Biochemical development of surface activity in mammalian lung. IV. Pulmonary lecithin synthesis in the human fetus and newborn and etiology of the respiratory distress syndrome

Abstract

The surface-active complex lining alveoli in normal lung lowers surface tension on expiration, thus preventing alveolar collapse. Surface activity follows a developmental timetable. Infants with idiopathic respiratory distress syndrome (RDS) almost exclusively are prematurely born, and their lungs lack adequate surface activity and are deficient in the principal surface-active component, lecithin. This deficiency implies that RDS is a “disease of development,” with fetal and neonatal timetables for lecithin synthesis. The biosynthesis of lung lecithin in the living human infant was studied by examining phospholipids in lung effluent (pharyngeal aspirates, mucus), which have identical phospholipids to those in lung lavage (alveolar wash). The fatty acid esters of isolated lecithin and phosphatidyl dimethylethanolamine (PDME) were examined. The β-carbon fatty acids are indicators of the primary pathways of synthesis of lecithin: (1) a preponderance of palmitic acid signifying cytidine diphosphate choline (CDP-choline) + D-α, β-diglyceride → lecithin (choline incorporation pathway) and (2) a preponderance of myristic acid signifying phosphatidyl ethanolamine (PE) + 2CH3 → PDME + CH3 → lecithin (methylation pathway). Fetal lung of 18 and 20 weeks showed slight incorporation by CDP-choline pathway, absence of PDME, and almost no methylation. Salivary lecithin had totally different fatty acids from lecithin in aspirates. Phosphatidyl dimethylethanolamine (PDME) (therefore methylation) was identified in aspirates as early as 22-24 week-gestation. Lecithin fatty acid esters in aspirates from premature infants after birth or those with no RDS closely resembled PDME fatty acids. With RDS, PDME disappears and β-carbon palmitic acid (therefore dipalmitoyl lecithin) increases. With recovery, PDME reappears, as does the premature infant’s major lecithin, palmitoylmyristoyl. Full term infants are born with more β-carbon palmitic acid (20-40%) and by 12-18 hr have equal palmitic and myristic acids, indicating function of both lecithin synthesis pathways. Stress (hypoxia acidosis, hypothermia) cause disappearance of PDME and loss of β-carbon myristic acid. Similar changes in full term infants who do not get RDS are due to adequate lecithin synthesis by the GDP-choline pathway. The capacity to synthesize lecithin in the lung by methylation in the human fetus and newborn allows the human to be born prematurely; rabbits and sheep lack this capacity and cannot be prematures, but die from respiratory insufficiency if born too soon. The diagnosis of RDS can be made objectively by looking for PDME in aspirates (lung effluent). Prognosis also can be established by lack or presence of PDME. The effects of various therapies also can be assessed this way. The techniques and consideration described herein can be employed to study biochemically the effects of other stresses to lung, including oxygen toxicity and anesthesia. © 1972 International Pediatric Research Foundation, Inc.