DISEASES OF ALVEOLAR HOMEOSTASIS: RDS and BPD

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DISEASES OF ALVEOLAR HOMEOSTASISRDS and BPD

• Jeffrey A. Whitsett, M.D.
• Cincinnati Childrens Hospital Medical Center
• Divisions of Neonatology and Pulmonary Biology
• 3333 Burnet Avenue
• Cincinnati, OH 45229-3039

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Burden of Disease Related to Pulmonary Immaturity
in USA

• 4,000,000 Births
• 11 Preterm lt 37 weeks 440,000
• 1.3 lt1500g 52,000
• 0.75 lt1 kg 32,000
• 66?RDS
• 24?BPD

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Major Lung Diseases of the Premature

• RDS - Surfactant deficiency
• BPD - Injury/disrupted lung development/dysplas
  tic repair

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Normal Pediatric Lung Immunohistochemistry
proSP-C
SP-B
SP-B and SP-C are synthesized in alveolar Type 2
cells.
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Alveolar Structure
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Surfactant Composition

• SP-B
• SP-C
• SP-A
• SP-D

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Surfactant homeostasis
Type II cell
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Pathophysiology of RDS
Surfactant Treatment
Recycling
Surfactant Pool
Surfactant Function

• Lung Development
• Gestational Age
• Prenatal Stress
• Corticosteroids

Surfactant Inactivation
Leaky Epithelial and Endothelial Barriers
Severity of RDS
Pulmonary Edema
Lung Structure
Tissue Function
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Measurements to Evaluate Surfactant Metabolism
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Surfactant Concentration in Alveoli of Human Lung
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Adapted from Mulrooney et al., AJRCCM, 2005
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Appearance of Labeled Surfactant PC in Airway
Samples
Data from Multiple Sources
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Clearance of Labeled Surfactant PC from Airspaces
Data from Multiple Sources
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Persistent Effects of Surfactant Depend on
Metabolic Characteristics of Surfactant in the
Preterm Lung
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Surfactant Labeling and Secretion in Ventilated
Infants with RDS (13C-glucose labeling of PC)
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Metabolic Characteristics of Surfactant in the
Preterm with RDS

• Endogenous pool sizes are small (0-10 mg/kg)
• Synthesis/secretion of new surfactant is slow
  (70h)
• Catabolism and lung clearance is slow (days)
• Surfactant lipid and protein components are
  substrate for the metabolic pathways are recycled
  as intact components.
• ?A treatment dose is large and its chemical
  components persist for days

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Pro- and Anti-inflammatory Influences on Preterm
Lung
Chorioamnionitis Resuscitation
Mechanical Oxygen
Nosocomial Ventilation
Infection
Altered Lung Development and BPD
Preterm Fetal Lung
Transitional Lung
Preterm Postnatal Lung
Nn
Antenatal Corticosteroids
Indomethacin Postnatal

Corticosteroids
Anti-inflammatory
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