Biological Basis of Surfactant Therapy in Respiratory Distress Syndrome

Surfactant treatment is the standard therapy for infants with Respiratory Distress Syndrome (RDS), who present a reduced surfactant lipid pool (less than 10 mg/kg), and an immature lung structure with low diffusion distance and surface area, which limits lung function. Moreover, the preterm infant with RDS is at higher risk to develop lung injury and edema.
Surfactant is an aggregate of highly organized lipids and specific proteins; the preterm infant with RDS has a surfactant with different composition and a reduced surface tension. Normally the catabolism of surfactant is performed by macrophages or surfactant can be recycled by type II cells. The acute treatment response (within minutes) depends on rapid distribution of surfactant to the distal lung and on the low amount of surfactant needed for treatment response. The persistence of the surfactant treatment response is explained by surfactant metabolism in the preterm lung. Although the synthesis of surfactant lipids and proteins is rapid, surfactant storage and subsequent secretion occur over many hours, or even days in preterm infants with RDS. However, catabolism is also very slow: a large surfactant dose results in an increase in the total surfactant pool, which persists for days, while the infant himself is synthesizing new surfactant. Moreover, because surfactant components are recycled, the treatment surfactant acts as substrate for recycling in the uninjured preterm lung.
The exogenous surfactant differs in composition from natural one; however, within hours of surfactant treatment, the preterm lung can transform treatment surfactant into natural surfactant, because of recycling. Therefore, the persistence of a surfactant response is based on the integration of the exogenous surfactant into endogenous surfactant metabolism by uninjured lung, a process that continues over many days.
A single treatment can therefore cure the surfactant deficiency disease component of RDS in most infants; the crucial variable for the need for a second dose of surfactant is lung injury, which, if resulting in edema, can inhibit surfactant function. Lung injury also interferes with the normal metabolism of surfactant by type II cells, with a subsequent loss of biophysical properties and deterioration in lung function. The infant may respond favourably to a second dose of surfactant, but few infants improve with subsequent doses. Virtually all preterm infants with surfactant deficiency respond to surfactant. The non responders either have lung injury prior to birth, lung injury after birth and prior to treatment, pulmonary hypoplasia, or a cardiovascular explanation for the lack of response. The clinician should seek for different diagnoses in the preterm infant who has respiratory failure and is not responding to surfactant.
Some variables can alter surface treatment response. For instance, activation of exogenous surfactant is less effective at early gestational ages, because of an immaturity of the lung and of its metabolic capabilities. There is no consensus about the optimal timing of surfactant treatments for RDS. Evidence suggests that therapy requires delivery room intubation and treatment and that neither extreme of very early or late treatment is optimal. In fact, if intubation and treatment are delayed until signs of early RDS, the infant will not be overventilated as easily during initial stabilization, and infants not affected with RDS will not be treated with surfactant. Many of very low birth weight infants probably have minimal RDS, and if lung injury is avoided, the infants may do well with continuous positive air pressure (CPAP) therapy alone. Experience with CPAP suggests that lung injury from ventilation can contribute to the development of RDS by causing surfactant inactivation, when a small endogenous surfactant pool might otherwise be adequate.

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