SURFACTANT PROTEIN-A, PHOSPHATIDYLCHOLINE, AND SURFACTANT INHIBITORS IN EPITHELIAL LINING FLUID - CORRELATION WITH SURFACE-ACTIVITY, SEVERITY OF RESPIRATORY-DISTRESS SYNDROME, AND OUTCOME IN SMALL PREMATURE-INFANTS

Although surfactant deficiency at birth is the major cause of respiratory distress syndrome (RDS), there is insufficient data on surfactant and surfactant inhibitors after birth. In the present study, a total of 345 airway specimens (AS) from 61 neonates of gestational age of 24 to 29 wk (54 with RDS) were analyzed for concentrations of phosphatidylcholine (PC), saturated PC (SPC), surfactant protein A (SP-A), nonsedimentable protein, and free amino acids in epithelial lining fluid (ELF). The relationship between surfactant indices, surface activity, and severity of RDS was studied. Treatment with human surfactant containing SP-A increased [PC]ELF and [SPC]ELF to levels found in infants without RDS. In placebo-treated infants similar concentrations were first reached between Days 4 and 7. Surfactant treatment increased the low SP-A/SPC ratio, although this ratio remained lower than that in exogenous surfactant. In RDS, the concentrations of free amino acids in ELF were 6 to 31 times higher than in infants without RDS. The nonsedimentable proteins of AS and cationic amino acids increased the minimum surface tension of SP-A-deficient surfactant from AS. Addition of SP-A improved the surface activity. According to multiple regression analysis, In [PC]ELF (P < 0.0001), SPC/PC ratio (p < 0.0001), In SP-A/SPC ratio (p < 0.0002), and [protein]ELF (p < 0.01) correlated with alveolar-arterial oxygen pressure gradient. Of the infants weighing < 1,000 g, those who were going to die or develop bronchopulmonary dysplasia had a strikingly lower SP-A/SPC ratio during the first week (< 25 ng/nmol) than those surviving without BPD. These results indicate that lack of SP-A increases the susceptibility to surfactant inhibitors and is characteristic of infants vulnerable to serious injury.