1080 Neonatal Respiratory Distress Syndrome (Rubin, Ramirez, King) Mucus Rheology and Transport in Neonatal Respiratory Distress Syndrome and the Effect of Surfactant Therapy* Bruce K. Rubin, M.D. , F.C.C.P; Oscar Ramirez, M.D.; and Malcolm King, Ph.D. , F.C.C.P Background: Neonatal respiratory distress syndrome (RDS) is caused by a deficiency of pulmonary surfactant. Alveolar collapse and obstruction of conducting airways leads to mismatch of ventilation and perfusion and profound hy- poxemia. We postulated that surfactant deficiency could alter the properties of respiratory mucus in such a way that it would be poorly cleared from airways and promote airway luminal obstruction and that these changes might be reversed by the exogenous administration of a synthetic surfactant preparation. Methods: Respiratory mucus coating an endotracheal tube (ETT) or suction catheter was collected from 14 neonates (gestational age, 24 to 36 weeks; birth weight, 600 to 2,400 g) with RDS who required tracheal intubation and venti- lation. Eight of these neonates received 5 mI/kg of an intratracheal artificial surfactant preparation (Exosurf), given between 2 and 10 h of age and six neonates received 5 mI/kg of air. Mucus viscoelasticity, hydration (percentage of solid composition of mucus), and mucociiary clearability (NFPTR) were measured for each specimen. Results: The total volume of mucus collected from the surfactant-treated and control infants was similar, but mucus hydration was significantly less in babies with RDS who did not receive Exosurf (percentage of solid composi- tion of mucus 18.7 vs 11.4; pO.Ol3). Ciliary transporta- biity was also less in the untreated babies (NFPTR 0.39 vs 0.86; pO.Ol8) and this mucus was more rigid (increased viscoelasticity: log G 1 rad/s 2.28 vs 1.50; pO.000l) Conclusions: These data suggest that airway obstruction in RDS may be due, in part, to abnormal mucus properties and impaired ciiary transport. Surfactant therapy appears to improve mucus clearability. Exogenously administered surfactant may also be beneficial for the treatment of other selected respiratory conditions associated with impaired mucus clearance. (Chest 1992; 101:1080-85) ETT = endotracheal tube; NFPTR normalized mucus trans- port rate on the frog palate (mucociliary clearabiity %SC percent solids composition of the mucus; RDS respiratory distress syndrome of the neonate M ore than 30 years ago, Avery and Mead’ demon- strated that deficiency of pulmonary surfactant is the cause ofhyaline membrane disease or respiratory distress syndrome of the newborn (RDS). Surfactant deficiency leads to mismatch of ventilation and per- fusion, and hypoxemia that may be due in part to mucus obstruction of the airways.2 We postulated that surfactant deficiency might also alter the surface tension of airway mucus causing poor mucociliary coupling or increased mucus adherence to the epithe- hum, thus promoting airway obstruction. We further postulated that mucus abnormalities might be amelio- rated by the administration ofsurfactant to the airways ofbabies with RDS. Since 1980, the topical application of surfactant preparations has been studied for therapy of RDS One such synthetic product, an artificial surfactant *Fmm the University of Alberta Pulmonary Defense Research Group, Edmonton, Alberta, Canada, and St. Louis University School of Medicine Pediatric Research Institute, St. Louis, Mo. Presented in part at the 56th Annual Scientific Assembly, American College ofChest Physicians, Toronto, October 26-30, 1991, where this work was a finalist in the 1990 Cecile Lehman Mayer Research Award Competition. Manuscript received April 1; revision accepted September 11. Reprint requests: Dr. Rubin, Division of Pulmonology, 1465 South Grand, St. Louis 63104 preparation (Exosurf) (Burroughs Wellcome Co, Re- search Triangle Park, NC), was first successfully used to treat prematurely delivered rabbit pups5 and is now being used in prematurely born neonates for the treatment of RDS. The studies reported herein were conducted in babies at the Royal Alexandra Hospital in Edmonton, Alberta, who were enrolled in an Exosurf rescue trial designed by the manufacturer. MATERIALS AND METHODS We collected respiratory mucus from eight premature neonates with RDS who received airway treatment with Exosurf, and six neonates with RDS who did not receive Exosurf. All babies were intubated for 48 h or less (range, 6 to 48 h) at the time of mucus sampling. No baby received any medication other than parenteral antibiotics. Surfactant treatment group was determined by random allocation. Neonates were excluded from the study if they did not have RDS or if they had a secondary pulmonary diagnosis as well as RDS such as pneumonia. RDS was diagnosed using standard criteria, that is, progressive respiratory insufficiency and hypoxemia noted during the first hours oflife in a prematurely born infant with roentgenographic changes of bilateral interstitial pulmonary infil- trates and air bronchograms. Exosurf was reconstituted with sterile water immediately before use so that each 1 ml of solution contained 13.5 mg of dipalmitoyl- phosphatidylcholine, 1.5 mg ofcetyl alcohol, 1 mg oftyloxapol, and 5.85 mg of sodium chloride. In a modified Wilhelmy balance, an Exosurffilm has a minimal surface tension ofless than 10 dynecm I when its surface is compressed, and regains nearly all of the film Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21642/ on 04/18/2017