Abstract
BackgroundCongenital diaphragmatic hernia is a severe congenital anomaly with significant mortality and morbidity, for instance chronic lung disease. Sphingolipids have shown to be involved in lung injury, but their role in the pathophysiology of chronic lung disease has not been explored. We hypothesized that sphingolipid profiles in tracheal aspirates could play a role in predicting the mortality/ development of chronic lung disease in congenital diaphragmatic hernia patients. Furthermore, we hypothesized that sphingolipid profiles differ between ventilation modes; conventional mechanical ventilation versus high-frequency oscillation.MethodsSphingolipid levels in tracheal aspirates were determined at days 1, 3, 7 and 14 in 72 neonates with congenital diaphragmatic hernia, born after > 34 weeks gestation at four high-volume congenital diaphragmatic hernia centers. Data were collected within a multicenter trial of initial ventilation strategy (NTR 1310).Results36 patients (50.0%) died or developed chronic lung disease, 34 patients (47.2%) by stratification were initially ventilated by conventional mechanical ventilation and 38 patients (52.8%) by high-frequency oscillation. Multivariable logistic regression analysis with correction for side of the defect, liver position and observed-to-expected lung-to-head ratio, showed that none of the changes in sphingolipid levels were significantly associated with mortality /development of chronic lung disease. At day 14, long-chain ceramides 18:1 and 24:0 were significantly elevated in patients initially ventilated by conventional mechanical ventilation compared to high-frequency oscillation.ConclusionsWe could not detect significant differences in temporal sphingolipid levels in congenital diaphragmatic hernia infants with mortality/development of chronic lung disease versus survivors without development of CLD. Elevated levels of ceramides 18:1 and 24:0 in the conventional mechanical ventilation group when compared to high-frequency oscillation could probably be explained by high peak inspiratory pressures and remodeling of the alveolar membrane.
Highlights
In patients with congenital diaphragmatic hernia (CDH), lung related problems such as chronic lung disease (CLD) and pulmonary vascular disease including pulmonary hypertension are the primary causes of mortality [1] with ventilator-induced lung injury (VILI) and high concentrations of oxygen predisposing newborns to develop CLD as prime morbidity [2].Since 2008, CDH neonates are treated according to the same neonatal treatment protocol, developed during a consensus meeting of the CDH EURO Consortium [3]
36 patients (50.0%) died or developed chronic lung disease, 34 patients (47.2%) by stratification were initially ventilated by conventional mechanical ventilation and 38 patients (52.8%) by high-frequency oscillation
Multivariable logistic regression analysis with correction for side of the defect, liver position and observed-to-expected lung-to-head ratio, showed that none of the changes in sphingolipid levels were significantly associated with mortality /development of chronic lung disease
Summary
In patients with congenital diaphragmatic hernia (CDH), lung related problems such as chronic lung disease (CLD) and pulmonary vascular disease including pulmonary hypertension are the primary causes of mortality [1] with ventilator-induced lung injury (VILI) and high concentrations of oxygen predisposing newborns to develop CLD as prime morbidity [2].Since 2008, CDH neonates are treated according to the same neonatal treatment protocol, developed during a consensus meeting of the CDH EURO Consortium [3]. In a randomized clinical trial (the VICI-trial) looking at initial ventilation strategy (CMV vs HFO) of prenatally diagnosed CDH infants, 41 of the 91 patients (45.1%) initially ventilated with CMV died or had CLD by day 28 compared to 43 of the 80 patients (53.8%) using HFO [4]. This difference, did not reach statistical significance. We hypothesized that sphingolipid profiles in tracheal aspirates could play a role in predicting the mortality/ development of chronic lung disease in congenital diaphragmatic hernia patients. We hypothesized that sphingolipid profiles differ between ventilation modes; conventional mechanical ventilation versus high-frequency oscillation.
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