Calf's lung surfactant extract in acute hypoxemic respiratory failure in children

Willson, Douglas F.; Jiao, J.-H.; Bauman, Loren A.; Zaritsky, Arno; Craft, Hugh; Dockery, Keith; Conrad, Debra; Dalton, Heidi J.

doi:10.1097/00003246-199608000-00008

Cited by 96 publications

(62 citation statements)

References 18 publications

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“…A number of uncontrolled and controlled studies have documented clinical benefit from exogenous surfactant replacement therapy in term infants, children, and adults with acute respiratory failure (ALI/ARDS) [66][67][68][69]154,[186][187][188][189][190][191][192][193][194][195][196][197][198][199][200] ( Table 2). Of the 19 positive studies listed in Table 2, 9 were controlled trials [67][68][69]154,192,[197][198][199][200] and 10 were uncontrolled treatment trials, in which the risk of selection bias is inherent.…”

Section: Human Studiesmentioning

confidence: 99%

“…That trial followed an initial uncontrolled treatment study by the same group, which found improved oxygenation in 24 children (ages 0.1-16 y) with ALI/ ARDS treated with instilled calfactant. 191 A controlled study by Moller et al 199 also reported that children with ARDS showed immediate oxygenation improvement and less need for rescue therapy following treatment with beractant, but the trial was underpowered to assess more definitive longer-term outcomes. A larger and more recent blinded controlled study in 2005 by Willson et al, 154 in patients up to age 21 years with ALI/ARDS, found that treatment with calfactant, relative to placebo, was associated with immediate oxygenation benefit and a significant survival advantage (Table 3).…”

Section: Human Studiesmentioning

confidence: 99%

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The Future of Exogenous Surfactant Therapy

Willson

Notter

2011

Respir Care

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Since the identification of surfactant deficiency as the putative cause of the infant respiratory distress syndrome (RDS) by Avery and Mead in 1959, our understanding of the role of pulmonary surfactant in respiratory physiology and the pathophysiology of acute lung injury (ALI) has advanced substantially. Surfactant replacement has become routine for the prevention and treatment of infant RDS and other causes of neonatal lung injury. The role of surfactant in lung injury beyond the neonatal period, however, has proven more complex. Relative surfactant deficiency, dysfunction, and inhibition all contribute to the disturbed physiology seen in ALI and acute respiratory distress syndrome (ARDS). Consequently, exogenous surfactant, while a plausible therapy, has proven to be less effective in ALI/ ARDS than in RDS, where simple deficiency is causative. This failure may relate to a number of factors, among them inadequacy of pharmaceutical surfactants, insufficient dosing or drug delivery, poor drug distribution, or simply an inability of the drug to substantially impact the underlying pathophysiology of ALI/ARDS. Both animal and human studies suggest that direct types of ALI (eg, aspiration, pneumonia) may be more responsive to surfactant therapy than indirect lung injury (eg, sepsis, pancreatitis). Animal studies are needed, however, to further clarify aspects of drug composition, timing, delivery, and dosing before additional human trials are pursued, as the results of human trials to date have been inconsistent and largely disappointing. Further study and perhaps the development of more robust pharmaceutical surfactants offer promise that exogenous surfactant will find a place in our armamentarium of treatment of ALI/ARDS in the future. Key words: surfactant; infant respiratory distress syndrome; RDS; acute lung injury; ALI; acute respiratory distress syndrome; ARDS; neonatal. [Respir Care 2011;56(9):1369 -1386.

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Section: Human Studiesmentioning

confidence: 99%

Section: Human Studiesmentioning

confidence: 99%

The Future of Exogenous Surfactant Therapy

Willson

Notter

2011

Respir Care

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“…A significant number of clinical studies have reported benefits following the instillation of exogenous surfactants to term infants, children, or adults with ALI/ARDS or related acute respiratory failure [25,[120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135] (Table 4). However, many of these are small case series or pilot studies, and found only improvements in acute lung function (oxygenation).…”

Section: Current Studies On Surfactant Replacement Therapy In Patmentioning

confidence: 99%

“…Studies of surfactant therapy in children and adults with ALI/ARDS show positive results in a number of case reports or relatively small pilot trials [120,121,[124][125][126][127][128]. However, particularly in adults, controlled clinical trials have been less successful.…”

Section: Current Studies On Surfactant Replacement Therapy In Patmentioning

confidence: 99%

“…A randomized but unblinded controlled trial by Willson et al [125] in 42 children at eight centers with ALI/ARDS showed that those receiving Infasurf® (70 mg/kg) had immediate improvement in oxygenation and fewer ventilator days and days in intensive care ( Figure 2). This unblinded trial followed an initial open-label study by the same group demonstrating improved oxygenation in 29 children (0.1-16 yrs) treated with instilled Infasurf® [124]. In addition, a clinical trial by Moller et al [146] reported that children with ARDS showed an immediate improvement in oxygenation and less need for rescue therapy following treatment with Survanta®, although this latter study was underpowered for more definitive outcomes.…”

Section: Current Studies On Surfactant Replacement Therapy In Patmentioning

confidence: 99%

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Surfactant for Pediatric Acute Lung Injury

Willson¹,

Chess²,

Notter³

2008

Pediatric Clinics of North America

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SynopsisThis article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is on reviewing clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS, including the multifaceted pathology of inflammatory lung injury, the effectiveness of surfactant delivery in injured lungs, and composition-based activity differences among clinical exogenous surfactant preparations.

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Effect of Exogenous Surfactant (Calfactant) in Pediatric Acute Lung Injury<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>

Willson

Thomas

Markovitz

et al. 2005

JAMA

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374

279

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CUTE RESPIRATORY DISTRESS syndrome (ARDS) was originally termed the adult respiratory distress syndrome because it resembled the clinical picture of infant respiratory distress syndrome (IRDS), and both exhibited hyaline membranes at autopsy. 1,2 Avery and Mead 3 first reported that lung surfactant quantity and activity were abnormal in infants with IRDS and surfactant replacement has subsequently become standard therapy for premature infants at risk for or having IRDS. Petty and Ashbaugh 2 described qualitative and quantitative surfactant deficiencies in their initial description of ARDS and the subsequent scientific literature (recently reviewed by Notter 4) has supported the role of surfactant dysfunction in both ARDS and less severe acute lung injury (ALI). 5 Surfactant replacement in ARDS and ALI has been Author Affiliations and Participating Hospitals and Collaborating Investigators are listed at the end of this article. Financial Disclosures: Dr Willson has received research grants from ONY Inc (Amherst, NY). Dr Egan is president and equity owner of ONY Inc.

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Calf's lung surfactant extract in acute hypoxemic respiratory failure in children

Abstract: Administration of calf's lung surfactant appears to be safe and is associated with rapid improvement in oxygenation and moderation of ventilator support in children with acute hypoxemic respiratory failure. These results set the stage for a randomized, controlled study.

Cited by 96 publications

References 18 publications

The Future of Exogenous Surfactant Therapy

The Future of Exogenous Surfactant Therapy

Surfactant for Pediatric Acute Lung Injury

Effect of Exogenous Surfactant (Calfactant) in Pediatric Acute Lung Injury<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>

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