A5000479420- Chronic Obstructive Pulmonary Disease (COPD) Research
- Asthma and respiratory diseases
- Respiratory Support and Mechanisms
- COVID-19 Clinical Research Studies
- Pediatric health and respiratory diseases
- SARS-CoV-2 and COVID-19 Research
- Neonatal Respiratory Health Research
- Respiratory and Cough-Related Research
- interferon and immune responses
- Long-Term Effects of COVID-19
- Smoking Behavior and Cessation
- Intensive Care Unit Cognitive Disorders
- Pediatric Hepatobiliary Diseases and Treatments
- IL-33, ST2, and ILC Pathways
- Liver Diseases and Immunity
- Blood Pressure and Hypertension Studies
- Immune Response and Inflammation
- Phagocytosis and Immune Regulation
- Eosinophilic Esophagitis
- Venous Thromboembolism Diagnosis and Management
- Immune cells in cancer
- Gallbladder and Bile Duct Disorders
- Chronic Kidney Disease and Diabetes
- Erythrocyte Function and Pathophysiology
- Cholesterol and Lipid Metabolism
Manchester University NHS Foundation Trust
2019-2024
University of Manchester
2013-2024
Manchester Academic Health Science Centre
2014-2023
University of Bristol
2023
Intensive Care National Audit & Research Centre
2021-2023
Oxford University Hospitals NHS Trust
2023
Medicines Evaluation Unit
2016-2023
Furness General Hospital
2022-2023
Royal Lancaster Infirmary
2022-2023
University of Alberta
2022
The use of electronic cigarettes (e-cigs) is increasing and there widespread perception that e-cigs are safe. E-cigs contain harmful chemicals; more research needed to evaluate the safety e-cig use. Our aim was investigate effects on inflammatory response human neutrophils.Neutrophils were exposed vapour extract (ECVE) expression CD11b CD66b measured by flow cytometry MMP-9 CXCL8 ELISA. We also activity neutrophil elastase (NE) MMP-9, along with activation signalling pathways. Finally we...
Objective Mortality from coronavirus disease 2019 (COVID‐19) is increased in patients with chronic obstructive pulmonary (COPD). Furthermore, higher BMI related to severe disease. Severe acute respiratory syndrome 2 utilizes angiotensin converting enzyme (ACE2) gain cellular entry. Methods Whether ACE2 bronchial epithelial expression COPD who have overweight compared those do not was investigated by RNA sequencing. Results Increased observed (mean BMI, 29 kg/m ) without 21 ( P = 0.004)....
Abstract Outcomes following SARS-CoV-2 infection are variable; whilst the majority of patients recover without serious complications, a subset develop prolonged illness termed Long COVID or post-acute sequelae (PASC). The pathophysiology underlying remains unclear but appears to involve multiple mechanisms including persistent inflammation, coagulopathy, autoimmunity, and organ damage. Studies suggest that microclots, also known as fibrinaloids, play role in COVID. In this context, we...
Background: Electronic cigarettes (e-cigs) are used to help smoking cessation. However, these devices contain harmful chemicals, and there safety concerns. We have investigated the effects of e-cigs on inflammatory response viability COPD bronchial epithelial cells (BECs). Methods: BECs from patients controls were exposed e-cig vapor extract (ECVE) levels interleukin (IL)-6, C-X-C motif ligand 8 (CXCL8), lactate dehydrogenase release measured. also examined effect ECVE pretreatment...
Background: Interleukin (IL)-6 trans-signalling (IL-6TS) is emerging as a pathogenic mechanism in chronic respiratory diseases; however, the drivers of IL-6TS airways and phenotypic characteristic patients with increased pathway activation remain poorly understood. Objective: Our aim was to identify characterise COPD airway elucidate biological activation. Methods: We used an IL-6TS-specific sputum biomarker profile (soluble IL-6 receptor (sIL-6R), IL-6, IL-1β, IL-8, macrophage inflammatory...
Small airways (<2 mm diameter) are major sites of airflow obstruction in chronic obstructive pulmonary disease (COPD). This study aimed to quantify the impact small airway disease, characterized by narrowing, occlusion, and obliteration, on parameters smokers end-stage patients with COPDs. We performed computational fluid dynamics (CFD) simulations inspiratory three lung groups: control non-used donor lungs (no smoking/emphysema history), a smoking history emphysema, explanted COPD lungs....
Nrf2 regulates cellular antioxidant defence in lung cells, including epithelial cells and alveolar macrophages (AM). The Nrf2/Keap-1 pathway can be modulated by activators with different modes of action; electrophilic compounds protein-protein interaction (PPI) inhibitors. We assessed Keap-1 protein gene levels COPD compared to controls the effect on AM.Lung resected tissue from non-smokers, smokers patients were analysed for AM expression imunoshistochemistry qPCR isolated AM. cultured...
There is large variation in the therapeutic response to inhaled corticosteroids (ICS) COPD patients. We present a pooled analysis of our previous studies investigating effects on lung macrophages, order robustly determine whether corticosteroid sensitivity cells reduced compared controls, and also evaluate degree between individual drug response.
Rationale: ADAM8 (a disintegrin and metalloproteinase domain-8) is expressed by leukocytes epithelial cells in health, but its contribution to the pathogenesis of chronic obstructive pulmonary disease (COPD) unknown.Objectives: To determine whether expression increased lungs patients with COPD cigarette smoke (CS)-exposed mice, promotes development COPD.Methods: levels were measured lung, sputum, plasma, and/or BAL fluid samples from COPD, smokers, nonsmokers, wild-type (WT) mice exposed CS...
Proteinases with a disintegrin and metalloproteinase domain (ADAMs) have not been well studied in COPD. We investigated whether ADAM9 is linked to COPD humans mice.
Emerging data from clinical studies have shown pro-inflammatory effects associated with e-cigarette use. Fractional exhaled nitric oxide (FeNO) is a biomarker of pulmonary type 2 (T2) inflammation. The effect chronic use on FeNO unclear. aim this study was to compare levels in COPD ex-smokers who e-cigarettes (COPDE + e-cig) COPDE (COPDE) and current smokers (COPDS). were significantly higher e-cig (median 16.2 ppb) 18.0 compared COPDS 7.6 (p = 0.0003 p < 0.0001 respectively). There no...
Abstract The numbers of macrophages are increased in the lungs chronic obstructive pulmonary disease (COPD) patients. COPD lung have reduced ability to phagocytose microbes and efferocytose apoptotic cells. Inhaled corticosteroids (ICSs) widely used anti-inflammatory drugs COPD; however, their role beyond suppression cytokine release has not been explored macrophages. We examined effects on macrophage phenotype function. Lung from controls patients were treated with corticosteroids; gene...
A subset of chronic obstructive pulmonary disease (COPD) patients have increased numbers airway eosinophils associated with elevated markers T2 inflammation. This analysis focussed on mast cell counts and cell-related gene expression in COPD higher vs lower eosinophil counts.We investigated tryptase (TPSAB1), carboxypeptidase A3 (CPA3), chymase (CMA1) two specific signatures; a bronchial biopsy signature (MCbb) an IgE (MCIgE) using sputum cells epithelial brushings. Gene was conducted by...
Inhaled corticosteroids (ICS) prevent chronic obstructive pulmonary disease (COPD) exacerbations [1]. Randomised controlled trials (RCTs) have shown that higher blood eosinophil counts (BEC) are associated with better clinical responses to ICS treatment in COPD patients a history of The Global initiative for lung (GOLD) report recommends using BEC identify individuals most likely benefit from Higher increased type-2 (T2) inflammation [2–4], potentially explaining the differential response...
Poor asthma control is associated with increased airway neutrophils. Leukotriene B4 (LTB4) a potent neutrophil chemoattractant. We examined the levels of LTB4 in sputum patients and relationship disease severity. 47 (categorised according to Global Initiative for Asthma treatment stage) 12 healthy controls provided samples that were processed first PBS obtain supernatants secondly dithiothreitol (DTT) supernatants. determined by ELISA. significantly higher step 1 (steroid naïve) 3 (inhaled...