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(BQ) Part 1 book “Kendig''s disorders of the respiratory tract in children” has contents: The history and physical examination, molecular determinants of lung morphogenesis, basic genetics and epigenetics of childhood lung disease, environmental contributions to respiratory disease in children, the surfactant system,… and other contents.
Kendig's Disorders of the Respiratory Tract in Children NINTH EDITION Robert William Wilmott, BSc, MB, BS, MD, FRCP (UK) IMMUNO Professor and Chair Department of Pediatrics Saint Louis University Pediatrician in Chief SSM Cardinal Glennon Children's Medical Center St Louis, Missouri, United States Robin Deterding, MD Chief Pediatric Pulmonary Medicine Professor of Pediatrics Department of Pediatrics University of Colorado Aurora, Colorado, United States Albert Li, MBBch, MD, MRCPCH, MRCP(UK), FHKAM(Paeds), FHKCPaed Assistant Dean (Education) Faculty of Medicine Professor of Paediatrics Prince of Wales Hospital The Chinese University of Hong Kong Shatin, Hong Kong Felix Ratjen, MD, PhD, FRCP(C), FERS Head Division of Respiratory Medicine Program Head Translational Medicine Sellers Chair of Cystic Fibrosis Professor University of Toronto Hospital for Sick Children Toronto, Ontario, Canada Peter Sly, MBBS, MD, FRACP, DSc Director Children's Lung Environment and Asthma Research Group University of Queensland Brisbane, Australia Heather J Zar, MBBCh, FCPaeds, FRCP (Edinburgh), PhD Professor and Chair Department of Paediatrics & Child Health Director MRC Unit on Child & Adolescent Health Red Cross War Memorial Children's Hospital University of Cape Town Cape Town, South Africa Andrew Bush, MB BS(Hons), MA, MD, FRCP, FRCPCH, FERS Professor of Paediatrics and Head of Section Imperial College London Professor of Paediatric Respirology National Heart and Lung Institute Consultant Paediatric Chest Physician Royal Brompton Harefield NHS Foundation Trust London, Great Britain Table of Contents Instructions for online access Cover image Title Page Copyright Preface Contributors Video Contents Section General Basic and Clinical Considerations The History and Physical Examination The History The Physical Examination Common Signs and Symptoms of Chest Disease in Children Conclusion Suggested Reading Molecular Determinants of Lung Morphogenesis Introduction Organogenesis of the Lung Molecular Mechanisms Directing Lung Development Development of the Pulmonary Host Defense Systems Gene Mutations in Lung Development and Function Summary References Basic Genetics and Epigenetics of Childhood Lung Disease Types of Genetic Variation Technologies to Identify Genetic Variation Interpretation of Genetic Variation When to Consider Clinical Genetic Testing Research Study Designs to Attribute Genetic Variation to Disease Epigenetics—Terminology and Technology “Multi-Omics” Approaches to Refine Genotype-Phenotype Associations Websites References Environmental Contributions to Respiratory Disease in Children Vulnerability of Children to Adverse Environmental Exposures Environmental Contributions to Acute Respiratory Illness and Pneumonia Environmental Contributions to Asthma Summary References The Surfactant System Surfactant Composition and Metabolism Surfactant Metabolism and Secretion Alveolar Life Cycle of Surfactant Surfactant Function Pressure-Volume Curves Host Defense Functions of Surfactant Surfactant Deficiency Surfactant Treatment of Surfactant Deficiency References The Structural and Physiologic Basis of Respiratory Disease Normal Lung Anatomy and Cell Function Airways Alveolar Region Pulmonary Vascular System Lymphatic System Innervation of the Lung Interstitium Growth and Development of the Lung The Lung at Birth Postnatal Lung Growth Ventilation and Mechanics of Breathing Definitions and Symbols Elastic Recoil of the Lung Compliance of the Lung Elastic Properties of the Chest Wall Lung Volumes Regional Lung Volumes Dynamic (Flow-Resistive) Properties of the Lung Distribution of Ventilation Pulmonary Circulation Pulmonary Vascular Pressures Pulmonary Vascular Resistance Distribution of Blood Flow Methods of Evaluating the Pulmonary Circulation Muscles of Respiration Gas Exchange Alveolar Ventilation Dead Space Diffusion Shunt and Ventilation-Perfusion Relationships Systemic Gas Transport Oxygen Therapy Carbon Dioxide Transport and Acid-Base Balance Tissue Respiration Regulation of Respiration Sensory Feedback System Metabolic Functions of the Lung References Biology and Assessment of Airway Inflammation Introduction Allergic Inflammation Acute Inflammation Chronic Inflammation Inflammatory Cells Structural Cells as Sources of Mediators Inflammatory Mediators Neural Mechanisms Transcription Factors Antiinflammatory Mechanisms Direct Measurements of Airway Inflammation Noninvasive Assessment of Airway Inflammation Is AHR an Inflammatory Surrogate? Other Potential Indirect Inflammatory Markers 10 the stomach The lung fields are almost clear again, but there is a chest tube on the right side that has drained a pneumothorax subsequent to right-sided aspiration pneumonia Nonpulmonary Sequelae Hypothermia Hypothermia is a common manifestation of drowning in water of almost any temperature, and there is anecdotal evidence that rapid hypothermia in a submersion incident is neuroprotective, particularly in children Conductive losses through the skin are compounded by rapid heat exchange across the pulmonary capillaries if a significant volume of water is inhaled In a canine model, dogs breathing water at 4°C demonstrated a decrease in carotid artery blood temperature of 8°C within minutes.19 Cooling occurs most rapidly in small infants who have a relatively large surface area.37 In cases of extreme hypothermia, rewarming will be essential to allow return of cardiac function.38,39 Hypothermia can also play a major role in facilitating aspiration in immersion victims As the core temperature drops below 35°C, muscular incoordination and weakness occur, which can interfere with swimming As the core temperature decreases further, obtundation develops At core temperatures below 30°C, unconsciousness can occur and the myocardium becomes irritable Atrial fibrillation can occur, and at temperatures below 28°C, ventricular fibrillation is likely Electrolyte Imbalances Electrolyte imbalances may arise if a significant amount of nonisotonic water is aspirated, although this is unusual in regular seawater.40 Although freshwater immersion victims have decreased serum sodium, and saltwater immersion victims have elevated serum sodium and chloride levels,20 these are rarely substantial or clinically significant Even in the Dead Sea, which has electrolyte concentrations approximately 10 times higher than seawater, immersion victims rarely have severe abnormalities of sodium or 2347 chloride, although hypercalcemia and hypermagnesemia are common.41,42 Hemolysis due to aspiration of hypotonic or hypertonic fluids appears to be an extremely infrequent complication Trauma Traumatic injuries resulting from a fall into water must be considered but are generally of lesser importance than the immersion itself Cervical spine injuries are the most critical to consider but are uncommon, occurring in only 0.5% of all nonfatal drowning cases, and only then in cases with a clear history of diving, motorized vehicle crash, or fall from a height.43 Hypoxic-Ischemic Damage All organs are susceptible to hypoxic-ischemic injury following prolonged low cardiac output, and inadequate oxygenation and multiorgan failure is an almost inevitable consequence of severe submersion/immersion injury Clinically, the brain is particularly susceptible, with the liver and the gastrointestinal tract being the most resistant Management Management of the pulmonary injury will usually require supplemental oxygen, diuretic administration for pulmonary edema, and the most severe cases will require support with intubation and mechanical ventilation Many of these serious immersion accidents occur in relatively isolated locales, and often children are intubated in the field or in outside facilities where there may be little experience managing children Endotracheal tube sizes can be too large and sufficient to cause significant damage to the larynx if not recognized and promptly downsized after arriving at the receiving pediatric institution In addition, with severe cases, the lung injury will comprise all the features of PARDS The management of this disorder is addressed in Chapter 38 Instillation of surfactant has been reported44–46 and is an appealing therapeutic intervention given that the majority of 2348 victims aspirate a quantity of fluid that will denature and wash out existing surfactant However, the temptation to administer surfactant should be considered in the context of recent randomized controlled trials demonstrating a lack of efficacy of surfactant in PARDS.47–50 Administration of steroids appears to be effective in animal models of seawater aspiration,51 and there is evidence to support the use of steroids in PARDS,52 although this is by no means universally accepted.53 Broad-spectrum antibiotics should be administered to treat likely bacterial contamination of the lungs, such as after drowning in stagnant water.36 The incidence of neurological infection is stated to be high, with a number of case reports in children.54 Most drowning victims will be hypothermic at the time of presentation In cases of extreme hypothermia, rewarming will be essential to allow return of cardiac function,38,39 and if the core temperature is below 26°C–28°C, or the patient is in cardiac arrest, rewarming is probably best achieved using cardiopulmonary bypass.55 Given the potential benefits of hypothermia on hypoxic CNS injury, it is our view that modest hypothermia (core temperature 32°C–34°C) should be maintained immediately following the injury until the patient reaches the receiving hospital if there is any suspicion of the patient having sustained a hypoxic brain injury While duration of submersion, but not water temperature, is reported to be more associated with drowning outcome,56 excellent neurological outcomes have been reported after prolonged immersion in very cold water, with several case reports indicating full neurological recovery after periods of up to 66 minutes in near-freezing water.38,57,58 Children lose body heat more rapidly than adults, and if significant brain cooling occurs prior to cessation of circulation, then some degree of neuroprotection may occur It has been estimated that brain temperature needs to fall by at least 3°C within the first minutes of immersion for cerebral protection to be effective.37 The role of induced hypothermia for neuroprotection following drowning remains less certain Some recent studies have highlighted the beneficial effects of hypothermia on a variety of hypoxic CNS injuries in humans.59,60 However, these studies had control arms of “usual care,” and some patients became 2349 hyperthermic with potential harmful effects and made the hypothermia group outcomes appear better.61,62 In a Canadian trial using hypothermia in drowned children to reduce intracranial pressure and limit brain injury,63 the death rate in the hypothermic group was higher than in the normothermic group, with most deaths attributed to neutropenic sepsis However, this trial was relatively small, and the hypothermia group was also managed with hyperventilation and high-dose phenobarbitone, which may have influenced the outcomes A randomized, controlled trial of therapeutic hypothermia versus normothermia after cardiac arrest outside of the hospital has been undertaken by 38 pediatric centers in the United States and Canada under the auspices of the National Institutes of Health This study showed no benefit of hypothermia over rigorously controlled normothermia in either mortality or neurodevelopmentally in the 1-year follow-up of 295 survivors.64 However, this study excluded patients with cardiac arrest secondary to drowning in ice water who had a core temperature of ≤32°C on presentation In a subsequent report of the subset of the 74 pediatric cardiac arrest patients due to drowning from this study, it was concluded that hypothermia did not result in a statistically significant benefit in survival with good functional outcome or mortality at year, as compared to normothermia.65 Current Pediatric Advanced Life Support guidelines no longer recommend consideration of cooling to 32°C–34°C for 12–24 hours in comatose children following cardiac arrest, but support rigorous temperature control to avoid heating.66 Outcome of Pulmonary Injury Routine tests of pulmonary function have been reported as normal in adults67 following a drowning accident However, in a series of 10 functionally normal children68 studied months to 8.5 years (mean 3.3 years) after the submersion incident, only one had completely normal pulmonary function Seven had abnormal methacholine challenges demonstrating a high incidence of bronchial hyperreactivity, and five had clear evidence of peripheral airways disease Whether these abnormalities were related solely to aspiration inherent in the drowning episode or further related to 2350 PARDS was not addressed.69,70 It is possible these children are at risk for developing chronic lung disease, especially if exposed to further airway or parenchymal irritants Outcome Prediction of Neurological Injury The best prognostic indicators are observed in the field The strongest predictor of good outcome is duration of immersion Poor outcomes are observed in 60%–100% of subjects immersed for greater than 10 minutes, compared to 0%–30% of those immersed for ≤5 minutes.56 Good outcomes are also associated with the presence of sinus rhythm, reactive pupils, and neurologic responsiveness at the scene.71 The presence of a detectable heartbeat and hypothermia (