History of Surfactant up to 1980

Obladen, Michael

doi:10.1159/000084878

Cited by 34 publications

(22 citation statements)

References 65 publications

(37 reference statements)

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“…In 1957, he published an article reporting the surface tension of films from the lungs of rats, cats and dogs. 5 Together with Chris Macklin, a pathologist working with phosgene in Canadian chemical warfare laboratories in 1954 6,7 it is remarkable how they and Pattle came to the same conclusions independently and within a few months of each other. Clearly some good came from studies in three countries of the adverse effects of nerve gases on the lungs.…”

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confidence: 99%

Surfactants: past, present and future

2008

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In 1929 Kurt von Neergaard performed experiments suggesting the presence of pulmonary surfactant and its relevance to the newborn's first breath. Almost 25 years later, Richard Pattle, John Clements and Chris Macklin, each working on the effects of nerve gases on the lungs, contributed to the understanding of the physiology of pulmonary surfactant. About 5 years later Mary Ellen Avery and Jere Mead published convincing evidence that preterm neonates dying of hyaline membrane disease (respiratory distress syndrome, RDS) had a deficiency of pulmonary surfactant. The first trials of nebulized synthetic (protein-free) surfactant to prevent RDS were published soon after Patrick Bouvier Kennedy (son of President John F Kennedy) died of this disorder after treatment in Boston. These trials were unsuccessful; however, Goran Enhorning and Bengt Robertson in the early 1970s demonstrated that natural surfactants (containing proteins) were effective in an immature rabbit model of RDS. Soon after this Forrest Adams showed that a natural surfactant was also effective in an immature lamb model. Working with him was Tetsuro Fujiwara who 2 years later, after returning to Japan, published the seminal article reporting the responses of 10 preterm infants with RDS to a bolus of modified bovine surfactant. During the 1980s there were numerous randomized controlled trials of many different natural and synthetic surfactants, demonstrating reductions in pulmonary air leaks and neonatal mortality. Subsequently natural surfactants were shown to be superior to the protein-free synthetic products. Recently there have been a number of randomized trials comparing different natural surfactant preparations. Commercially available bovine surfactants may have similar efficacy but there is some evidence that a porcine surfactant used to treat RDS with an initial dose of 200 mg kg À1 is more effective than a bovine surfactant used in an initial dose of 100 mg kg -1 . Bovine and porcine surfactants have not been compared in trials of prophylaxis. Very recently a new synthetic surfactant with a surfactant protein mimic has been compared with other commercially available natural and synthetic surfactants in two trials. The new surfactant may be superior to one of the older protein-free synthetic surfactants but there is no evidence of its superiority over established natural products and it is currently not approved for clinical use. A number of other new synthetic surfactants have been tested in animal models or in treatment of adults with ARDS, but so far there have been no reports of treatment of neonatal RDS. Natural surfactants work best if given by a rapid bolus into the lungs but less invasive methods such as a laryngeal mask, pharyngeal deposition or rapid extubation to CPAP have showed promise. Unfortunately, delivery of surfactant by nebulization has so far been ineffective. Surfactant treatment has been tried in a number of other neonatal respiratory disorders but only infants with meconium aspiration seem to benefit although larger and mo...

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Surfactants: past, present and future

2008

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“…A series of carefully controlled multicentre clinical trials has made surfactant substitution an exceptionally well-studied form of treatment. 6,7 Trials of prophylactic administration of surfactant attempted to identify infants at high risk of developing RDS. Randomised controlled trials that compare the prophylactic administration of surfactant to control treatment have been carried out using natural surfactant extracts as well as synthetic surfactant preparations.…”

Section: Discussionmentioning

confidence: 99%

Role of prophylactic surfactant in preterm infants

Singh¹,

Rana²,

Mathai

2011

Medical Journal Armed Forces India

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INTRODUCTIONRespiratory distress syndrome (RDS) in preterm neonates is caused by a deficiency or dysfunction of pulmonary surfactant. Surfactant lines the alveolar surface and prevents atelectasis at end expiration. Pulmonary surfactant is predominantly dipalmitoylphosphatidylcholine with lesser amounts of other phospholipids including phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylinositol. Pulmonary surfactant also contains neutral lipids and distinct surfactant proteins. The physiologic function of surfactant includes the ability to lower surface tension, as well as the ability to rapidly adsorb and spread, associated with the respiratory cycle. The first attempts to utilise synthetic surfactants occurred in the 1960s. The first successful animal model of surfactant replacement therapy was conducted by Enhorning and coworkers in 1972. Enhorning administered a crude natural surfactant extract obtained from lavage of the lungs of mature rabbits 1 directly into the trachea of immature rabbits. Improvement in lung compliance and alveolar expansion was noted. Success in animal models led to widespread clinical trials of surfactant therapy in the human newborns. A systematic review of the seven randomised controlled trials that compare the prophylactic administration of synthetic surfactant to control treatment in preterm infants at risk of developing RDS suggests that prophylactic administration of synthetic surfactant leads to a significant decrease in the risk of pneumothorax, pulmonary interstitial emphysema, and neonatal mortality.2-4 So far, no trials of prophylactic surfactant in preterm neonates were carried out in our country because of the prohibitive cost of the imported drug. During the last decade, preparations of exogenous surfactant have been marketed in our country. This has made it possible to evaluate the prophylactic role of surfactant in preventing respiratory distress syndrome and its associated morbidities in preterm neonates. The present study was designed to find out whether prophylactic administration of surfactant leads to a significant decrease in the risk of neonatal mortality and neonatal morbidity. MATERIALS AND METHODSThis was an experimental study in which a total of 125 preterm newborns less than 34 weeks gestation were studied. The study was carried out in two phases from December 2003 to November 2006. The inclusion criteria were designed to include newborn babies who were less than 34 weeks gestational age at the time of birth. The gestational age assessment was Role of prophylactic surfactant in preterm infants

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“…Further trials found that early treatment is superior to late treatment [151], multiple doses are better than a single dose [122] and prophylactic surfactant is associated with better outcome than is rescue treatment [125]. Excellent reviews on the history of surfactant are available [57,107].…”

Section: Surfactant In Rdsmentioning

confidence: 99%