Surfactant Levels in Congenital Diaphragmatic Hernia

C ongenital diaphragmatic hernia (CDH), which occurs in one in 2,500 live births [1], is the most life-threatening cause of lung hypoplasia and is associated with high mortality, morbidity, cost, and suffering. The lungs are abnormally " stiff " in neonates with CDH [2], necessitating mechanical ventilation, often at high airway pressures, to prevent atelectasis and maximize the surface area available for gas exchange. The cause of low lung compliance in CDH is multifactorial and may involve aberrant remodeling of lung structure and/or a primary surfactant defi ciency. In the sheep model of CDH, the compliance of liquid-fi lled lungs is reduced [3], indicating involvement of surfactant-independent mechanisms; liquid fi lling of the lungs eliminates surface tension forces generated by the alveolar air−liquid interface. Indeed, increased thickness of inter-airspace walls and/or excessive collagen deposition in lung parenchyma have been reported in CDH [4]. On the other hand, a primary surfactant defi ciency has been implicated as a cause of abnormal lung hysteresis (see Glossary) in neonates with CDH, although the role of surfactant defi ciency in CDH remains controversial. Pulmonary surfactant is a phospholipid–protein complex synthesized and secreted exclusively by alveolar epithelial type II (AEII) cells that lowers surface-tension forces at the alveolar air−liquid interface, thereby increasing lung compliance. Of the four surfactant-associated proteins (SPA ,-B,-C, and-D), it is the two smaller hydrophobic proteins, SP-B and SP-C, that interact with alveolar phospholipids to prevent alveolar collapse at low lung volumes. SPA and SP-D are centrally involved in the innate immunity of the lung. Mechanical ventilation with high levels of inspired oxygen can impair surfactant synthesis and function, and should therefore be considered when evaluating studies involving human CDH. Why should a primary surfactant defi ciency in newborns with CDH be of serious concern, given the availability of prophylactic surfactant preparations that signifi cantly improve lung compliance, pulmonary blood fl ow, and gas exchange? Clinically, the question of whether infants with CDH should receive exogenous surfactant therapy is important because such therapy can transiently compromise these fragile infants with minimal respiratory reserve. Moreover, if human CDH is indeed associated with a primary surfactant defi ciency, we may opt for alternative treatment strategies (such as antenatal glucocorticoids or fetal lung gene therapy) to enhance endogenous surfactant production before birth. Surfactant phospholipids in CDH. Data from human studies support the premise that production of phospholipids is normal in CDH. In human fetuses with …