A5043576559- Asthma and respiratory diseases
- Respiratory and Cough-Related Research
- IL-33, ST2, and ILC Pathways
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Allergic Rhinitis and Sensitization
- Inhalation and Respiratory Drug Delivery
- Eosinophilic Esophagitis
- Pediatric health and respiratory diseases
- Delphi Technique in Research
- Neonatal Respiratory Health Research
- Respiratory viral infections research
- Immune Cell Function and Interaction
- Mast cells and histamine
- COVID-19 Clinical Research Studies
- Long-Term Effects of COVID-19
- Urticaria and Related Conditions
- Influenza Virus Research Studies
- Metabolomics and Mass Spectrometry Studies
- Food Allergy and Anaphylaxis Research
- SARS-CoV-2 and COVID-19 Research
- Immune cells in cancer
- Bioinformatics and Genomic Networks
- Immune Response and Inflammation
- Pharmaceutical studies and practices
- Advanced Chemical Sensor Technologies
University of Southampton
2016-2025
University Hospital Southampton NHS Foundation Trust
2016-2025
NIHR Southampton Biomedical Research Centre
2016-2025
Southampton General Hospital
2010-2024
NIHR Southampton Respiratory Biomedical Research Unit
2015-2024
Imperial College London
2016-2024
National Institute for Health Research
2014-2024
GlaxoSmithKline (India)
2024
Regeneron (United States)
2024
Cayman Chemical (United States)
2024
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...
Asthma is characterized by the presence of an inflammatory cell infiltrate in bronchial mucosa consisting activated mast cells, eosinophils, and T cells. Several cytokines are considered to play a pivotal role this response, particularly interleukin (IL)-4, IL-5, IL-6, tumor necrosis factor-alpha (TNF-alpha). In study, we have used immunohistochemistry applied thin glycol methacrylate sections mucosal biopsies define cellular provenance these normal asthmatic airways. Both contained numerous...
A thickened bronchial epithelial basement membrane has long been regarded as a histopathologic characteristic of asthma. As we had previously demonstrated that this phenomenon is due to the deposition interstitial collagens and fibronectin, have now sought determine nature cell responsible for process by studying endobronchial biopsies from eight normal seven asthmatic volunteers immunohistochemistry electron microscopy. Biopsies were stained with PR 2D3, monoclonal antibody myofibroblasts...
The effect of inhaled corticosteroid therapy on airway mucosal inflammation was investigated in 10 symptomatic atopic asthmatic patients treated with albuterol and whose disease severity required preventative antiinflammatory treatment. Endobronchial biopsies were obtained by fiberoptic bronchoscopy before after 6 wk beclomethasone dipropionate (2,000 µg/day for 2 followed 1,000 4 wk). Following treatment, there a significant increase mean morning peak expiratory flow (p < 0.05) baseline...
IgE plays an important role in allergic asthma. We hypothesized that reducing the airway mucosa would reduce inflammation. Forty-five patients with mild to moderate persistent asthma sputum eosinophilia of 2% or more were treated humanized monoclonal antibody against (omalizumab) (n = 22) placebo 23) for 16 weeks. Outcomes included inflammatory cells induced and bronchial biopsies, methacholine responsiveness. Treatment omalizumab resulted marked reduction serum a IgE+ mucosa. The mean...
In order to investigate the relationship between airways inflammation and disease severity, improve understanding of persistent asthma, 74 asthmatics, with severity ranging from intermittent, mild moderate severe (classified according Global Initiative for Asthma [GINA] guidelines), 22 nonatopic control subjects were studied using method induced sputum. Sputum was analyzed total differential cell counts concentrations albumin, levels eosinophil cationic protein (ECP), myeloperoxidase (MPO),...
As physiologic and autopsy evidence suggests that peripheral airways parenchyma are involved in asthma, we hypothesized significant alveolar tissue inflammation is present patients with stable, chronic asthma. Eleven nocturnal asthma (NA) 10 non-nocturnal (NNA) were studied. Each subject underwent two bronchoscopies proximal airway endobronchial distal transbronchial biopsy a random order at 4:00 P.M. A.M. Morphometric analysis was used to determine the number per volume (Nv) of inflammatory...
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...
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...
We have used fiberoptic bronchoscopy to obtain endobronchial biopsies in which mast cells and eosinophils were enumerated using monoclonal antibodies directed against cell tryptase (AA1) the eosinophil cationic protein (EG2). Eleven symptomatic atopic asthmatics treated with β2-agonists alone six normal subjects studied. Over a period of 2 wk prior bronchoscopy, patients recorded asthma symptom scores, bronchodilator usage, twice-daily peak expiratory flow. Five days before methacholine...
Airway wall remodeling is an established pathological feature in asthma. Its causes are not well understood, but one mediator of potential relevance transforming growth factor-beta 1 (TGF- β 1). We have measured levels immunoreactive TGF- bronchoalveolar lavage (BAL) fluid from clinically stable atopic asthmatics and healthy control subjects. also examined the influence allergen exposure on release airways using a segmental bronchoprovocation model, with BAL performed at two time points...
Asthma is characterised by heterogeneous clinical phenotypes. Our objective was to determine molecular phenotypes of asthma analysing sputum cell transcriptomics from 104 moderate-to-severe asthmatic subjects and 16 nonasthmatic subjects. After filtering on the differentially expressed genes between eosinophil- noneosinophil-associated inflammation, we used unbiased hierarchical clustering 508 gene set variation analysis specific sets. We defined three transcriptome-associated clusters...
Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-β. Exogenous IFN-β restores activity.To compare efficacy and safety inhaled placebo administered after onset cold symptoms prevent or attenuate respiratory viruses.A total 147 on corticosteroids (British Thoracic Society Steps 2-5), a history virus-associated exacerbations, were randomized 14-day treatment (n = 72) 75) within 24...
Few genetic studies that focus on moderate-to-severe asthma exist. We aimed to identity novel variants associated with asthma, see whether previously identified for all types of contribute and provide mechanistic insights using expression analyses in patients asthma.In this genome-wide association study, we used a two-stage case-control design. In stage 1, genotyped patient-level data from two UK cohorts (the Genetics Asthma Severity Phenotypes [GASP] initiative the Unbiased BIOmarkers...
Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity relationships to asthma severity are unclear.We performed comprehensive assessment of TH17 cells, regulatory T mucosal-associated invariant (MAIT) other T-cell subsets, granulocyte in asthmatic patients.Sixty patients with mild-to-severe 24 control subjects underwent detailed clinical provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, blood samples. Adaptive cytokines,...
Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms.Using transcriptomic profiling of airway tissues, we sought to define the molecular phenotypes severe asthma.The transcriptome derived from bronchial biopsies epithelial brushings 107 subjects with moderate asthma were annotated gene set variation analysis using 42 signatures relevant asthma, inflammation, immune function. Topological data clinical histologic was performed derive clusters, nearest...