A5005514153- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Respiratory Support and Mechanisms
- Asthma and respiratory diseases
- Occupational exposure and asthma
- Inhalation and Respiratory Drug Delivery
- Occupational and environmental lung diseases
- Sarcoidosis and Beryllium Toxicity Research
- Autoimmune and Inflammatory Disorders Research
- Respiratory and Cough-Related Research
- Pulmonary Hypertension Research and Treatments
- Adolescent and Pediatric Healthcare
- Medical Imaging and Pathology Studies
- Systemic Sclerosis and Related Diseases
- Lung Cancer Treatments and Mutations
- Eosinophilic Disorders and Syndromes
- Neonatal Respiratory Health Research
- Pneumonia and Respiratory Infections
- Cystic Fibrosis Research Advances
- Emergency and Acute Care Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Dysphagia Assessment and Management
- Musculoskeletal Disorders and Rehabilitation
- Pharmaceutical studies and practices
- Chronic Disease Management Strategies
GlaxoSmithKline (Netherlands)
2016-2025
GlaxoSmithKline (United Kingdom)
2017-2024
Guy's and St Thomas' NHS Foundation Trust
2023-2024
Harefield Hospital
2023-2024
Regional West Medical Center
2023
University of Michigan
2023
GlaxoSmithKline (India)
2022
Budapest University of Technology and Economics
2020
University of Freiburg
2020
University of Southern Mississippi
2020
BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high mortality, uncertain cause, and few treatment options. Studies have identified significant genetic risk associated the development of IPF; however, mechanisms by which factors promote IPF remain unclear. We aimed to identify variants susceptibility provide mechanistic insight using gene protein expression analyses.MethodsWe used two-stage approach: genome-wide association study in patients European...
Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterized by scarring of the that believed to result from an atypical response injury epithelium. Genome-wide association studies have reported signals implicating multiple pathways including host defense, telomere maintenance, signaling, and cell-cell adhesion.Objectives: To improve our understanding factors increase IPF susceptibility identifying previously unreported genetic associations.Methods: We conducted...
Phosphatidylinositol 3-kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is potent inhibitor PI3K/mTOR. A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study omipalisib subjects with IPF was conducted ( NCT01725139 ) to test safety, tolerability, pharmacokinetics pharmacodynamics. dosed at 0.25 mg, 1 mg 2 twice daily for 8 days four cohorts...
Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk progression. Longitudinal change in markers ECM synthesis was assessed 145 newly-diagnosed with IPF.Serum levels collagen neoepitopes, PRO-C3 PRO-C6 (collagen type 3 6), were elevated IPF compared controls at baseline, progressive disease versus stable during follow...
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. A better understanding of the molecular drivers IPF progression needed.
Minimizing the risk of disease progression and exacerbations is key goal COPD management, as these are well-established indicators poor prognosis. We developed a novel composite end point assessing three important aspects (lung function, health status, exacerbations) worsening in COPD. The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically deteriorations (CIDs) versus placebo or bronchodilator monotherapy.This study post hoc...
The RGD-integrin, αvβ6, plays a role in the pathogenesis of pulmonary fibrosis through activation transforming growth factor beta (TGFβ). This study sought to quantify expression αvβ6 lungs healthy humans and subjects with using αvβ6-selective [
Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with poor prognosis and significant unmet medical need. This study evaluated the safety, pharmacokinetics (PK) target engagement in lungs, of GSK3008348, novel inhaled alpha-v beta-6 (αvβ6) integrin inhibitor, participants IPF. Methods was phase 1b, randomised, double-blind (sponsor unblind) study, conducted UK (two clinical sites, one imaging unit) between June 2017 July 2018 (NCT03069989)....
Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal condition for which there are lack of effective biomarkers to guide therapeutic decision making. Objectives: To determine the relationship between serum concentrations cytokeratin fragment CYFRA 21-1 disease progression mortality in individuals with IPF enrolled Prospective Observation Fibrosis Lung Clinical Endpoints (PROFILE) study. Methods: was identified by immunohistochemistry samples human lung...
Cough is a commonly reported symptom in idiopathic pulmonary fibrosis (IPF) that negatively impacts patient-reported quality of life (QoL). However, both the burden cough at diagnosis and behavior over time have not been systematically described patients with IPF.
Background: The long-acting muscarinic antagonists umeclidinium (UMEC) and tiotropium (TIO) are approved once-daily maintenance therapies for COPD. This study investigated the efficacy safety of UMEC versus TIO in Methods: was a 12-week, multicenter, randomized, blinded, double-dummy, parallel-group, non-inferiority study. Patients were randomized 1:1 to 62.5 µg plus placebo or 18 placebo. primary end point trough forced expiratory volume 1 second (FEV ) at day 85 (non-inferiority margin -50...
Background The phosphatidylinositol 3-kinase delta isoform (PI3Kδ) belongs to an intracellular lipid kinase family that regulate lymphocyte metabolism, survival, proliferation, apoptosis and migration has been successfully targeted in B-cell malignancies. Primary Sjögren’s syndrome (pSS) is a chronic immune-mediated inflammatory disease characterised by exocrine gland lymphocytic infiltration hyperactivation which results systemic manifestations, autoantibody production loss of glandular...
Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits lung function health status versus monotherapy. The aim of this study was to determine whether early initiation dual monotherapy reduced the risk deterioration COPD. This post hoc pooled analysis investigated efficacy safety umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared tiotropium (TIO) 18 maintenance-naïve (MN) subgroup relative...
ABSTRACT Background Idiopathic pulmonary fibrosis (IPF) is a rare, incurable lung disease with median survival of 3-5 years after diagnosis. Treatment options are limited. Genetic association studies can identify new genes involved in that might represent potential drug targets, and it has been shown targets support from genetic more likely to be successful clinical development. Previous genome-wide (GWAS) IPF susceptibility have identified than 20 signals implicating multiple mechanisms,...
Introduction: Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a combination. This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients moderate remained tiotropium (TIO). Methods: In this randomized, blinded, double-dummy, parallel-group (NCT01899742), (N=494) were prescribed TIO for ≥3 months at screening (forced expiratory volume 1 s [FEV ]: 50%–70% predicted; modified Medical...
Our aim was to investigate total and regional lung delivery of salbutamol in subjects with idiopathic pulmonary fibrosis (IPF). The TOPICAL study a 4-period, partially-randomised, controlled, crossover four aerosolised approaches IPF subjects. Nine were randomised receive 99mTechnetium-labelled monodisperse (1.5 μm or 6 μm; periods 1 2). Subjects also received radio-labelled using polydisperse nebuliser (period 3) unlabelled (400 μg) pressurized metered dose inhaler volumatic spacer (pMDI;...
Background: The combination of the inhaled muscarinic antagonist umeclidinium (UMEC) with long-acting β2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared UMEC, VI, or placebo (PBO) patients chronic obstructive pulmonary disease (COPD). This study was specifically designed support these findings by assessing health-related quality life and symptomatic outcomes a similar population. Methods: 12-week multicenter, randomized, double-blind,...
Background Considerable clinical heterogeneity in idiopathic pulmonary fibrosis (IPF) suggests the existence of multiple disease endotypes. Identifying these endotypes would improve our understanding pathogenesis IPF and could allow for a biomarker-driven personalised medicine approach. We aimed to identify clinically distinct groups patients with that represent Methods co-normalised, pooled clustered three publicly available blood transcriptomic datasets (total 220 cases). compared traits...
Background Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition that 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 association signals have been reported IPF susceptibility, but these discovered when combining and Objectives assess whether there need consider sex-specific...