A5063587197- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- IL-33, ST2, and ILC Pathways
- Neonatal Respiratory Health Research
- Pediatric health and respiratory diseases
- Respiratory and Cough-Related Research
- NF-κB Signaling Pathways
- Cytokine Signaling Pathways and Interactions
- Respiratory Support and Mechanisms
- Immune Response and Inflammation
- Histone Deacetylase Inhibitors Research
- Inhalation and Respiratory Drug Delivery
- Estrogen and related hormone effects
- Epigenetics and DNA Methylation
- COVID-19 Clinical Research Studies
- Eosinophilic Esophagitis
- Immune Cell Function and Interaction
- MicroRNA in disease regulation
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Air Quality and Health Impacts
- SARS-CoV-2 and COVID-19 Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Delphi Technique in Research
- Pulmonary Hypertension Research and Treatments
Imperial College London
2016-2025
Lung Institute
2014-2025
NIHR Imperial Biomedical Research Centre
2021-2025
Hunter Medical Research Institute
2017-2024
Royal Brompton Hospital
2004-2024
Royal Brompton & Harefield NHS Foundation Trust
2015-2024
British Airways (United Kingdom)
2009-2024
St Vincent's Clinic
2023
UNSW Sydney
2023
St Vincent's Health
2023
Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed definition provided recommendations guidelines on evaluation treatment of severe in children adults. literature review was performed, followed discussion an expert committee according to GRADE (Grading Recommendations, Assessment, Development Evaluation) approach for development specific clinical...
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation that greater in patients with advanced disease. We asked whether there a link between the severity of and reduction histone deacetylase (HDAC) activity peripheral lung tissue COPD varying severity. HDAC key molecule repression production proinflammatory cytokines alveolar macrophages.
We have investigated the ability of dexamethasone to regulate interleukin-1β (IL-1β)-induced gene expression, histone acetyltransferase (HAT) and deacetylase (HDAC) activity. Low concentrations (10−10 M) repress IL-1β-stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) expression fail stimulate secretory leukocyte proteinase inhibitor expression. Dexamethasone (10−7 IL-1β (1 ng/ml) both stimulated HAT activity but showed a different pattern H4 acetylation. targeted lysines...
Glucocorticoids are the most effective antiinflammatory agents for treatment of chronic inflammatory diseases even though some diseases, such as obstructive pulmonary disease (COPD), relatively glucocorticoid insensitive. However, molecular mechanism this insensitivity remains uncertain. We show that a defect receptor (GR) deacetylation caused by impaired histone deacetylase (HDAC) 2 induces toward nuclear factor (NF)-κB–mediated gene expression. Specific knockdown HDAC2 RNA interference...
The molecular mechanism for the anti-inflammatory action of theophylline is currently unknown, but low-dose an effective add-on therapy to corticosteroids in controlling asthma. Corticosteroids act, at least part, by recruitment histone deacetylases (HDACs) site active inflammatory gene transcription. They thereby inhibit acetylation core histones that necessary We show both vitro and vivo enhances HDAC activity epithelial cells macrophages. This increased then available corticosteroid...
U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective improving understanding asthma disease mechanisms using systems biology approach. This cross-sectional assessment adults severe asthma, mild/moderate healthy controls from countries consisted analyses patient-reported outcomes, lung function, blood airway inflammatory measurements. Patients (nonsmokers, n=311; smokers/ex-smokers, n=110) had more...
This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available relevant European Respiratory Society/American Thoracic Society Task Force's questions. The was appraised using GRADE (Grading Recommendations, Assessment, Development and Evaluation) approach results summarised in profiles. syntheses discussed formulated by a multidisciplinary Force asthma experts, who made...
Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory of the lungs with little or no response to glucocorticoids and high level oxidative stress. Histone deacetylase (HDAC) activity reduced in cells cigarette smokers, low concentrations theophylline can increase HDAC activity. We measured effect on gene expression alveolar macrophages (AM) from patients COPD. AM normal smokers showed decrease compared control subjects, this was further COPD (51% decrease, P <...
Exhaled nitric oxide (FE(NO)) has been proposed as a noninvasive marker of airway inflammation in asthma, and may reflect eosinophilia. We examined the relationship between FE(NO) eosinophilic endobronchial biopsies from 31 children with difficult asthma (mean age [range] 11.9 [6-17] yr), following 2 wk prednisolone (40 mg/d). Endobronchial biopsy was also performed seven without asthma. Biopsy eosinophils were detected using antibody to major basic protein, point-counting used derive an...
SPECIFIC AIMSGlucocorticoidsact, at least in part, through recruitment of histone deacetylases (HDACs) to sites inflammatory gene transcription. In this study we show that cigarette smoke, an oxidative stress, decreased HDAC activity human biopsies and macrophages vivo. This reduced correlated with enhanced induction cytokines a reduction glucocorticoid responsiveness vitro.PRINCIPAL FINDINGS1. HAT expression bronchial alveolar macrophages.The acetyltransferases (HATs) CBP HDAC1 HDAC2 are...
Asthma is associated with increased expression of inflammatory proteins including cytokines, enzymes, and adhesion molecules. Induction many the genes for these regulated by transcription factor, nuclear factor- κ B (NF- B). We therefore examined whether airway cells from patients asthma show activation NF- B. Nuclear were extracted induced sputum bronchial biopsies normal subjects asthma. B-binding to its consensus DNA binding site, as investigated 32P-labeled oligonucleotides...
The expression of nuclear factor (NF)-κB is an indicator cellular activation and inflammatory mediator production. aim the present study was to characterise localisation p65, major subunit NF-κB, in bronchial mucosa patients with chronic obstructive pulmonary disease (COPD), examine relationship between p65 status. Bronchial biopsies were obtained from 14 smokers COPD, 17 normal lung function 12 nonsmokers function. number positive (+) cells quantified by immunohistochemistry three groups...
BackgroundInflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial might be involved driving the stress–induced pathology.ObjectiveWe sought to determine effects of on mitochondrial function pathophysiology airway inflammation ozone-exposed mice human smooth muscle (ASM) cells.MethodsMice were exposed ozone, lung inflammation, hyperresponsiveness (AHR), determined. Human ASM cells isolated from bronchial biopsy...