGNOSTIC CONSIDERATIONS 1459
THERAPEUTIC CONSIDERATIONS 1466
CONCLUSION 1467
References 1467
Chapter 80 - Approach to the Patient with Recurrent Infections 1469
INTRODUCTION 1469
THE MEDICAL HISTORY IN IMMUNODEFICIENCY 1470
PHYSICAL EXAMINATION 1478
SCREENING LABORATORY TESTS FOR THE EVALUATION OF PATIENTS wITH RECURRENT INFECTIONS 1482
EVALUATION FOR B-CELL IMMUNODEFICIENCY 1483
SUMMARY AND CONCLUSIONS 1484
References 1484
Chapter 81 - Asthma and Allergic Diseases during Pregnancy 1487
INTRODUCTION 1487
MATERNAL RESPIRATORY PHYSIOLOGIC CHANGES 1487
DETERMINANTS OF FETAL OXYGENATION 1488
MATERNAL IMMUNE FUNCTION 1488
GENERAL THERAPEUTIC PRINCIPLES 1490
COURSE AND MANAGEMENT OF SPECIFIC DISEASES 1497
References 1507
Section F - THERAPEUTICS 1509
Chapter 82 - Allergen Control in the Prevention and Management of Allergic Disease 1511
INTRODUCTION 1511
ENVIRONMENTAL CONTROL MEASURES 1512
ENVIRONMENTAL CONTROL THE MANAGEMENT OF ALLERGIC DISEASE 1514
ENVIRONMENTAL CONTROL IN THE PREVENTION OF ALLERGIC DISEASE 1517
CONCLUSIONS 1519
References 1519
Chapter 83 - Principles of ­Pharmacotherapeutics 1523
GOALS OF THERAPY 1523
BASIC PRINCIPLES OF CLINICAL PHARMACOLOGY 1524
PHARMACODYNAMICS 1524
PHARMACEUTICS 1526
PHARMACOKINETIC PRINCIPLES 1527
PHARMACODYNAMIC ­VARIABILITY 1531
DRUG INTERACTIONS 1533
CONCLUSIONS 1534
References 1534
Chapter 84 - Adherence 1537
INTRODUCTION 1537
DEFINITIONS OF ADHERENCE 1537
EXTENT OF NON-ADHERENCE WITH ASTHMA THERAPIES 1538
BARRIERS TO ADHERENCE 1538
MEASURING ADHERENCE 1542
INTERVENTIONS TO IMPROVE ­ADHERENCE 1543
CONCLUSION 1545
References 1545
Chapter 85 - Beta-Adrenergic Agonists 1549
INTRODUCTION 1549
CATECHOLAMINE STRUCTURE-FUNCTION RELATIONSHIP 1550
SPECIFIC β2-ADRENERGIC \nBRONCHODILATORS 1550
ROUTES OF ADMINISTRATION 1553
PATIENT AND DEVICE VARIABLES IN INHALATION THERAPY 1554
NON-BRONCHODILATOR ACTIONS \nOF β2-ADRENERGIC AGONISTS 1556
ADVERSE EFFECTS 1557
β2-RECEPTOR DESENSITIZATION 1559
LOSS OF BRONCHOPROTECTION 1559
INCREASED BRONCHIAL RESPONSIVENESS 1559
TOXICITIES OF β2-AGONIST ENANTIOMERS 1559
CONCERNS OVER REGULAR \nβ-ADRENERGIC AGONIST USE 1560
ASTHMA DEATHS 1561
CLINICAL ROLE IN ASTHMA THERAPY 1561
LONG-TERM CONTROL MEDICATIONS 1562
COMPARISON WITH THEOPHYLLINE 1562
COMPARISON WITH LEUKOTRIENE MODIFIERS 1562
CONCLUSIONS 1563
FUTURE PARADIGMS IN ASTHMA MANAGEMENT 1563
References 1563
Chapter 86 - Theophylline and Phosphodiesterase Inhibitors 1569
INTRODUCTION 1569
CHEMISTRY 1569
MOLECULAR MECHANISMS OF ACTION 1570
CELLULAR EFFECTS 1572
PHARMACOKINETICS 1574
ROUTES OF ADMINISTRATION 1575
CLINICAL USE 1575
SIDE EFFECTS 1576
FUTURE OF THEOPHYLLINE 1576
PHOSPHODIESTERASE INHIBITORS 1576
References 1578
Chapter 87 - Histamine and H1-Anti­histamines 1581
INTRODUCTION 1581
HISTAMINE AND HISTAMINE ­RECEPTORS: MOLECULAR BASIS OF ACTION 1582
H1-ANTIHISTAMINES 1588
SUMMARY AND FUTURE DIRECTIONS 1607
References 1608
Chapter 88 - Pharmacology of Glucocorticoids in Allergic Disease 1613
INTRODUCTION 1613
PHARMACOLOGY 1613
TOXICITY, METABOLIC EFFECTS, AND STRESS 1617
MOLECULAR BIOLOGY 1618
GLUCOCORTICOID RESISTANCE 1621
ARACHIDONIC ACID METABOLISM 1621
ADRENERGIC SYSTEM 1622
CELLULAR AND MOLECULAR MECHANISMS 1622
ANTIGEN CHALLENGE 1630
CONCLUSIONS 1630
References 1631
Chapter 89 - Glucocorticoids: Clinical ­Pharmacology 1639
INTRODUCTION 1639
MANAGEMENT PRINCIPLES: EFFICACY 1639
MANAGEMENT PRINCIPLES: ­ADVERSE EFFECTS 1647
References 1652
Chapter 90 - The Chromones: Cromolyn Sodium and Nedocromil Sodium 1655
CHEMISTRY 1655
PHARMACOKINETICS 1656
EXPERIMENTAL ­PHARMA­COLOGY 1657
HUMAN TRIALS 1659
ANTIINFLAMMATORY EFFECTS 1659
MECHANISM OF ACTION 1660
CLINICAL TRIALS 1660
SAFETY AND TOXICITY 1663
References 1663
Chapter 91 - Cholinergic Mechanisms and Anticholinergic Therapy in ­Respiratory Diseases 1667
INTRODUCTION 1667
PARASYMPATHETIC PHYSIOLOGY AND PHARMACOLOGY IN THE LUNGS 1668
PARASYMPATHETIC NERVES ­SUPPLYING AIRWAYS 1669
DYSFUNCTION OF ­MUSCARINIC RECEPTORS ON CHOLINERGIC NERVES 1670
PHARMACOLOGY OF ANTICHOLINERGIC DRUGS 1671
RATIONALE FOR USE OF ANTICHOLINERGIC DRUGS IN TREATMENT OF AIRWAY DISEASE 1672
THERAPEUTIC USE OF ANTICHOLINERGIC MEDICATIONS 1676
CHRONIC OBSTRUCTIVE PULMONARY DISEASE 1677
RHINITIS 1678
CONCLUSIONS 1678
References 1678
Chapter 92 - Antileukotriene Therapy in Asthma 1683
INTRODUCTION 1683
THE LEUKOTRIENE PATHWAY 1684
BIOLOGIC PROPERTIES OF LEUKOTRIENES 1685
INHIBITION/ANTAGONISM OF LEUKOTRIENES IN RELATION TO HUMAN ASTHMATIC INFLAMMATION 1686
EFFICACY IN CHRONIC ASTHMA 1688
SAFETY 1692
POSITIONING OF ANTILEUKOTRIENE THERAPY IN ASTHMA GUIDELINES 1693
References 1693
Chapter 93 - Pharmacogenomics of Asthma Therapies 1697
INTRODUCTION 1697
PHARMACOGENOMICS: DEFINITION AND BACKGROUND 1697
GENETIC VARIATIONS ASSOCIATED WITH CLINICAL OUTCOMES 1697
PHARMACOGENOMIC MECHANISMS 1698
APPROACHES TO PHARMACOGENOMIC ANALYSIS 1699
VARIABILITY IN RESPONSE TO ASTHMA THERAPIES 1699
PHARMACOGENOMICS OF β -AGONISTS 1700
OTHER β2-AR PHARMACOGENOMIC ASSOCIATIONS 1701
PHARMACOGENOMICS OF LEUKOTRIENE MODIFIERS 1702
CORTICOSTEROID PHARMACOG­ENOMICS 1703
PHARMACOGENOMICS OF OTHER ASTHMA THERAPIES 1704
CAVEATS IN INTERPRETING ­PHARMACOGENETIC ASSOCIATIONS 1704
IMPLICATIONS AND APPLICABILITY OF PHARMACOGENOMIC FINDINGS 1705
References 1705
Chapter 94 - Immunomodulators 1707
INTRODUCTION 1707
METHOTREXATE 1707
IMMUNOPHILIN-BINDING AGENTS AND CALCINEURIN INHIBITORS: CYCLOSPORIN, TACROLIMUS, AND PIMECROLIMUS 1709
INTRAVENOUS IMMUNOGLOBULIN 1712
DNA-BASED THERAPIES 1713
MYCOBACTERIAL VACCINES 1717
CYTOKINE-BASED THERAPY 1718
CONCLUSIONS 1719
References 1719
Chapter 95 - Immunotherapy for Inhalant Allergens 1721
HISTORICAL DEVELOPMENT 1721
CLINICAL EFFICACY OF ALLERGEN IMMUNOTHERAPY 1722
IMMUNOLOGIC RESPONSE TO INHALANT IMMUNOTHERAPY (Box 95.1) 1726
PRACTICAL CONSIDERATIONS IN ALLERGEN IMMUNOTHERAPY 1728
ALTERNATIVE EXTRACTS AND METHODS OF ADMINISTRATION 1733
CONCLUSION 1737
References 1738
Chapter 96 - Anti-IgE Therapy 1743
BACKGROUND 1743
MECHANISM OF ACTION 1744
OMALIZUMAB DISEASE-SPECIFIC EFFECTS 1746
DOSING 1750
SAFETY 1750
Conclusions 1751
References 1751
Chapter 97 - Unconventional Theories and Unproven Methods in ­Allergy 1755
INTRODUCTION 1755
UNPROVEN DIAGNOSTIC TESTS 1756
INAPPROPRIATE DIAGNOSTIC TESTS 1759
UNPROVEN TREATMENT METHODS 1761
INAPPROPRIATE THERAPY 1763
UNCONVENTIONAL THEORIES OF ALLERGIC DISEASE 1764
REMOTE PRACTICE OF ALLERGY 1769
CURRENT VS HISTORICAL PRACTICES 1769
PERSPECTIVE 1770
References 1770
Appendix A: CD molecules 1775
Appendix B: Internet Resources for Allergy and Immunology Professionals 1803
Appendix C: National Asthma Education and Prevention Program (NAEPP) and Global Initiative for Asthma (GINA) Guidelines 1807
Index 1831