Surfactant Phospholipid Kinetics in Ventilated Children after Therapeutic Surfactant Supplementation.

Acute lung Injury leads to alterations in surfactant lipid composition and metabolism. Although several mechanisms contribute to dysregulated surfactant metabolism, studies investigating in vivo surfactant metabolism are limited. The aim of this study is to characterise surfactant phospholipid composition and flux utilising a stable isotope labelling technique in mechanically ventilated paediatric patients.

Oxidative stress, redox status and surfactant metabolism in mechanically ventilated patients receiving different approaches to oxygen therapy (MecROX): An observational study protocol for mechanistic evaluation.

Background: MecROX is a mechanistic sub-study of the UK-ROX trial which was designed to evaluate the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care. This is based on the scientific rationale that excess oxygen is harmful. Epithelial cell damage with alveolar surfactant deficiency is characteristic of hyperoxic acute lung injury.

In Vivo Cellular Phosphatidylcholine Kinetics of CD15+ Leucocytes and CD3+ T-Lymphocytes in Adults with Acute Respiratory Distress Syndrome.

Mammalian cell membranes composed of a mixture of glycerophospholipids, the relative composition of individual phospholipids and the dynamic flux vary between cells. In addition to their structural role, membrane phospholipids are involved in cellular signalling and immunomodulatory functions. In this study, we investigate the molecular membrane composition and dynamic flux of phosphatidylcholines in CD15+ leucocytes and CD3+ lymphocytes extracted from patients with acute respiratory distress syndrome (ARDS).

Membrane lipid composition of bronchial epithelial cells influences antiviral responses during rhinovirus infection.

Lipids and their mediators have important regulatory functions in many cellular processes, including the innate antiviral response. The aim of this study was to compare the lipid membrane composition of in vitro differentiated primary bronchial epithelial cells (PBECs) with ex vivo bronchial brushings and to establish whether any changes in the lipid membrane composition affect antiviral defense of cells from donors without and with severe asthma. Using mass spectrometry, we showed that the lipid membrane of in vitro differentiated PBECs was deprived of polyunsaturated fatty acids (PUFAs) compared to ex vivo bronchial brushings.

Stratification of asthma by lipidomic profiling of induced sputum supernatant.

Background: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features.

Objective: We performed a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as from healthy controls.

DEPEND study protocol: early detection of patients with pancreatic cancer - a pilot study to evaluate the utility of faecal elastase-1 and C-mixed triglyceride breath test as screening tools in high-risk individuals.

Introduction: Pancreatic cancer (PC) is the fifth leading cause of cancer-related death in the UK. The incidence of PC is increasing, with little or no improvement in overall survival and the best chance for long-term survival in patients with PC relies on early detection and surgical resection. In this study, we propose the use of a diagnostic algorithm that combines tests of pancreatic exocrine function (faecal elastase-1 (FE-1) test and the C-mixed triglyceride (C-MTG) breath test) to identify patients with PC that urgently needs imaging studies.

Postnatal adaptations of phosphatidylcholine metabolism in extremely preterm infants: implications for choline and PUFA metabolism.

Background: Lipid metabolism in pregnancy delivers PUFAs from maternal liver to the developing fetus. The transition at birth to diets less enriched in PUFA is especially challenging for immature, extremely preterm infants who are typically supported by total parenteral nutrition.

Objective: The aim was to characterize phosphatidylcholine (PC) and choline metabolism in preterm infants and demonstrate the molecular specificity of PC synthesis by the immature preterm liver in vivo.

The glycomic sialylation profile of GNE Myopathy muscle cells does not point to consistent hyposialylation of individual glycoconjugates.

GNE Myopathy is a recessive neuromuscular disorder characterized by adult-onset, slowly progressive distal and proximal muscle weakness, and a typical muscle pathology. Although GNE, which is the mutated gene in the disease, is well known as the key enzyme in the biosynthesis pathway of sialic acid, the pathophysiological pathway leading from GNE mutations to the muscle phenotype in GNE Myopathy is still unclear. The obvious hypothesis of impaired sialylation in patients' skeletal muscle as the cause of the disease is still controversial.

Bedside breath tests in children with abdominal pain: a prospective pilot feasibility study.

Background: There is no definitive method of accurately diagnosing appendicitis before surgery. We evaluated the feasibility of collecting breath samples in children with abdominal pain and gathered preliminary data on the accuracy of breath tests.

Methods: We conducted a prospective pilot study at a large tertiary referral paediatric hospital in the UK.

Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers.

Background: Lung epithelial lining fluid (ELF)-sampled through sputum induction-is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood.

Objectives: To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort.

Ready-to-use therapeutic food with elevated n-3 polyunsaturated fatty acid content, with or without fish oil, to treat severe acute malnutrition: a randomized controlled trial.

Background: Ready-to-use therapeutic foods (RUTF) are lipid-based pastes widely used in the treatment of acute malnutrition. Current specifications for RUTF permit a high n-6 polyunsaturated fatty acid (PUFA) content and low n-3 PUFA, with no stipulated requirements for preformed long-chain n-3 PUFA. The objective of this study was to develop an RUTF with elevated short-chain n-3 PUFA and measure its impact, with and without fish oil supplementation, on children's PUFA status during treatment of severe acute malnutrition.

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

Background: Acute 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.

Phospholipid composition and kinetics in different endobronchial fractions from healthy volunteers.

Background: Alterations in surfactant phospholipid compositions are a recognized feature of many acute and chronic lung diseases. Investigation of underlying mechanisms requires assessment of surfactant phospholipid molecular composition and kinetics of synthesis and turnover. Such studies have recently become possible in humans due to the development of stable isotope labelling combined with advances in analytical methods in lipidomics.

Application of 'omics technologies to biomarker discovery in inflammatory lung diseases.

Inflammatory lung diseases are highly complex in respect of pathogenesis and relationships between inflammation, clinical disease and response to treatment. Sophisticated large-scale analytical methods to quantify gene expression (transcriptomics), proteins (proteomics), lipids (lipidomics) and metabolites (metabolomics) in the lungs, blood and urine are now available to identify biomarkers that define disease in terms of combined clinical, physiological and patho-biological abnormalities. The aspiration is that these approaches will improve diagnosis, i.

Regulation of lung surfactant phospholipid synthesis and metabolism.

The alveolar type II epithelial (ATII) cell is highly specialised for the synthesis and storage, in intracellular lamellar bodies, of phospholipid destined for secretion as pulmonary surfactant into the alveolus. Regulation of the enzymology of surfactant phospholipid synthesis and metabolism has been extensively characterised at both molecular and functional levels, but understanding of surfactant phospholipid metabolism in vivo in either healthy or, especially, diseased lungs is still relatively poorly understood. This review will integrate recent advances in the enzymology of surfactant phospholipid metabolism with metabolic studies in vivo in both experimental animals and human subjects.

Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome--where do we go from here?

Acute lung injury and acute respiratory distress syndrome (ARDS) are characterised by severe hypoxemic respiratory failure and poor lung compliance. Despite advances in clinical management, morbidity and mortality remains high. Supportive measures including protective lung ventilation confer a survival advantage in patients with ARDS, but management is otherwise limited by the lack of effective pharmacological therapies.

Lipidomic profiling in Crohn's disease: abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition.

Crohn's disease is a chronic inflammatory condition largely affecting the terminal ileum and large bowel. A contributing cause is the failure of an adequate acute inflammatory response as a result of impaired secretion of pro-inflammatory cytokines by macrophages. This defective secretion arises from aberrant vesicle trafficking, misdirecting the cytokines to lysosomal degradation.