Respiratory Outcomes in Preterm Infants: From Infancy through Adulthood (Respiratory Medicine)

This book presents pulmonary outcomes of prematurity, from their emergence in infancy through to their consequences in adulthood. With an increasing number of preterm births and more infants surviving, there is now a larger population of adults with lung disease originating in infancy requiring specialized care. Looking at the whole group of preterm infants, not just those with bronchopulmonary dysplasia, this text covers a wide spectrum of pulmonary outcomes, including: pulmonary hypertension, wheezing, and alterations in sleep. The chapter authors focus on critically appraising what is and is not known about each outcome and suggest key questions that still need to be answered. __Respiratory Outcomes in Preterm Infants:__ __Sequelae from Infancy through Adulthood__ is an ideal reference for the multidisciplinary group that cares for these preterm infants and the adults they become, including: neonatologists, pediatric pulmonologists, pediatricians, adult pulmonologists, primary care physicians, nurses, and fellows. Preface 6 Contents 8 Contributors 10 The Problem of the Preterm Lung: Definitions, History, and Epidemiology 12 Lung Parenchymal Disease 12 Small Airways Disease 14 Large Airways Disease 15 Vascular Disease 16 Control of Breathing 17 Upper Airway Obstruction 17 Conclusions 18 References 18 Why Do Preterm Infants Wheeze? Clues from Epidemiology 26 Definitions 26 Bronchopulmonary Dysplasia 26 Newer Criteria 27 Wheeze 27 Asthma (WHO Definition; See http://www.who.int/respiratory/asthma/definition/en/) 27 Introduction 28 Which Respiratory Symptoms Are Described in Preterm-Born Infants? 28 Does Wheezing Occur in Former Preterm-Born Children, Adolescents, or Adults? 30 Does Gestational Age Matter? 32 Which Putative Mechanisms Are to Be Expected? 32 Lung Growth 33 Inflammation 34 Structural Changes 35 Which Risk Factors Are Described for Respiratory Problems in Former Preterm-Born Children? 35 Conclusion 36 References 37 Why Do Former Preterm Infants Wheeze? Clues from the Laboratory 41 Introduction 41 Maturational Changes in Airway Reactivity 41 Cholinergic Efferent Output 42 Sympathetic Control of the Lower Airways 44 Nonadrenergic Noncholinergic Control of the Lower Airways 44 Contributors to Abnormal Airway Function 46 Hyperoxic Exposure 46 Pressure Effects 48 Infectious/Inflammatory Contribution 49 Conclusion/Speculation 50 References 50 The Bronchopulmonary Dysplasia Diagnosis: Definitions, Utility, Limitations 54 Bronchopulmonary Dysplasia: Description and Clinical Definitions 54 Bronchopulmonary Dysplasia: Physiologic Definitions and Considerations 57 Validation of the Diagnosis of BPD: Respiratory Morbidity Outcomes 59 Validation of the Diagnosis of BPD: Pulmonary Function 60 Validation of the Diagnosis of BPD: Nonpulmonary Outcomes 63 Implications of BPD Definitions: Clinical Practice and Clinical Trials 64 Conclusion 65 References 65 Structural and Functional Changes in the Preterm Lung 70 Introduction 71 Part I: Stages of Lung Development 71 Embryonic Stage 72 Pseudoglandular Stage 72 Cannalicular Stage 72 Saccular Stage 73 Alveolar Stage 73 Part II: Pathogenesis of BPD 73 Part III: Long-Term Respiratory Outcomes of BPD Survivors 75 Respiratory Symptoms 76 Structural Abnormalities 77 Radiographic Abnormalities 79 Abnormal Pulmonary Function 79 Long-Term Respiratory Outcomes in Late-Preterm-Born Infants 82 Conclusions 84 References 84 Diagnostic Modalities: Pulmonary Function Testing and Imaging 90 Introduction 90 Infant PFT Findings 90 Overview of Infant Pulmonary Function Testing 91 Dynamic Measurements of Respiratory Mechanics 91 Passive Expiratory Mechanics 91 Tidal Breathing Measurements 93 Forced Expiratory Flows 93 Lung Volume Measurements 94 Measurements of Ventilation Homogeneity 95 Diffusion Capacity 95 Lung Function in Preschool Aged Preterm Children 95 Lung Function in Older Children and Adults Born Prematurely 96 Spirometry Results 96 Lung Volume Measurements 97 Diffusion Capacity 97 Evolution of Lung Function Over Time in Preterm Children and Adults 97 Summary 98 Imaging Studies 98 Chest Radiograph 98 Chest Computed Tomography 99 Magnetic Resonance Imaging 100 Conclusions 101 References 101 Longer Term Sequelae of Prematurity: The Adolescent and Young Adult 108 Introduction 108 The Big Picture: 2012 and 2015 Meta-analyses 111 Respiratory Symptoms and Morbidity 111 Airway Disease After Premature Delivery 112 Parenchymal Disease 116 Impaired Exercise Performance 118 Abnormal Control of Breathing 119 Pulmonary Circulatory Disease 120 Developmental Origins of Health and Disease Hypothesis (DOHAD) 120 Management of the Adult Survivor of Prematurity 121 Summary and Conclusions 121 References 122 Adverse Outcomes Do Not Stop at Discharge: Post-NICU Health Care Use by Prematurely Born Infants 128 Hospital Readmissions 129 Epidemiology of Readmissions in the Prematurely Born Infants 129 Impact of Gestational Age and Infant Complications 133 RSV Hospitalizations 135 Emergency Department Visits 137 Outpatient Health Care Use 137 Discussion and Future Directions 139 Role of Hospital and Outpatient Care 140 Social Determinants of Health 141 Moderate and Late Preterm Infants 142 Preterm Infants in a Population’s Health 142 Summary 142 References 142 Opportunities to Promote Primary Prevention of Post Neonatal Intensive Care Unit Respiratory Morbidity in the Premature Infant 147 Introduction 147 The Importance of Lung Trajectories in the Prevention of Post-­NICU Respiratory Morbidity in the Premature Infant 147 Preterm Birth Epidemiology and Complications 148 Preconception Interventions Before Pregnancy to Prevent Post NICU Respiratory Morbidities 149 Maternal Nutrition and Weight Preconception 149 Preconception and Intergenerational Smoking Cessation 149 Prenatal Interventions to Decrease Post NICU Respiratory Morbidities 150 Decreasing In Utero (and Second Hand) Smoke Exposure During Pregnancy 150 Clinical Benefits 150 Pulmonary Function Tests and Lung Development After Maternal Smoking in Pregnancy 151 Smoking Cessation/Decreasing Maternal Smoking Reduces Preterm Birth 152 Nicotine Replacement Therapies (NRT) 154 Vitamin Supplementation to Decrease the Effects of In Utero Nicotine on Offspring Pulmonary Function 154 Decrease in Air Pollution to Decrease Preterm Birth 155 Normalizing or Maximizing Prenatal Growth 156 Perinatal Interventions 157 Avoiding Iatrogenic Preterm Deliveries and Cesarean Sections 157 Postnatal Interventions 157 Growth and Nutrition 157 Breast-Feeding 158 Avoidance of Second Hand Smoke 158 Avoiding Early Postnatal Pollution Exposure 159 Importance of Avoidance of Viral Infections and Prophylaxis When Available 159 Avoidance of Personal Smoking in Former Premature Infants 160 Treatment of Post-NICU Respiratory Morbidity 161 Research Priorities for the Primary Prevention of Post NICU Respiratory Morbidities in Premature Infants 162 References 163 Sleep Outcomes in Children Born Prematurely 168 Overview of Respiratory Control and Sleep State Maturation in Infancy 169 Disordered Breathing During Sleep Across the Life Span (Fig. 1) 170 Preterm Infants at Term Postconceptual Age 170 First Year of Life and Sudden Infant Death Syndrome 172 Sleep-Disordered Breathing: Preschool to Adolescence 173 Sleep-Disordered Breathing in Preschool Children 174 Middle Childhood and Obstructive Sleep Apnea Syndrome 176 Adolescents and Young Adults and Sleep-Disordered Breathing 178 Impact of Preterm Birth on Sleep Architecture and Circadian Rhythm (Fig. 2) 179 Overview of Circadian Entrainment in the Neonatal Period 179 Sleep Architecture in the First Year of Life 180 Sleep Patterns and Behaviors in Preschool and School-Aged Children 180 Preterm Birth and Circadian Rhythms in Adolescents and Adults 182 Summary 183 References 183 Airway Outcomes 187 Introduction 187 Base of Tongue 188 Supraglottis 189 Glottis 190 Subglottis 192 Description/Classification 192 Epidemiology 193 Pathophysiology 194 Treatment 194 Trachea 196 Summary 198 References 198 Pulmonary Hypertension in Bronchopulmonary Dysplasia 202 Introduction 202 The Abnormal Pulmonary Circulation in BPD 204 Diagnostic Approach to PH in BPD 206 Treatment of PH in BPD 211 Conclusions 215 References 215 Infection and Inflammation: Catalysts of Pulmonary Morbidity in Bronchopulmonary Dysplasia 219 Introduction 219 Antenatal Infection and Inflammation 220 Does Chorioamnionitis Cause BPD? 221 Does Chorioamnionitis Make the Lung Susceptible to BPD? 222 Bacterial Sepsis and BPD 223 Cytomegalovirus Infection and BPD 224 Respiratory Viral Infection and BPD 225 Future Directions 227 References 228 Index 234 Front Matter....Pages i-x The Problem of the Preterm Lung: Definitions, History, and Epidemiology....Pages 1-14 Why Do Preterm Infants Wheeze? Clues from Epidemiology....Pages 15-29 Why Do Former Preterm Infants Wheeze? Clues from the Laboratory....Pages 31-43 The Bronchopulmonary Dysplasia Diagnosis: Definitions, Utility, Limitations....Pages 45-60 Structural and Functional Changes in the Preterm Lung....Pages 61-80 Diagnostic Modalities: Pulmonary Function Testing and Imaging....Pages 81-98 Longer Term Sequelae of Prematurity: The Adolescent and Young Adult....Pages 99-118 Adverse Outcomes Do Not Stop at Discharge: Post-NICU Health Care Use by Prematurely Born Infants....Pages 119-137 Opportunities to Promote Primary Prevention of Post Neonatal Intensive Care Unit Respiratory Morbidity in the Premature Infant....Pages 139-159 Sleep Outcomes in Children Born Prematurely....Pages 161-179 Airway Outcomes....Pages 181-195 Pulmonary Hypertension in Bronchopulmonary Dysplasia....Pages 197-213 Infection and Inflammation: Catalysts of Pulmonary Morbidity in Bronchopulmonary Dysplasia....Pages 215-229 Back Matter....Pages 231-235