Time-dependent changes in pulmonary surfactant function and composition in acute respiratory distress syndrome due to pneumonia or aspiration

Schmidt, Reinhold E.; Markart, Philipp; Ruppert, Clemens; Wygrecka, Małgorzata; Kuchenbuch, Tim; Walmrath, D.; Seeger, Werner; Güenther, Andreas

doi:10.1186/1465-9921-8-55

Cited by 71 publications

(63 citation statements)

References 42 publications

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“…The decreased fractional PC16:0/16:0 content in our patient group is comparable with a previous study of patients with ARDS, where the disaturated PC content of from patients was only 17% of that of controls [11]. Apparent differences with other previous reports in ARDS are largely due to a combination of less severe disease [5] and alternative methodologies and analysis of purifying isolated surfactant fractions [2,5,12]. This deficit in total PC and fractional PC16:0/16:0 concentration may be due to reduced synthesis, increased breakdown, or dilution by pulmonary oedema.…”

Section: Discussionsupporting

confidence: 80%

Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome

et al. 2014

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BackgroundAcute respiratory distress syndrome (ARDS) is a life-threatening critical illness, characterised by qualitative and quantitative surfactant compositional changes associated with premature airway collapse, gas-exchange abnormalities and acute hypoxic respiratory failure. The underlying mechanisms for this dysregulation in surfactant metabolisms are not fully explored. Lack of therapeutic benefits from clinical trials, highlight the importance of detailed in-vivo analysis and characterisation of ARDS patients according to patterns of surfactant synthesis and metabolism.MethodsTen patients with moderate to severe ARDS were recruited. Most (90%) suffered from pneumonia. They had an infusion of methyl-D9-choline chloride and small volume bronchoalveolar lavage fluid (BALF) was obtained at 0,6,12,24,48,72 and 96 hours. Controls were healthy volunteers, who had BALF at 24 and 48 hours after methyl-D9-choline infusion. Compositional analysis and enrichment patterns of stable isotope labelling of surfactant phosphatidylcholine (PC) was determined by electrospray ionisation mass spectrometry.ResultsBALF of patients with ARDS consisted of diminished total PC and fractional PC16:0/16:0 concentrations compared to healthy controls. Compositional analysis revealed, reductions in fractional compositions of saturated PC species with elevated levels of longer acyl chain unsaturated PC species. Molecular specificity of newly synthesised PC fraction showed time course variation, with lower PC16:0/16:0 composition at earlier time points, but achieved near equilibrium with endogenous composition at 48 hours after methyl-D9-choline infusion. The enrichment of methyl-D9-choline into surfactant total PC is nearly doubled in patients, with considerable variation between individuals.ConclusionsThis study demonstrate significant alterations in composition and kinetics of surfactant PC extracted from ARDS patients. This novel approach may facilitate biochemical phenotyping of ARDS patients according to surfactant synthesis and metabolism, enabling individualised treatment approaches for the management of ARDS patients in the future.

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Section: Discussionsupporting

confidence: 80%

Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome

et al. 2014

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“…92,93,[108][109][110][111][112][113] Regardless of mechanism, the practical consequences of surfactant dysfunction in ALI/ARDS are not dissimilar to those in RDS. As a result of decreased surfactant activity, the lungs become less compliant, develop progressive loss of aerated volume, and manifest a worsening ventilation/perfusion mismatch.…”

Section: Pharmaceutical Surfactantsmentioning

confidence: 99%

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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“…For example, the hydrophilic SP, SP-A, has been shown to inhibit sPLA 2 -mediated surfactant hydrolysis (6), but little is known regarding SP-B effects on sPLA 2 . SPs may be depleted in acute lung injury (ALI) and ARDS (14,43). Such depletion may alter the balance of sPLA 2 -mediated hydrolytic damage to surfactant in patients with ALI/ARDS.…”

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confidence: 99%

Surfactant protein B inhibits secretory phospholipase A₂hydrolysis of surfactant phospholipids

Hite

Grier

Waite

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Time-dependent changes in pulmonary surfactant function and composition in acute respiratory distress syndrome due to pneumonia or aspiration

Cited by 71 publications

References 42 publications

Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome

Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome

The Future of Exogenous Surfactant Therapy

Surfactant protein B inhibits secretory phospholipase A₂hydrolysis of surfactant phospholipids

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Time-dependent changes in pulmonary surfactant function and composition in acute respiratory distress syndrome due to pneumonia or aspiration

Cited by 71 publications

References 42 publications

Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome

Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome

The Future of Exogenous Surfactant Therapy

Surfactant protein B inhibits secretory phospholipase A2hydrolysis of surfactant phospholipids

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Surfactant protein B inhibits secretory phospholipase A₂hydrolysis of surfactant phospholipids