The Lung

Development, Aging and the Environment

3rd Edition - August 1, 2024
Imprint: Academic Press
Editors: Kent Pinkerton, Richard Harding, Elizabeth Georgian
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 9 1 8 2 4 - 4
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 1 5 7 0 - 0

The Lung: Development, Aging and the Environment, Third Edition provides an understanding of the multifaceted nature of lung development, aging and the environment influence… Read more

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The Lung: Development, Aging and the Environment, Third Edition provides an understanding of the multifaceted nature of lung development, aging and the environment influences of these processes. As an essential resource to respiratory, pulmonary and thoracic scientists and physicians, this book provides an interface between the "normal" and "disease" cluster of chapters, allowing for a natural complement. The interface between different lung diseases affecting the pediatric lung also adds a useful source for comparing how different lung diseases share key pathophysiological features. This same complementarity comes across in the logical line up of chapters dealing with the "normal" pediatric lung.

New research, including cell-based strategies for infant lung function, epigenetics and prenatal environmental exposure (including wildfires) on lung development and function are some of the important additions to this edition of this reference work.

Title of Book
Cover image
Title page
Table of Contents
Copyright
Contributors
Introduction to the Third Edition
Part I. Critical events in normal development and aging
Chapter 1. Lung progenitor cell specification and morphogenesis
Introduction
Onset of lung development
Specification of respiratory progenitors and formation of the lung primordium
Formation of the trachea
Branching morphogenesis
Cell fate choice and differentiation of the airway epithelium
Conclusions
Chapter 2. Alveolar development
Introduction
Formation of the airways and first gas-exchange area: A brief overview
Embryonic period/organogenesis (weeks 4–7)
Pseudoglandular stage (weeks 5–17)
Canalicular stage (weeks 16–26)
Saccular stage (weeks 24–38)
Alveolarization: Increase of pulmonary surface area and maturation of the alveolar septa (week 36–young adulthood)
Classical alveolarization (week 36–approximately 3 years)
Microvascular maturation (week 36–young adulthood)
Continued alveolarization (∼2 years–young adulthood)
Pulmonary acinus/pulmonary ventilatory unit
Alveolarization of the respiratory bronchioles
Clinical aspects of alveolarization
Disclosures
Chapter 3. Development of the innervation of the lower airways: structure and function
Introduction
Anatomy, morphology, and distribution in the prenatal lung
Origin of the innervation: The fetal mouse lung
Mapping the innervation: Fetal pig and human lung
Pseudoglandular stage
Canalicular stage
Saccular stage
Exposures in utero and the developing lower airways
Function of the airway innervation during fetal life
Summary: Ontogeny of lung innervation before birth
Anatomy, morphology, and distribution in the postnatal lung
Early postnatal period to late adulthood
Density of innervation
Orientation of airway smooth muscle bundles
Efferent nerves: Long preganglionic and short postganglionic fibres
The pulmonary neuroendocrine cell system and its innervation
Definition, general morphologic features, and distribution
Development of PNECs/NEBs
PNEC/NEB innervation and its development
Proposed function(s) and pathobiology of PNECs/NEBs
Role of PNEC/NEB in lung defences and pulmonary inflammation
PNEC function as progenitors and progenitor niches
Ontogeny and reflex control of airway smooth muscle: Functional consequences
Prenatal airway smooth muscle function
Postnatal airway smooth muscle function
Reflex control of airway smooth muscle in the newborn lung
Muscarinic receptors in the lung
Muscarinic receptors: Their development and pharmacological antagonists
Chapter 4. Pulmonary vascular development
Introduction
Cellular basis of vessel morphogenesis
Overview
Developmental stages of the lung
Vascular channel formation in the lung
Development (formation and growth) of endothelial channels
Overview
Vasculogenesis
Angiogenesis (sprouting)
Angiogenesis (expansion)
Angiogenesis (IMG, IAR, and IBR)
Endothelial cell fate (arterial-venous and lymphatic specification)
Development of vascular mural cells
Overview
Pericytes
Smooth muscle cells and elastic laminae
Fibroblasts
Cell–cell signaling: Endothelial/mural cell development
Overview
Endothelial channel formation: VEGF/VEGF-R
Mural cell development: PDGF, ANG, and TGFβ
Embryonic and fetal vascular development
Overview
Early vessel development
Conventional and supernumerary arteries and veins
Vessel wall structure
Distribution of intra-acinar vessels
Development of bronchial arteries and veins
Postnatal vascular development and growth
Overview
Conventional and supernumerary arteries and veins
Vessel wall structure
Distribution of intra-acinar vessels
Bronchial artery to pulmonary artery connections
Vascular growth and reorganization in the adult
Overview
Conventional and supernumerary arteries and veins
Vascular wall structure
Distribution of intra-acinar vessels
Vessell wall reorganization in aging
Overview
Vascular wall structure
Failure to develop the normal quota of vascular units and a functionally “normal” lung
Overview
Single lung in agenesis
Repair of congenital diaphragmatic hernia
Musculoskeletal disorders
Chapter 5. Developmental physiology of the pulmonary circulation
Introduction
Lung vascular growth during development
Physiology of the fetal pulmonary circulation
Control of the ductus arteriosus
Mechanisms of pulmonary vasodilation at birth
Mechanisms that cause failure of pulmonary vasodilation at birth
Conclusions
Chapter 6. Physical, endocrine, and growth factors in lung development
Role of physical factors in regulating fetal lung development
Regulation of the basal degree of lung expansion in the fetus
Role of the upper airway and the trans-pulmonary pressure gradient in regulating fetal lung liquid volume
Role of the chest wall in maintaining lung volumes
Evidence for the role of basal lung expansion in lung development
Evidence for the role of phasic lung expansion in lung development
Mechanotransduction mechanisms
The role of the ECM and “outside-in” cell signaling
Stretch-induced activation of intracellular signaling pathways
Role of locally produced factors in promoting lung growth and maturation
Role of growth factors in lung development
MicroRNAs involved in fetal lung growth and development
Circulating factors and metabolic influences on lung development
The role of corticosteroids in fetal lung growth and development
The role of retinoids in fetal lung growth and development
Other circulating factors involved in fetal lung growth and development
Metabolic influences on lung development—hypoxia and nutrition
Treatments for infants with inappropriate lung development
Conclusions
Chapter 7. The development and function of the pulmonary surfactant system in health, prematurity, and genetic disease
Composition of pulmonary surfactant
Lipids
Proteins
Assembly and release of surfactant
Biophysical function of surfactant
Modeling of surfactant film function
Functions of the pulmonary surfactant system
Lung stability
Alveolar interdependence and anti-adherence
Prevention of pulmonary edema and maintenance of airway patency
Host defense
Regulation of surfactant secretion
Lamellar body exocytosis
Signaling mechanisms of surfactant secretion
Autonomic agonists
Ventilation
Development of the pulmonary surfactant system
Regulation of surfactant system development
Neurohormonal factors
Mechanical factors
Newborn respiratory distress syndrome: Role of surfactant immaturity or deficiency
Surfactant system immaturity associated with preterm birth
Genetic factors affecting surfactant composition and function
SP-B deficiency
ABCA3 mutations
SP-C mutations
NKX2.1 mutations
Altered pulmonary surfactant contributes to respiratory dysfunction in the lysosomal storage diseases
Conclusions
Chapter 8. Ontogeny of the pulmonary immune system
Introduction
Postnatal maturation of systemic immunity
Innate immunity
Adaptive immunity
Postnatal maturation of pulmonary mucosal immunity
Resident immune/inflammatory cells of developing airways
Developmental expression of pulmonary cytokines and chemokines
Developmental regulation of pulmonary immune/inflammatory cell trafficking
Pulmonary defense mechanisms during infancy
Conclusions
Chapter 9. Macrophages and the lung
Introduction
The origin of macrophages
Macrophages in the lungs
Conclusions
Chapter 10. Adaptation to mechanical signals in the lung: Recruitment of reserves, remodeling, and regrowth
Introduction
Tissue and mechanical forces during lung development
Mechanical forces following pneumonectomy
Post-pneumonectomy compensatory response
Recruitment of physiologic reserves
Acinar and septal remodeling
Re-initiation of alveolar septal growth
Limits of compensatory response
Compensatory response during somatic maturation
Manipulating mechanical signals in compensatory lung growth
Bronchovascular growth and remodeling
Regulatory pattern in developmental and compensatory lung growth
Interventions to augment compensatory lung growth
Role of cytoprotection in compensatory lung growth
Summary and conclusions
Chapter 11. Pulmonary transition at birth
Introduction
Fetal lung maturation, glucocorticoids and birth
Airway liquid clearance before birth
Lung liquid clearance at birth
Airway liquid clearance after birth
The physiological consequences of lung aeration
Changes in pulmonary blood flow at birth
Dynamic changes in the ductus arteriosus at birth
Fetal breathing and the onset of continuous breathing at birth
Conclusions
Chapter 12. Normal aging of the lung
Introduction
Aging, body mass, and the lungs in mammals
Lifespan characteristics of the mouse
The aging mouse lung
Changes in lung volume during aging in mice
Tracheobronchial airways of aging mice
Parenchymal lung structure in aging mice
Macrophages and lung aging in mice
Antioxidant enzyme activity in the aging mouse
Conclusions on lung aging in the mouse
Lifespan characteristics of the rat
The aging rat lung
The tracheobronchial tree and epithelium of the aging rat
Parenchymal lung structure in the aging rat
Alveolar tissue compartments in the aging rat
Alveolar macrophages in the aging rat
Conclusions on lung aging in the rat
General characteristics of the lungs in aging dogs
The tracheobronchial tree of the aging dog
Parenchymal lung structure in the aging dog
Conclusions on lung aging in the dog
General characteristics of the lungs in the aging rhesus monkey
Lung structure in the aging rhesus
Conclusions on lung aging in the rhesus monkey
Overall conclusions
Part II. Environmental and disease influences on lung development and aging
Chapter 13. Epigenetics and the developmental origins of lung disease
Introduction
Understanding the developmental origins of lung disease
Human evidence for the developmental origins of lung disease
Lessons from animal studies
Epigenetics in the developmental origins of lung disease
Epigenetic basics
Epigenetics in the developmental origins of lung disease
Future perspectives
Conclusions
Chapter 14. Pulmonary consequences of preterm birth
Introduction
Causes of preterm birth
Definition of preterm birth
Incidence of preterm birth
Factors leading to preterm birth
Preterm birth and perinatal mortality
Preterm birth and morbidities and adverse outcomes
Preterm birth as an environmental influence on lung development
Respiratory distress syndrome
Bronchopulmonary dysplasia
Conclusions
Chapter 15. Preterm birth and the developing lung: Long-term programming effects on respiratory function
Pathways leading to preterm birth
Respiratory consequences following preterm birth in humans
Respiratory outcomes in infants born preterm
Respiratory outcomes in children born preterm
Respiratory outcomes in adolescents and adults born preterm
Prenatal factors contributing to altered lung development and lung function
Lung development following prenatal infection and inflammation: Human data
Lung development following prenatal infection and inflammation: Experimental data
Potential genetic and epigenetic mechanisms by which prenatal inflammation affects the developing lung
Antenatal corticosteroids
Lung development following antenatal corticosteroid exposure: Human data
Lung development following antenatal corticosteroid exposure: Experimental data
Postnatal factors contributing to altered lung development and lung function
Supplemental oxygen therapy
Potential genetic and epigenetic mechanisms by which neonatal hyperoxia affects the developing lung
Mechanical ventilation
Lung development following mechanical ventilation: Human data
Lung development following mechanical ventilation: Experimental data
Potential genetic and epigenetic mechanisms by which neonatal mechanical ventilation affects the developing lung
Non-invasive assisted ventilation
Lung development following non-invasive assisted ventilation: Human data
Lung development following non-invasive assisted ventilation: Experimental data
Future directions
Summary and conclusions
Chapter 16. The effects of neonatal oxygen exposure on lung development
Introduction
Preterm birth
What are the known effects of neonatal hyperoxia on functional outcomes?
Long-term pulmonary outcomes of preterm birth
Pulmonary outcomes during infancy
Pulmonary outcomes during childhood
Pulmonary outcomes during adolescence and adulthood
Effects of neonatal hyperoxia on lung development
Effects of hyperoxia on development of alveoli
Effects of hyperoxia on development of conducting airways
Effects of neonatal hyperoxia on later lung function
Mechanisms of altered lung development
Oxidative stress
Inflammation
Potential therapies
Angiogenic factors
Antioxidant and anti-inflammatory factors
Stem/progenitor cells
Conclusions
Chapter 17. Restricted growth during early development: long-term effects on lung structure and function
Introduction
Fetal growth restriction
Pulmonary consequences of fetal growth restriction in humans
Experimental data on the impact of restricted fetal growth on lung development
Pulmonary circulation
Physical environment of the fetal lung
Glucocorticoids (corticosteroids)
Potential genetic and epigenetic mechanisms by which induction of FGR affects the developing lung
Future research directions
Summary and conclusions
Chapter 18. Cell-based strategies for the treatment of injury to the developing lung
Introduction
Stem cells: The basics
General classification
Stem cell types relevant to neonatal lung injury repair
Mesenchymal stromal cells (MSCs)
Isolation of MSCs
Characterization of MSCs
Therapeutic potential of exogenous MSCs
Advantages of MSCs as therapeutic cells
MSC proposed mechanism of action in neonatal lung injury
MSCs in experimental BPD animal studies
Clinical trials of MSCs in preterm infants with BPD
Pitfalls and challenges to MSC clinical translation: MSC heterogeneity
Intrinsic MSC heterogeneity
MSC heterogeneity due to culture conditions
MSC heterogeneity due to extrinsic/environmental factors in the setting of neonatal lung injury
MSC production: From cell culture to cell product
Human amnion epithelial cells (hAECs)
Isolation and characterization of hAECs
Therapeutic potential of hAECs
Proposed mechanism of action
Advantages of hAECs as therapeutic cells
hAEC cells in experimental neonatal lung injury studies
Conclusions
Chapter 19. Effects of environmental tobacco smoke during early life stages
Introduction
Conditions of early life ETS exposure
ETS and cotinine
Lung maturation
Immune system and allergen
Critical life stages and ETS
In utero exposure
Postnatal exposure: Infancy and childhood
In utero versus postnatal exposure
Perinatal exposure versus adult exposure
Effects of prenatal and postnatal smoke exposure on the development of disease later in life
Asthma
COPD and cancer
Cardiovascular disease
Cognitive decline
Respiratory/pulmonary infection
Conclusions
Chapter 20. Nicotine exposure during early development: Effects on the lung
Introduction
Uptake of nicotine
Daily nicotine intake
Absorption, distribution, and metabolism of nicotine in pregnancy
Effects of maternal nicotine intake during gestation and lactation on the placenta and fetal growth
Effects of nicotine exposure on lung development
Nicotine and cell signaling: Apoptosis and lung development
Maternal nicotine exposure during pregnancy and lactation: Effect of restoration of maternal antioxidant status
Transgenerational effect of grand-maternal nicotine exposure
Conclusions
Chapter 21. Implications of early life exposures to electronic nicotine delivery system (ENDS) aerosols
Introduction
General context
Prevalence of ENDS use during pregnancy
Maternal health effects associated with ENDS use during pregnancy
Fetal health effects associated with ENDS use during pregnancy
Health effects in prenatally and secondhand ENDS aerosol-exposed infants/children
Experimental animal studies
Neonatal outcomes (birth weight, body length, and body weight gain) in offspring exposed prenatally and in early life to ENDS aerosols
Pulmonary health effects in offspring exposed prenatally and in early life to ENDS aerosols
Other health effects in offspring exposed prenatally and in early life to ENDS aerosols
Cardio/cerebral-vascular and renal systems
Neurobehavioral impacts
Prenatal exposures to ENDS aerosols and the developmental origin of health and disease (DOHaD) paradigm
Conclusions
Chapter 22. Exposure to allergens during development
Introduction
Principles of allergic sensitization: Induction of type 1 hypersensitivity
Immune modulation by helper T cell subsets
Influence of in utero exposure to allergens on development of the atopic phenotype
Maternal influences on the immune status of the fetus
The influence of genetics on response to allergen exposure during development
Neonatal exposure to allergens
The T helper cell type 2 phenotype in the neonate
Role of dietary factors in allergen sensitization
The role of infectious diseases in modulating the effects of inhaled allergen during the neonatal period
Hygiene hypothesis
Exposure to allergens during the juvenile period
Interaction of allergens with environmental factors during development
Summary
Chapter 23. Effect of environment on the developing and adult pulmonary surfactant system and in the aging lung
Effect of the intrauterine environment on the developing pulmonary surfactant system
Intrauterine growth restriction
Maternal chronic hypoxia
Umbilical placental embolization
Single uterine artery ligation
Carunclectomy
Roles and interactions of fetal hypoxia, glucocorticoids, and glucose in regulating surfactant development in the IUGR fetus
Maternal nutrition
Overnutrition
Undernutrition
Maternal addiction/drug use
Smoking
Alcohol
Illicit drugs
Intrauterine and neonatal respiratory infection
Chorioamnionitis
Respiratory syncytial virus (RSV)
Coronaviruses
Effects of environmental factors on the adult pulmonary surfactant system
Effects of changing oxygen on the mature surfactant system
Experimental hypoxia
High altitude hypoxia
Experimental hyperoxia
Effects of environmental pollutants on the mature pulmonary surfactant system
Properties and toxic effects of pollutants
Ozone
Particulate pollutants
Interactive effects on the pulmonary surfactant system of pollutants in the aging lung
Conclusions
Chapter 24. Environmental determinants of lung aging
Introduction
Factors that influence susceptibility of the lung to premature aging
Cellular homeostasis
Oxidative stress and lung antioxidant defenses
Innate and acquired immunity
Matrix remodeling
Nutrition, body mass, and physical activity
Early lung injury
Regulation of breathing
Gas exchange
Endocrine function, diurnal rhythm and airway receptors
Genetic and familial factors related to a decline in lung function
Deposition, retention, and clearance of particulates
Effect of aging on airflow limitation
Markers of accelerated decline in lung function
Environmental factors that accelerate declines in lung function
Ambient air pollution
Oxidant gases: Nitrogen dioxide and ozone
Particulates
Airborne particles and experimental studies
Micro-plastics
Ultrafine particles (UFP)
Cigarette smoke
Effect of smoking cessation on age-related decline in lung function
Infections
Non-neoplastic diseases of the lung associated with aging
Chronic obstructive pulmonary disease (COPD)
Emphysema
Asthma
Effects of age and environmental exposures
Atopy and IgE
Environmental triggers of asthma
Interstitial lung disease and pulmonary fibrosis
Can we slow and/or reverse the aging process?
Conclusions and future directions
Chapter 25. The role of epigenetic mechanisms in lung diseases and environmental exposure
Introduction
The definition of epigenetics and its features
DNA methylation
Histone modifications
Noncoding RNA (ncRNA) and transcriptional gene silencing
Interactions between epigenetics, genetics, and environmental exposures
Epigenetic regulation in asthma
Introduction
DNA methylation changes in asthma and asthma-related exposures
The role of histone modifications and noncoding RNA in asthma and asthma-related exposures
Direct contributions of epigenetic modifiers to asthma
Epigenetic contributions to chronic obstructive pulmonary disease (COPD)
Introduction
The role of DNA methylation in COPD
The role of histone modifications in COPD
The role of noncoding RNA (ncRNA) in COPD
Epigenetics–environment interactions in COPD and the contribution of genetic factors
Conclusions
Chapter 26. Dynamic microbiotal changes in the human lung
Background
Dynamic changes of the human lung microbiota
Establishment of the lung microbiota in the fetus
The microbiota during lung development in newborns to 3-year-olds
Lung microbiota during lung maturation in 3- to 60-year-olds
Lung microbiota during lung aging in ≥60-year-olds
Human lung microbiota, host health, and diseases throughout the human lifespan
Establishment of the lung microbiota in the fetus
The microbiota during lung development in newborns to 3-year-olds
Lung microbiota during lung maturation in 3- to 60-year-olds
Lung microbiota during lung aging in ≥60-year-olds
The gut–lung axis
Conclusions
Chapter 27. Viral respiratory pathogens and acute lung injury in pregnancy, with a focus on epidemiology and pathophysiology of ARDS amidst the COVID-19 pandemic
Introduction
Epidemiology
Pregnancy-related ARDS
Pregnancy and H1N1, SARS, and MERS epidemics
Pregnancy and COVID-19
ARDS pathophysiology
General overview
Viral-induced ARDS sub-phenotype
RNA viruses: Orthomyxoviruses (i.e., influenza)
RNA viruses: Coronaviruses
Physiologic considerations in pregnancy and development of ARDS
Respiratory changes of pregnancy
Immunity and pregnancy
COVID-19 and mechanisms of maternal–fetal immunopathology
Viral-induced ARDS and fetal outcomes
H1N1, SARS, and MERS epidemics and fetal outcomes
COVID-19 and fetal outcomes
Conclusions
Chapter 28. The lung exposome: Accelerating precision respiratory health
Introduction
Evolution of the exposome concept
The impact of exposome research on lung health across the lifespan
Perinatal exposome and lung health in early life
Plasticity of lung health and the personal exposome
Exposure memory and lung aging
Exposome research insights into precision medicine
Technology operationalizing exposome research
External exposome at the individual level
Internal exposome at the molecular level
Data science in exposome research
Integrative omics and systems biology
Concluding remarks and future perspectives
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

The Lung

Development, Aging and the Environment

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Kent Pinkerton

Richard Harding

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