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What's New in Surfactant?

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What's New in Surfactant? View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Eur J Pediatr (2007) 166:889–899 DOI 10.1007/s00431-007-0501-4 REVIEW What’s new in surfactant? A clinical view on recent developments in neonatology and paediatrics Jasper V. Been & Luc J. I. Zimmermann Received: 26 March 2007 /Accepted: 18 April 2007 / Published online: 22 May 2007 # Springer-Verlag 2007 Abstract Surfactant therapy has significantly changed evolving and recent developments include further evolution clinical practice in neonatology over the last 25 years. of synthetic surfactants, evaluation of surfactant as a Recent trials in infants with respiratory distress syndrome therapeutic option in lung diseases other than RDS and (RDS) have not shown superiority of any natural surfactant the discovery of genetic disorders of surfactant metabolism. over another. Advancements in the development of syn- Ongoing research is essential to continue to improve thetic surfactants are promising, yet to date none has been therapeutic prospects for children with serious respiratory shown to be superior to natural preparations. Ideally, disease involving disturbances in surfactant. surfactant would be administered without requiring mechanical ventilation. An increasing number of studies Keywords Surfactant . Lung disease . investigate the roles of alternative modes of administration Respiratory distress syndrome . Preterm . Therapy and the use of nasal continuous positive airway pressure to minimise the need for mechanical ventilation. Whether Abbreviations children with other lung diseases benefit from surfactant ABCA3 ATP-binding cassette transporter A3 therapy is less clear. Evidence suggests that infants with ALI acute lung injury meconium aspiration syndrome and children with acute ARDS acute respiratory distress syndrome lung injury/acute respiratory distress syndrome may benefit, bLES bovine lipid extract surfactant while no positive effect of surfactant is seen in infants with BPD bronchopulmonary dysplasia congenital diaphragmatic hernia. However, more research is CHD congenital diaphragmatic hernia needed to establish potential beneficial effects of surfactant CLD chronic lung disease administration in children with lung diseases other than ECMO extracorporeal membrane oxygenation RDS. Furthermore, genetic disorders of surfactant metabo- MAS meconium aspiration syndrome lism have recently been linked to respiratory diseases of nCPAP nasal continuous positive airway pressure formerly unknown origin. It is important to consider these RCT randomised controlled trial disorders in the differential diagnosis of unexplained RDS respiratory distress syndrome respiratory distress although no established treatment is rSP recombinant surfactant protein yet available besides lung transplantation for the most RSV respiratory syncytial virus severe cases. Conclusion: Research around surfactant is SP surfactant protein Funding: Jasper Been is supported by a Profileringsfonds grant from the Maastricht University Hospital. J. V. Been (*) : L. J. I. Zimmermann Introduction Department of Paediatrics, Research Institute Growth and Development, Surfactant is a complex mixture of lipids (90%) and Maastricht University Hospital, Maastricht, The Netherlands proteins (10%) lining the epithelial surface of the lung. e-mail: [email protected] Four surfactant apoproteins have been described: the 890 Eur J Pediatr (2007) 166:889–899 hydrophobic surfactant protein B (SP-B) and SP-C and the In recent years knowledge of the in vivo surfactant hydrophilic SP-A and SP-D. Surfactant is synthesised by metabolism in RDS patients has increased as a result of alveolar type II cells, stored in lamellar bodies that are metabolic studies. Preterm infants were shown to have a exocytosed and taken up into the monolayer lining the decreased surfactant pool size with decreased synthesis but alveolar epithelium. Traditionally, surfactant is recognised increased recycling of surfactant when compared to term for its surface tension-lowering properties, by which infants [152]. Furthermore, it was found that both prenatal alveolar collapse is prevented and gas exchange is steroids and exogenous surfactant administration after birth facilitated. More recently, surfactant has been shown to stimulate endogenous surfactant synthesis [25, 26]. have an important additional role in innate defence of the Recent developments in surfactant treatment for RDS lung. Key players in this role are SP-A and D, members of include new comparative trials of natural surfactants, the collectin family of proteins. Among their functions are exploration of alternative modes of administration and binding, opsonisation and clearance of microbes from the evaluation of the use of nasal continuous positive airway lung and regulation of immune cell activity. Several pressure (nCPAP) either to decrease the need for surfactant reviews have addressed their role in detail [80, 148]. or as an adjuvant therapy following surfactant administra- Evidence is now accumulating that SP-B, SP-C and the tion. Moreover, much effort is put into the development of surfactant lipids may be involved in modulation of synthetic surfactants for treatment of respiratory distress. pulmonary inflammation as well [21, 30, 44, 71, 101, 117]. This topic is discussed separately. The relevance of surfactant for pulmonary physiology is highlighted by the respiratory distress syndrome (RDS) Natural surfactant seen in preterm infants, caused by an absolute deficiency of surfactant. Affected infants experience respiratory In recent years, several clinical trials have compared the insufficiency often requiring mechanical ventilation. The efficacy of different natural surfactants in the treatment of introduction of exogenous surfactant administration for RDS. Natural surfactants are generally derived from either these infants is generally regarded as one of the most lung lavage or minced lung of bovine or porcine origin. important advancements in the field of neonatology, Four studies have compared beractant (Survanta) and having significantly decreased neonatal mortality over the poractant-α (Curosurf) [12, 93, 112, 126]. Curosurf was last 25 years. Nowadays, the potential benefit of surfactant found to have a more rapid onset of action in most studies therapy is evaluated in a wide range of respiratory [93, 112, 126]. A meta-analysis of these studies plus one disorders in both neonates and paediatric patients. More- unpublished study suggested a significant decrease in over, several disease entities of formerly unknown origin neonatal mortality after Curosurf treatment [57]. However, have recently been linked to genetic disorders of surfactant three of these studies have compared a Curosurf dose of metabolism. 200 mg/kg with a Survanta dose of 100 mg/kg [93, 112, The purpose of this review is to give an overview of 126]. When these studies were excluded from analysis, the these and other recent developments in the field of difference in mortality after treatment with comparable surfactant, focusing on clinically relevant issues in neona- doses of both surfactants was not statistically significant tology and paediatrics. [57]. Malloy and colleagues reported a significant decrease in the incidence of persistent ductus arteriosus after Curosurf treatment [93]. None of the other studies found Surfactant in RDS such an effect and it is unclear whether this difference may be explained by the dosing difference as well. In 1959 Avery and Mead established the relationship Baroutis and colleagues compared the effects of three between surfactant deficiency and RDS seen in preterm different surfactant preparations: Curosurf, Survanta and infants [9]. Twenty years later, exogenous surfactant was Alveofact [12]. Treatment with either Curosurf or Alveofact successfully administered to preterm infants with RDS and was associated with a decrease in days on the ventilator, shown to dramatically improve oxygenation in these babies days on oxygen and hospital stay, but no significant [51]. In subsequent clinical trials, reductions in neonatal improvement in morbidity and mortality. A more recent mortality and incidence of pneumothorax were found after study comparing Survanta and Alveofact reported a surfactant administration [1]. Further trials found that early decrease in chronic lung disease (CLD) with Survanta treatment is superior to late treatment [151], multiple doses [59]. However, CLD was defined as oxygen need at 28 days are better than a single dose [122] and prophylactic of age, a definition that does not take into account the surfactant is associated with better outcome than is rescue gestational age of the infant and is generally regarded to be treatment [125]. Excellent reviews on the history of surfactant imprecise and outdated. There was a decrease in days on are available [57, 107]. the ventilator, days on oxygen and length of hospital stay Eur J Pediatr (2007) 166:889–899 891 with Survanta. The need for postnatal steroids was surfactant followed by extubation to nCPAP was associated decreased in the Survanta group as well; however, their with decreased ventilator requirement, but an increase in overall use was very high compared to current standards. number of surfactant administrations when compared to Two studies have compared Survanta and Infasurf selective surfactant and continued ventilation [129]. No (calfactant) for the treatment of RDS [7, 17]. The largest difference in BPD incidence was detected.
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