Exogenous Surfactant Kinetics in Infant Respiratory  Distress Syndrome: A Novel Method with Stable Isotopes

Torresin, Mirka; Zimmermann, Luc J. I.; Cogo, Paola; Cavicchioli, Paola; Badon, Tamara; Giordano, Giuseppe; Zacchello, Franco; Sauer, Pieter J. J.; Carnielli, Virgilio P.

doi:10.1164/ajrccm.161.5.9905088

Cited by 73 publications

(86 citation statements)

References 27 publications

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“…Thus, our data are again consistent with these studies, which suggests true differences in surfactant production between those term infants with mild and severe disease. The concomitant use of stable isotopically labeled exogenous surfactant preparations will permit the more reliable estimates of surfactant pool size necessary for fully interpreting the indices of endogenous surfactant metabolism (36,37).…”

Section: Discussionmentioning

confidence: 99%

Endogenous Surfactant Metabolism in Newborn Infants with and without Respiratory Failure

et al. 2003

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Studies using stable isotopically labeled glucose and palmitate as precursors of pulmonary surfactant synthesis have demonstrated slow surfactant turnover in premature infants with respiratory distress syndrome (RDS). However, only limited data about surfactant turnover are available for term infants. Because acetate is a direct precursor of de novo synthesized surfactant fatty acid, we measured [1-13 C 1 ]acetate incorporation into surfactant of term infants without respiratory dysfunction (control group), preterm infants with RDS, and term infants with primary respiratory failure to determine whether stable isotopically labeled acetate would yield similar results to previous studies of preterm infants with RDS and, furthermore, would distinguish normal from abnormal surfactant turnover. Despite similar amounts of phospholipids and acetate precursor enrichment, the control group had higher fractional synthetic rate and shorter half-life of clearance than preterm infants with RDS, (fractional synthetic rate, 15.4 Ϯ 2.4 versus 2.2 Ϯ 0.4%/d, p Ͻ 0.001; half-life of clearance, 27 Ϯ 3 versus 105 Ϯ 11 h, p Ͻ 0.001). Term infants with severe respiratory failure had a lower fractional synthetic rate than those with mild disease (2.9 Ϯ 0.6 versus 13.8 Ϯ 3.5%/d, p ϭ 0.014) and a reduced amount of phospholipids recovered from tracheal aspirates (54 Ϯ 17 versus 300 Ϯ 28 nmol, severe versus mild disease, respectively, p Ͻ 0.001). The amount of phospholipids in tracheal aspirates correlated inversely with disease severity, (r ϭ Ϫ0.75, p ϭ 0.01). We conclude that normal surfactant turnover in term infants is faster than in preterm infants with RDS. Surfactant turnover in term infants with severe respiratory failure is similar to that of preterm infants with RDS, suggesting either delayed maturity of the surfactant system or disruption from the underlying disease process. (Pediatr Res 54: 185-191, 2003) Abbreviations DPPC, dipalmitoylphosphatidylcholine E max , maximum enrichment FSR, fractional synthetic rate FiO 2 , fraction of inspired oxygen GC/MS, gas chromatography/mass spectrometry MIDA, mass isotopomer distribution analysis RDS, respiratory distress syndrome T1/2, half-life of clearance TA, tracheal aspirate T app , time of appearance T max , time of maximum enrichment TTR, tracer to tracee ratio RDS in premature infants is caused by a quantitative deficiency of pulmonary surfactant, but understanding of surfactant metabolism in the neonatal period is limited (1). Surfactant is synthesized, assembled, secreted, degraded, and recycled in a complex metabolic cycle (2). The principal surface-active material in surfactant is DPPC. Fatty acids for DPPC synthesis in the pulmonary type II cell can be derived from catabolism of triacylglycerols and recycled phospholipids, from preformed plasma fatty acids (i.e. palmitate), or from de novo synthesis from precursors such as glucose, lactate, or acetate (3).Animal studies using radioactively labeled palmitate, acetate, and choline as precursors of surfactant synthesis have demons...

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Section: Discussionmentioning

confidence: 99%

Endogenous Surfactant Metabolism in Newborn Infants with and without Respiratory Failure

et al. 2003

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“…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.…”

Section: Methodsmentioning

confidence: 99%

“…13 C-palmitate enrichment was measured by gas-chromatography-mass-spectrometry (GC-MS, 6890N-5973 inert, Agilent Technologies, Milan, Italy). Results were expressed as mole percent excess referring to a calibration curve (31,38).…”

Section: Methodsmentioning

confidence: 99%

Surfactant protein B and A concentrations are increased in neonatal pneumonia

et al. 2015

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Background: Term newborns with pneumonia show a reduced pulmonary compliance due to multiple and illdefined factors. Surfactant proteins' (SPs) changes could have a role in the reduced compliance but the matter is still unsettled. The aim of this study was to clarify the meaning of SPs changes during pneumonia in term newborns. Methods: In 28 term ventilated newborns, 13 with pneumonia and 15 with no lung disease, we measured SP-B, SP-A, disaturated-phosphatidylcholine (DSPC), and total phospholipids (PL) concentrations in tracheal aspirates at intubation and close to extubation. We also measured DSPC kinetics using (U-13 C-PA)dipalmitoyl-phosphatidylcholine. results: At baseline, SP-B, expressed as % of PL, was significantly different between the groups, being 3.5-fold higher in pneumonia than controls. Conversely, SP-A did not vary between the groups. At extubation, SP-B and SP-A concentrations had decreased significantly in newborns with pneumonia, while there was no significant change in controls. DSPC t 1/2 was significantly shorter in the pneumonia group (11.8 (5.5-19.8) h vs. 26.6 (19.3-63.6) h, P = 0.011). conclusion: In term newborns with pneumonia, SP-B increases with respect to PL, and DSPC is turned over at a faster rate. Disease's resolution is associated with the restoration of the normal ratio between SP-B and PL.

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“…Hallman et al 35 and Griese et al 36 showed an apparent phospholipid pool size of E16 mg kg -1 in human preterm neonates with RDS, by using PG as label to measure surfactant pool size. Pool size measurements in preterm infants with RDS using endotracheally administered stable isotope ( 13 C-DPPC) in combination with a treatment dose of surfactant (100 mg kg -1 ) showed an endogenous surfactant PC pool size (before treatment) ranging from 1 to 15 mg kg -1 , 37 whereas term infants without RDS have three or more times that value. 38 As synthetic rates of surfactant in preterm infants are low, it is clear that pulmonary surfactant can only be rapidly increased by surfactant replacement therapy.…”

Section: Surfactant Pool Sizementioning

confidence: 99%

Pulmonary surfactant kinetics of the newborn infant: novel insights from studies with stable isotopes

et al. 2009

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Deficiency or dysfunction of the pulmonary surfactant plays a critical role in the pathogenesis of respiratory diseases of the newborn. After a short review of the pulmonary surfactant, including its role in selected neonatal respiratory conditions, we describe a series of studies conducted by applying two recently developed methods to measure surfactant kinetics. In the first set of studies, namely 'endogenous studies', which used stable isotope-labeled intravenous surfactant precursors, we have shown the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors, including plasma glucose, plasma fatty acids and body water. In the second set of studies, namely 'exogenous studies', which used a stable isotope-labeled phosphatidylcholine (PC) tracer given endotracheally, we estimated the surfactant disaturated phosphatidylcholine (DSPC) pool size and half-life. The major findings of our studies are presented here and can be summarized as follows: (a) the de novo synthesis and turnover rates of the surfactant (DSPC) in preterm infants with respiratory distress syndrome (RDS) are very low with either precursor; (b) in preterm infants with RDS, pool size is very small and half-life much longer than what has been reported in animal studies; (c) patients recovering from RDS who required higher continuous positive airway pressure pressure after extubation or reintubation have a lower level of intrapulmonary surfactant than those who did well after extubation; (d) term newborn infants with pneumonia have greatly accelerated surfactant catabolism; and (e) infants with uncomplicated congenital diaphragmatic hernia (CDH) and on conventional mechanical ventilation have normal surfactant synthesis, but those requiring extracorporeal membrane oxygenated (ECMO) do not. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases.

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Exogenous Surfactant Kinetics in Infant Respiratory Distress Syndrome: A Novel Method with Stable Isotopes

Cited by 73 publications

References 27 publications

Endogenous Surfactant Metabolism in Newborn Infants with and without Respiratory Failure

Endogenous Surfactant Metabolism in Newborn Infants with and without Respiratory Failure

Surfactant protein B and A concentrations are increased in neonatal pneumonia

Pulmonary surfactant kinetics of the newborn infant: novel insights from studies with stable isotopes

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