Surfactant Therapy for Acute Lung Injury and Acute Respiratory Distress Syndrome

Raghavendran, Krishnan; Willson, Douglas F.; Notter, Robert H.

doi:10.1016/j.ccc.2011.04.005

Cited by 116 publications

(94 citation statements)

References 267 publications

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“…Although some early SRT large-animal and adult clinical trials were successful (5)(6)(7)(8), subsequent studies were failures (9)(10)(11). The field is looking for direction, with concerns ranging from the delivered surfactant biochemistry to the persistence of the underlying ARDS disease to the adequacy of delivery (12). The model presented here addresses the delivery issue and shows that simulations of these adult SRT studies produce significantly different delivery distributions that can explain success vs. failure.…”

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confidence: 96%

Three-dimensional model of surfactant replacement therapy

Filoche

Tai

Grotberg

2015

Proc. Natl. Acad. Sci. U.S.A.

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Surfactant replacement therapy (SRT) involves instillation of a liquid-surfactant mixture directly into the lung airway tree. It is widely successful for treating surfactant deficiency in premature neonates who develop neonatal respiratory distress syndrome (NRDS). However, when applied to adults with acute respiratory distress syndrome (ARDS), early successes were followed by failures. This unexpected and puzzling situation is a vexing issue in the pulmonary community. A pressing question is whether the instilled surfactant mixture actually reaches the adult alveoli/acinus in therapeutic amounts. In this study, to our knowledge, we present the first mathematical model of SRT in a 3D lung structure to provide insight into answering this and other questions. The delivery is computed from fluid mechanical principals for 3D models of the lung airway tree for neonates and adults. A liquid plug propagates through the tree from forced inspiration. In two separate modeling steps, the plug deposits a coating film on the airway wall and then splits unevenly at the bifurcation due to gravity. The model generates 3D images of the resulting acinar distribution and calculates two global indexes, efficiency and homogeneity. Simulating published procedural methods, we show the neonatal lung is a well-mixed compartment, whereas the adult lung is not. The earlier, successful adult SRT studies show comparatively good index values implying adequate delivery. The later, failed studies used different protocols resulting in very low values of both indexes, consistent with inadequate acinar delivery. Reasons for these differences and the evolution of failure from success are outlined and potential remedies discussed.surfactant replacement therapy | pulmonary drug delivery | biological fluid mechanics | respiratory distress syndrome | biological transport processes S ince the early 1980s, surfactant replacement therapy (SRT) has been successful in applications to prematurely born neonates to treat their lack of surfactant production, which normally initiates late in gestation (1). Because surfactant reduces the surface tension between the air and the lung's liquid lining, its deficiency creates high surface tensions and collapsed, stiff lungs making them difficult to inflate. The resulting clinical entity of labored breathing and poor oxygenation is called neonatal respiratory distress syndrome (NRDS), or hyaline membrane disease, and is a risk of premature birth increasing with decreasing gestational age. The incidence is ∼1% of all births, equating to 40,000 cases annually in the United States (2). The mortality associated with NRDS dropped from 4,997 deaths in 1980 to 861 in 2005, and SRT played an important role in this success (3).SRT has also been tried in adults whose surfactant systems are compromised by acute respiratory distress syndrome (ARDS). ARDS results from overwhelming infections, mechanical injuries, and other insults either directly or indirectly to the lung. ARDS cases in the United States total 190,600 annually wit...

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confidence: 96%

Three-dimensional model of surfactant replacement therapy

Filoche

Tai

Grotberg

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Improvement in ventilation characteristics were noted in several nonrandomised trials of exogenous surfactant therapy in children with ARDS [55], although the number of patients in each study were small. Overall, there seem to be short-term benefits in exogenous surfactant, although further larger trials are warranted.…”

Section: Surfactant Use In Childrenmentioning

confidence: 99%

Pulmonary surfactant in newborn infants and children

Chakraborty

Kotecha

2013

Breathe

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N To understand the composition, secretory pathways and functions of pulmonary surfactant.N To review the clinical evidence regarding the use of surfactants in newborn infants and children.N To develop an understanding of rarer disorders of surfactant metabolism. N To understand recent developments and future prospects in the field of surfactants. SummaryPulmonary surfactant is a complex mixture of specific lipids, proteins and carbohydrates, which is produced in the lungs by type II alveolar epithelial cells. The mixture is surface active and acts to decrease surface tension at the air-liquid interface of the alveoli. The presence of such molecules with surface activity had been suspected since the early 1900s and was finally confirmed in the mid-1900s. Since then, the chemical, physical and biological properties of the surfactant mixture have been revealed due to the work of several groups of investigators. The surfactant mixture is an essential group of molecules to support air breathing. Thus, preterm infants, who are born with immature lungs and are surfactant deficient, develop respiratory distress syndrome after being born. Replacement of natural surfactant therapy with purified surfactant from lungs of nonhuman species is one of the most significant advances in neonatology and has resulted in improved limits of viability of preterm infants. Although preterm infants are the primary population, exogenous surfactant treatment may also have a role to play in other respiratory diseases of term-born infants and older children. HERMES syllabus link: module E.1.16

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“…Decreases in surfactant production induced by prematurity or disease cause alveolar collapse, hypoxemia and reductions in lung compliance, thereby requiring greater distending pressures to inflate the lung and increases in the work of breathing 2. Prior studies dating back >30 years have shown that alveolar hypocapnia causes depletion of lamellar bodies in ATII cells and decreases surfactant production 3.…”

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confidence: 99%