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Development of the Respiratory System (Including the Preterm Infant)

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Pediatric and Neonatal Mechanical Ventilation

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Abstract

The developing mammalian lung is challenged by the requisite need for a gas-exchange surface area extensive enough to meet the needs of an organism’s oxygen consumption and CO2 removal. This is achieved first by the transformation of the primitive endoderm into the 105 conducting and 107 respiratory airways by iterative branching morphogenesis, followed by the extensive subdivision and successive maturation of the terminal airways into alveoli: the hundreds of millions of thin spherical cavities which facilitate gas exchange between the airways and the vascular system. Since the process of alveolar formation (alveolarization) occurs largely after birth, premature infants are at increased susceptibility to respiratory distress, often necessitating prolonged assisted ventilation. Despite major advances in the management of perinatal infant care, including improved mechanical ventilation modalities, prenatal steroid administration, and surfactant therapy, many such infants do not undergo normal alveolar development, resulting in the chronic lung disease, bronchopulmonary dysplasia (BPD). An appreciation of the complex cell and molecular interactions which govern normal lung morphogenesis is essential for understanding the aetiology of—and advancing treatments for—pulmonary diseases such as BPD.

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Abbreviations

ARDS:

Acute respiratory distress syndrome

BASCs:

Bronchoalveolar stem cells

BPD:

Bronchopulmonary dysplasia

CDH:

Congenital diaphragmatic hernia

DLCO :

Pulmonary diffusing capacity for carbon monoxide

E:

Embryonic day

ECM:

Extracellular matrix

FGF:

Fibroblast growth factor

Flk-1:

Fetal liver kinase-1

Flt-1:

Fms-like tyrosine kinase

Fox:

Forkhead box

GC:

Glucocorticoid

Hif:

Hypoxia-inducible factor

Hox:

Homeobox

IPF:

Idiopathic pulmonary fibrosis

MMP:

Matrix metalloproteinase

NF-κB:

Nuclear factor kB

PDA:

Patent ductus arteriosus

PDGF:

Platelet-derived growth factor

pnd:

Postnatal day

RA:

Retinoic acid

RDS:

Respiratory distress syndrome

SHH:

Sonic hedgehog

SP-C:

Surfactant protein C

TGF-β:

Transforming growth factor beta

TIMP:

Tissue inhibitor of metalloproteinases

TTF-1:

Thyroid transcription factor 1

V A :

Alveolar volume

VEGF-A:

Vascular endothelial growth factor A

VEGFR:

Vascular endothelial growth factor receptor

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Authors and Affiliations

  1. Lung Biology Group, Program of Physiology and Experimental Medicine, Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, ON, M5G1X8, Canada

    Stephen Joza & Martin Post

  2. Departments of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada

    Stephen Joza & Martin Post

  3. Departments of Laboratory Medicine and Pediatrics, University of Toronto, Toronto, ON, Canada

    Martin Post

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  1. Service of Neonatology and Pediatric Intensive Care, Department of Pediatrics, University Hospital of Geneva, Geneve, Switzerland

    Peter C. Rimensberger

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Joza, S., Post, M. (2015). Development of the Respiratory System (Including the Preterm Infant). In: Rimensberger, P. (eds) Pediatric and Neonatal Mechanical Ventilation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-01219-8_1

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