Intervention Review

Protein containing synthetic surfactant versus animal derived surfactant extract for the prevention and treatment of respiratory distress syndrome

  1. Robert H. Pfister1,*,
  2. Roger Soll2,
  3. Thomas E Wiswell3

Editorial Group: Cochrane Neonatal Group

Published Online: 17 OCT 2007

Assessed as up-to-date: 12 AUG 2007

DOI: 10.1002/14651858.CD006069.pub3


How to Cite

Pfister RH, Soll R, Wiswell TE. Protein containing synthetic surfactant versus animal derived surfactant extract for the prevention and treatment of respiratory distress syndrome. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD006069. DOI: 10.1002/14651858.CD006069.pub3.

Author Information

  1. 1

    Fletcher Allen Health Care, Division of Neonatal Perinatal Medicine, Burlington, VT, USA

  2. 2

    University of Vermont, Division of Neonatal-Perinatal Medicine, Burlington, Vermont, USA

  3. 3

    Center for Neonatal Care, Neonatology, Orlando, Florida, USA

*Robert H. Pfister, Division of Neonatal Perinatal Medicine, Fletcher Allen Health Care, Smith #582, 111 Colchester Avenue, Burlington, VT, 05401, USA. robert.pfister@vtmednet.org.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 17 OCT 2007

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. Plain language summary

Background

Respiratory distress syndrome (RDS) is a significant cause of morbidity and mortality in preterm infants. RDS is caused by a deficiency, dysfunction, or inactivation of pulmonary surfactant. Numerous surfactants of either animal extract or synthetic design have been shown to improve outcomes. New surfactant preparations that include peptides or whole proteins that mimic endogenous surfactant protein have recently been developed and tested.

Objectives

To assess the effect of administration of synthetic surfactant containing surfactant protein mimics compared to animal derived surfactant extract on the risk of mortality, chronic lung disease, and other morbidities associated with prematurity in preterm infants at risk for or having RDS.

Search methods

Standard search methods of the Cochrane Neonatal Review Group were used. The search included MEDLINE (1966 - May 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) in all languages. In addition, published abstracts of the Society of Pediatric Research were searched electronically. For abstract books that did not include key words, the search was limited to the relevant sections on pulmonary and neonatology. The bibliography cited in each publication was obtained and searched in order to identify additional relevant articles.

Selection criteria

Randomized and quasi-randomized controlled clinical trials were considered for this review. Studies that enrolled preterm infants or low birth weight infants at risk for or having RDS who were treated with either a synthetic surfactant containing surfactant protein mimics or an animal-derived surfactant preparation were included for this review. Studies that either attempted to treat or prevent respiratory distress syndrome were included.

Data collection and analysis

Primary outcome measures, including mortality, chronic lung disease and multiple secondary outcome measures were abstracted by the reviewers. Statistical analysis was performed using Review Manager software. Categorical data was analyzed using relative risk, risk difference, and number needed to treat. 95% confidence intervals reported. A fixed effects model was used for the meta-analysis. Heterogeneity was assessed using the I-squared statistic.

Main results

Two studies were identified that compared protein containing synthetic surfactants to animal derived surfactant preparations. In a meta-analysis of these two studies, infants who received protein containing synthetic surfactant compared to animal derived surfactant extract did not demonstrate significantly different risks of prespecified primary outcomes: mortality at 36 weeks [typical RR 0.81 (95% CI 0.64, 1.03)], chronic lung disease at 36 weeks [typical RR 0.99 (95% CI 0.84, 1.18)], or the combined outcome of mortality or chronic lung disease at 36 weeks [typical RR 0.96 (95% CI 0.82, 1.12)]. There were also no differences in any of the secondary outcomes regarding complications of prematurity between the two surfactant groups with the exception of necrotizing enterocolitis. A decrease in the risk of necrotizing enterocolitis was noted in infants who received protein containing synthetic surfactants compared to animal derived surfactant extract [typical RR 0.60 (95% CI 0.42, 0.86)]. However, this was a secondary outcome in both of the primary studies and there was moderate heterogeneity between the studies.

Authors' conclusions

In two trials of protein containing synthetic surfactants compared to animal derived surfactant extract, no statistically different clinical differences in death and chronic lung disease were noted. In general, clinical outcomes between the two groups were similar. Further well designed studies of adequate size and power will help confirm and refine these findings.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. Plain language summary

Protein containing synthetic surfactant versus animal derived surfactant extract for the prevention and treatment of respiratory distress syndrome

Respiratory distress syndrome (RDS) is a significant cause of illness in preterm infants. Respiratory distress syndrome is caused by a deficiency or a dysfunction of the chemicals that line the lung, called pulmonary surfactant. Numerous preparations that contain surfactants of either animal origin or synthetic design have been developed and tested to treat or prevent respiratory distress syndrome. In general, these surfactant preparations have decreased lung rupture (pneumothorax), decreased the risk of dying, and increased the number of survivors without lung damage. From previous research, the surfactants that are obtained from animals seem to have a better effect than the synthetic surfactants. This might be due to the surfactant proteins contained in animal surfactant that are absent in the previously available synthetic surfactants.

Recently developed synthetic surfactant preparations include whole surfactant proteins or parts of the proteins (called peptides) that act like surfactant protein. These preparations have been recently tested in comparison to the animal derived surfactant preparations.

Two recent trials of protein containing synthetic surfactant compared to animal derived surfactant preparations have demonstrated a trend towards decreasing death and decreasing rates of bowel disease (necrotizing enterocolitis), while other clinical outcomes were similar. Further studies will help refine recommendations concerning use of protein containing synthetic surfactants.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. Plain language summary

背景

含蛋白質之人工合成表面張力素與動物萃取所衍生的表面張力素用於預防及治療呼吸窘迫症候群

呼吸窘迫症候群(RDS)對於早產兒是導致罹病與死亡的重要因素。呼吸窘迫症候群的發生原因是因為肺部表面張力素缺乏、功能障礙或者是不活化所導致。許多從動物萃取所衍生的或是人工合成的表面張力素已被證實可以改善預後。近來已經有近似於內生性表面張力素、含胜(月太)或整個蛋白質的新的表面張力素發展出來,也經過試驗。

目標

比較以含有近似於內生性表面張力素蛋白質之人工合成的表面張力素與從動物萃取衍生的表面張力素,這兩者用於治療有呼吸窘迫症候群的早產兒,對於降低死亡率、慢性肺疾病、及其他因早產而合併的併發症之效果。

搜尋策略

使用Cochrane Neonatal Review Group的標準搜尋方式,搜尋包括在MEDLINE (1966  May 2007) 和the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) 各種語言的文章。除此之外,藉由網路搜尋方式尋找在Society of Pediatric Research有發表的摘要。未包含有關鍵字的摘要,則侷限在呼吸學與新生兒科學相關的部分。每一篇文章所引用的文獻均進一步搜尋取得相關內容。

選擇標準

本篇文獻回顧網羅所有隨機及近似隨機臨床控制試驗。以含有近似於內生性表面張力素蛋白質之人工合成的表面張力素或從動物萃取衍生的表面張力素治療患有呼吸窘迫症候群的早產而或低體重兒的研究均被納入。試圖治療或預防呼吸窘迫症候群的研究亦被納入。

資料收集與分析

主要預後的評估,包含死亡率與慢性肺疾病及其他次要預後的評估均由評論者節錄出。 統計分析則是用Review Manager 這套軟體。用相對危險性、危險性差異、及治療次數來分析不同分類的資料,以95%信賴區間做為報告。利用固定效用模式來進行整合分析。異質性則是以Isqared分析法評估。

主要結論

經資料搜尋有二個研究比較含蛋白質人工合成表面張力素與動物萃取衍生的表面張力素。經由整合分析這二個研究,使用含蛋白質人工合成表面張力素治療的嬰兒與使用動物萃取衍生的表面張力素治療的嬰兒比較起來,對於主要預後的評估:36週時的死亡率(RR 0.81,95%CI 0.64 – 1.03)、36週時的慢性肺疾病(RR 0.99,95%CI 0.84 – 1.18)、或綜合36週死亡率與慢性肺疾病(RR 0.96,95%CI 0.82 – 1.12)並無顯示明顯差異。對於次要預後的評估(關於因早產而產生之併發症),在這二群病人當中,除了壞死性腸炎之外, 二者並無顯著差異。和使用動物萃取衍生的表面張力素治療的嬰兒比較起來,使用含蛋白質人工合成表面張力素治療的嬰兒發生壞死性腸炎的危險性降低(RR 0.60,95%CI 0.42 – 0.86)。然而,此情況均為這二個原始研究的次要預後的評估,而這二個研究期間存在中等程度的異質性。

作者結論

在比較含蛋白質人工合成表面張力素與動物萃取衍生的表面張力素的二個臨床試驗中,對於死亡率及慢性肺疾病並沒有統計上的差異。整體而言,這二群的病人其臨床結果是類似的。進一步設計良好具足夠樣本數的研究將有助於證實並使這些發現更加完善。

翻譯人

本摘要由高雄醫學大學附設醫院郭昶宏翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

呼吸窘迫症候群(RDS)是造成早產兒罹病的重要原因。呼吸窘迫症候群是因為附著在肺組織的化學物質(又稱表面張力素)缺乏或功能障礙所導致。已經有許多不管是來自動物或者是人工合成的表面張力素被發展並測試用於治療或預防呼吸窘迫症候群。整體來說,經由使用這些表面張力素,可以減少肺組織破裂(即所謂氣胸)、降低死亡率及增加無肺部損傷的存活率。先前的研究指出,從動物萃取衍生的表面張力素似乎比人工合成的表面張力素效果佳。這可能是因為先前人工合成的表面張力素缺少了在動物萃取衍生的表面張力素中所含的表面張力素蛋白質。近來發展出的人工合成的表面張力素已經包含有作用近似表面張力素蛋白質的全表面張力素蛋白或胜(月太)。這些已被試驗用以比較與動物萃取衍生的表面張力素之差異。最近二個比較含蛋白質人工合成表面張力素與動物萃取衍生的表面張力素的臨床試驗中,顯示含蛋白質人工合成表面張力素有降低死亡率及壞死性腸炎的趨勢,而其他臨床的預後則是類似。對含蛋白質人工合成表面張力素的使用,需要進一步的研究使建議更加完善。

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. Plain language summary

Usporedba sintetskog surfaktanta s potrebnim proteinima i surfaktanta životinjskog porijekla za prevenciju i liječenje sindroma respiracijskog distresa

Usporedba sintetskog surfaktanta s potrebnim proteinima i surfaktanta životinjskog porijekla za prevenciju i liječenje sindroma respiracijskog distresa

Sindrom respiracijskog distresa (SRD) je značajan uzrok bolesti u nedonoščadi. SRD je uzrokovan manjkom ili poremećenom funkcijom kemijske tvari koja oblaže pluća, zvane plućni surfaktant (površinski aktivna tvar u vodi koja smanjuje površinsku napetost). Brojni preparati koji sadrže surfaktant, bilo životinjskog porijekla bilo sintetske proizvodnje, razvijeni su i testirani za liječenje ili prevenciju sindroma respiracijskog distresa. Ovi preparati surfaktanta smanjili su rupturu pluća (pneumotoraks) i smanjili rizik od smrti te povećali broj preživjelih bez oštećivanja pluća. Iz prethodnih istraživanja je proizišlo da surfaktanti životinjskog porijekla imaju bolji učinak od sintetskih surfaktanata. Razlog bi mogao biti taj što proteine koje sadrži životinjski surfaktant nisu sadržavali sintetski surfaktanti koji su ranije bili dostupni.

Nedavno razvijeni preparati sintetskog surfaktanta uključuju cijele proteine, ili dijelove istih (zvane peptidi), koji se ponašaju kao surfaktantski protein. Ovi preparati su nedavno testirani i uspoređeni s preparatima derivata životinjskog surfaktanta.

Dva nedavna istraživanja, koja uspoređuju sintetski surfaktant koji sadrži protein sa surfaktantima životinjskog porijekla pokazala su napredak u smanjenju smrtnosti i smanjenju učestalosti crijevnih bolesti (nekrotski enterokolitis), dok su ostali klinički ishodi bili slični.
Daljnja istraživanja će pomoći u definiranju preporuke o korištenju sintetskog surfaktanta koji sadrži protein.

Translation notes

Prevela Ivana Miosic

Translated by: Croatian Branch of the Italian Cochrane Centre