In Vivo Effect of Pneumonia on Surfactant Disaturated-Phosphatidylcholine Kinetics in Newborn Infants

Abstract

BackgroundBacterial pneumonia in newborns often leads to surfactant deficiency or dysfunction, as surfactant is inactivated or its production/turnover impaired. No data are available in vivo in humans on the mechanism of surfactant depletion in neonatal pneumonia. We studied the kinetics of surfactant's major component, disaturated-phosphatidylcholine (DSPC), in neonatal pneumonia, and we compared our findings with those obtained from control newborn lungs.MethodsWe studied thirty-one term or near-term newborns (gestational age 39.7±1.7 weeks, birth weight 3185±529 g) requiring mechanical ventilation. Fifteen newborns had pneumonia, while 16 newborns were on mechanical ventilation but had no lung disease. Infants received an intratracheal dose of 13C labeled dipalmitoyl-phosphatidylcholine at the study start. We measured the amount and the isotopic enrichment of DSPC-palmitate from serial tracheal aspirates by gas chromatography and gas chromatography-mass spectrometry, respectively, and we calculated the DSPC half-life (HL) and pool size (PS) from the isotopic enrichment curves of surfactant DSPC-palmitate.ResultsThe mean DSPC amount obtained from all tracheal aspirates did not differ between the two groups. DSPC HL was 12.7 (6.5–20.2) h and 25.6 (17.9–60.6) h in infants with pneumonia compared with control infants (p = 0.003). DSPC PS was 14.1 (6.6–30.9) mg/kg in infants with pneumonia and 34.1 (25.6–65.0) mg/kg in controls, p = 0.042. Myeloperoxidase (MPO) activity, as a marker of lung inflammation, was 1322 (531–2821) mU/ml of Epithelial Lining Fluid (ELF) and 371(174–1080) mU/ml ELF in infants with pneumonia and in controls, p = 0.047. In infants with pneumonia, DSPC PS and HL significantly and inversely correlated with mean Oxygenation Index (OI) during the study (DSPC PS vs. OI R = −0.710, p = 0.004 and HL vs. OI R = −0.525, p = 0.044, respectively).ConclusionsWe demonstrated for the first time in vivo in humans that DSPC HL and PS were markedly impaired in neonatal pneumonia and that they inversely correlated with the degree of respiratory failure.

Surfactant protein B and A concentrations are increased in neonatal pneumonia

“…The administration of a tracer dose of (U-13 C-PA)dipalmitoyl-phosphatidylcholine allowed us to measure the DSPC kinetics, confirming previous findings of our research group (15). We found that in newborns with pneumonia DSPC PS and t 1/2 are, respectively, lower and shorter compared to controls.…”

“…If additional parental consent was obtained, we also measured DSPC turnover with a tracer dose of (U-13 C-PA)dipalmitoyl-phosphatidylcholine mixed with 2-5 mg/kg of Curosurf, used as a spreading agent. Administration of the tracer dose and TA collection and processing were performed as previously reported (15,31). Processed samples were stored at −80 °C until analysis.…”

“…We compared the concentrations of SP-B and SP-A in tracheal aspirates (TAs) obtained soon after intubation and after clinical improvement just before extubation, in both groups. We also investigated if SP-B and SP-A levels correlate with the degree of respiratory failure and with disaturated-phosphatidylcholine (DSPC) turnover rate, that is known to be increased, with shorter t 1/2 values, during various acute lung diseases (14,15).…”

Streptococcus pneumoniae inhibits purinergic signaling and promotes purinergic receptor P2Y2 internalization in alveolar epithelial cells

“…The effect of this (or: the described) mechanism on the course of infection and cellular damage can only be speculated about. During pneumococcal pneumonia, surfactant breakdown and impaired surfactant synthesis are hallmarks of infection in the alveolar epithelium and contribute to its severity (62,63). In the healthy lung, surfactant secretion is regulated by purinergic signaling and mediated by ATP in a paracrine manner.…”

Investigation of urine proteome of preterm newborns with respiratory pathologies

“…Respiratory disorders reflect the severe destruction of lung tissue associated in particular with the deficiency or dysfunction of the surfactant [42]. Differential diagnosis of respiratory pathologies of non-infectious origin and congenital pneumonia in premature infants still remains an unsolved problem in neonatology.…”