Surface film formation in vitro by infant and therapeutic surfactants: role of surfactant protein B

Danhaive, Olivier; Chapin, Cheryl J.; Horneman, Hart; Cogo, Paola; Ballard, Philip L.

doi:10.1038/pr.2014.176

Cited by 16 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With storage of supplemented calfactant at room temperature for 24 or 48 hours, STmin increased slightly but significantly, but remained in the normal range, whereas there was no significant change in time to STmin. Thus, there was no apparent adverse effect of budesonide on calfactant activity, in agreement with other observations (8,25), or on stability. Half-maximal repression values were calculated from dose-response experiments (mean 6 SD (n = 7).…”

Section: Surface Tensionsupporting

confidence: 91%

Antiinflammatory Effects of Budesonide in Human Fetal Lung

Barrette¹,

Roberts

Chapin³

et al. 2016

Am J Respir Cell Mol Biol

Self Cite

View full text Add to dashboard Cite

Lung inflammation in premature infants contributes to the development of bronchopulmonary dysplasia (BPD), a chronic lung disease with long-term sequelae. Pilot studies administering budesonide suspended in surfactant have found reduced BPD without the apparent adverse effects that occur with systemic dexamethasone therapy. Our objective was to determine budesonide potency, stability, and antiinflammatory effects in human fetal lung. We cultured explants of second-trimester fetal lung with budesonide or dexamethasone and used microscopy, immunoassays, RNA sequencing, liquid chromatography/tandem mass spectrometry, and pulsating bubble surfactometry. Budesonide suppressed secreted chemokines IL-8 and CCL2 (MCP-1) within 4 hours, reaching a 90% decrease at 12 hours, which was fully reversed 72 hours after removal of the steroid. Half-maximal effects occurred at 0.04-0.05 nM, representing a fivefold greater potency than for dexamethasone. Budesonide significantly induced 3.6% and repressed 2.8% of 14,500 sequenced mRNAs by 1.6-to 95-fold, including 119 genes that contribute to the glucocorticoid inflammatory transcriptome; some are known targets of nuclear factor-kB. By global proteomics, 22 secreted inflammatory proteins were hormonally regulated. Two glucocorticoid-regulated genes of interest because of their association with lung disease are CHI3L1 and IL1RL1. Budesonide retained activity in the presence of surfactant and did not alter its surface properties. There was some formation of palmitate-budesonide in lung tissue but no detectable metabolism to inactive 16a-hydroxy prednisolone. We concluded that budesonide is a potent and stable antiinflammatory glucocorticoid in human fetal lung in vitro, supporting a beneficial antiinflammatory response to lung-targeted budesonide:surfactant treatment of infants for the prevention of BPD.

show abstract

Section: Surface Tensionsupporting

confidence: 91%

Antiinflammatory Effects of Budesonide in Human Fetal Lung

Barrette¹,

Roberts

Chapin³

et al. 2016

Am J Respir Cell Mol Biol

Self Cite

View full text Add to dashboard Cite

show abstract

“…The hypothesized higher efficiency of poractant-α may be related to two factors: 1) the phospholipid profile, as some minor phospholipids may protect surfactant from its catabolism; [58] 2) the hydrophobic protein content, especially for surfactant protein-B, which is needed to stabilize surfactant film and allow its spreading at the air/liquid interface and also to protect phospholipids from phospholipase- induced hydrolysis [59, 60]. While more basic research is needed to identify the best lipid profile, the role of surfactant proteins is well known, as older synthetic protein-free surfactants are clinically inferior to animal-derived surfactants, which at least carry some amounts of proteins [8].…”

Section: Discussionmentioning

confidence: 99%

Porcine vs bovine surfactant therapy for preterm neonates with RDS: systematic review with biological plausibility and pragmatic meta-analysis of respiratory outcomes

2019

View full text Add to dashboard Cite

BackgroundBovine surfactants are known to be clinically equivalent but it is unclear if porcine or bovine surfactants at their licensed dose should be preferred to treat respiratory distress syndrome in preterm neonates.MethodsWe performed a comprehensive review of biochemical and pharmacological features of surfactants to understand the biological plausibility of any clinical effect. We then performed a pragmatic meta-analysis comparing internationally marketed porcine and bovine surfactants for mortality and respiratory outcomes. Search for randomised controlled trials with no language/year restrictions and excluding “grey” literature, unpublished or non-peer reviewed reports was conducted, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the most recent methodological recommendations.ResultsSixteen articles were included in the review and 14 in the meta-analysis (1491 neonates). 200 mg/kg poractant-α (a porcine surfactant) was associated with lower BPD/mortality (OR 0.632[95%CI:0.494, 0.809];p < 0.001),BPD (OR 0.688[95%CI:0.512, 0.925];p = 0.013), retreatment (OR 0.313[95%CI:0.187, 0.522];p < 0.0001), airleaks (OR 0.505[95%CI:0.308, 0.827];p = 0.006) and lung haemorrhage (OR 0.624[95%CI:0.388, 1];p = 0.051). Gestational age is associated with effect size for BPD (coefficient: 0.308 [95%CI:0.063, 0.554];p = 0.014) and surfactant retreatment (coefficient: -0.311 [95%CI:-0.595, − 0.028];p = 0.031).Conclusion200 mg/kg poractant-α is associated with better respiratory outcomes compared to bovine surfactants at their licensed dose. The effect of poractant-α on BPD and surfactant retreatment is greater at lowest and highest gestational ages, respectively.Trial registrationPROSPERO n.42017075251.Electronic supplementary materialThe online version of this article (10.1186/s12931-019-0979-0) contains supplementary material, which is available to authorized users.

show abstract

“…Lamellar bodies are intracellular, easily measurable, surfactant storage granules released from type II-pneumocytes [8, 9]. Once in the alveolar space, lamellar bodies are subjected to the breathing cycle and form the surfactant layer adsorbed at the gas/liquid interface [9, 10]. Thus, lamellar body count (LBC) is an estimation of the available endogenous surfactant.…”

Section: Introductionmentioning

confidence: 99%

Estimation of early life endogenous surfactant pool and CPAP failure in preterm neonates with RDS

et al. 2019

View full text Add to dashboard Cite

Background It is not known if the endogenous surfactant pool available early in life is associated with the RDS clinical course in preterm neonates treated with CPAP. We aim to clarify the clinical factors affecting surfactant pool in preterm neonates and study its association with CPAP failure. Methods Prospective, pragmatic, blind, cohort study. Gastric aspirates were obtained (within the first 6 h of life and before the first feeding) from 125 preterm neonates with RDS. Surfactant pool was measured by postnatal automated lamellar body count based on impedancemetry, without any pre-analytical treatment. A formal respiratory care protocol based on European guidelines was applied. Clinical data and perinatal risk factors influencing RDS severity or lamellar body count were real-time recorded. Investigators performing lamellar body count were blind to the clinical data and LBC was not used in clinical practice. Results Multivariate analysis showed gestational age to be the only factor significantly associated with lamellar body count (standardized β:0.233; p = 0.023). Lamellar body count was significantly higher in neonates with CPAP success (43.500 [23.750–93.750]bodies/μL), than in those failing CPAP (20.500 [12.250–49.750] bodies/μL; p = 0.0003).LBC had a moderate reliability to detect CPAP failure (AUC: 0.703 (0.615–0.781); p < 0.0001; best cut-off: ≤30,000 bodies/μL). Upon adjustment for possible confounders, neither lamellar body count, nor its interaction factor with gestational age resulted associated with CPAP failure. Conclusions Early postnatal lamellar body count on gastric aspirates in CPAP-treated preterm neonates with RDS is significantly influenced only by gestational age. Lamellar bodies are not associated with CPAP failure. Thus, the endogenous surfactant pool available early in life only has a moderate reliability to predict CPAP failure.

show abstract

Surface film formation in vitro by infant and therapeutic surfactants: role of surfactant protein B

Cited by 16 publications

References 30 publications

Antiinflammatory Effects of Budesonide in Human Fetal Lung

Antiinflammatory Effects of Budesonide in Human Fetal Lung

Porcine vs bovine surfactant therapy for preterm neonates with RDS: systematic review with biological plausibility and pragmatic meta-analysis of respiratory outcomes

Estimation of early life endogenous surfactant pool and CPAP failure in preterm neonates with RDS

Contact Info

Product

Resources

About