Decreased sodium ion absorption across nasal epithelium of very premature infants with respiratory distress syndrome Pierre M, Barker, MBChB, C. W. Gowen, MD, Edward E, Lawson, MD, and Michael R. Knowles, MD From the Department of Pediatrics and Medicine, Universityof North Carolina at Chapel Hill,and the Department of Pediatrics,University of EasternVirginia and Hospital of the Kings Daughters, Norfolk, Virginia Objective and study design: Successful adaptation to air breathing at birth depends on rapid absorption of fetal lung liquid that is mediated by activation of amiloride-sensitive sodium ion channels. To test the relationship between respira- tory epithelial Na ÷ transport and development of respiratory distress syndrome (RDS), we measured nasal transepithelial potential difference (PD) in 31 very pre- mature (-<30 weeks of gestation) newborn infants. Infants were retrospectively assigned to RDS (22 infants) and non-RDS (9 infants) groups on the basis of clinical and chest x-ray criteria. Results: Maximal nasal epithelial PD increased with birth weight (-1.2 mV/100 gm) and was lower in infants with RDS (-16.5 ± 0.6 mV) than in those without RDS (-22.0 ± 1.3 mV). Infants without RDS had PD values similar to normal fullterm in- fants. Amiloride inhibition of PD, an index of Na ÷ absorption,, was significantly lower, within the first 24 hours of life, in infants in whom RDS developed (3.8 ± 0.2 mV; 29.5% ± 0.8% inhibition) than in those without RDS (6. I ± 0.6 mV; 38.6% ± 0.5% inihibition). Maximal and amiloride-sensitive PD returned to normal during the re- covery phase of RDS. Conclusions: We conclude that Na ÷ absorption across nasal epithelium increases wiith increasing birth weight and that impairment of Na ÷ absorption across the respiratory epithelia of very premature infants may contribute to the pathogen- esis of RDS. (J Pediatr 1997;130:373-7) During fetal life the lungs are expanded by liquid secretion that depends on active transport of the chloride ion across the pulmonary epithelium, t During labor and after delivery, liq- uid secretion diminishes and the airspaces are cleared by ab- sorption of liquid out of the lung lumen. 2 Liquid absorption is driven by amiloride-blockable sodium ion transport 3, 4 and is initiated during labor and delivery, at least in part, by a sharp rise in circulating fetal epinephrine concentration. 2 Intraalveolar and interstitial pulmonary edema is a con- sistent histologic feature of respiratory distress syndrome, 5-7 See commentary, p. 342. ENaC Epithelialsodium channel PD Potential difference [electrical] RDS Respiratory distress syndrome Supported by the Cystic Fibrosis Foundation. Submitted for publication April 17, 1996; accepted Aug. 19, 1996. Reprint requests: Pierre M. Barker, MBChB, Department of Pedi- atrics, University of North Carolina at Chapel Hill, 635 Burnett- Womack Building, Manning Drive, Chapel Hill NC 27599-7220. Copyright © 1997 by Mosby-Year Book, Inc. 0022-3476/97/$5.00 + 0 9/21/77395 but a primary etiologic role for ion transport abnormalities of the immature respiratory epithefium in this disease has not been shown. Because the capacity of the fetal lung to absorb 373