Raised FGF23 Correlates to Increased Mortality in Critical Illness, Independent of Vitamin D.

Background: Fibroblast Growth Factor (FGF23) is an endocrine hormone classically associated with the homeostasis of vitamin D, phosphate, and calcium. Elevated serum FGF23 is a known independent risk factor for mortality in chronic kidney disease (CKD) patients. We aimed to determine if there was a similar relationship between FGF23 levels and mortality in critically ill patients.

Vitamin D attenuates lung injury via stimulating epithelial repair, reducing epithelial cell apoptosis and inhibits TGF-β induced epithelial to mesenchymal transition.

Vitamin D regulates cell proliferation, inhibits cytokines release at sites of inflammation and reduces inflammatory responses. In this study, the aim was to investigate whether exogenous vitamin D attenuates LPS-induced lung injury via modulating epithelial cell proliferation, migration, apoptosis and epithelial mesenchymal transition (EMT). Murine and in vitro primary type II alveolar epithelial cell work were included in this study.

Early identification of severe community-acquired pneumonia: a retrospective observational study.

Background: Community-acquired pneumonia (CAP) is a leading cause of sepsis worldwide. Prompt identification of those at high risk of adverse outcomes improves survival by enabling early escalation of care. There are multiple severity assessment tools recommended for risk stratification; however, there is no consensus as to which tool should be used for those with CAP.

Simvastatin Improves Neutrophil Function and Clinical Outcomes in Pneumonia. A Pilot Randomized Controlled Clinical Trial.

Population studies suggest improved sepsis outcomes with statins, but the results of randomized controlled trials in patients with sepsis and organ dysfunction in critical care settings have broadly been negative. data suggest that statins modulate age-related neutrophil functions, improving neutrophil responses to infection, but only in older patients and at high doses. To determine if high-dose simvastatin improves neutrophil functions and is safe and tolerated in hospitalized older adults with community-acquired pneumonia with sepsis (CAP + S) not admitted to critical care.

Dysregulated alveolar function and complications in smokers following oesophagectomy.

Acute respiratory distress syndrome (ARDS) has a significant impact on post-operative morbidity and mortality following oesophagectomy. Smoking is a risk factor for the development of ARDS, although the mechanism is unclear. We examined the effect of smoking on alveolar and systemic inflammation, in addition to alveolar-capillary permeability, leading to ARDS in patients undergoing oesophagectomy.

Vitamin D to Prevent Lung Injury Following Esophagectomy-A Randomized, Placebo-Controlled Trial.

Objectives: Observational studies suggest an association between vitamin D deficiency and adverse outcomes of critical illness and identify it as a potential risk factor for the development of lung injury. To determine whether preoperative administration of oral high-dose cholecalciferol ameliorates early acute lung injury postoperatively in adults undergoing elective esophagectomy.

Design: A double-blind, randomized, placebo-controlled trial.

ARDS following oesophagectomy: a comparison of two trials.

Introduction: The Beta Agonist Lung Injury Trial-Prevention (BALTI-P) translational substudy and Vitamin D to Prevent Acute Lung Injury Following Oesophagectomy (VINDALOO) trials recruited patients undergoing oesophagectomy, 4 years apart. The acute respiratory distress syndrome (ARDS) rates were lower in the VINDALOO trial. We sought to identify changes between these two trials and identify risk factors for ARDS in oesophagectomy.

ResolvinD stimulates epithelial wound repair and inhibits TGF-β-induced EMT whilst reducing fibroproliferation and collagen production.

Acute and chronic inflammatory lung diseases are often associated with epithelial cell injury/loss and fibroproliferative responses. ResolvinD (RvD1) is biosynthesized during the resolution phase of inflammatory response and exerts potent anti-inflammatory and promotes resolution of inflammatory lung diseases. The aim of this study was to investigate whether RvD1 exerts protective effects on alveolar epithelial cell function/differentiation and protects against fibroproliferative stimuli.

Statin therapy in patients with community-acquired pneumonia.

Community-acquired pneumonia (CAP) is the leading cause of death from infection in developed countries. There is evidence of an association between improved survival from infection and statin use. The possible beneficial effects of statins are complicated by the common use of macrolide antibiotics for pneumonia, with current guidance suggesting that concurrent macrolide and statin use is contraindicated.

Pulmonary Infections in the Elderly Lead to Impaired Neutrophil Targeting, Which Is Improved by Simvastatin.

Rationale: Dysregulated neutrophil functions with age and sepsis are described. Statins are associated with improved infection survival in some observational studies, but trials in critically ill patients have not shown benefit. Statins also alter neutrophil responses in vitro.

Lipoxin A promotes lung epithelial repair whilst inhibiting fibroblast proliferation.

Therapy that promotes epithelial repair whilst protecting against fibroproliferation is critical for restoring lung function in acute and chronic respiratory diseases. Primary human alveolar type II cells were used to model the effects of lipoxin A upon wound repair, proliferation, apoptosis and transdifferention. Effects of lipoxin A upon primary human lung fibroblast proliferation, collagen production, and myofibroblast differentiation were also assessed.

Vitamin D Deficiency in Human and Murine Sepsis.

Objectives: Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and ICU mortality but causality of these associations has not been demonstrated. To determine whether sepsis and severe sepsis are associated with vitamin D deficiency and to determine whether vitamin D deficiency influences the severity of sepsis.

Design, Setting, And Patients: Sixty-one patients with sepsis and severe sepsis from two large U.

Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS).

Rationale: Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome (ARDS). Causality of these associations has never been demonstrated.

Objectives: To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity.

Simvastatin to modify neutrophil function in older patients with septic pneumonia (SNOOPI): study protocol for a randomised placebo-controlled trial.

Background: Community-acquired pneumonia (CAP) is considered the leading cause of death from infectious disease in developed countries, while complications of CAP - sepsis being the most common and challenging - increase the risk of mortality. During the progression of sepsis, a state of neutrophil 'paralysis' develops resulting in the impairment of neutrophil anti-microbial functions including: chemotaxis, production of reactive oxygen species, and formation of neutrophil extracellular traps (NETs). Mechanisms underlying defective neutrophil function remain elusive although NET formation has been implicated in the immunosuppression and increased rates of sepsis observed in neonates.

Regulatory T cells and COPD.

While the innate immune system has long been implicated in the pathogenesis of COPD, a role for the acquired immune system is less well studied. The increasing recognition that COPD shares features with autoimmune disease has led to interest in a potential role for regulatory T cells, which are intimately involved in the control of autoimmunity. The suggestion that regulatory T cell numbers are increased in patients with COPD may indicate their dysfunction or resistance to suppression by target cells.

Vitamin D to prevent acute lung injury following oesophagectomy (VINDALOO): study protocol for a randomised placebo controlled trial.

Background: Acute lung injury occurs in approximately 25% to 30% of subjects undergoing oesophagectomy. Experimental studies suggest that treatment with vitamin D may prevent the development of acute lung injury by decreasing inflammatory cytokine release, enhancing lung epithelial repair and protecting alveolar capillary barrier function.

Methods/design: The 'Vitamin D to prevent lung injury following oesophagectomy trial' is a multi-centre, randomised, double-blind, placebo-controlled trial.