Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk.

Genome-wide SNP-sex interaction analysis of susceptibility to idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition that is more prevalent in males than females. The reasons for this are not fully understood, with differing environmental exposures due to historically sex-biased occupations, or diagnostic bias, being possible explanations. To date, over 20 independent genetic variants have been identified to be associated with IPF susceptibility, but these have been discovered when combining males and females.

Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF and a prior association of the gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Due to the important role that the Human Leukocyte Antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk.

Neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms in patients with newly diagnosed glioblastoma.

Background: In addition to poor survival rates, individuals with glioblastoma (GBM) are at risk of neurocognitive impairment due to multiple factors. This study aimed to characterize neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms in newly diagnosed GBM patients; and to examine whether neurobehavioral symptoms, fatigue, sleep, and depressive symptoms influence neurocognitive performance.

Methods: This study was part of a prospective, inception cohort, single-arm exercise intervention in which GBM patients underwent a neuropsychological assessment shortly after diagnosis (median 4 weeks; ie, baseline) and 3, 6, 12, and 18 months later, or until tumor progression.

Canadian Stroke Best Practice Recommendations: Rehabilitation, Recovery, and Community Participation following Stroke. Part Two: Transitions and Community Participation Following Stroke.

The sixth update of the is a comprehensive set of evidence-based guidelines addressing issues faced by people following an acute stroke event. Establishing a coordinated and seamless system of care that supports progress achieved during the initial recovery stages throughout the transition to the community is more essential than ever as the medical complexity of people with stroke is also on the rise. All members of the health-care team engaged with people with stroke, their families, and caregivers are responsible for partnerships and collaborations to ensure successful transitions and return to the community following stroke.

Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterized by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of association implicating multiple pathways including host defense, telomere maintenance, signaling, and cell-cell adhesion. To improve our understanding of factors that increase IPF susceptibility by identifying previously unreported genetic associations.

VEGF (Vascular Endothelial Growth Factor) and Fibrotic Lung Disease.

Interstitial lung disease (ILD) encompasses a group of heterogeneous diseases characterised by varying degrees of aberrant inflammation and fibrosis of the lung parenchyma. This may occur in isolation, such as in idiopathic pulmonary fibrosis (IPF) or as part of a wider disease process affecting multiple organs, such as in systemic sclerosis. Anti-Vascular Endothelial Growth Factor (anti-VEGF) therapy is one component of an existing broad-spectrum therapeutic option in IPF (nintedanib) and may become part of the emerging therapeutic strategy for other ILDs in the future.

Lung Function, Inflammation, and Endothelin-1 in Congenital Heart Disease-Associated Pulmonary Arterial Hypertension.

Background: Breathlessness is the most common symptom in people with pulmonary arterial hypertension and congenital heart disease (CHD-APAH), previously thought to be caused by worsening PAH, but perhaps also by inflammation and abnormalities of lung function. We studied lung function and airway inflammation in patients with CHD-APAH and compared the results with controls.

Methods And Results: Sixty people were recruited into the study: 20 CHD-APAH, 20 CHD controls, and 20 healthy controls.

Phenotypes of organ involvement in sarcoidosis.

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.

Effects of hypoxia and hyperoxia on the differential expression of VEGF-A isoforms and receptors in Idiopathic Pulmonary Fibrosis (IPF).

Dysregulation of VEGF-A bioavailability has been implicated in the development of lung injury/fibrosis, exemplified by Idiopathic Pulmonary Fibrosis (IPF). VEGF-A is a target of the hypoxic response via its translational regulation by HIF-1α. The role of hypoxia and hyperoxia in the development and progression of IPF has not been explored.

Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high mortality, uncertain cause, and few treatment options. Studies have identified a significant genetic risk associated with the development of IPF; however, mechanisms by which genetic risk factors promote IPF remain unclear. We aimed to identify genetic variants associated with IPF susceptibility and provide mechanistic insight using gene and protein expression analyses.

Development of tools to facilitate palliative and supportive care referral for patients with idiopathic pulmonary fibrosis.

Objectives: Palliative care is underused in non-malignant respiratory diseases, including interstitial lung diseases (ILDs). We investigated current practices around palliative and supportive care and explored the impact of a supportive care decision aid tool.

Methods: This was a single centre study in a UK ILD centre.

Differential Expression of VEGF-A Isoforms Is Critical for Development of Pulmonary Fibrosis.

Rationale: Fibrosis after lung injury is related to poor outcome, and idiopathic pulmonary fibrosis (IPF) can be regarded as an exemplar. Vascular endothelial growth factor (VEGF)-A has been implicated in this context, but there are conflicting reports as to whether it is a contributory or protective factor. Differential splicing of the VEGF-A gene produces multiple functional isoforms including VEGF-Aa and VEGF-Ab, a member of the inhibitory family.

VEGF isoforms have differential effects on permeability of human pulmonary microvascular endothelial cells.

Background: Alternative splicing of Vascular endothelial growth factor-A mRNA transcripts (commonly referred as VEGF) leads to the generation of functionally differing isoforms, the relative amounts of which have potentially significant physiological outcomes in conditions such as acute respiratory distress syndrome (ARDS). The effect of such isoforms on pulmonary vascular permeability is unknown. We hypothesised that VEGFa and VEGFb isoforms would have differing effects on pulmonary vascular permeability caused by differential activation of intercellular signal transduction pathways.

A comparison of published multidimensional indices to predict outcome in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) has an unpredictable course and prognostic factors are incompletely understood. We aimed to identify prognostic factors, including multidimensional indices from a significant IPF cohort at the Bristol Interstitial Lung Disease Centre in the UK. Patients diagnosed with IPF between 2007 and 2014 were identified.

The role of microRNA-155/liver X receptor pathway in experimental and idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF; therefore, microRNAs may reveal novel pathogenic pathways.

Ambulatory and short-burst oxygen for interstitial lung disease.

Background: A large subgroup of people with interstitial lung disease (ILD) are normoxic at rest, but rapidly desaturate on exertion. This can limit exercise capacity and worsen dyspnoea. The use of ambulatory or short-burst oxygen when mobilising or during other activities, may improve exercise capacity and relieve dyspnoea.

Rituximab in autoimmune connective tissue disease-associated interstitial lung disease.

Objective: CTD-associated interstitial lung disease (ILD) often fails to respond to conventional immunomodulatory agents. There is now considerable interest in the use of rituximab in systemic autoimmune CTD in patients refractory to standard treatments. The aim of this study was to review the experience of North Bristol NHS Trust managing patients with CTD-associated ILD with rituximab and explore possible associations with treatment response.

Advances in understanding of the pathogenesis of acute respiratory distress syndrome.

The clinical syndrome of acute lung injury (ALI) occurs as a result of an initial acute systemic inflammatory response. This can be consequent to a plethora of insults, either direct to the lung or indirect. The insult results in increased epithelial permeability, leading to alveolar flooding with a protein-rich oedema fluid.

Improving care for patients with idiopathic pulmonary fibrosis (IPF) in the UK: a round table discussion.

This article is the result of a round table discussion held at BMA House. Its purpose is to outline the challenges facing both patients and doctors in managing idiopathic pulmonary fibrosis. A number of recommendations for service development and research have been identified.