A5056795918- Asthma and respiratory diseases
- Allergic Rhinitis and Sensitization
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Respiratory and Cough-Related Research
- Pediatric health and respiratory diseases
- Inhalation and Respiratory Drug Delivery
- IL-33, ST2, and ILC Pathways
- Respiratory viral infections research
- Eosinophilic Esophagitis
- Eosinophilic Disorders and Syndromes
- Immune Cell Function and Interaction
- Food Allergy and Anaphylaxis Research
- Neonatal Respiratory Health Research
- Dermatology and Skin Diseases
- Respiratory Support and Mechanisms
- Cell Adhesion Molecules Research
- Urticaria and Related Conditions
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Receptor Mechanisms and Signaling
- Diagnosis and treatment of tuberculosis
- Pharmaceutical studies and practices
- Tuberculosis Research and Epidemiology
- Cytokine Signaling Pathways and Interactions
Imperial College London
2013-2025
Lung Institute
2003-2025
Asthma UK
2013-2023
Medical Research Council
2017-2023
British Lung Foundation
2021
Royal Brompton & Harefield NHS Foundation Trust
2020
St Mary's Hospital
2006-2019
Northwestern University
2018
St. Mary’s Hospital
2016-2018
St Mary's Hospital
2010-2018
Activation of lymphocyte subpopulations was determined in conjunction with levels cytokines peripheral blood and bronchoalveolar lavage (BAL) asthmatics. Allergic asthmatics had increased numbers CD4+ IL-2R+ T cells BAL, T-cell activation closely correlated low-affinity IgE receptor (CD23) bearing B cells. In contrast, nonallergic both CD8+ from BAL expression IL-2R, HLA-DR, VLA-1. Furthermore, the were decreased but BAL. Cytokine fluid supernatants purified enriched preparations....
Accumulation of eosinophils in the bronchial mucosa individuals with asthma is considered to be a central event pathogenesis asthma. In animal models, airway eosinophil recruitment and hyperresponsiveness response allergen challenge are reduced by specific targeting interleukin-5. A previous small dose-finding study found that mepolizumab, humanized anti-interleukin-5 monoclonal antibody, had no effect on humans.To investigate three intravenous infusions 250 or 750 mg at monthly intervals,...
The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, whom 57% became infected. Mucosal neutrophil activation before was highly predictive symptomatic RSV disease. This associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed IL-17- tumor necrosis factor-related pathways. Vulnerability not baseline...
The use of noninvasive methods monitoring airway inflammation, such as exhaled nitric oxide (eNO) and induced sputum, has been shown to improve asthma optimize treatment in adult patients with asthma. There is a lack comparable data children. Forty children stable eligible for inhaled steroid reduction were reviewed every 8 weeks, their dose halved if clinically indicated. eNO, sputum induction combined bronchial hyperreactivity testing, breath condensate collection performed at each visit...
Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In present study we investigated distribution leukocytes, lymphocyte subsets, their activation state, and cytokine profile BAL fluid from patients with various lung diseases associated eosinophilia. For this purpose, analyzed levels IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, IFN-gamma, as well soluble IL-2 TNF receptors, concentrated bronchoalveolar lavage (BAL)...
Rationale: Neutralization of tumor necrosis factor-α (TNF-α) is an effective antiinflammatory therapy for several chronic inflammatory diseases.Methods and Objectives: We undertook a double-blind, placebo-controlled, parallel-group design study in 38 patients with moderate asthma treated inhaled corticosteroids but symptomatic during run-in phase. Infliximab (5 mg/kg) or placebo was administered by intravenous infusion at Weeks 0, 2, 6. assessed clinical response monitoring lung function,...
The inducible isoenzyme of nitric oxide synthase (iNOS) generates (NO) in inflammatory diseases such as asthma. prodrug L-N6-(1-iminoethyl)lysine 5-tetrazole amide (SC-51) is rapidly converted vivo to the active metabolite (L-NIL). Initially, we performed vitro experiments human primary airway epithelial cells demonstrate that L-NIL causes inhibition iNOS. In a randomized double-blind placebo-controlled crossover trial, SC-51 was administered single oral dose (20 or 200 mg) separate cohorts...
Cilomilast (Ariflo), a new oral phosphodiesterase-4 selective inhibitor, improves lung function in chronic obstructive pulmonary disease (COPD). We have evaluated its antiinflammatory effects 59 patients with COPD randomized to receive cilomilast, 15 mg two times day, or placebo for 12 weeks. Induced sputum differential cell counts were obtained at baseline and five further visits. Interleukin-8 neutrophil elastase measured supernatant. Bronchial biopsies Week 10 immunostained counted...
Skeletal muscle depletion is an important complication of chronic obstructive pulmonary disease (COPD) but little prospective data exists about the rate at which it occurs and factors that promote its development. We therefore prospectively investigated impact severity, exacerbation frequency treatment with corticosteroids on change in body composition maximum isometric quadriceps strength (QMVC) over one year.64 patients stable COPD (FEV1 mean (SD) 35.8(18.4) %predicted) were recruited from...
Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease believed to result from uncontrolled viral replication, an excessive immune response, or both.To determine RSV load mediator levels nasal mucosal lining fluid by serial sampling fluids cases moderate severe over the course infection.Infants with necessitating admission (n = 55) were recruited pediatric center during 2016 2017. Of these, 30 infected (18 "moderate" 12...
Abstract Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing children, but a correlate protection for LAIV remains unclear. Studying young adult volunteers, we observe induces distinct, compartmentalized, antibody mucosa blood. Seeking immunologic correlates these distinct...
Rationale: Children with severe asthma experience persistent symptoms despite maximal conventional treatment. Fraction of exhaled nitric oxide (FeNO) and sputum eosinophils are used as markers airway inflammation to guide treatment steroids, but no data available on how reliable they in predicting eosinophilia assessed bronchoscopically these children.Objectives: To determine FeNO predict measured both bronchoalveolar lavage (BAL) endobronchial biopsy.Methods: Twenty-seven children moderate...
Sputum from symptomatic asthmatics is a rich source of eosinophils the respiratory tract. Following liquefaction sputum with dithioerythritol (DTE), cell suspension for indirect double immunofluorescence flow cytometry was obtained. Eosinophils were identified using anti-CD9 fluorescein conjugate, and particular surface markers measured relevant mouse MoAb followed by goat anti-mouse immunoglobulin phycoerythrin conjugate. Blood eosinophil determined in parallel not receiving steroid...
Abstract We present evidence that human blood eosinophils produce interleukin (IL)‐8 when stimulated with calcium ionophore. Following in vitro culture of 99 % pure ionophore, released IL‐8 was detectable by enzymelinked immunosorbent assay supernatants. Eosinophil production considerably greater than IL‐3 or granulocyte macrophage colony‐stimulating factor. Furthermore, eosinophil the presence ionophore could be inhibited immunomodulating agent cyclosporin A and protein synthesis inhibitor...