Novel insights from studies on pulmonary surfactant kinetics

Surfactant is a complex mixture of lipids (˜90%) and proteins (˜10%). Among lipids, 80-90% are phospholipids, of which phosphatidylcholine (PC) is quantitatively the most important, accounting for 70 to 80% of the total. Approximately 60% of the PC contains two saturated fatty acids, of which dipalmitoyl is the most abundant.
Dipalmitoyl phosphatidylcholine (DPPC) is the main surface tension-lowering component of pulmonary surfactant.
Surfactant PC is synthesized from phospholipid precursors (for example, fatty acids, glycerol, choline, glucose) in the Golgi apparatus. The time required for de novo PC synthesis, secretion and significant alveolar accumulation has been studied in animals using radioactively labeled substrates, using different approaches. These studies led to important clinical observations. For instance, it has been observed that surfactant de novo synthesis occurs at a low rate; this implies that, once surfactant is released into the alveolar space, it takes a long time before newly-synthesized surfactant could be detected. Therefore, if an increase in the pulmonary surfactant is necessary, exogenous surfactant therapy must be administrated.
In a small study conducted in full term infants with pneumonia and in preterm babies with RDS, it has been shown that the amount of disaturated phosphatidylcholine (DSPC) recovered from the tracheal aspirates was not different between the study groups, whereas its half-life was significantly shorter in infants with pneumonia (19.3±7.3 h) than in preterms with RDS (28.7±15.9 h). Even if larger randomized trials are required to further investigate this issue, it can be preliminarily suggested that the dose and time intervals of exogenous surfactant therapy should be different in patients with neonatal pneumonia from the patients with RDS.
Other analyses, conducted in infants with meconium aspiration syndrome (MAS), suggested that surfactant inactivation could play a more important role in the pathophysiology of MAS than surfactant deficiency. In particular, it was observed that surfactant synthesis is impaired in the sickest MAS infants on extracorporeal membrane oxygenation (ECMO). For this reason some clinical results indicated that surfactant therapy may be an effective therapeutic strategy in MAS infants, and should probably be given at a high dose and at an early stage in the development of the disease.
Last, kinetic studies have helped in clarifying that infants with congenital diaphragmatic hernia (CDH) and on conventional mechanical ventilation have normal surfactant synthesis, whereas CDH babies requiring ECMO do not. Some preliminary studies could suggest a potential role of surfactant prophylaxis in high-risk neonates with CDH.
These examples show that complex kinetic studies could produce novel information on in vivo surfactant kinetics, which will likely provide new answers to clinical questions regarding pulmonary surfactant and will help a better tailoring of exogenous surfactant treatment in neonatal lung diseases.

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