BOOK
Kendig's Disorders of the Respiratory Tract in Children E-Book
Robert W. Wilmott | Andrew Bush | Robin R Deterding | Felix Ratjen | Peter Sly | Heather Zar | Albert P. Li
(2018)
Additional Information
Book Details
Abstract
Now in a fully updated 9th Edition, Kendig's Disorders of the Respiratory Tract in Children, by Drs. Robert Wilmott, Andrew Bush, Robin Deterding, and Felix Ratjen, continues to provide authoritative, evidence-based information to residents, fellows, and practitioners in this wide-ranging specialty. Bringing key knowledge from global experts together in one easy-to-understand volume, it covers everything from the latest basic science and its relevance to today’s clinical issues, to improving patient outcomes for the common and rare respiratory problems found in newborns and children worldwide.
- Uses succinct, straightforward text, numerous tables and figures, summaries at the end of each chapter, and more than 500 full-color images to convey key information in an easy-to-digest manner.
- Contains new chapters reflecting expanding knowledge on the respiratory complications of Down syndrome and other genetic disorders, modern molecular therapies for cystic fibrosis and asthma, and pulmonary embolism and thromboembolic disease.
- Features a new templated format with more descriptive headings and bulleted text for quick reference and navigation.
- Covers today’s key issues, including the genetic basis of respiratory disease, new and emerging respiratory infections, interstitial lung diseases in infants and young children, technology and diagnostic techniques for pulmonary function tests, emerging lung infections, and new therapies for cystic fibrosis and asthma.
- Provides up-to-date instruction on important procedures, such as bronchoscopy and pulmonary function testing.
- Highlights the knowledge and expertise of three new editors, as well as more than 100 world authorities in the fields of pediatrics, pulmonology, neurology, microbiology, cardiology, physiology, diagnostic imaging, critical care, otolaryngology, allergy, and surgery.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Inside Front Cover | ifc1 | ||
| Kendig's Disorders of the Respiratory Tract in Children | i | ||
| Copyright Page | iv | ||
| Preface | v | ||
| Contributors | vi | ||
| Table Of Contents | xix | ||
| Video Contents | xxii | ||
| 1 General Basic and Clinical Considerations | 1 | ||
| 1 The History and Physical Examination | 2 | ||
| Abstract | 2.e1 | ||
| Keywords | 2.e1 | ||
| The History | 2 | ||
| General Principles | 2 | ||
| Structure of the Pediatric History | 2 | ||
| The Physical Examination | 4 | ||
| Inspection | 4 | ||
| Palpation | 8 | ||
| Percussion | 9 | ||
| Auscultation | 10 | ||
| Thoracic Acoustics | 10 | ||
| Technique of Auscultation | 12 | ||
| Taste and Smell | 14 | ||
| Common Signs and Symptoms of Chest Disease in Children | 14 | ||
| Cough and Sputum | 14 | ||
| Noisy Breathing | 16 | ||
| Wheezing | 16 | ||
| Cyanosis | 17 | ||
| Digital Clubbing | 18 | ||
| Cardiovascular Signs | 19 | ||
| Exercise Limitation and Dyspnea | 21 | ||
| Chest Pain | 22 | ||
| Conclusion | 23 | ||
| Suggested Reading | 24 | ||
| General Reading | 24 | ||
| Respiratory Sounds | 24 | ||
| Pulsus Paradoxus | 24 | ||
| Digital Clubbing | 24 | ||
| Cough and Wheezing | 24 | ||
| Chest Pain | 25 | ||
| Cyanosis | 25 | ||
| Exercise Limitation and Dyspnea | 25 | ||
| 2 Molecular Determinants of Lung Morphogenesis | 26 | ||
| Abstract | 26.e1 | ||
| Keywords | 26.e1 | ||
| Introduction | 26 | ||
| Organogenesis of the Lung | 26 | ||
| Formation of the Basic Body Plan | 26 | ||
| Specification of the Foregut Endoderm | 26 | ||
| Lung Morphogenesis | 26 | ||
| The Embryonic Period (3–7 Weeks Postconception) | 27 | ||
| The Pseudoglandular Period (6–17 Weeks Postconception) | 29 | ||
| The Canalicular Period (16–26 Weeks Postconception) | 30 | ||
| The Saccular (26–36 Weeks Postconception) and Alveolar Periods (36 Weeks Postconception Through Adolescence) | 30 | ||
| Molecular Mechanisms Directing Lung Development | 31 | ||
| Transcriptional Mechanisms Regulating Gene Expression | 31 | ||
| Transcription Factors and Gene Regulatory Networks | 31 | ||
| Cis-Regulatory Networks Controlling Gene Expression | 33 | ||
| Epigenetic Mechanisms: DNA Methylation and Chromatin State | 34 | ||
| Epigenetic Mechanisms: Chromatin Topology/3D Structure | 34 | ||
| Nontranscriptional Mechanisms Regulating Morphogenesis | 34 | ||
| Noncoding RNA | 34 | ||
| Receptor-Mediated Signal Transduction | 35 | ||
| Gradients of Signaling Molecules and Localization of Receptor Molecules | 35 | ||
| Epithelial-Mesenchymal Interactions and Lung Morphogenesis | 35 | ||
| Branching Morphogenesis, Vascularization, and Alveologenesis | 35 | ||
| Control of Lung Proliferation During Branching Morphogenesis | 36 | ||
| Role of Extracellular Matrix, Cell Adhesion, and Cell Shape | 36 | ||
| Autocrine-Paracrine Interactions in Lung Injury and Repair | 37 | ||
| Development of the Pulmonary Host Defense Systems | 37 | ||
| Mucociliary Clearance | 37 | ||
| Innate and Acquired Immunity | 37 | ||
| Innate Defenses | 38 | ||
| Gene Mutations in Lung Development and Function | 38 | ||
| Summary | 39 | ||
| References | 39 | ||
| Suggested Reading | 39 | ||
| References | 39.e1 | ||
| 3 Basic Genetics and Epigenetics of Childhood Lung Disease | 40 | ||
| Abstract | 40.e1 | ||
| Keywords | 40.e1 | ||
| Types of Genetic Variation | 40 | ||
| Technologies to Identify Genetic Variation | 41 | ||
| Interpretation of Genetic Variation | 43 | ||
| When to Consider Clinical Genetic Testing | 44 | ||
| Research Study Designs to Attribute Genetic Variation to Disease | 44 | ||
| Epigenetics—Terminology and Technology | 46 | ||
| “Multi-Omics” Approaches to Refine Genotype-Phenotype Associations | 47 | ||
| References | 48 | ||
| Suggested Reading | 48 | ||
| Websites | 48 | ||
| References | 48.e1 | ||
| 4 Environmental Contributions to Respiratory Disease in Children | 49 | ||
| Abstract | 49.e1 | ||
| Keywords | 49.e1 | ||
| Vulnerability of Children to Adverse Environmental Exposures | 49 | ||
| Mechanisms Underlying the Increased Disease Risk From Adverse Environmental Exposures | 50 | ||
| Individual Susceptibility, Gene by Environmental Interactions, and Epigenetic Mechanisms Contributing to Respiratory Disease in Children | 50 | ||
| Epigenetic Mechanisms Increasing the Risk of Disease. | 50 | ||
| Antioxidant Defense. | 51 | ||
| Microbial Recognition. | 51 | ||
| Allergic Inflammation. | 51 | ||
| Low Lung Function/Reduced Lung Growth, Delayed Immune Maturation, and Somatic Growth Restriction Predisposing to Respiratory Disease | 53 | ||
| Common Pathways to Respiratory Diseases | 53 | ||
| Environmental Contributions to Acute Respiratory Illness and Pneumonia | 55 | ||
| Environmental Contributions to Asthma | 55 | ||
| Summary | 55 | ||
| References | 56 | ||
| Suggested Reading | 56 | ||
| References | 56.e1 | ||
| 5 The Surfactant System | 57 | ||
| Abstract | 57.e1 | ||
| Keywords | 57.e1 | ||
| Surfactant Composition and Metabolism | 57 | ||
| Composition | 57 | ||
| Surfactant Metabolism and Secretion | 58 | ||
| Alveolar Life Cycle of Surfactant | 58 | ||
| Surfactant Function | 58 | ||
| Alveolar Stability | 58 | ||
| Pressure-Volume Curves | 59 | ||
| Host Defense Functions of Surfactant | 59 | ||
| Surfactant Deficiency | 60 | ||
| The Preterm Infant With Respiratory Distress Syndrome | 60 | ||
| The Injured Mature Lung | 60 | ||
| Genetic Deficiencies of Surfactant in Mice and Humans | 61 | ||
| Surfactant Treatment of Surfactant Deficiency | 61 | ||
| Respiratory Distress Syndrome | 61 | ||
| Acute Respiratory Distress Syndrome | 62 | ||
| References | 62 | ||
| Suggested Reading | 62 | ||
| References | 62.e1 | ||
| 6 The Structural and Physiologic Basis of Respiratory Disease | 63 | ||
| Abstract | 63.e1 | ||
| Keywords | 63.e1 | ||
| Normal Lung Anatomy and Cell Function | 63 | ||
| Airways | 63 | ||
| Alveolar Region | 66 | ||
| Pulmonary Vascular System | 68 | ||
| Lymphatic System | 68 | ||
| Innervation of the Lung | 69 | ||
| Interstitium | 69 | ||
| Growth and Development of the Lung | 70 | ||
| Prenatal Lung Growth | 70 | ||
| The Lung at Birth | 71 | ||
| Postnatal Lung Growth | 71 | ||
| Ventilation and Mechanics of Breathing | 73 | ||
| Definitions and Symbols | 73 | ||
| Properties of Gases | 74 | ||
| Elastic Recoil of the Lung | 75 | ||
| Compliance of the Lung | 75 | ||
| Elastic Properties of the Chest Wall | 76 | ||
| Lung Volumes | 76 | ||
| Definition | 76 | ||
| Measurement | 78 | ||
| Interpretation | 78 | ||
| Regional Lung Volumes | 78 | ||
| Dynamic (Flow-Resistive) Properties of the Lung | 78 | ||
| Gas Flow Within Airways | 78 | ||
| Measurement of Resistance | 79 | ||
| Sites of Airway Resistance | 79 | ||
| Factors That Affect Airway Resistance | 80 | ||
| Dynamic Airway Compression | 80 | ||
| Work of Breathing | 80 | ||
| Distribution of Ventilation | 81 | ||
| Pulmonary Circulation | 81 | ||
| Physiologic Classification of Pulmonary Vessels | 81 | ||
| Pulmonary Vascular Pressures | 81 | ||
| Pulmonary Vascular Resistance | 82 | ||
| Distribution of Blood Flow | 82 | ||
| Methods of Evaluating the Pulmonary Circulation | 83 | ||
| Muscles of Respiration | 83 | ||
| Gas Exchange | 85 | ||
| Alveolar Ventilation | 86 | ||
| Dead Space | 86 | ||
| Alveolar Ventilation and Alveolar Gases | 86 | ||
| Diffusion | 88 | ||
| Principles | 88 | ||
| Measurement | 88 | ||
| Shunt and Ventilation-Perfusion Relationships | 89 | ||
| Systemic Gas Transport | 89 | ||
| Oxygen Transport | 89 | ||
| Assessment of Blood Oxygenation | 91 | ||
| Oxygen Delivery to Tissues | 92 | ||
| Oxygen Therapy | 92 | ||
| Increased Inspired Mixtures | 92 | ||
| Administration of Oxygen | 93 | ||
| Hazards of High Oxygen Mixtures | 93 | ||
| Carbon Dioxide Transport and Acid-Base Balance | 94 | ||
| Buffering and Transport | 94 | ||
| Acid-Base Balance | 96 | ||
| Difference Between Additions of CO2 to Blood in vitro and in vivo | 97 | ||
| Tissue Respiration | 97 | ||
| Aerobic Metabolism | 97 | ||
| Anaerobic Metabolism | 97 | ||
| Relationship between V̇O2 and V̇CO2 | 98 | ||
| Regulation of Respiration | 98 | ||
| Sensory Feedback System | 98 | ||
| O2 and CO2 | 99 | ||
| The Newborn Infant | 99 | ||
| Metabolic Functions of the Lung | 99 | ||
| Acknowledgments | 100 | ||
| References | 100 | ||
| Suggested Reading | 100 | ||
| Normal Lung Anatomy and Cell Function | 100 | ||
| Pulmonary Circulation | 100 | ||
| Growth and Development of the Lung | 100 | ||
| Lung Physiology | 100 | ||
| Pulmonary Function Testing | 100 | ||
| Respiratory Muscle Testing | 100 | ||
| Control of Breathing | 100 | ||
| References | 100.e1 | ||
| 7 Biology and Assessment of Airway Inflammation | 101 | ||
| Abstract | 101.e1 | ||
| Keywords | 101.e1 | ||
| Introduction | 101 | ||
| Allergic Inflammation | 101 | ||
| Acute Inflammation | 101 | ||
| Chronic Inflammation | 102 | ||
| Structural Changes and Repair | 102 | ||
| Inflammatory Cells | 103 | ||
| Mast Cells | 103 | ||
| Macrophages | 104 | ||
| Dendritic Cells | 105 | ||
| Eosinophils | 105 | ||
| Neutrophils | 106 | ||
| T-Lymphocytes | 106 | ||
| Innate Lymphoid Cells | 107 | ||
| B-Lymphocytes | 107 | ||
| Basophils | 108 | ||
| Structural Cells as Sources of Mediators | 108 | ||
| Inflammatory Mediators | 108 | ||
| Cytokines | 109 | ||
| Lipid Mediators | 110 | ||
| Chemokines | 110 | ||
| Oxidative Stress | 111 | ||
| Nitric Oxide | 111 | ||
| Growth Factors | 111 | ||
| Neural Mechanisms | 111 | ||
| Transcription Factors | 112 | ||
| Antiinflammatory Mechanisms | 113 | ||
| Direct Measurements of Airway Inflammation | 114 | ||
| Noninvasive Assessment of Airway Inflammation | 115 | ||
| Induced Sputum | 116 | ||
| Peripheral Blood | 116 | ||
| Exhaled Gases | 116 | ||
| Exhaled Nitric Oxide | 116 | ||
| Other Exhaled Gases | 117 | ||
| Exhaled Breath Condensate | 117 | ||
| Is AHR an Inflammatory Surrogate? | 118 | ||
| Other Potential Indirect Inflammatory Markers | 118 | ||
| Is There a Role for Assessing Inflammation in Pediatric Respiratory Disease? | 118 | ||
| Therapeutic Implications | 118 | ||
| Conclusion | 118 | ||
| References | 119 | ||
| References | 119.e1 | ||
| 8 Lung Defenses | 120 | ||
| Abstract | 120.e1 | ||
| Keywords | 120.e1 | ||
| Intrinsic Lung Defenses | 120 | ||
| Aerodynamic Filtering | 120 | ||
| Humidification | 120 | ||
| Airway Reflexes | 120 | ||
| The Mechanics of Cough and Abnormalities in the Cough Reflex | 121 | ||
| Innate Lung Defenses | 121 | ||
| Mucus and Airway Surface Liquid | 121 | ||
| Disorders of the Mucociliary System | 122 | ||
| Adhesion Proteins | 122 | ||
| Pattern-Recognition Receptors in Lung Innate Immunity | 123 | ||
| Toll-Like Receptors | 123 | ||
| C-Type Lectin Receptors | 124 | ||
| Nodlike Receptors | 124 | ||
| RIG-Like Receptors | 125 | ||
| Absent-in-Melanoma-Like Receptors | 125 | ||
| Soluble Extracellular Pattern-Recognition Proteins | 125 | ||
| Complement | 125 | ||
| Collectins | 125 | ||
| Antimicrobial Peptides | 125 | ||
| Cellular Defenses: at the Crossroads of Innate and Adaptive Immunity | 126 | ||
| The Respiratory Epithelium | 126 | ||
| Resident Cell Defenses: At the Interface of Innate and Adaptive Immunity | 126 | ||
| Dendritic Cells. | 126 | ||
| Macrophages. | 127 | ||
| Mast Cells. | 127 | ||
| Recruited Cellular Defenses | 127 | ||
| Neutrophils. | 128 | ||
| Eosinophils. | 128 | ||
| Innate Lymphocytes: Innate Lymphocyte Cells and Natural Killer Cells. | 129 | ||
| Adaptive Lung Defenses | 129 | ||
| Bridging the Adaptive and Innate Defenses | 129 | ||
| T Lymphocytes and Lung Defense | 130 | ||
| B Lymphocytes | 130 | ||
| Humoral Immunity | 131 | ||
| Immunoglobulin A | 131 | ||
| Immunoglobulin G | 131 | ||
| Immunoglobulin E | 132 | ||
| Immunoglobulin M | 132 | ||
| Role of Programmed Cell Death and “Clearing the Garbage” in Lung Homeostasis | 132 | ||
| Summary | 133 | ||
| References | 133 | ||
| Suggested Reading | 133 | ||
| References | 133.e1 | ||
| 9 Bronchoscopy and Bronchoalveolar Lavage in Pediatric Patients | 134 | ||
| Abstract | 134.e1 | ||
| Keywords | 134.e1 | ||
| Instrumentation | 134 | ||
| Rigid Bronchoscopes | 134 | ||
| Flexible Bronchoscopes | 134 | ||
| Care and Maintenance of Bronchoscopes | 135 | ||
| Techniques for Bronchoscopy | 135 | ||
| Facilities for Bronchoscopy | 135 | ||
| Rigid Bronchoscopy | 135 | ||
| Flexible Bronchoscopy | 136 | ||
| Anesthesia for Bronchoscopy | 136 | ||
| Indications for Diagnostic Bronchoscopy | 137 | ||
| Contraindications to Bronchoscopy | 139 | ||
| Bronchoalveolar Lavage | 139 | ||
| Indications for Bronchoalveolar Lavage | 139 | ||
| Techniques for Bronchoalveolar Lavage | 140 | ||
| Processing of Bronchoalveolar Lavage Specimens | 141 | ||
| Interpretation of Bronchoalveolar Lavage Findings | 141 | ||
| Research Applications of Bronchoalveolar Lavage | 142 | ||
| Diagnostic Techniques Other Than Bronchoalveolar Lavage | 143 | ||
| Biopsy | 143 | ||
| Bronchial Brushing | 143 | ||
| Visual Analysis | 143 | ||
| Therapeutic Bronchoscopy | 143 | ||
| Complications of Bronchoscopy | 145 | ||
| Economic Aspects of Bronchoscopy | 146 | ||
| References | 146 | ||
| Suggested Reading | 146 | ||
| References | 146.e1 | ||
| 10 Diagnostic Imaging of the Respiratory Tract | 147 | ||
| Abstract | 147.e1 | ||
| Keywords | 147.e1 | ||
| Plain Radiography | 147 | ||
| Specific Features of the Chest Radiograph in Children | 147 | ||
| The Thymus | 147 | ||
| The Cardiothoracic Ratio | 147 | ||
| Kink of the Trachea to the Right | 147 | ||
| Soft Tissue | 148 | ||
| Pleural Fluid | 148 | ||
| Systematic Review of the Chest Radiograph | 148 | ||
| General Degree of Lung Inflation | 148 | ||
| Asymmetrical Lung Volume | 148 | ||
| Lobar Overinflation | 149 | ||
| Mediastinal Distortion | 150 | ||
| Hilar Expansion | 151 | ||
| Lung Opacities | 151 | ||
| Focal and Multifocal Lung Densities | 153 | ||
| Pulmonary Interstitial Emphysema | 154 | ||
| Lung Abscess | 154 | ||
| Diffuse Interstitial Lung Disease | 154 | ||
| Pneumothorax | 154 | ||
| Skeletal Abnormalities Associated With Respiratory Disorders | 156 | ||
| Fluoroscopic Techniques | 156 | ||
| Computed Tomography | 157 | ||
| Isotropic Computed Tomography | 157 | ||
| Data Processing | 158 | ||
| Multiplanar Reconstruction | 158 | ||
| Multiplanar Volume Reconstructions: Maximum Intensity Projection and Minimum Intensity Projection | 158 | ||
| Volume-Rendering Technique | 159 | ||
| Virtual Bronchoscopy | 159 | ||
| Further Advanced Postprocessing | 159 | ||
| Review of Findings | 161 | ||
| Pitfalls | 162 | ||
| Radiation Dose | 163 | ||
| High-Resolution Computed Tomography | 165 | ||
| Controlled Ventilation Technique | 165 | ||
| Interpretation | 165 | ||
| Regional or Generalized Increased Density | 165 | ||
| Regional or Generalized Decreased Density | 166 | ||
| Septal Thickening | 166 | ||
| Nodules | 167 | ||
| Bronchial Change | 167 | ||
| Architectural Distortion | 168 | ||
| Angiography | 168 | ||
| Magnetic Resonance Imaging | 169 | ||
| Endobronchial Ultrasonography | 170 | ||
| Ultrasonography | 170 | ||
| Radionuclide Imaging | 172 | ||
| Conclusion | 173 | ||
| References | 173 | ||
| Suggested Reading | 173 | ||
| References | 173.e1 | ||
| 11 Pulmonary Function Tests in Infants and Children | 174 | ||
| Abstract | 174.e1 | ||
| Keywords | 174.e1 | ||
| Introduction | 174 | ||
| Indications and Special Considerations for Pulmonary Function Tests in Infants | 174 | ||
| Technical and Staff Requirements | 174 | ||
| Lung Function Test in Sedated Infants | 175 | ||
| Indications and Special Considerations for Pulmonary Function Tests in Children | 175 | ||
| Technical and Staff Requirements | 175 | ||
| Measurement of Lung Volumes | 176 | ||
| Summary | 176 | ||
| Whole Body Plethysmography | 177 | ||
| Summary | 177 | ||
| Physiological Principles and Assumptions | 177 | ||
| Quality Control, Acceptability Criteria, and Limitations | 178 | ||
| Spirometric Measurements of Lung Volumes in Cooperative Children | 178 | ||
| Gas Dilution Technique | 178 | ||
| Summary | 178 | ||
| Physiological Principles and Assumptions | 179 | ||
| Quality Control, Acceptability Criteria, and Limitations | 180 | ||
| Interpretation of Lung Volumes in Infants and Young Children | 180 | ||
| Measurement of Diffusing Capacity of Carbon Monoxide | 181 | ||
| Summary | 181 | ||
| Physiological Principles and Assumptions | 181 | ||
| Quality Control, Acceptability Criteria, and Limitations | 181 | ||
| Interpretation of DLCO | 182 | ||
| Measurement of Forced Expiration | 182 | ||
| Physiological Principles and Assumptions | 182 | ||
| Measurement of Forced Expiratory Flow and Volume in Cooperative Subjects | 184 | ||
| Summary | 184 | ||
| Quality Control, Acceptability Criteria, and Limitations | 184 | ||
| Measurement of Forced Expiratory Flow and Volume in Infants | 185 | ||
| Summary | 185 | ||
| Rapid Thoracoabdominal Compression and Raised Volume-Rapid Thoracoabdominal Compression | 185 | ||
| Quality Control, Acceptability Criteria, and Limitations | 186 | ||
| Rapid Thoracoabdominal Compression- Specific Considerations | 187 | ||
| Raised Volume-Rapid Thoracoabdominal Compression-Specific Considerations | 187 | ||
| Interpretation and Clinical Application of the Flow-Volume Curve | 188 | ||
| The Assessment of Bronchodilator Response | 189 | ||
| Measurement of Resistance and Compliance | 189 | ||
| Physiological Principles and Assumptions | 190 | ||
| Interpretation of Resistance and Compliance | 191 | ||
| Summary | 191 | ||
| General Considerations for the Measurement of Resistance and Compliance | 194 | ||
| Single-Breath Occlusion Technique | 194 | ||
| Summary | 194 | ||
| Quality Control, Acceptability Criteria, and Limitations | 196 | ||
| Potential Clinical Applications in Infants | 196 | ||
| Measurement of Interrupter Resistance | 196 | ||
| Summary | 197 | ||
| Quality Control, Acceptability Criteria, and Limitations | 197 | ||
| Plethysmographic Measurement of Airway Resistance | 198 | ||
| Summary | 198 | ||
| Quality Control, Acceptability Criteria, and Limitations | 198 | ||
| Forced Oscillation Technique | 199 | ||
| Summary | 199 | ||
| Main Outcome Measures and Their Interpretation | 200 | ||
| Quality Control, Acceptability Criteria, and Limitations | 202 | ||
| Potential Clinical Applications in Children | 203 | ||
| Measurement of Gas Mixing | 205 | ||
| Multiple Breath Washout Technique | 205 | ||
| Summary | 205 | ||
| Physiological Principles and Assumptions | 205 | ||
| Main Outcome Measures of Multiple Breath Washout | 206 | ||
| Feasibility in Older Children | 207 | ||
| Quality Control, Acceptability Criteria, and Limitations | 207 | ||
| Potential Clinical Applications in Infants and Children | 209 | ||
| References | 210 | ||
| Suggested Reading | 210 | ||
| References | 211.e1 | ||
| 12 Exercise and Lung Function in Child Health and Disease | 212 | ||
| Abstract | 212.e1 | ||
| Keywords | 212.e1 | ||
| The Biological Importance of Physical Activity in the Growing Child | 212 | ||
| From the Playground to the Bench to the Physician’s Office | 212 | ||
| Integrating Laboratory Cardiopulmonary Exercise Testing and Field Assessments of Physical Fitness | 212 | ||
| What Can We Learn From Cardiopulmonary Exercise Testing (Fig. 12.3) | 213 | ||
| Physiologic Response to Progressive Exercise Testing | 214 | ||
| The Challenge of Scaling Cardiopulmonary Exercise Testing to Body Mass in Children and Adolescents and the Special Case of Obesity | 215 | ||
| Development of Physiological Responses to Exercise in Children and Adolescents and Predicting Cardiopulmonary Health Across the Lifespan | 216 | ||
| Searching for Normal Values in Pediatric Cardiopulmonary Exercise Testing | 216 | ||
| Asthma and Exercise | 217 | ||
| The Role of Exercise and Physical Activity in Asthma | 217 | ||
| Exercise-Induced Bronchoconstriction | 218 | ||
| Exercise Challenge Test | 219 | ||
| Pretest | 219 | ||
| Exercise and Other Tests for Bronchial Reactivity | 220 | ||
| The Mechanism of Exercise-Induced Bronchoconstriction Remains Enigmatic | 220 | ||
| Air Quality, Exercise, and Asthma | 221 | ||
| Exercise-Induced Bronchoconstriction in Nonasthmatics | 221 | ||
| Exercise, Asthma, and Bronchoconstriction: Treatment Considerations | 221 | ||
| Nonpharmacological Approaches | 221 | ||
| Pharmacological Approaches | 222 | ||
| Physical Activity, Exercise and Cystic Fibrosis | 223 | ||
| Safety | 225 | ||
| Recommendations | 225 | ||
| Physical Activity, Exercise, and Lung Disease of Prematurity | 225 | ||
| Exercise Capacity | 225 | ||
| Exercise at Altitude in Child Health | 226 | ||
| High Altitude and Children With Chronic Lung Disease | 226 | ||
| Asthma | 226 | ||
| Cystic Fibrosis | 227 | ||
| Bronchopulmonary Dysplasia | 227 | ||
| Exercise and Laryngeal Obstruction | 227 | ||
| Toward the Future: Exercise in the Age of Omics | 229 | ||
| References | 230 | ||
| References | 230.e1 | ||
| 13 Integrating Patient-Reported Outcomes Into Research and Clinical Practice | 231 | ||
| Abstract | 231.e1 | ||
| Keywords | 231.e1 | ||
| Definition of a Patient-Reported Outcome | 231 | ||
| Development and Utilization of Patient-Reported Outcomes | 231 | ||
| Health-Related Quality of Life Measures | 231 | ||
| Developmental Considerations | 232 | ||
| Use of Proxy-Respondents | 233 | ||
| Clinical Utility | 233 | ||
| Summary | 234 | ||
| Review of Disease-Specific Respiratory Health-Related Quality of Life Measures | 234 | ||
| Aerodigestive Disorders | 234 | ||
| Vocal Cord Dysfunction | 234 | ||
| 2 Infections of the Lung | 395 | ||
| 22 Microbiological Diagnosis of Respiratory Illness | 396 | ||
| Abstract | 396.e1 | ||
| Keywords | 396.e1 | ||
| Respiratory Pathogens and Syndromes | 396 | ||
| Use of the Clinical Microbiology Laboratory | 396 | ||
| Clinical Specimens for Respiratory Pathogen Diagnosis | 399 | ||
| Throat and Nasopharyngeal Specimens | 400 | ||
| Induced Sputum | 400 | ||
| Bronchoscopy Specimens | 400 | ||
| Endotracheal Aspirates | 400 | ||
| Transthoracic Lung Aspiration | 400 | ||
| Lung Tissue | 401 | ||
| Blood Specimens | 401 | ||
| Urine | 401 | ||
| Microbiological Tools | 401 | ||
| Microscopy | 401 | ||
| Culture | 401 | ||
| Antigen Detection Assays | 402 | ||
| Serology | 402 | ||
| Molecular Methods | 403 | ||
| Antimicrobial Susceptibility Testing | 403 | ||
| Diagnostic Approach by Syndrome | 404 | ||
| Common Cold | 404 | ||
| Pharyngitis | 404 | ||
| Croup | 404 | ||
| Sinusitis | 404 | ||
| Epiglottitis | 404 | ||
| Bronchiolitis | 404 | ||
| Pneumonia | 404 | ||
| Pleural Effusion and Empyema | 404 | ||
| Lung Abscess | 404 | ||
| Infections Associated With Cystic Fibrosis | 404 | ||
| Microbiome | 404 | ||
| Future Prospects | 405 | ||
| References | 405 | ||
| References | 405.e1 | ||
| 23 Acute Infections That Produce Upper Airway Obstruction | 406 | ||
| Abstract | 406.e1 | ||
| Keywords | 406.e1 | ||
| Viral Laryngotracheobronchitis | 406 | ||
| Epidemiology | 406 | ||
| Etiology | 407 | ||
| Pathology | 407 | ||
| Clinical Features | 408 | ||
| Mild | 408 | ||
| Moderate | 408 | ||
| Severe | 408 | ||
| Diagnosis and Differential Diagnosis | 409 | ||
| Recurrent or Spasmodic Croup | 409 | ||
| Noninfective Causes of Acute Airway Obstruction | 409 | ||
| Management of Viral Laryngotracheobronchitis | 409 | ||
| Supportive Care | 410 | ||
| Humidification | 410 | ||
| Corticosteroids | 410 | ||
| Optimal Route of Administration, Formulation, and Dosing Regimen | 410 | ||
| Nebulized Epinephrine (Adrenaline). | 410 | ||
| Other Treatments for Severe Cases. | 411 | ||
| Endotracheal Intubation | 411 | ||
| Prevention | 411 | ||
| Prognosis and Further Evaluation | 411 | ||
| Epiglottitis | 412 | ||
| Epidemiology | 412 | ||
| Etiology | 412 | ||
| Pathology | 412 | ||
| Clinical Features | 413 | ||
| Management | 413 | ||
| Bacterial Tracheitis | 414 | ||
| Epidemiology | 414 | ||
| Etiology | 414 | ||
| Pathology | 414 | ||
| 3 Pulmonary Disease in the Intensive Care Unit | 547 | ||
| 34 Principles of Mechanical Ventilation | 548 | ||
| Abstract | 548.e1 | ||
| Keywords | 548.e1 | ||
| History | 548 | ||
| Indications for Mechanical Ventilation | 548 | ||
| Composition of a Mechanical Ventilator | 548 | ||
| Modes of Ventilation | 548 | ||
| Noninvasive Ventilation | 550 | ||
| High-Frequency Ventilation | 550 | ||
| Neurally Adjusted Ventilator Assistance | 551 | ||
| Hemodynamic Effects of Mechanical Ventilation | 551 | ||
| Mechanical Ventilation in Specific Conditions | 551 | ||
| Normal Lungs | 551 | ||
| Acute Respiratory Distress Syndrome | 551 | ||
| Status Asthmaticus | 552 | ||
| Bronchiolitis | 553 | ||
| The Neonate | 553 | ||
| Congenital Heart Disease | 553 | ||
| Management During Mechanical Ventilation | 553 | ||
| Monitoring | 553 | ||
| Comfort | 553 | ||
| Suctioning | 553 | ||
| Synchronization | 554 | ||
| Gas Humidification | 554 | ||
| Fluid Management | 554 | ||
| Weaning and Extubation | 554 | ||
| Neuromuscular Blockade | 554 | ||
| Complications of Mechanical Ventilation | 554 | ||
| Conclusion | 554 | ||
| References | 554 | ||
| Suggested Reading | 554 | ||
| References | 555.e1 | ||
| 35 Childhood Pulmonary Arterial Hypertension | 556 | ||
| Abstract | 556.e1 | ||
| Keywords | 556.e1 | ||
| Introduction | 556 | ||
| Definition and Classification | 556 | ||
| Evolution of the Classification of Pulmonary Hypertension | 556 | ||
| Epidemiology and Etiology | 557 | ||
| Gender | 559 | ||
| Genetics of PAH | 560 | ||
| Neonatal Pulmonary Hypertension | 560 | ||
| Persistent Pulmonary Hypertension of the Newborn | 560 | ||
| Bronchopulmonary Dysplasia and Pulmonary Hypertension | 560 | ||
| Associated Pulmonary Arterial Hypertension With Congenital Heart Disease | 561 | ||
| Survival in APAH-CHD | 564 | ||
| Idiopathic/Heritable Pulmonary Arterial Hypertension | 564 | ||
| Epidemiology | 564 | ||
| Natural History | 564 | ||
| Pathogenesis and Pathobiology of Pediatric Pulmonary Arterial Hypertension | 565 | ||
| Important Pathways Thought to Be Responsible for Vasoconstriction | 566 | ||
| Endothelial Dysfunction | 567 | ||
| Cell Proliferation and Apoptosis | 568 | ||
| Growth Factors | 568 | ||
| Apoptosis | 568 | ||
| Inflammation and Thrombosis | 568 | ||
| Pathophysiology | 568 | ||
| Clinical Presentation | 569 | ||
| Physical Examination Findings | 569 | ||
| Diagnosis and Assessment | 570 | ||
| Echocardiography in Pediatric Pulmonary Arterial Hypertension | 570 | ||
| Hemodynamics/Cardiac Catheterization | 571 | ||
| Magnetic Resonance Imaging | 572 | ||
| Assessment of Functional Capacity | 572 | ||
| The 6-Minute Walk Distance (6MWD) Test. | 572 | ||
| Cardiopulmonary Exercise Testing. | 572 | ||
| Laboratory Testing. | 572 | ||
| Management | 572 | ||
| General Measures | 572 | ||
| Anticoagulation | 572 | ||
| Calcium Channel Blockade | 573 | ||
| Serial Reevaluations | 573 | ||
| Targeted Pulmonary Arterial Hypertension Therapy | 573 | ||
| Prostacyclin Analogues | 575 | ||
| Intravenous Prostacyclin (Epoprostenol) | 575 | ||
| Inhaled Prostacyclin Analogues (Iloprost, Treprostinil) | 575 | ||
| Subcutaneous/Intravenous Prostacyclin Analogue (Treprostinil) | 576 | ||
| Oral Prostacyclin Analogues | 576 | ||
| Oral Prostacyclin Analogue. | 576 | ||
| Endothelin Receptor Antagonists | 576 | ||
| Inhaled Nitric Oxide | 577 | ||
| Phosphodiesterase Inhibitors | 577 | ||
| Gene Therapy | 577 | ||
| Oxygen | 577 | ||
| Additional Pharmacotherapy: Cardiac Glycosides, Diuretics, Antiarrhythmic Therapy, Inotropic Agents, and Nitrates | 578 | ||
| Atrial Septostomy | 578 | ||
| Potts Shunt in Severe Pulmonary Arterial Hypertension | 578 | ||
| Lung Transplantation | 578 | ||
| Conclusions | 579 | ||
| References | 579 | ||
| References | 579.e1 | ||
| 36 Pulmonary Edema | 580 | ||
| Abstract | 580.e1 | ||
| Keywords | 580.e1 | ||
| Anatomic Considerations | 580 | ||
| Factors Responsible for Fluid Movement | 581 | ||
| Vascular Forces | 582 | ||
| Interstitial Forces | 582 | ||
| Microvascular Filtration Coefficient and Vascular Permeability | 582 | ||
| Lymphatic Clearance | 582 | ||
| Surface Tension | 583 | ||
| Safety Factors That Oppose Edema Formation | 583 | ||
| Mechanisms That Cause Pulmonary Edema | 583 | ||
| Increased Hydrostatic Pressure in the Pulmonary Microvasculature | 583 | ||
| Decreased Plasma Colloid Osmotic Pressure | 583 | ||
| Decreased Interstitial Hydrostatic Pressure | 583 | ||
| Increased Pulmonary Vascular Surface Area | 583 | ||
| Increased Vascular Permeability in Fluid-Exchanging Vessels | 584 | ||
| Clearance of Pulmonary Edema Fluid | 584 | ||
| Pathophysiologic Consequences of Edema | 585 | ||
| Clinical Presentation | 586 | ||
| Physical Examination | 586 | ||
| Pulmonary Function Tests | 586 | ||
| Imaging Studies | 586 | ||
| The Chest Radiograph | 586 | ||
| Computed Tomography and Magnetic Resonance Imaging | 587 | ||
| Distinguishing High-Pressure from Low-Pressure Pulmonary Edema | 587 | ||
| Quantitation of Pulmonary Edema in Patients | 588 | ||
| Clinical Disorders Causing Pulmonary Edema | 588 | ||
| High-Pressure Pulmonary Edema | 588 | ||
| Airway Obstruction | 589 | ||
| Reexpansion Pulmonary Edema | 589 | ||
| Neonatal Respiratory Distress Syndrome | 590 | ||
| Neurogenic Pulmonary Edema | 590 | ||
| Acute Lung Injury and the Acute Respiratory Distress Syndrome | 590 | ||
| High Altitude Pulmonary Edema | 590 | ||
| Inhalation of Toxic Agents | 591 | ||
| Intravenous Agents | 591 | ||
| Narcotic-Induced and Medication-Induced Pulmonary Edema | 591 | ||
| Therapy | 591 | ||
| Reversing the Hypoxemia | 592 | ||
| Reduce the Rate of Fluid Filtration | 592 | ||
| Minimize Treatment-Related Lung Damage | 593 | ||
| Augment the Rate of Clearance of Airspace Fluid | 593 | ||
| References | 595 | ||
| Suggested Reading | 595 | ||
| References | 595.e1 | ||
| 37 Respiratory Complications of Intensive Care | 596 | ||
| Abstract | 596.e1 | ||
| Keywords | 596.e1 | ||
| History of Pediatric Intensive Care | 596 | ||
| Indications for Intubation and Mechanical Ventilation | 596 | ||
| Ventilation Strategies | 596 | ||
| Conventional Versus Oscillatory Ventilation | 596 | ||
| Extracorporeal Membranous Oxygenation | 598 | ||
| Complications of Mechanical Ventilation | 598 | ||
| Mucus Plugging | 598 | ||
| Atelectasis | 599 | ||
| Ventilator-Induced Lung Injury | 600 | ||
| Air Leak Syndromes | 601 | ||
| Ventilator-Associated Pneumonia | 601 | ||
| Special Pulmonary Consideration in Pediatric Patients With Neuromuscular Disorders | 603 | ||
| Pulmonary Hemorrhage | 603 | ||
| Intensive Care Unit Neuromyopathy | 603 | ||
| Special Pulmonary Considerations in Pediatric Patients With Congenital Heart Disease | 604 | ||
| Special Pulmonary Considerations in Pediatric Patients With Malignancy or Hematopoietic Stem Cell Transplantation | 604 | ||
| Conclusion | 605 | ||
| References | 605 | ||
| Suggested Reading | 605 | ||
| References | 605.e1 | ||
| 38 Acute Respiratory Distress Syndrome | 606 | ||
| Abstract | 606.e1 | ||
| Keywords | 606.e1 | ||
| Epidemiology | 606 | ||
| Etiology | 606 | ||
| Outcome | 606 | ||
| Definition and Diagnosis | 606 | ||
| Pathophysiology | 607 | ||
| Pulmonary (Direct) Versus Extrapulmonary (Indirect) Acute Lung Injury/Acute Respiratory Distress Syndrome | 608 | ||
| Severity Score | 609 | ||
| Genetic Modifiers of Acute Respiratory Distress Syndrome | 609 | ||
| Differences Between Children and Adults | 609 | ||
| Treatment | 609 | ||
| Conventional Mechanical Ventilation | 609 | ||
| Other Modalities of Ventilation | 610 | ||
| Noninvasive Ventilation | 610 | ||
| High-Frequency Oscillatory Ventilation | 611 | ||
| Airway Pressure Release Ventilation | 611 | ||
| Neurally Adjusted Ventilatory Assist | 611 | ||
| Adjuvants to Mechanical Ventilation | 612 | ||
| Corticosteroids | 612 | ||
| Prone Positioning | 612 | ||
| Inhaled Nitric Oxide | 612 | ||
| Surfactant | 613 | ||
| Neuromuscular Blocking Agents | 613 | ||
| Beta-Adrenergic Agonists | 613 | ||
| Extracorporeal Life Support in Pediatric Acute Respiratory Distress Syndrome | 613 | ||
| Tracheostomy | 614 | ||
| Summary/Conclusion | 614 | ||
| References | 614 | ||
| Suggested Reading | 614 | ||
| References | 614.e1 | ||
| 39 Pulmonary Disease Associated With Congenital Heart Disease | 615 | ||
| Abstract | 615.e1 | ||
| Keywords | 615.e1 | ||
| Introduction | 615 | ||
| Airway Compression Due to Vascular Rings and Slings | 615 | ||
| Background | 615 | ||
| Clinical Presentation | 619 | ||
| Diagnosis | 619 | ||
| Treatment | 619 | ||
| Pulmonary Hypertension and Postoperative Pulmonary Hypertensive Crisis | 619 | ||
| Background | 619 | ||
| Risk Factors | 620 | ||
| Pathophysiology | 621 | ||
| Evaluation and Monitoring | 621 | ||
| Treatment | 621 | ||
| Pulmonary Vein Stenosis | 621 | ||
| Background | 621 | ||
| Presentation | 622 | ||
| Imaging | 622 | ||
| Treatment | 622 | ||
| Reperfusion Pulmonary Edema in Children Undergoing Procedures for Tetralogy of Fallot, Pulmonary Atresia and Multiple Aortopulmonary Collateral Arteries | 622 | ||
| Pulmonary Disease Associated With the Fontan Repair of Single Ventricle Physiology | 624 | ||
| Pathophysiology | 624 | ||
| Clotting Abnormalities | 624 | ||
| Pulmonary Vascular Resistance | 624 | ||
| Plastic Bronchitis | 624 | ||
| Heterotaxy Syndrome | 624 | ||
| Pulmonary Complications Related to Cardiac Surgery and Cardiopulmonary Bypass | 625 | ||
| Conclusion | 625 | ||
| References | 625 | ||
| Suggested Reading | 625 | ||
| References | 625.e1 | ||
| 40 Lung Injury From Hydrocarbon Aspiration and Smoke Inhalation | 626 | ||
| Abstract | 626.e1 | ||
| Keywords | 626.e1 | ||
| Epidemiology | 626 | ||
| Etiology | 626 | ||
| Pathology | 626 | ||
| Pathophysiology | 626 | ||
| Clinical Findings | 627 | ||
| Diagnosis and Differential Diagnosis | 627 | ||
| Management and Treatment | 627 | ||
| Prevention | 628 | ||
| Prognosis | 628 | ||
| Hydrocarbon “Sniffing” | 628 | ||
| Respiratory Complications of Smoke Inhalation | 628 | ||
| Epidemiology | 628 | ||
| Etiology | 629 | ||
| Pathogenesis | 629 | ||
| Carbon Monoxide Poisoning | 629 | ||
| Pathology | 629 | ||
| Pathophysiology | 630 | ||
| Clinical Findings | 631 | ||
| Diagnosis and Differential Diagnosis | 631 | ||
| Management and Treatment | 631 | ||
| The Relationship of Pulmonary Injury From Smoke Inhalation to the Pulmonary Complications of Surface Burns | 632 | ||
| Prevention | 633 | ||
| Prognosis | 633 | ||
| References | 633 | ||
| Suggested Reading | 633 | ||
| References | 633.e1 | ||
| 41 Drowning | 634 | ||
| Abstract | 634.e1 | ||
| Keywords | 634.e1 | ||
| Definitions | 634 | ||
| Epidemiology | 634 | ||
| Drowning Sequence | 634 | ||
| Sequelae of Submersion/Immersion Events | 634 | ||
| Pulmonary Injury | 634 | ||
| Nonpulmonary Sequelae | 635 | ||
| Hypothermia | 635 | ||
| Electrolyte Imbalances | 635 | ||
| Trauma | 636 | ||
| Hypoxic-Ischemic Damage | 636 | ||
| Management | 636 | ||
| Outcome of Pulmonary Injury | 636 | ||
| Outcome Prediction of Neurological Injury | 637 | ||
| Prevention | 637 | ||
| References | 638 | ||
| Suggested Reading | 638 | ||
| References | 638.e1 | ||
| 4 Asthma | 639 | ||
| 42 The Epidemiology of Asthma | 640 | ||
| Abstract | 640.e1 | ||
| Keywords | 640.e1 | ||
| Overview | 640 | ||
| Epidemiologic Approaches to the Study of Asthma | 640 | ||
| Defining Asthma in Epidemiologic Studies | 641 | ||
| The Prevalence of Asthma | 642 | ||
| Temporal Variation | 642 | ||
| Spatial Variation | 644 | ||
| Variation by Gender and Ethnicity | 645 | ||
| Outcomes of Childhood Asthma | 646 | ||
| Severity and Mortality | 646 | ||
| Hospitalization | 646 | ||
| Severe Asthma | 647 | ||
| Asthma Deaths | 647 | ||
| Quality of Life and Economic Impact of Asthma | 648 | ||
| Phenotypic Variation | 648 | ||
| Temporal Progression of Symptoms | 648 | ||
| Inflammatory Subtypes | 650 | ||
| Severe Asthma | 650 | ||
| Atopic and Nonatopic Asthma | 650 | ||
| The Genetics of Asthma | 651 | ||
| Genetics | 651 | ||
| Gene–Environment Interactions | 652 | ||
| Epigenetics | 652 | ||
| Environmental Influences on Asthma | 653 | ||
| Pregnancy and Childbirth | 653 | ||
| Maternal Factors | 653 | ||
| Maternal Lifestyle and Environment | 654 | ||
| Fetal Growth and Birth Size | 654 | ||
| Mode of Delivery | 655 | ||
| Early Childhood | 655 | ||
| Breast-Feeding Diet | 655 | ||
| Childhood Diet. | 656 | ||
| Obesity | 656 | ||
| Infections | 657 | ||
| Farming Studies | 659 | ||
| Physical Activity | 660 | ||
| Air Quality | 661 | ||
| Outdoor Air Pollution | 661 | ||
| Indoor Air Quality. | 662 | ||
| Allergy, Asthma, and the Allergic March | 663 | ||
| Conclusions | 664 | ||
| References | 664 | ||
| Suggested Reading | 664 | ||
| References | 664.e1 | ||
| 43 The Immunopathogenesis of Asthma | 665 | ||
| Abstract | 665.e1 | ||
| Keywords | 665.e1 | ||
| Altered Pulmonary Immunity in Asthma Inception | 665 | ||
| Cells, Molecules, and Cytokines Involved in Pediatric Allergic Asthma | 665 | ||
| Eosinophils and Interleukin-5 | 665 | ||
| Mast Cells in Asthma | 667 | ||
| Lymphoid Cells | 667 | ||
| T-Lymphocytes | 667 | ||
| Innate Lymphoid Cells | 668 | ||
| Neutrophils | 669 | ||
| School-Age Allergic Asthma: Pathology and Mechanisms | 669 | ||
| The Clinical Relevance of Eosinophilic Inflammation in School-Age Asthma | 670 | ||
| Stability of Eosinophilic Inflammation in Pediatric Asthma and Impact on Therapy | 670 | ||
| Noninvasive Biomarkers of Eosinophilic Inflammation | 670 | ||
| Essential Role of Structural Airway Cells in Pulmonary Immunity and Asthma Pathogenesis | 670 | ||
| Pulmonary Epithelium | 670 | ||
| Airway Smooth Muscle | 671 | ||
| Preschool Wheeze: A Unique Maturing Immune Environment | 671 | ||
| Phenotypes of Preschool Wheeze and Response to Currently Available Antiinflammatory Therapies | 671 | ||
| Airway Inflammation in Infection Associated Preschool Wheeze Exacerbations | 671 | ||
| Airway Pathology in Preschool Wheezers With Symptoms During and in Between Exacerbations | 672 | ||
| Impact of Eosinophilic Inflammation on Disease Inception | 672 | ||
| Eosinophilic Inflammation and Disease Persistence | 672 | ||
| Impact of Immune Maturation and the Developing Airway Microbiome on Preschool Wheeze—Mechanistic Studies | 673 | ||
| Gene–Environment Interactions: the Developing Microbiome and Protection From Preschool Wheeze | 673 | ||
| Gaps in Knowledge and Thoughts for the Future | 673 | ||
| Severity and Frequency of Acute Wheezing Episodes and Progression to Asthma | 674 | ||
| Specific Clinical Scenarios for Consideration | 674 | ||
| Immunology of Asthma Exacerbations | 674 | ||
| Severe Theraphy Resistant Asthma: A Unique Pulmonary Immune Environment | 674 | ||
| Summary | 676 | ||
| References | 676 | ||
| References | 676.e1 | ||
| 44 Asthma in the Preschool Age Child | 677 | ||
| Abstract | 677.e1 | ||
| Keywords | 677.e1 | ||
| Epidemiology and Burden | 677 | ||
| Diagnosis | 677 | ||
| Natural History | 679 | ||
| Environmental Factors | 679 | ||
| Clinical Patterns of Wheeze | 679 | ||
| Pathology | 679 | ||
| Treatment | 680 | ||
| Treatment—Nonpharmacological | 680 | ||
| Treatment—Pharmacological | 680 | ||
| Challenge to Personalizing Therapy | 680 | ||
| Preventive Management—“Green Zone” | 680 | ||
| Daily Preventive Monotherapy | 680 | ||
| What Is the Best Preventive Strategy for Specific Wheezy Children? | 681 | ||
| Adjunct Therapy | 681 | ||
| Preemptive Therapy—Yellow Zone | 682 | ||
| Preemptive Inhaled Corticosteroids | 682 | ||
| Preemptive Leukotriene Receptor Antagonists | 682 | ||
| Preemptive Oral Corticosteroids | 682 | ||
| Step-Up of Daily Therapy Dose at the Onset of an Exacerbation | 683 | ||
| Which Preemptive Strategy Is Most Effective? | 683 | ||
| Daily Versus Preemptive Asthma Controller: What Is the Best and Safest Approach? | 683 | ||
| Safety Profile. | 683 | ||
| Treatment—Initial Management of Exacerbations in the Acute Care Setting | 683 | ||
| Bronchodilators | 683 | ||
| Oral Corticosteroids | 684 | ||
| Inhaled Corticosteroids | 685 | ||
| Magnesium Sulfate | 685 | ||
| Antibiotics | 685 | ||
| Future Directions | 685 | ||
| References | 685 | ||
| Suggested Reading | 685 | ||
| References | 685.e1 | ||
| 45 Wheezing in Older Children | 686 | ||
| Abstract | 686.e1 | ||
| Keywords | 686.e1 | ||
| Introduction | 686 | ||
| Pathology | 686 | ||
| Pathophysiology | 687 | ||
| Inflammatory Cell Biology and Asthma Etiology and Pathophysiology | 688 | ||
| Natural History and Prognosis | 689 | ||
| Asthma Mortality | 690 | ||
| Diagnosis of Asthma | 690 | ||
| Physical Examination | 691 | ||
| Asthma Triggers | 692 | ||
| Allergens | 692 | ||
| Irritants | 692 | ||
| Weather Changes | 692 | ||
| Infections | 692 | ||
| Exercise | 693 | ||
| Emotional Factors | 693 | ||
| Gastroesophageal Reflux | 693 | ||
| Allergic Rhinitis and Sinusitis | 693 | ||
| Nonallergic Hypersensitivity to Drugs and Chemicals | 693 | ||
| Endocrine Factors | 694 | ||
| Nocturnal Asthma | 694 | ||
| Laboratory Diagnosis | 695 | ||
| Lung Function Tests | 695 | ||
| Bronchial Challenge Tests | 695 | ||
| Exercise Challenge Test | 696 | ||
| Other Tests | 696 | ||
| Complete Blood Cell Count | 696 | ||
| Cytologic Examination of Sputum | 696 | ||
| Exhaled Nitric Oxide | 696 | ||
| Serum Tests | 697 | ||
| Sweat Test | 698 | ||
| Radiographs | 698 | ||
| Allergy Testing | 698 | ||
| Therapeutic Considerations | 698 | ||
| Classification of Asthma | 699 | ||
| Other Measures for Assessing Asthma Severity and Control | 701 | ||
| Pharmacologic Management of Asthma in Children Older Than 5 Years of Age | 701 | ||
| Reliever Medications: Short-Acting β Agonists | 701 | ||
| Anticholinergic Agents | 703 | ||
| Controller Medications | 703 | ||
| Inhaled Corticosteroids | 703 | ||
| Fluticasone Propionate | 704 | ||
| Budesonide | 704 | ||
| Beclomethasone | 704 | ||
| Mometasone | 705 | ||
| Ciclesonide | 705 | ||
| Other Inhaled Corticosteroids | 705 | ||
| Mechanism of Action and Clinical Use | 705 | ||
| Adverse Effects of Inhaled Corticosteroids | 706 | ||
| Systemic Corticosteroids | 706 | ||
| Long-Acting β Agonists | 706 | ||
| Leukotriene Antagonists | 709 | ||
| Long-Acting Muscarinic Antagonists | 710 | ||
| Methylxanthines: Theophylline | 710 | ||
| Biologic Therapy for Asthma | 710 | ||
| Management of Chronic Asthma | 711 | ||
| Intermittent Asthma | 711 | ||
| Mild Persistent Asthma | 712 | ||
| Moderate Persistent Asthma | 713 | ||
| Severe Persistent Asthma | 713 | ||
| Holding Chambers and Spacer Devices | 714 | ||
| Peak Expiratory Flow Rate Monitoring | 714 | ||
| Nonpharmacologic Measures | 715 | ||
| Management of an Acute Episode | 717 | ||
| Hospital Management of Asthma | 719 | ||
| General Treatment | 719 | ||
| References | 721 | ||
| Suggested Reading | 721 | ||
| References | 721.e1 | ||
| 46 Severe Asthma | 722 | ||
| Abstract | 722.e1 | ||
| Keywords | 722.e1 | ||
| Overarching Principles | 722 | ||
| Definitions | 722 | ||
| A New Approach: Airways Disease Deconstructed and Placed in Context | 723 | ||
| Initial Evaluation: Problematic Severe Asthma | 723 | ||
| Problematic Severe Asthma: Not Asthma at All | 724 | ||
| Airway Disease in Context: Asthma Plus (Extrapulmonary Comorbidities) | 724 | ||
| Obesity | 725 | ||
| Gastroesophageal Reflux | 725 | ||
| Food Allergy | 725 | ||
| Rhinosinusitis | 725 | ||
| Sleep Disordered Breathing | 726 | ||
| Syndromes of Vocal Cord Dysfunction and Other Functional Breathing Issues | 726 | ||
| Airway Disease in Context: Environmental/Lifestyle (Difficult Asthma) | 726 | ||
| Adherence | 727 | ||
| Prescription Records | 727 | ||
| The Home Visit | 727 | ||
| Parental Supervision | 727 | ||
| Use of Inhaler Devices | 727 | ||
| Electronic Monitoring: Towards a Definitive Test | 728 | ||
| Environmental Factors | 728 | ||
| Allergen Exposure | 728 | ||
| Home Exposure. | 728 | ||
| School Exposure. | 729 | ||
| Passive and Active Smoking. | 729 | ||
| Psychosocial Morbidity | 729 | ||
| Asthma Education | 729 | ||
| Safeguarding Issues: Symptom Reporting | 729 | ||
| Increasingly Important in the Assessment Process: A Hospital Admission | 729 | ||
| Difficult Asthma: Summary | 730 | ||
| Severe, Therapy-Resistant Asthma: Deconstructing the Airway Disease | 730 | ||
| Protocol: Invasive Investigation of Severe, Therapy-Resistant Asthma | 730 | ||
| Assessment of Airway Inflammation | 731 | ||
| Assessment of Steroid Responsiveness | 732 | ||
| Assessment of Persistent Airflow Limitation | 732 | ||
| Treatment of Severe, Therapy-Resistant Asthma | 733 | ||
| A Difficult Specific Problem: Treatment of the Exacerbating Phenotype | 734 | ||
| Monitoring the Child With Severe, Therapy-Resistant Asthma on Treatment | 735 | ||
| Monitoring Treatment Benefit | 735 | ||
| Monitoring Side Effects | 735 | ||
| The Role of an Annual Assessment | 735 | ||
| Summary and Conclusions | 735 | ||
| References | 735 | ||
| Suggested Reading | 735 | ||
| References | 736.e1 | ||
| 47 The Influence of Upper Airway Disease on the Lower Airway | 737 | ||
| Abstract | 737.e1 | ||
| Keywords | 737.e1 | ||
| Allergic Rhinitis and Asthma | 737 | ||
| The Epidemiologic Relationship Between Allergic Rhinitis and Asthma | 737 | ||
| Common Immunopathology of Allergic Rhinitis and Asthma | 738 | ||
| Effects of Rhinitis Therapy on Asthma | 738 | ||
| Intranasal Corticosteroids | 738 | ||
| Antihistamines. | 739 | ||
| Pathophysiologic Connections Between Allergic Rhinitis and Asthma | 739 | ||
| Systemic Effects of Nasal Inflammation on the Lower Airways | 739 | ||
| Impaired Mucosal Function | 739 | ||
| Nasal-Bronchial Reflex | 740 | ||
| Mouth Breathing Caused by Nasal Obstruction | 740 | ||
| Postnasal Drip of Inflammatory Material | 740 | ||
| Diagnostic and Therapeutic Implications | 741 | ||
| Diagnosis | 741 | ||
| Allergen Avoidance | 741 | ||
| Pharmacotherapy | 741 | ||
| Specific Allergen Immunotherapy | 742 | ||
| Summary | 742 | ||
| Chronic Rhinosinusitis and Asthma | 742 | ||
| Epidemiologic Relationship Between Chronic Rhinosinusitis and Asthma | 742 | ||
| Unique Features of Chronic Rhinosinusitis in Asthmatics | 743 | ||
| Clinical Features | 743 | ||
| Chronic Rhinosinusitis With Nasal Polyps. | 743 | ||
| Histopathology | 743 | ||
| Microbiology | 744 | ||
| Allergic Fungal Sinusitis | 744 | ||
| Effects of Sinus Therapy on Severity of Asthma | 744 | ||
| Surgical Treatment | 744 | ||
| Medical Treatment | 744 | ||
| Pathophysiologic Links Between Chronic Sinusitis and Asthma | 745 | ||
| Diagnostic and Therapeutic Implications | 745 | ||
| Summary | 746 | ||
| References | 746 | ||
| Suggested Reading | 746 | ||
| References | 746.e1 | ||
| 48 Modern Molecular Therapies for Application in Managing Childhood Asthma | 747 | ||
| Abstract | 747.e1 | ||
| Keywords | 747.e1 | ||
| Introduction | 747 | ||
| Allergen Immunotherapy | 747 | ||
| Indications and Patient Selection | 747 | ||
| Administration | 747 | ||
| Mechanism of Action | 748 | ||
| Impact on Asthma Control | 748 | ||
| Persistent Clinical Effects After Discontinuation | 749 | ||
| Prevention of Asthma and Allergic Sensitivity Development | 749 | ||
| Safety | 749 | ||
| Omalizumab | 750 | ||
| Mechanism of Action | 750 | ||
| Pharmacology | 751 | ||
| Pharmacodynamics | 751 | ||
| Pharmacokinetics | 751 | ||
| Bioavailability. | 751 | ||
| Distribution. | 751 | ||
| Elimination. | 751 | ||
| Mode of Administration | 751 | ||
| Dosing Strategies | 751 | ||
| Clinical Studies | 751 | ||
| Adult Studies | 751 | ||
| Child Studies | 751 | ||
| Safety | 751 | ||
| Clinical Application—Current and Future Considerations | 752 | ||
| Age | 752 | ||
| Biomarkers | 752 | ||
| Target Response Expected | 752 | ||
| Other Diseases | 752 | ||
| Cost Effectiveness | 752 | ||
| Mepolizumab | 752 | ||
| Mechanism of Action and Target Effects | 752 | ||
| Pharmacology | 753 | ||
| Pharmacodynamics | 753 | ||
| Pharmacokinetics | 753 | ||
| Mode of Administration and Dosing | 753 | ||
| Biomarkers to Direct Use | 753 | ||
| Clinical Studies | 753 | ||
| Safety | 754 | ||
| Other Biologics | 754 | ||
| Reslizumab | 754 | ||
| Benralizumab | 754 | ||
| Dupilumab | 754 | ||
| Conclusion | 754 | ||
| References | 755 | ||
| Suggested Reading | 755 | ||
| References | 755.e1 | ||
| 5 Cystic Fibrosis | 756 | ||
| 49 Genetics and Pathophysiology of Cystic Fibrosis | 757 | ||
| Abstract | 757.e1 | ||
| Keywords | 757.e1 | ||
| CFTR Gene | 757 | ||
| Structure | 757 | ||
| Splicing | 757 | ||
| DNA Variants | 758 | ||
| CFTR Protein | 758 | ||
| Characteristics | 758 | ||
| Biogenesis | 759 | ||
| Function | 759 | ||
| Cellular Distribution and Function | 759 | ||
| Developmental Expression and Function | 759 | ||
| Postnatal Expression and Function | 759 | ||
| Tissue Distribution | 759 | ||
| Genotype-Phenotype Correlations | 760 | ||
| Molecular Consequences of Variants | 760 | ||
| Clinical Consequences of Variants | 761 | ||
| Pathophysiology | 762 | ||
| Airways Dehydration and Disruption of Mucociliary Clearance | 762 | ||
| Cystic Fibrosis Animal Models | 763 | ||
| Lung Phenotypes | 763 | ||
| Gastrointestinal Phenotypes | 763 | ||
| Vas Deferens Phenotype | 764 | ||
| Cystic Fibrosis-Related Diabetes | 764 | ||
| Characteristics of Systemic Disease | 765 | ||
| Airways, Upper and Lower | 765 | ||
| Inflammation | 766 | ||
| Infection | 766 | ||
| Gastrointestinal Disease | 766 | ||
| Sweat Gland Effects | 767 | ||
| Reproductive Tissues | 767 | ||
| Other Disorders Related to the Cystic Fibrosis Transmembrane Conductance Regulator | 767 | ||
| Congenital Bilateral Absence of the Vas Deferens | 767 | ||
| Pancreatitis | 768 | ||
| Sinusitis | 768 | ||
| References | 768 | ||
| References | 768.e1 | ||
| 50 Diagnosis and Presentation of Cystic Fibrosis | 769 | ||
| Abstract | 769.e1 | ||
| Keywords | 769.e1 | ||
| Diagnostic Criteria for Cystic Fibrosis | 769 | ||
| Making the Diagnosis of Cystic Fibrosis | 769 | ||
| Clinical Suspicion | 769 | ||
| The Sweat Test | 769 | ||
| Mutation Analysis | 771 | ||
| Assessment for Organ Involvement | 772 | ||
| Transepithelial Potential Difference Measurements | 772 | ||
| Antenatal Testing for Cystic Fibrosis | 772 | ||
| Neonatal Screening for Cystic Fibrosis | 773 | ||
| The Phenotypic Spectrum of Cystic Fibrosis— Influencing Factors | 774 | ||
| Cystic Fibrosis Phenotypes | 775 | ||
| Classical CF | 775 | ||
| CFTR-Related Disorders | 775 | ||
| CFSPID/CRMS | 775 | ||
| References | 776 | ||
| Suggested Reading | 776 | ||
| References | 776.e1 | ||
| 51 Pulmonary Disease in Cystic Fibrosis | 777 | ||
| Abstract | 777.e1 | ||
| Keywords | 777.e1 | ||
| Epidemiology | 777 | ||
| Etiology and Pathogenesis | 777 | ||
| Clinical Features | 780 | ||
| Symptoms and Physical Findings | 780 | ||
| Imaging and Laboratory Studies | 781 | ||
| Monitoring Lung Disease | 782 | ||
| Management and Treatment | 782 | ||
| Airway Clearance | 782 | ||
| Inhaled Mucolytics | 783 | ||
| Antibiotic Therapy | 783 | ||
| Cystic Fibrosis Transmembrane Conductance Regulator Modulators | 784 | ||
| Antiinflammatory Therapy | 784 | ||
| Preventative Care | 785 | ||
| Lung Transplantation | 786 | ||
| Emerging Therapies | 786 | ||
| Prognosis | 786 | ||
| Conclusions | 787 | ||
| References | 787 | ||
| Suggested Reading | 787 | ||
| References | 787.e1 | ||
| 52 Nonpulmonary Manifestations of Cystic Fibrosis | 788 | ||
| Abstract | 788.e1 | ||
| Keywords | 788.e1 | ||
| Pancreatic Disease | 788 | ||
| Pathobiology | 788 | ||
| Pancreatic Insufficiency | 788 | ||
| Pancreatic Sufficiency | 789 | ||
| Assessment of Pancreatic Function | 790 | ||
| Management of Pancreatic Insufficiency | 790 | ||
| Fibrosing Colonopathy | 790 | ||
| Treatment of Fibrosing Colonopathy | 790 | ||
| Pancreatitis | 791 | ||
| Hepatobiliary Disease | 791 | ||
| Clinical Presentation of Liver Disease | 791 | ||
| Diagnosis of Liver Disease | 792 | ||
| Management of Liver Disease | 793 | ||
| Gallbladder Disease | 794 | ||
| Infertility | 794 | ||
| Cystic Fibrosis Transmembrane Conductance Regulator Actions in the Small Bowel | 794 | ||
| Meconium Ileus | 794 | ||
| Constipation | 795 | ||
| Distal Intestinal Obstruction Syndrome | 796 | ||
| Distal Intestinal Obstruction Syndrome Management | 796 | ||
| Rectal Prolapse | 796 | ||
| Gastric Emptying and Small Bowel Motility | 796 | ||
| Small Intestine Bacterial Overgrowth | 796 | ||
| Microbiome | 796 | ||
| GI Cancers | 797 | ||
| Nutrition | 797 | ||
| Cystic Fibrosis–Related Diabetes | 798 | ||
| Conclusion | 799 | ||
| References | 799 | ||
| References | 799.e1 | ||
| 53 Molecular Therapies for Cystic Fibrosis | 800 | ||
| Abstract | 800.e1 | ||
| Keywords | 800.e1 | ||
| Introduction | 800 | ||
| Small Molecule Cystic Fibrosis Transmembrane Conductance Regulator Modulators | 800 | ||
| Identifying Candidate Drugs | 800 | ||
| Impact of Cystic Fibrosis Transmembrane Conductance Regulator Mutations on Protein Expression, Maturation, or Function | 800 | ||
| Targeting Cystic Fibrosis Transmembrane Conductance Regulator Protein With Small Molecule Drugs | 801 | ||
| Read-Through Agents | 801 | ||
| Potentiators | 803 | ||
| Correctors | 804 | ||
| Combination Therapy | 804 | ||
| Other Noncystic Fibrosis Transmembrane Conductance Regulator–Based Approaches | 805 | ||
| Cystic Fibrosis Gene Therapy | 805 | ||
| Viral Versus Nonviral Gene Transfer Agents | 806 | ||
| Lung Is a Challenging Target Organ | 806 | ||
| Recent Progress in the Field | 806 | ||
| More Recent Vector Development and Upcoming Clinical Trials | 808 | ||
| Outstanding Questions | 808 | ||
| How Much Cystic Fibrosis Transmembrane Conductance Regulator Expression Do We Need? | 808 | ||
| Which Cells Do We Need to Target for Restoration of Cystic Fibrosis Transmembrane Conductance Regulator Function? | 809 | ||
| Should Studies in Cystic Fibrosis Models Form a “Go/No-Go” Decision Point Before Progression Into Clinical Trials? | 809 | ||
| Are There Other Genetic Medicine-Based Approaches? | 809 | ||
| Evaluating Therapies Targeting the Basic Defect in Clinical Trials | 810 | ||
| Challenges for the Field | 810 | ||
| Summary | 811 | ||
| Declaration of Interests | 811 | ||
| Acknowledgments | 811 | ||
| References | 811 | ||
| References | 811.e1 | ||
| 6 Interstitial Lung Disease | 812 | ||
| 54 New Concepts in Children’s Interstitial and Diffuse Lung Disease | 813 | ||
| Abstract | 813.e1 | ||
| Keywords | 813.e1 | ||
| New Concepts, Terminology, and Classification | 813 | ||
| General Diagnostic Approach | 814 | ||
| Resources for Families and Physicians | 816 | ||
| References | 816 | ||
| Suggested Reading | 816 | ||
| References | 816.e1 | ||
| 55 Rare Childhood Lung Disorders | 817 | ||
| Abstract | 817.e1 | ||
| Keywords | 817.e1 | ||
| Introduction | 817 | ||
| Respiratory Disorders of the Lymphatic System | 817 | ||
| Pulmonary Lymphangiectasia | 817 | ||
| Epidemiology | 817 | ||
| Etiology and Pathogenesis | 817 | ||
| Clinical Features | 817 | ||
| Imaging | 818 | ||
| Management | 818 | ||
| Prognosis | 818 | ||
| Lymphangioma, Lymphangiomatosis, and Gorham-Stout Disease | 819 | ||
| Lymphangioleiomyomatosis | 819 | ||
| Pulmonary Alveolar Microlithiasis | 820 | ||
| Epidemiology | 820 | ||
| Etiology and Pathogenesis | 820 | ||
| Clinical Features | 820 | ||
| Diagnosis and Differential Diagnosis | 820 | ||
| Management and Prognosis | 820 | ||
| Ataxia Telangiectasia | 821 | ||
| Gaucher Disease | 821 | ||
| 7 Miscellaneous Disorders of the Lung | 886 | ||
| 60 Pulmonary Embolism and Thromboembolic Disease | 887 | ||
| Abstract | 887.e1 | ||
| Keywords | 887.e1 | ||
| Epidemiology | 887 | ||
| Etiology | 887 | ||
| Age-Specific Etiologies | 888 | ||
| Inherited and Acquired Thrombophilia | 888 | ||
| Disease-Specific Etiologies | 888 | ||
| Treatment-Specific Etiologies | 888 | ||
| Pathology/Pathogenesis | 888 | ||
| Clinical Features | 889 | ||
| Diagnosis and Differential Diagnosis | 889 | ||
| Imaging | 890 | ||
| Additional Diagnostic Testing | 891 | ||
| Ultrasonography | 891 | ||
| Echocardiography | 891 | ||
| Pulmonary Angiography | 891 | ||
| Management | 891 | ||
| Prevention | 892 | ||
| References | 892 | ||
| Suggested Reading | 892 | ||
| References | 892.e1 | ||
| 61 Diffuse Alveolar Hemorrhage in Children | 893 | ||
| Abstract | 893.e1 | ||
| Keywords | 893.e1 | ||
| Etiology of Diffuse Alveolar Hemorrhage | 893 | ||
| Immune-Mediated Alveolar Hemorrhage | 893 | ||
| Pathophysiology | 893 | ||
| Antineutrophil Cytoplasmic Antibody Associated Vasculitis | 895 | ||
| Granulomatosis With Polyangiitis. | 895 | ||
| Microscopic Polyangiitis. | 896 | ||
| Treatment of ANCA-Associated Vasculitis | 897 | ||
| Anti-GBM Disease | 897 | ||
| Isolated Pulmonary Capillaritis | 898 | ||
| COPA Syndrome | 899 | ||
| Nonimmune-Mediated Alveolar Hemorrhage | 899 | ||
| Idiopathic Pulmonary Hemosiderosis | 899 | ||
| Approach to the Child With Pulmonary Hemorrhage | 899 | ||
| Diagnosis | 899 | ||
| Treatment | 901 | ||
| Summary | 902 | ||
| References | 902 | ||
| Suggested Reading | 902 | ||
| References | 902.e1 | ||
| 62 The Lung in Sickle Cell Disease | 903 | ||
| Abstract | 903.e1 | ||
| Keywords | 903.e1 | ||
| Epidemiology | 903 | ||
| Etiology | 903 | ||
| Pathogenesis | 903 | ||
| Clinical Features | 904 | ||
| Acute Chest Syndrome | 904 | ||
| Risk Factors | 904 | ||
| Clinical Features | 905 | ||
| Sickle Chronic Lung Disease | 905 | ||
| Pulmonary Hypertension | 905 | ||
| Sleep-Disordered Breathing | 905 | ||
| Lung Function Abnormalities | 905 | ||
| Etiology of the Lung Function Abnormalities | 906 | ||
| Exercise Capacity | 906 | ||
| Diagnosis | 906 | ||
| Management | 906 | ||
| Acute Chest Syndrome | 906 | ||
| Pulmonary Hypertension | 907 | ||
| Monitoring | 907 | ||
| Prevention | 907 | ||
| Prognosis | 908 | ||
| References | 908 | ||
| Suggested Reading | 908 | ||
| References | 908.e1 | ||
| 63 Primary Immunodeficiency and Other Diseases With Immune Dysregulation | 909 | ||
| Abstract | 909.e1 | ||
| Keywords | 909.e1 | ||
| Chronic Granulomatous Disease | 909 | ||
| Clinical Features | 909 | ||
| Pulmonary Complications | 910 | ||
| Laboratory Findings and Diagnosis | 911 | ||
| NADPH Oxidase | 913 | ||
| Molecular Defects and Inheritance | 914 | ||
| Management | 915 | ||
| Hematopoietic Cell Transplantation and Gene Therapy | 916 | ||
| Common Variable Immunodeficiency Disorders | 917 | ||
| Clinical Features | 917 | ||
| Pulmonary Complications | 918 | ||
| Laboratory Findings and Diagnosis | 919 | ||
| Molecular Defects and Inheritance | 919 | ||
| Management | 919 | ||
| Other Immunodeficiencies With Pulmonary Manifestations | 920 | ||
| B-Cell Immunodeficiencies | 920 | ||
| Combined Cellular and Humoral Immunodeficiencies | 920 | ||
| Severe Combined Immunodeficiencies | 920 | ||
| Ataxia Telangiectasia | 921 | ||
| Hyper-Ige Syndromes | 921 | ||
| Deficiencies of the Innate Immune System | 922 | ||
| References | 922 | ||
| Suggested Reading | 922 | ||
| References | 922.e1 | ||
| 64 Pulmonary Disease in the Pediatric Patient With Acquired Immunodeficiency States | 923 | ||
| Abstract | 923.e1 | ||
| Keywords | 923.e1 | ||
| Introduction | 923 | ||
| Pulmonary Infections in the Immunocompromised Pediatric Host | 923 | ||
| Clinical Presentation of Pulmonary Infection in the Immunocompromised Child | 923 | ||
| Infectious Risks Shared by Malignancy, Solid Organ Transplantation, and Stem Cell Transplantation | 924 | ||
| Common Pulmonary Infectious Agents in the Immunocompromised Pediatric Host | 924 | ||
| Viral Pathogens (See Also Chapter 25) | 924 | ||
| Cytomegalovirus | 924 | ||
| Respiratory Syncytial Virus and Other Common Respiratory Viruses | 926 | ||
| Varicella-Zoster Virus and Herpes Simplex Virus | 926 | ||
| Herpesvirus Type 6 | 926 | ||
| Human Metapneumovirus | 926 | ||
| Adenovirus | 927 | ||
| Fungal Pathogens (See Also Chapter 31) | 927 | ||
| Pneumocystis jirovecii (Formerly P. carinii) | 927 | ||
| Aspergillus Species | 928 | ||
| Mucor and Rhizopus | 929 | ||
| Candida Species | 929 | ||
| Histoplasmosis and Blastomycosis | 929 | ||
| Cryptococcus Neoformans | 930 | ||
| Rarer Fungal Pneumonias | 930 | ||
| Bacterial Pathogens (See Also Chapter 25) | 930 | ||
| Mycobacteria (See Also Chapters 29 and 30) | 930 | ||
| Legionella Pneumophila | 931 | ||
| Parasitic Agents (See Also Chapter 33) | 931 | ||
| Toxoplasma Gondii and Cryptosporidium Parvum | 931 | ||
| Pulmonary Coinfections | 931 | ||
| Pulmonary Complications Following Solid-Organ Transplantation | 931 | ||
| Pulmonary Edema, Pleural Effusions, and Acute Respiratory Distress Syndrome | 931 | ||
| Impairment of Respiratory Mechanics | 931 | ||
| Medication Toxicity | 932 | ||
| Posttransplant Lymphoproliferative Disease | 932 | ||
| Other Noninfectious Pulmonary Complications of Solid-Organ Transplantation | 933 | ||
| Pulmonary Complications of Childhood Tumors and Their Treatment | 934 | ||
| Pulmonary Complications of Hematopoietic Stem Cell Transplantation | 935 | ||
| Pretransplant Factors | 935 | ||
| Early Noninfectious Posttransplant Complications (Fig. 64.6) | 936 | ||
| Oral and Perioral Complications | 936 | ||
| Pulmonary Edema and Capillary Leak Syndrome | 936 | ||
| Peri-Engraftment Respiratory Distress Syndrome | 936 | ||
| Idiopathic Pneumonia Syndrome | 937 | ||
| Diffuse Alveolar Hemorrhage | 937 | ||
| Pulmonary and Hepatic Veno-Occlusive Disease | 937 | ||
| Pulmonary Function Following Human Stem Cell Transplantation | 937 | ||
| Late Noninfectious Posttransplant Complications | 938 | ||
| Obliterative Bronchiolitis (“Bronchiolitis Obliterans Syndrome”) | 938 | ||
| Interstitial Lung Diseases | 939 | ||
| Cryptogenic Organizing Pneumonia | 939 | ||
| Posttransplant Lymphoproliferative Disorder | 939 | ||
| Pulmonary Alveolar Proteinosis | 939 | ||
| Respiratory Failure | 939 | ||
| Approach to Pulmonary Disease in the Immunocompromised Pediatric Host | 940 | ||
| Radiographic Testing | 940 | ||
| Noninvasive Diagnostic Studies | 940 | ||
| Invasive Diagnostic Studies | 941 | ||
| Flexible Bronchoscopy and Bronchoalveolar Lavage | 941 | ||
| Transthoracic Needle Aspiration Biopsy | 941 | ||
| Open-Lung Biopsy | 942 | ||
| Prevention Strategies | 942 | ||
| References | 942 | ||
| Suggested Reading | 942 | ||
| References | 943.e1 | ||
| 65 Hypersensitivity Pneumonitis and Eosinophilic Lung Diseases | 944 | ||
| Abstract | 944.e1 | ||
| Keywords | 944.e1 | ||
| Hypersensitivity Pneumonitis | 944 | ||
| Epidemiology | 944 | ||
| Etiology | 944 | ||
| Bird Fancier’s Lung | 944 | ||
| Other Environmental Exposures | 946 | ||
| Pathology/Pathogenesis | 947 | ||
| Type III and Type IV Hypersensitivity Responses | 947 | ||
| Clinical Features | 948 | ||
| Symptoms and Physical Findings | 948 | ||
| Acute Stage | 948 | ||
| Subacute Stage | 949 | ||
| Chronic Stage | 949 | ||
| Immunologic Studies | 949 | ||
| Radiologic Findings | 949 | ||
| Pulmonary Function Testing and Bronchial Challenge | 950 | ||
| Bronchoalveolar Lavage and Lung Biopsy | 950 | ||
| Management and Treatment | 951 | ||
| Prevention | 951 | ||
| Prognosis | 951 | ||
| Eosinophilic Pulmonary Diseases | 952 | ||
| 8 The Aerodigestive Model | 1093 | ||
| 75 The Aerodigestive Model | 1094 | ||
| Abstract | 1094.e1 | ||
| Keywords | 1094.e1 | ||
| Historical Perspective | 1094 | ||
| Patient Selection | 1094 | ||
| Screening and Evaluating Potential Patients | 1094 | ||
| The Interdisciplinary Team | 1095 | ||
| Value in Coordinated Aerodigestive Care | 1096 | ||
| Summary | 1096 | ||
| References | 1096 | ||
| References | 1096.e1 | ||
| 76 Aspiration | 1097 | ||
| Abstract | 1097.e1 | ||
| Keywords | 1097.e1 | ||
| Introduction | 1097 | ||
| Aspiration Caused by Swallowing Dysfunction | 1097 | ||
| Development of Swallowing | 1098 | ||
| Swallowing Dysfunction in Specific Populations | 1098 | ||
| Evaluation of Swallowing | 1100 | ||
| Role of Radiographic and Endoscopic Tests in the Evaluation of Aspiration | 1100 | ||
| Aspiration of Gastroesophageal Reflux | 1101 | ||
| Evaluation of Reflux Aspiration | 1101 | ||
| Biomarkers of Aspiration | 1101 | ||
| Treatment Considerations for Reflux Aspiration | 1102 | ||
| Aspiration of Oral Secretions | 1103 | ||
| Evaluation of Salivary Aspiration | 1103 | ||
| Treatment of Salivary Aspiration | 1103 | ||
| Evaluation of Lung Injury Caused by Aspiration | 1103 | ||
| Multidisciplinary Approach to Chronic Aspiration | 1104 | ||
| Evaluation of the Aerodigestive Tract | 1104 | ||
| References | 1105 | ||
| Suggested Reading | 1105 | ||
| References | 1105.e1 | ||
| 77 Feeding and Swallowing Disorders | 1106 | ||
| Abstract | 1106.e1 | ||
| Keywords | 1106.e1 | ||
| Introduction | 1106 | ||
| Epidemiology | 1106 | ||
| Anatomy, Physiology, and Development | 1106 | ||
| Feeding Skill Development | 1107 | ||
| Phases of Swallowing | 1107 | ||
| Etiology/Pathogenesis | 1108 | ||
| Conditions Associated With Feeding, Swallowing, and Airway Protection Problems | 1108 | ||
| Specific Airway Conditions and the Effect on Feeding and Swallowing | 1109 | ||
| Imaging, Instrumental Assessment of Swallowing Function, and Airway Protection | 1109 | ||
| Videofluoroscopic Swallow Study | 1110 | ||
| Fiberoptic Endoscopic Evaluation of Swallowing | 1110 | ||
| Diagnosis, Management, and Treatment | 1112 | ||
| Evaluation and Management | 1112 | ||
| Treatment Strategies | 1112 | ||
| Summary | 1113 | ||
| References | 1113 | ||
| References | 1113.e1 | ||
| 78 Gastroesophageal Reflux Disease and Eosinophilic Esophagitis in Children With Complex Airway Disease | 1114 | ||
| Abstract | 1114.e1 | ||
| Keywords | 1114.e1 | ||
| Gastroesophageal Reflux Disease | 1114 | ||
| Epidemiology | 1114 | ||
| Pathophysiology | 1114 | ||
| Clinical Features/Symptoms | 1114 | ||
| Diagnosis/Testing | 1115 | ||
| Management | 1115 | ||
| Disorders of Motility | 1115 | ||
| Eosinophilic Esophagitis | 1116 | ||
| Pathophysiology | 1116 | ||
| Diagnosis of Eosinophilic Esophagitis | 1116 | ||
| Treatment of Eosinophilic Esophagitis | 1116 | ||
| References | 1117 | ||
| Suggested Reading | 1117 | ||
| GERD | 1117 | ||
| Eosinophilic Esophagitis | 1117 | ||
| References | 1117.e1 | ||
| 79 Laryngeal and Tracheal Airway Disorders | 1118 | ||
| Abstract | 1118.e1 | ||
| Keywords | 1118.e1 | ||
| Introduction | 1118 | ||
| Operative Assessment | 1118 | ||
| Flexible Bronchoscopy | 1118 | ||
| Microlaryngoscopy and Rigid Bronchoscopy | 1118 | ||
| Esophagogastroduodenoscopy | 1119 | ||
| Swallowing and Voice Evaluations | 1119 | ||
| Mitigating Factors | 1119 | ||
| Bacterial Colonization | 1119 | ||
| Eosinophilic Esophagitis | 1120 | ||
| Gastroesophageal Reflux Disease | 1120 | ||
| Obstructive Sleep Apnea | 1120 | ||
| Pulmonary Disease | 1120 | ||
| Patient Selection | 1120 | ||
| Optimization | 1120 | ||
| Management of Airway Pathology | 1121 | ||
| Laryngomalacia | 1121 | ||
| Vocal Cord Paralysis | 1121 | ||
| Laryngeal Webs | 1122 | ||
| Subglottic Stenosis | 1122 | ||
| Vascular Compression | 1123 | ||
| Posterior Laryngeal Clefts | 1123 | ||
| Tracheomalacia | 1124 | ||
| Complete Tracheal Rings | 1124 | ||
| References | 1124 | ||
| References | 1124.e1 | ||
| 80 Sudden Infant Death Syndrome and Apparent Life-Threatening Events | 1125 | ||
| Abstract | 1125.e1 | ||
| Keywords | 1125.e1 | ||
| Acute Life-Threatening Events (ALTE) and BRUE | 1125 | ||
| Epidemiology | 1125 | ||
| Diagnosis and Differential Diagnosis | 1125 | ||
| Etiology and Pathology/Pathogenesis | 1125 | ||
| Clinical Features of an Apparent Life-Threatening Event | 1128 | ||
| Symptoms | 1128 | ||
| Physical Findings | 1128 | ||
| Management and Treatment of Apparent Life-Threatening Event | 1128 | ||
| Imaging and Laboratory Findings | 1129 | ||
| Prevention: Home Apnea Monitors and Feeding Infants With Exaggerated Laryngeal ChemoReflex Apnea | 1129 | ||
| Apnea in Premature Infants | 1130 | ||
| Diagnosis and Differential Diagnosis | 1130 | ||
| Pathogenesis of Apnea of Prematurity | 1130 | ||
| Prognosis of Apnea of Prematurity | 1132 | ||
| Management and Treatment for Apnea of Prematurity | 1133 | ||
| Monitoring Premature Infants at Home | 1134 | ||
| Sudden Infant Death Syndrome | 1134 | ||
| Pathogenesis: Triple Risk Model | 1134 | ||
| Potentially Lethal Mechanisms Linked to Sleep Position and Sleep Environment | 1136 | ||
| Epidemiology | 1136 | ||
| Newer Approaches to the Pathology and Physiology of Sudden Infant Death Syndrome | 1137 | ||
| Programmed Cell Death Within the Central Nervous System | 1137 | ||
| Neural Receptors and Sudden Infant Death Syndrome | 1138 | ||
| Fatty Acid Oxidation Deficiencies and the Contribution of Genetic Diseases of Metabolism to Sudden Infant Death Syndrome | 1138 | ||
| Prolonged Electrocardiogram QT Intervals and Lethal Cardiac Arrhythmias | 1139 | ||
| The Use of Investigations of the Scene and Circumstances of Sudden Infant Death | 1139 | ||
| Physiology Related to the Sleep Environment That May Make Infants More Vulnerable to SIDS | 1140 | ||
| Arousal and Prone Positioning | 1140 | ||
| Soft Bedding and Learned Infant Behaviors as Effect Modifiers | 1140 | ||
| Bed Sharing and Racial Disparities | 1141 | ||
| Summary | 1141 | ||
| Acknowledgments | 1142 | ||
| References | 1142 | ||
| Suggested Reading | 1142 | ||
| References | 1142.e1 | ||
| 81 Disorders of Breathing During Sleep | 1143 | ||
| Abstract | 1143.e1 | ||
| Keywords | 1143.e1 | ||
| Basic Mechanisms and Architecture of Normal Sleep | 1143 | ||
| Neural Circuitry of Sleep and Waking | 1143 | ||
| Developmental Aspects of Sleep | 1143 | ||
| Respiratory Control Mechanisms | 1144 | ||
| The Respiratory Rhythm Generator | 1144 | ||
| Sleep and Breathing During Development | 1144 | ||
| Central Chemoreceptors and Their Development | 1145 | ||
| Multiplicity of Central Chemosensitive Centers | 1146 | ||
| Peripheral Chemoreflexes | 1146 | ||
| The Upper Airway | 1147 | ||
| Upper Airway Control | 1147 | ||
| Upper Airway Dysfunction | 1148 | ||
| Apnea | 1149 | ||
| Central Apnea or Hypoventilation Syndromes | 1149 | ||
| Congenital Central Hypoventilation Syndrome | 1149 | ||
| Diagnosis and Clinical Management | 1150 | ||
| Secondary Central Hypoventilation Syndromes | 1151 | ||
| Obstructive Sleep Apnea | 1152 | ||
| Epidemiology | 1152 | ||
| Pathophysiology | 1153 | ||
| Conditions Associated With OSA | 1154 | ||
| Clinical Evaluation and Diagnosis of Obstructive Sleep Apnea | 1156 | ||
| Polysomnography | 1156 | ||
| Short-Term and Long-Term Morbidity of Obstructive Sleep Apnea | 1157 | ||
| Treatment of Obstructive Sleep Apnea | 1159 | ||
| References | 1159 | ||
| References | 1159.e1 | ||
| Index | 1161 | ||
| A | 1161 | ||
| B | 1166 | ||
| C | 1168 | ||
| D | 1173 | ||
| E | 1175 | ||
| F | 1176 | ||
| G | 1177 | ||
| H | 1178 | ||
| I | 1180 | ||
| J | 1182 | ||
| K | 1182 | ||
| L | 1182 | ||
| M | 1184 | ||
| N | 1187 | ||
| O | 1188 | ||
| P | 1189 | ||
| Q | 1194 | ||
| R | 1194 | ||
| S | 1195 | ||
| T | 1198 | ||
| U | 1200 | ||
| V | 1201 | ||
| W | 1201 | ||
| X | 1202 | ||
| Y | 1202 | ||
| Z | 1202 | ||
| Inside Back Cover | ibc1 |