A5065327513- Asthma and respiratory diseases
- Cell Adhesion Molecules Research
- Eosinophilic Esophagitis
- Allergic Rhinitis and Sensitization
- Antimicrobial Peptides and Activities
- Respiratory and Cough-Related Research
- IL-33, ST2, and ILC Pathways
- Indoor Air Quality and Microbial Exposure
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- T-cell and B-cell Immunology
- Inhalation and Respiratory Drug Delivery
- Protease and Inhibitor Mechanisms
- Eosinophilic Disorders and Syndromes
- Immune Cell Function and Interaction
- Mast cells and histamine
- Pediatric health and respiratory diseases
- Drug-Induced Adverse Reactions
- COVID-19 epidemiological studies
- Complement system in diseases
- Adenosine and Purinergic Signaling
- Immunotherapy and Immune Responses
- Delphi Technique in Research
- S100 Proteins and Annexins
- SARS-CoV-2 and COVID-19 Research
University of Leicester
1999-2025
Glenfield Hospital
1995-2024
University Hospitals of Leicester NHS Trust
2002-2017
National Health Service
2016
National Institute for Health Research
2016
NIHR Leicester Respiratory Biomedical Research Unit
2013
University of Warwick
2003
The Honourable Society of Lincoln's Inn
2002
Cancer Research UK
2002
Sunderland Royal Hospital
2002
Asthma and eosinophilic bronchitis are characterized by similar inflammatory infiltrates in the submucosa of lower airway. However, differs from asthma that there is no variable airflow obstruction or airway hyperresponsiveness former condition. We tested hypothesis were differences between two conditions microlocalization mast cells within smooth muscle.
The relationship between airway inflammation and obesity in severe asthma is poorly understood.We sought to determine the sputum mediator profiles distribution of eosinophilic people with asthma.Clinical parameters eight mediators were assessed 131 subjects from a single center categorized into lean, overweight, obese groups defined by their body mass index. In an independent group (n = 45) healthy control 19) was enumerated bronchial submucosa, blood, related index.Sputum IL-5 geometric...
Significance Coexposure to airborne pollen enhances susceptibility respiratory viral infections, regardless of the allergy status. We hypothesized this could be also true for SARS-CoV-2 infections. To investigate this, we tested relationships between infection rates and concentrations, along with humidity, temperature, population density, lockdown effects. Our unique dataset derives from 130 sites in 31 countries across five continents. found that pollen, sometimes synergy humidity...
Abstract The lung is an important tertiary lymphoid organ with constant trafficking of T cells through the in both health and disease. cell migration controlled by a combination adhesion receptors chemokines expressed on vascular endothelium tissue, often organ-specific manner. This leads to selective accumulation different subsets, process called lymphocyte homing. There evidence for distinct lung-homing pathway, but no specific have been described. We analyzed chemokine receptor profile...
Abstract Background Airway smooth muscle infiltration by mast cells is a feature of asthma and not eosinophilic bronchitis. In asthma, Th2 cytokines have been implicated as playing critical role in the development airway inflammation hyper‐responsiveness. Whether inflammatory within release these unknown. Methods We undertaken comparative immunohistochemical study bronchial biopsies from 14 subjects with 10 bronchitis eight normal controls recruited two centres. Results The median number...
Tissue eosinophilia is a characteristic feature of number inflammatory diseases including asthma and nasal polyposis. Eosinophil migration into tissues controlled in part by interactions between eosinophil adhesion receptors counter-structures on the vascular endothelium. To determine used eosinophils to adhere endothelium allergic inflammation we have adapted Stamper-Woodruff frozen section assay (FSA) study polyp Immunohistology indicated that intercellular molecule 1 (ICAM-1), E-selectin...
Our recent studies have indicated an important role for P-selectin in eosinophil adhesion. We therefore compared and neutrophil binding with nasal polyp endothelium as well purified P-selectin. also the structure expression of ligands. Using frozen section assay, eosinophils bound to 2-fold more blood vessels within tissue than neutrophils. Up 10-fold neutrophils per unit length endothelium. Neutrophil was inhibited by a mAb against chimera which binds ligand. Eosinophils approximately...
Summary Background Chemokine receptors (CR) play an important role in T cell migration, but their contribution to lung trafficking is unclear. Objective We hypothesized that if a particular CR was involved homing its expression would be enriched on cells compared with peripheral blood (PBT). Methods have measured the BAL from patients sarcoid, other interstitial diseases (ILD), asthma and healthy volunteers. Results Of 14 studied CXCR6 most markedly increased blood, finding also seen ILD...
Pollen and fungal spores are important for human health in both outdoor indoor environments. They linked to several respiratory illnesses which range severity from minor deadly. Better detection forecasting of pollen would allow interventions be developed that reduce their risk health. The current methodologies available the either expensive or time consuming, often both. This hugely limits use. For example, UK Met Office currently only has 11 regulatory grade sites monitoring...
We have investigated the contribution of integrin α 4 β 7 to human peripheral blood eosinophil adhesive interactions. Immunofluorescence and flow cytometry demonstrated constitutive expression by eosinophils. Expression 1 or was not enhanced activation with platelet‐activating factor (PAF). confirmed immunoprecipitation 125 I‐labelled lysates analysed sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE). Approximately 20% unstimulated eosinophils were adherent L1‐2 cells...
Abstract Background The most recognizable phenotype of severe asthma comprises people who are blood eosinophil and FeNO‐high, driven by type 2 (T2) cytokine biology, which responds to targeted biological therapies. However, in many with asthma, these T2 biomarkers suppressed but poorly controlled persists. mechanisms driving the absence biology understood. Objectives To explore airway pathology biomarker‐high ‐low asthma. Methods (T2‐high, n = 17) was compared biomarker‐intermediate...
Patients with severe asthma appear relatively corticosteroid resistant. Corticosteroid responsiveness is closely related to the degree of eosinophilic airway inflammation. The extent which inflammation in responds treatment systemic corticosteroids not clear.To relate physiological and inflammatory response disease severity baseline inflammation.Patients mild/moderate were investigated before after 2 weeks oral prednisolone (Clintrials.gov NCT00331058 NCT00327197). We pooled results from two...
The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined.
Summary Background Eosinphil‐derived inflamatory mediators including cytolines are considered to be important in the pathogenesis of allergic inflammation. Fibronectin (Fn) has been shown a physiogical trigger autocrine cytokihne production by human eosinophils. Fn is encoded single gene, but alternate splicing primary RNA transcript results polypeptide diversity cell type‐specific fashion. Thus, tissue contains approxmately 50% more CS‐1 binding region recognized integrin α4 β1 compared...
Exposure to pollen and fungal spores can trigger asthma/allergic symptoms affect health. Rising temperatures from climate change have been associated with earlier seasons increasing intensity for some pollen, weaker evidence spores. It is unclear whether has resulted in changes the exposure-response function between temperature pollen/fungal spore concentrations over time. This study examined associations different time periods assessed potential adaptation using longest dataset existence...
The inflammatory process that underlies allergic diseases such as asthma is characterized by tissue infiltration of eosinophils and T cells. We have used the Stamper-Woodruff frozen-section assay to characterize receptors involved in adhesion human peripheral blood cells nasal polyp endothelium (NPE) a model cell migration disease. bound specifically NPE temperature-, concentration- shear stress-dependent fashion. Adhesion was inhibited approximately 70% antibodies against P-selectin its...
Eosinophils play an important role in the pathogenesis of asthma and can be activated by extracellular nucleotides released following cell damage or inflammation. For example, increased ATP concentrations were reported bronchoalveolar lavage fluids asthmatic patients. Although eosinophils are known to express several subtypes P2 receptors for nucleotides, their function contribution remain unclear. In this article, we show that transcripts P2X1, P2X4, P2X5 expressed healthy eosinophils. The...
We have used the Stamper-Woodruff frozen-section assay (FSA) to characterize integrin and activation steps involved in adhesion of peripheral blood eosinophils neutrophils nasal polyp endothelium (NPE). Eosinophil neutrophil was significantly inhibited by monoclonal antibodies (mAbs) against CD18 (beta2) CD11a-c. also a lesser extent mAbs CD29 (beta1), CD49d (alpha4), vascular cell molecule-1. The involvement integrins raised possibility an step being process. Although stimulation cells with...