Table of Contents

Cover image

Title Page

Copyright

Foreword

Preface

List of Contributors

Volume 1

Section A Basic Sciences Underlying Allergy and Immunology

1 Innate Immunity

Introduction

Microbial Pattern Recognition by the Innate Immune System

Resident Cellular Responses of Innate Immunity

Infiltrative Cellular Responses of Innate Immunity

Innate Instruction of Adaptive Immune Responses

Homeostasis in the Innate Immune System

Innate Immunity and Allergy

Summary

References

Self-Assessment Questions

2 Adaptive Immunity

Introduction

The Adaptive Immune Response in Allergic Disease

Components of the Adaptive Immune System

Features of the Adaptive Immune Response

Mechanisms of Diseases Involving Adaptive Immunity: Hypersensitivity Reactions

Conclusion

References

Self-Assessment Questions

3 Immunoglobulin Structure and Function

Introduction

B Lymphocytes and the Humoral Immune Response

Immunoglobulin Structure and Gene Rearrangement

Immunoglobulin Function

Immunoglobulins and Human Disease

Summary

References

Self-Assessment Questions

4 Immune Tolerance

Introduction

Central Tolerance in T Cells

Peripheral Tolerance Mechanisms

Antigen Presentation, Dendritic Cells, and Immune Tolerance

Regulatory T Cells

Transforming Growth Factor-β and Immune Tolerance

IL-10 and IL-10–Secreting Treg Cells

Therapeutic Application of Treg Cells

Breg Cells and Allergen Tolerance

Histamine Receptor 2 as a Major Player in Peripheral Tolerance

Immune Tolerance Induced in Sublingual Immunotherapy

Novel Allergen Immunotherapy Vaccines and Evidence for Induction of Peripheral Tolerance

Conclusion

References

Self-Assessment Questions

5 Cytokines in Allergic Inflammation

Introduction: Definition, Evolution of Cytokine Biology, and Nomenclature

Cytokine Production in Innate Immunity

Cytotoxic Immunity

Humoral Immunity

Cellular Immunity

Allergic Immunity

Antiinflammatory Cytokines

T Helper Lymphocyte Families

Summary

References

Self-Assessment Questions

6 Cellular Adhesion in Inflammation

Introduction

Selectins and Selectin Ligands

Integrins

Immunoglobulin Gene Superfamily

Galectins, Cadherins, and ORMDL3

Leukocyte Adhesion to Endothelium and Migration Across Endothelium

Leukocyte Adhesion to the Extracellular Matrix in Tissues

Regulation of Adhesion Molecule Expression

Human Disease Associated With Adhesion Molecule Deficiency

Adhesion Molecules in Human Allergic Inflammation

Potential Side Effects of Adhesion-Based Therapy: Progressive Multifocal Leukoencephalopathy

Summary

References

Self-Assessment Questions

7 Chemokines

Introduction

Definitions and Nomenclature

Chemokine Receptors and Signaling

Regulatory Mechanisms for the Chemokine Response

Biologic Roles of Chemokines

Human Allergic Diseases

Chemokine Receptor Mutations

Targeting the Chemokine System as a Therapeutic Strategy

Summary

References

Self-Assessment Questions

8 The Complement System

Overview

Introduction to the Complement System

The Classical Pathway

The Alternative Pathway

The Lectin Activation Pathway

The Membrane Attack Complex

Receptors and Biologic Functions

Regulation of Complement Activation

Disorders Associated With Complement Activation

Disorders Associated With Complement Deficiency

Management of Complement Deficiencies

Laboratory Assessment of Complement

References

Self-Assessment Questions

9 Lipid Mediators of Hypersensitivity and Inflammation

Generation of Lipid Mediator Precursors by Phospholipase A2

Eicosanoid Formation

Individual Prostanoids

Summary

References

Self-Assessment Questions

10 Molecular Biology and Genetic Engineering

Anatomy of the Gene

RNA and Protein Synthesis

DNA Repair

DNA Replication

Control of Gene Expression

DNA Rearrangement: Genetic Recombination

Recombinant DNA Technology

Epigenetics

Summary

References

Self-Assessment Questions

11 Biology of Lymphocytes

Introduction

T Lymphocytes

B Lymphocytes

Innate Lymphocytes

Innate Lymphoid Cells

Summary

References

Self-Assessment Questions

12 Innate Lymphoid Cells

Introduction

Innate Lymphoid Cell Development

Innate Lymphoid Cell Plasticity

Identification of Innate Lymphoid Cell 2s

Cytokine and Growth Factor Production by ILC2s

Regulation of ILC2 Function

ILC2s and Type 2 Inflammation in Preclinical Disease Models

ILC2 in Human Allergic Diseases

References

Self-Assessment Questions

13 Antigen-Presenting Dendritic Cells

Introduction

Dendritic Cell Terminology and Heterogeneity

Antigen Uptake

Antigen Presentation

Integrated Function of Dendritic Cells in the Immune Response

Role for Dendritic Cells in Allergic Sensitization in Humans

Dendritic Cells in Allergic Asthma

Concluding Remarks

References

Self-Assessment Questions

14 Biology of Mast Cells and Their Mediators

Introduction

Basic Mast Cell Biology

Mast Cell Homing to Tissue

Mast Cell Heterogeneity

Mast Cell Ultrastructure and Mediators

Mechanisms of Mast Cell Activation

Mast Cells in Allergic Diseases and Asthma

Conclusion

References

Self-Assessment Questions

15 Biology of Basophils

Introduction

Development and Morphology

Functional and Phenotypic Markers

Inflammatory Mediators

Basophil Activation

Pharmacologic Modulation of Secretion

Basophil Involvement in Disease

Summary

References

Self-Assessment Questions

16 Biology of Eosinophils

Introduction

Eosinophil Morphology, Production, and Tissue Distribution

Eosinophil-Derived Mediators

Eosinophil Phenotype

Eosinophil Recruitment and Accumulation

Eosinophil Activation and Effector Functions

Role of Eosinophils in Host Defense and Disease

Conclusion

References

Self-Assessment Questions

17 Biology of Neutrophils

Introduction

Neutrophil Migration

Mediators Released by Activated Neutrophils

Neutrophil Clearance and Death

Neutrophils in Asthma

Summary

References

Self-Assessment Questions

18 Biology of Monocytes and Macrophages

Introduction

Monocytes and Macrophage Subsets in the Lung

Origins of Monocytes and Macrophages

Phagocytosis

Elaboration of Mediators

Macrophage Activation and Polarization

Inflammation and Resolution

Macrophages in Asthma

Summary

References

Self-Assessment Questions

19 Airway Epithelial Cells

Introduction

Anatomy of the Airway Epithelium

Barrier Function of the Airway Epithelium

Airway Epithelium Repair Processes

Airway Epithelium Immune Responses

The Airway Epithelium in Asthma

Influence of Asthma Medications on the Asthmatic Epithelium

Summary

Acknowledgments

References

Self-Assessment Questions

20 Airway Smooth Muscle in Asthma

Introduction

Cellular and Molecular Mechanisms Regulating Smooth Muscle Cell Growth

Factors Regulating Airway Smooth Muscle Growth in Asthma

Signaling Pathways Affecting Airway Smooth Muscle Growth and Proliferation

Airway Smooth Muscle Contraction, Airway Hyperresponsiveness, and Relaxation

Summary

References

Self-Assessment Questions

21 Pathophysiology of Allergic Inflammation

Introduction

Inflammatory Cells

Nonatopic Allergic Disease

Inflammatory Mediators

Structural Cells

Neural Mechanisms

Transcription Factors

Antiinflammatory Mechanisms in Allergy

Therapeutic Implications

References

Self-Assessment Questions

22 Genetics and Epigenetics in Allergic Diseases and Asthma

Introduction

Phenotype Definition

Heritability Studies

Approaches to Study the Genetics of Common Disease

Genetics of Self-Reported and Doctor-Diagnosed Allergic Disease

Current Understanding of Allergic Disease Genetics

Missing Heritability in Allergic Disease

Functional Genomics Approaches, Translating Genetic Association Signals

Epigenetics and Allergic Disease

Pharmacogenetics of Asthma

Summary

References

Self-Assessment Questions

23 Systems Biology

Introduction

Technologic Advances

Methods for High-Dimensional Molecular Data Analysis

Concluding Remarks

References

Self-Assessment Questions

24 Immunobiology of IgE and IgE Receptors

Introducton

IgE Structure and Mechanisms of IgE Isotype Switching

FcεRI, the High-Affinity IgE Receptor

CD23, the Low-Affinity IgE Receptor

Relationships With Other Systems

Conclusion

References

Self-Assessment Questions

25 Neuronal Control of Airway Function in Allergy

Introduction

Lower Airway Innervation

Allergen-Induced Airway Neuromodulation

Clinical Allergy and the Neural Hypersensitive State

Conclusion

References

Self-Assessment Questions

Section B Aerobiology and Allergens

26 The Structure and Function of Allergens

Introduction

Allergens and Epitopes

Aeroallergens

Ingested Allergens

Injected Allergens

Pathogen-Derived Allergens and Autoallergens

Allergens and Allergenicity

Allergens and the Epithelial-Dendritic Cell Axis

Conclusion

Acknowledgments

References

Self-Assessment Questions

27 Aerobiology of Outdoor Allergens

Introduction (Aeroallergen Sources)

General Principles of Allergen Aerobiology

Characterized Allergens

Aeroallergen Sampling

Representative Pollens

Representative Fungi

Meteorologic Variables

Impact of Climate Change on Aeroallergens

References

Self-Assessment Questions

28 Indoor Allergens

History and Introduction

Relevance of Indoor Allergens to Asthma and Other Allergic Diseases

Sources and Characteristics of Indoor Allergens

Insects

Biology of Airborne Particles

Use of Recombinant Allergens and Peptides to Investigate or Treat the Immune Response to Indoor Allergens

Other Airborne Allergens and Airborne Endotoxin

Avoidance Measures for Indoor Allergens

Conclusion

References

Self-Assessment Questions

29 Preparation and Standardization of Allergen Extracts*

Introduction

Source Materials

Manufacture of Allergen Extracts

Stability of Allergen Extracts

Standardization of Allergen Extracts in the United States

Allergen Extracts in Europe

References

Self-Assessment Questions

30 Air Pollution

Introduction

Air Quality

Sources of Air Pollution

Types of Air Pollutants

Susceptibility to Air Pollutants

Management of Pollution Exposures

Summary

References

Self-Assessment Questions

31 Effect of the Food Matrix and Processing on the Allergenic Activity of Foods

Introduction

Development of Food Processing

Processing-Induced Modification of Food Proteins

Impact of Processing on Food Allergens

Future of Food Allergy Research

References

Self-Assessment Questions

Section C The Skin

32 Structure of the Skin and Cutaneous Immunology

Introduction

Cells and Structure of the Skin

Cutaneous Immunology

Immune Dysregulation and Skin Disease

Summary

References

Self-Assessment Questions

33 Atopic Dermatitis

Introduction

Clinical Aspects

Epidermal Barrier Abnormalities

Role of Allergens

Immunology

Management

Summary

References

Self-Assessment Questions

34 Contact Dermatitis

Introduction

Historical Perspective

Epidemiology

Pathogenesis and Etiology

Clinical Features

Patient Evaluation, Diagnosis, and Differential Diagnosis

Histopathology

Treatment

Conclusion

References

Self-Assessment Questions

35 Urticaria and Angioedema

Introduction and Historical Perspective

Definitions and Classifications

Epidemiology and Prevalence

Natural History and Prognosis

Pathogenesis and Etiology

Diagnostic Approach

Diseases Associated With Urticaria: Differential Diagnosis

Treatment

References

Self-Assessment Questions

36 Hereditary Angioedema and Bradykinin-Mediated Angioedema

Introduction

Historical Perspective

Epidemiology

Pathogenesis

Clinical Features

Patient Evaluation, Diagnosis, and Differential Diagnosis

Pathology

Treatment

Summary

References

Self-Assessment Questions

37 Immune Complexes and Allergic Disease

Immunochemical Factors in Immune Complex Bioactivity

Clearance of Immune Complexes

Immune Complex Interaction With Fc Receptor-Bearing Cells

Immune Complexes and Induction of the Immune Response

Endothelial Cells, Cell Adhesion Molecules, and Cytokines

Animal Models of Antibody-Mediated and Immune Complex–Mediated Tissue Damage

Methods of Detecting Circulating Immune Complexes

Diseases Mediated by Circulating Immune Complexes

Laboratory Findings

Treatment

References

Self-Assessment Questions

Section D The Eye

38 Allergic and Immunologic Diseases of the Eye

Introduction

Anatomy and Physiology of the Eye

Allergic Diseases of the Eye

Conjunctival Provocation Testing

Contact Dermatitis

Other Immunologic Diseases of the Eye

References

Self-Assessment Questions

Section E Respiratory Tract

39 The Nose and Control of Nasal Airflow

Introduction

Anatomy of the Nose and Paranasal Sinuses

Functions of the Nose

Control of Nasal Airflow

Pharmacology of the Nose

References

Self-Assessment Questions

40 Allergic and Nonallergic Rhinitis

Introduction

Epidemiology

Diagnosis

Pathophysiology

Treatment

Summary

References

Self-Assessment Questions

41 Rhinosinusitis and Nasal Polyps

Introduction

Acute and Chronic Rhinosinusitis Without Nasal Polyps

Chronic Rhinosinusitis With Nasal Polyps

Summary

References

Self-Assessment Questions

42 Development, Structure and Physiology in Normal Lung and in Asthma

Introduction

Lung Development

Airway Remodeling

Airflow Limitation

Airway Hyperresponsiveness

Lung Parenchyma

Airway Closure

Interpretation of Pulmonary Function Tests

Conclusion

References

Self-Assessment Questions

43 Respiratory Tract Mucosal Immunology

Introduction

Epithelium as a Component of the Innate Immune System

Nonstructural Innate Immune Mechanisms in the Lung

Adaptive Immune Mechanisms

Immunologic Tolerance as a Default Pathway of Mucosal Immunity

Allergic Immune Reactions in the Respiratory Tract

Microbes in the Early Programming of Mucosal Homeostasis

References

Self-Assessment Questions

44 Airway Mucus and Mucociliary System

Introduction

Epithelial Cells Lining Conducting Airways and Submucosal Glands

Nasal Passages and Submucosal Glands

Ciliated Cell Differentiation and Function

Goblet Cell Differentiation

Role of Submucosal Glands in Mucociliary Clearance

Mucus and Mucins

Therapeutic Approaches (Asthma/Chronic Obstructive Pulmonary Disease)

Therapeutic Approaches (Cystic Fibrosis)

Summary

Acknowledgments

References

Self-Assessment Questions

45 Epidemiology of Asthma and Allergic Diseases

Introduction

Definitions and Methods of Measurement

Estimates of Prevalence

Risk Factors

Natural History and Course of Asthma

Summary

References

Self-Assessment Questions

46 Ontogeny of Immune Development and Its Relationship to Allergic Diseases and Asthma

Introduction

A Paradigm for Developmental Origins

Epigenetic Perspectives on Immune Development

Nonlinear Layered Immune System Versus Linear Maturation

Tissue Signals: Limitations and Value of In Vitro Systems

Fetal Adaptive and Innate Immune Cell Development and Function

Perinatal and Postnatal Immune Maturation and Function

Early Life Immune Cell Phenotypic and Functional Associations With Risk for Allergic Disease

Impact of Environmental Exposures on Immune Maturation and Risk for Allergic Disease

Beyond the Immune System

Summary

References

Self-Assessment Questions

47 Asthma Pathogenesis

Introduction

Prevalence

Pathology

Origins of Asthma: Risk Factors for Disease

Triggers of Asthma and Mechanisms of Action

Regulation of Cellular Inflammation

Bronchial Hyperresponsiveness

Airflow Obstruction

Airway Remodeling

Asthma Heterogeneity

Asthma Exacerbations

Summary

References

Self-Assessment Questions

48 Mouse Models of Allergic Airways Disease

Introduction

Characteristics of Animal Models of Allergic Asthma

Characteristics and Assessment of the Allergic Asthma Phenotype

Dissecting Mechanisms in Mouse Models of Allergic Asthma

Using Mouse Models to Investigate Genetic Influences on Asthma

Influence Across the Lifecourse

Conclusion

References

Self-Assessment Questions

49 Diagnosis of Asthma in Infants and Children

Introduction

Epidemiology

Pathogenesis and Etiology

Clinical Features (Wheezing and Asthma Phenotypes)

Risk Factors for Asthma Development in Childhood and Adolescence

Patient Evaluation, Diagnosis, and Differential Diagnosis

Conclusion

References

Self-Assessment Questions

50 Management of Asthma in Infants and Children

Introduction

Chronic Asthma Management

Managing Exacerbations

Asthma Prevention

Conclusion

References

Self-Assessment Questions

51 Diagnosis of Asthma in Adults

Introduction

Definition of Asthma

Main Components of Asthma

Overdiagnosis and Underdiagnosis of Asthma

Airway Inflammation and Remodeling

Evaluation of Asthma

Assessment of Asthma Control and Future Risks of Events

Assessment of Asthma Severity

Evaluation of Asthma-Related Quality of Life

Phenotyping and Endotyping of Asthma

Assessment of Comorbidities

Special Considerations in Regard to Asthma Diagnosis

Differential Diagnosis: Conditions That May Mimic Asthma

Conclusions and Perspectives

References

Self-Assessment Questions

52 Management of Asthma in Adolescents and Adults

Introduction

Principles of Asthma Management

Assessment of Asthma and Disease Control

Establishment of a Partnership in Care

Control of Environmental Factors and Comorbid Conditions

The Role and Contribution of Fungal Disease in Asthma Severity

Medications for the Treatment of Asthma

Step Care Approach to Asthma Management and Control

Approaches to Treatment of Severe Asthma

Step-Up and Step-Down Considerations

Management of an Asthma Exacerbation

Summary

References

Self-Assessment Questions

53 Emergency Treatment and Approach to the Patient with Acute Asthma

Introduction

Evaluation

Treatment

Emerging Biologic Agents

Other Approaches to Care

Summary

Acknowledgments

References

Self-Assessment Questions

54 Approach to the Patient with Exercise-Induced Bronchoconstriction

Introduction

Epidemiology and Immunopathology

Pathogenesis and Etiology

Clinical Features

Patient Evaluation and Diagnosis

Treatment

Conclusion

References

Self-Assessment Questions

55 Asthma and Allergic Diseases During Pregnancy

Introduction

General Therapeutic Principles

Asthma

Rhinitis

Sinusitis

Anaphylaxis

Urticaria and Angioedema

Atopic Dermatitis and Other Dermatoses

Drug Hypersensitivity

Summary

References

Self-Assessment Questions

56 Occupational Allergy and Asthma

Introduction and Definitions

Epidemiologic Aspects

Pathogenesis and Etiology

Clinical Features

Patient Evaluation, Diagnosis, and Differential Diagnosis

Outcomes and Treatment

Prevention

Socioeconomic Impact and Medicolegal Aspects

Specific Agents Causing Occupational Asthma and Rhinitis

Work-Related Anaphylaxis

Summary

References

Self-Assessment Questions

57 Pathology of Asthma

Introduction

Classifying Asthma

Mild or Moderate Asthma

Severe or Fatal Asthma

Conclusion

References

Self-Assessment Questions

58 Allergic Bronchopulmonary Aspergillosis, Hypersensitivity Pneumonitis, and Epidemic Thunderstorm Asthma

Introduction

Allergic Bronchopulmonary Aspergillosis

Hypersensitivity Pneumonitis

Epidemic Thunderstorm Asthma

Summary

References

Self-Assessment Questions

59 Immunologic Nonasthmatic Diseases of the Lung

Introduction

Granulomatosis With Polyangiitis

Microscopic Polyangiitis

Eosinophilic Granulomatosis With Polyangiitis

Sarcoidosis

Antiglomerular Basement Membrane Antibody Disease

References

Self-Assessment Questions

60 Approach to the Patient with Chronic Cough

Introduction

Historical Perspective

Epidemiology, Pathogenesis, and Etiology

Explained Chronic Cough

Chronic Cough in Children

Unexplained Chronic Cough in Adults

Summary

References

Self-Assessment Questions

61 Bronchial and Nasal Challenge Testing

Bronchial Challenges

Indirect Airway Hyperresponsiveness

Nonselective Challenges: Clinical Utility

Treatment Monitoring

Allergen Challenge

Other Allergen Challenge Methods

Occupational Challenges

Nasal Challenge Testing

Acknowledgements

References

Self-Assessment Questions

62 Lung Imaging

Imaging

Standardization of Lung Imaging

Radiation Exposure in Lung Imaging

Use of Imaging as a Biomarker of Therapeutic Response

Clinical Utility of Imaging

References

Self-Assessment Questions

63 Aerosols and Aerosol Drug Delivery Systems

Introduction

Definition and Types of Aerosols

Definitions for Commonly Used Terms in Aerosol Delivery

Factors That Affect Aerosol Deposition

Aerosol Drug Delivery Devices

Future Directions

Inhaler Selection for Therapy

Summary

References

Self-Assessment Questions

Volume 2

Section F Gastrointestinal Tract

64 Gastrointestinal Mucosal Immunology

Introduction

Gastrointestinal Structure and Function

Organization of the Gastrointestinal Immune Tissue

Innate Immunity in the Gastrointestinal Tract

Adaptive Immunity in the Gastrointestinal Tract

References

Self-Assessment Questions

65 Eosinophilic Gastrointestinal Disorders

Introduction

Overview of Disorders

Clinical Evaluation

Eosinophilic Esophagitis

Eosinophilic Gastritis and Gastroenteritis

Eosinophilic Colitis

Conclusion

Acknowledgments

References

Self-Assessment Questions

Section G Systemic Disease

66 Clinical Significance of Immunoglobulin E

Introduction

Normal Immunoglobulin E Production

Immunoglobulin E in Allergic Disease

Immunoglobulin E in Infectious and Parasitic Disease

Immunoglobulin E in Nonatopic Diseases

Environmental Exposures and Immunoglobulin E

Summary

References

Self-Assessment Questions

67 In Vivo Methods for the Study and Diagnosis of Allergy

Introduction

Pathophysiology of the Skin Response

Techniques of Skin Tests

Factors That Affect Skin Tests

Interpretation of Skin Tests

Skin Tests Used for Nondiagnostic Purposes

Conclusion

References

Self-Assessment Questions

68 Approach to the Patient with Recurrent Infections

Introduction

The Medical History in Immunodeficiency

Physical Examination

Laboratory Tests for Screening Patients With Recurrent Infections

Conclusion

References

Self-Assessment Questions

69 Primary Immunodeficiency Diseases

Introduction

Cellular and Humoral Immunodeficiencies

Combined Immunodeficiencies

Syndromic Combined Immunodeficiencies (Table 69.4)

Antibody Deficiency Syndromes (Table 69.7)

Diseases of Immune Dysregulation (Table 69.8)

Disorders of Phagocytic Cells (Table 69.9)

Defects of Innate Immunity (Table 69.10)

Autoinflammatory Disorders (Table 69.11)

Complement Component Deficiencies (Table 69.12)

Phenocopies of Primary Immunodeficiency Diseases (Table 69.13)

Conclusion

References

Self-Assessment Questions

70 Treatment of Primary Immunodeficiency Diseases

Introduction

General Management Strategies in Primary Immunodeficiency Diseases

Immunizations

Immunoglobulin G Replacement Therapy

Antimicrobial Prophylaxis

Targeted Biologic Modifiers

Allogeneic Hematopoietic Cell Transplantation

Gene Therapy

Disease-Specific Considerations

References

Self-Assessment Questions

71 HIV Infection and Allergic Disease

Introduction

Immunopathogenesis of HIV Infection: Background

Immune Dysregulation Related to HIV Infection

Clinical Phenotypes of Allergic Disease in HIV Infection

Treatment of Atopic Disease in HIV-Infected Patients

Summary

Acknowledgments

References

Self-Assessment Questions

72 Laboratory Tests for Allergic and Immunodeficiency Diseases

Humoral Immune Responses Important in Allergic and Immunodeficiency Disease

Immunologic Methods for Quantifying Antigens and Antibodies

Assays for Antigens and Antibodies

Immunochemical Methods for Measurement of Immunoglobulin E Protein

Immunochemical Methods for Measurement of Immunoglobulin E Antibodies of Defined Allergen Specificity

Immunochemical Methods for Measurement of Allergen-Specific Immunoglobulin G Antibody

Immunglobulin G Subclass Protein and Antibodies

Other Analytes of Interest in Allergic Disorders and Asthma

Quantification of Environmental Allergens

Laboratory Methods in Cellular Immunology

Conclusion

References

Self-Assessment Questions

73 Eosinophilia and Eosinophil-Related Disorders

Introduction

Allergic and Immunologic Disorders

Rheumatologic Disorders

Skin and Soft Tissue Disorders

Pulmonary Diseases

Gastrointestinal Disorders

Medication- and Toxin-Related Eosinophilia

Infectious Diseases

Hematologic and Neoplastic Disorders

Renal and Urinary Tract Disorders

Rare Hypereosinophilic Syndromes

Treatment

Other Rare Causes of Eosinophilia

Summary

References

Self-Assessment Questions

74 Mastocytosis

Introduction

Historical Perspective

Epidemiology

Pathogenesis and Etiology

Pathologic Effects of Increased Mast Cells

Clinical Features

Patient Evaluation, Diagnosis, and Differential Diagnosis

Pathology

Treatment

Prognosis

Conclusion

Acknowledgment

References

Self-Assessment Questions

75 Anaphylaxis

Introduction

Historical Perspective

Epidemiology

Pathogenesis

Etiology

Clinical Features (Phenotypes)

Differential Diagnosis

Laboratory Findings

Pathology

Treatment

Fatalities

Prescription of Epinephrine for Outpatient Use

Conclusion

Acknowledgments

References

Self-Assessment Questions

76 Insect Allergy

Stinging Insect Allergy

Biting Insect Allergy

Inhalant Insect Allergy

Conclusion

References

Self-assessment questions

77 Drug Allergy

Introduction

Epidemiology of Adverse Drug Reactions

Immunomechanisms of Drug Allergy

Immunopathologic Features of Drug Allergy

Risk Factors for Drug Allergy

Nonallergic Drug Reactions

Diagnosis of Drug Allergy

Management of Drug Allergy

Summary

References

Self-Assessment Questions

78 Hypersensitivity to Aspirin and Other Nonsteroidal Antiinflammatory Drugs

Introduction and Historical Note

Classification

Cross-Reactive Nonsteroidal Antiinflammatory Drug Hypersensitivity

Allergic (or Immunologically Mediated) Types of Nonsteroidal Antiinflammatory Drug Hypersensitivity

References

Self-Assessment Questions

79 Reactions to Foods

Definitions and Historical Perspective

Epidemiology

Pathogenesis and Etiology

Food Allergens

Pathophysiology of Food Allergy

Clinical Manifestations of Food Allergy

Diagnosis and Management of Food Allergy

Natural History of Food Allergy

Summary

References

Self-Assessment Questions

80 Reactions to Food and Drug Additives

Introduction

Labeling of Additives

Prevalence of Reactions to Additives

Diagnosis of Adverse Reactions to Additives

Food and Drug Additives Known or Suspected to Cause Adverse Reactions

References

Self-Assessment Questions

81 Oral Food Challenge Testing

Introduction

Indications for Oral Challenge Testing

Methodology

Risk and Treatment of Oral Food Challenges

References

Self-Assessment Questions

82 Food Allergy Management

Introduction

Practical Management

Food Allergy Risk Factors and Prevention

Future Therapeutic Strategies

Summary

Acknowledgments

References

Self-Assessment Questions

83 Adverse Reactions to Vaccines

Putting Adverse Reactions to Vaccines in Perspective

Immunoglobulin E–Mediated Reactions to Vaccines

Non–Immunoglobulin E–Mediated Reactions to Vaccines

Adverse Reactions to Vaccines for Biologic Agents Used as Weapons

Controversies Regarding Long-Term Consequences of Vaccination

Vaccination Relative to Immunocompromise and Immunoglobulin Preparations

Vaccination During Pregnancy and Breastfeeding

Summary of Recommendations

References

Self-Assessment Questions

Section H Therapeutics

84 Allergen Control for Prevention and Management of Allergic Diseases

Introduction

Measurement of Allergen Exposure

Rationale for the Use of Allergen Control for Prevention and Management of Allergic Disease

Allergen Control Measures

Clinical Effectiveness of Allergen Control Measures

Allergen Control in the Prevention of Allergic Disease

Conclusion

References

Self-Assessment Questions

85 Injection Immunotherapy for Inhalant Allergens

Historical Development

Clinical Efficacy of Subcutaneous Allergen Immunotherapy

Immunologic Response to Inhalant Injection Immunotherapy (Box 85.1)

Practical Considerations in Allergen Immunotherapy

Alternative Extracts and Methods of Administration (Box 85.5)

Conclusion

References

Self-Assessment Questions

86 Sublingual Immunotherapy for Inhalant Allergens

Background

Allergen Extracts

Therapeutic Regimens

Mucosal Tolerance

Immunologic Mechanisms

Therapeutic Efficacy

Effects on Natural History of Allergic Disease

Safety and Cost-Effectiveness

Future Directions

Summary

References

Self-Assessment Questions

87 Principles of Pharmacotherapeutics

Introduction

Goals of Therapy

Basic Principles of Clinical Pharmacology

Pharmaceutics

Pharmacokinetic Principles

Pharmacodynamic Variability

Drug and Disease Interactions

Pharmacodynamic Interactions

Conclusion

References

Self-Assessment Questions

88 Precision Medicine in Allergic Disorders

Precision Medicine: Brief History and Definition

Evidence-Based vs. Precision Medicine

Precision Medicine in Allergic Disorders: Role of Omics

Immune Profiling of Allergic Disorders

Endotypes and Biomarkers

Pharmacogenomics and Drug Dosing

The Precision Medicine Revolution: CRISPR-Based Therapies

Precision Medicine and Racial Ancestry in Allergic Disorders

Machine Learning in Precision Medicine

Challenges in Precision Medicine

References

Self-Assessment Questions

89 Adherence

Introduction

Definitions

Extent of Nonadherence in Asthma and Other Diseases

Barriers to Adherence

Measuring Adherence

Interventions to Improve Adherence

Conclusion

References

Self-Assessment Questions

90 Anti-Immunoglobulin E Therapy

Background

Mechanism of Action

Omalizumab Disease-Specific Effects

Asthma/Allergy Dosing

Safety

Conclusion

References

Self-Assessment Questions

91 Cytokine-Specific Therapy in Asthma

Introduction

Cytokines

Chemokines

Summary

References

Self-Assessment Questions

92 Histamine and Antihistamines

Introduction

Molecular Basis of Histamine Action

Histamine Receptors

Histamine in Immune Response Regulation

Clinical Pharmacology of H1 Antihistamines

Allergic Rhinitis

Allergic Conjunctivitis

Urticaria

Other Diseases and Uses

Adverse Effects

Summary and Future Directions

Acknowledgments

References

Self-Assessment Questions

93 Inhaled β2-Agonists

Introduction

Historical Background

Pharmacology of β2-Agonists

β2-Receptor Structure and Activation

Efficacy of Inhaled β2-Agonists

Inhaled Corticosteroid/Long-Acting Inhaled β2-Agonist Combinations Used as Single-Inhaler Maintenance and Reliever Therapy

Conclusion

References

Self-Assessment Questions

94 Xanthines, Phosphodiesterase Inhibitors, and Chromones

Xanthines and Phosphodiesterase Inhibitors

The Chromones

References

Self-Assessment Questions

95 Anticholinergic Therapies

Introduction

Airway Cholinergic Hyperresponsiveness

Cholinergic Nervous System as a Target for Anticholinergic Agents

Pharmacology of Anticholinergic Agents

Short-Acting Anticholinergic Agents in Obstructive Lung Diseases

Long-Acting Anticholinergic Agents for Treating Chronic Obstructive Pulmonary Disease

Tiotropium for Treating Asthma

Anticholinergic Agents for Treating Rhinitis

Summary

References

Self-Assessment Questions

96 Glucocorticoids

Introduction

Chemical Structures

Pharmacokinetics

Metabolism and Excretion

Side Effects

Effects of Glucocorticoids on Asthmatic Inflammation

Effects of Glucocorticoids on Inflammatory Cells

Glucocorticoids Spare Innate Immune Responses

Effects of Glucocorticoids on Cell Recruitment to the Airways

Effects of Glucocorticoids on Airway Structural Cells

Cross-Talk Between the Adrenergic System and Glucocorticoids

Arachidonic Acid Metabolites

Inflammatory Gene Expression and Nuclear Factor-κB

Chromatin and Histone Modifications Regulate Inflammatory Gene Expression

Mechanisms of Glucocorticoid Action

Relative Steroid-Insensitive Asthma

Evidence of Mechanisms in Clinical Studies

Obesity and Relative Glucocorticosteroid Insensitivity

Smoking and Oxidative Stress in Relative Glucocorticosteroid Insensitivity

Infections and Relative Glucocorticosteroid Insensitivity

Clustering on Clinical Features and on Omics

Clinical Implications

Conclusion

Acknowledgments

References

Self-Assessment Questions

97 Antileukotriene Therapy in Asthma

Introduction

Leukotriene Biosynthesis

Historical Perspective

Leukotriene Receptors

Therapeutic Strategies to Inhibit Leukotrienes

Leukotriene Antagonism in Asthma

Treatment Trials in Chronic Asthma

Dosing

Safety

Leukotriene Antagonists in Asthma Treatment Guidelines

References

Self-Assessment Questions

98 Unconventional Theories and Unproven Methods in Allergy

Introduction

Unconventional Theories of Allergic Disease

Allergic Toxemia or Tension Fatigue Syndrome

Multiple Food and Chemical Sensitivities: Idiopathic Environmental Intolerance

Candida Hypersensitivity Syndrome

Food Additive Sensitivity

Unproven Diagnostic Tests

Inappropriate Diagnostic Tests

Unproven Treatment Methods

Therapies Based on Controlled Environmental Exposures

Current Versus Historical Practices

References

Self-Assessment Questions

99 Complementary and Alternative Medicine

Background

Overview of Complementary and Alternative Medicine Therapy for Allergic Rhinitis and Asthma

Alternative Medical Systems

Manipulation and Body-Based Therapies

Mind-Body Therapies

Yoga

Biologically Based Therapies

Summary

References

Self-Assessment Questions

Appendix A CD Molecules

Introduction

Symbols

List of Abbreviations Used

Further Reading

Answers

Index