Abstract
Background: We previously showed that sphingolipids, in particular ceramides, played a role in the pathogenesis of bronchopulmonary dysplasia (BPD) and are a target for therapeutic intervention in a mouse model.
Aims and objectives: To determine whether ceramides are detectable in tracheal aspirates (TAs) of prematurely born infants and to investigate whether ceramide profiles can predict the development of BPD.
Methods: Infants born ≤ 32 weeks of gestational age (GA) in need for mechanical ventilation in the first week of life were included. TAs were obtained directly after intubation, and at day 1, 3, 5, 7, and 14. Ceramide levels were measured by liquid chromatography tandem mass spectrometry. BPD was defined as ≥ 28 days supplemental oxygen at 36 weeks postmenstrual age (PMA).
Results: 122 infants were included (median GA (25-75th centile): 27.2 (25.6-29.6) weeks, median birthweight (25-75th centile): 967.5 (700.0-1263.8) gram). Fourteen infants died before 36 weeks PMA and 42 infants developed BPD. Infants with BPD had significantly higher concentrations of several ceramides at day 0, 5, 7 and 14.
Ceramides | Day 0 | Day 5 | Day 7 | Day 14 |
Cer14 | 0.056 | 0.209 | 0.014* | 0.383 |
CerDiHy16 | 0.044* | 0.232 | 0.060 | 0.185 |
Cer18 | 0.017* | 0.150 | 0.026* | 0.207 |
Cer18.1 | 0.150 | 0.015* | 0.008* | 0.628 |
CerDiHy18 | 0.049* | 0.232 | 0.007* | 0.258 |
Cer20 | 0.180 | 0.184 | 0.026* | 0.258 |
CerDiHy24 | 0.080 | 0.142 | 0.013* | 0.074 |
CerDiHy24.1 | 0.132 | 0.124 | 0.030* | 0.048* |
Mann-Whitney U tests. *p-values <0.050.
Conclusion: Ceramides were detectable in TAs of prematurely born infants and differed between infants with and without BPD. This confirms our observations in a mouse model, and suggests that ceramides are playing a role in the pathogenesis of BPD and might be a new target for therapeutic intervention.
- Copyright ©ERS 2015