Publications
2499 results found
Dekhuijzen PNR, Levy ML, Corrigan CJ, et al., 2022, Is Inhaler Technique Adequately Assessed and Reported in Clinical Trials of Asthma and Chronic Obstructive Pulmonary Disease Therapy? A Systematic Review and Suggested Best Practice Checklist, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 10, Pages: 1813-+, ISSN: 2213-2198
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- Citations: 3
Barnes PJ, 2022, Chemokine receptor CCR1: new target for asthma therapy, TRENDS IN PHARMACOLOGICAL SCIENCES, Vol: 43, Pages: 539-541, ISSN: 0165-6147
Devulder J, Baker JR, Odqvist L, et al., 2022, Transfer of microRNA Through Extracellular Vesicles Propagate Airway Epithelial Cells Senescence in COPD, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Baker JR, Fenwick PS, Koss CK, et al., 2022, Inhibition of the IL-36 Receptor Reduces Viral Induced Cross-Talk Between Small Airway Epithelial Cells and Fibroblast in COPD, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Fenwick P, Baker JR, Koss CK, et al., 2022, TRPV4 Identifies Phagocytic Macrophages and May Promote Phagocytosis in Both Healthy and COPD Cells, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Hassibi S, Baker JR, Barnes PJ, et al., 2022, COPD Macrophages Show Reduced Clearance of Senescent Airway Epithelial Cells, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Wysoczanski R, Baker JR, Fenwick P, et al., 2022, Defective Phagocytosis in COPD Macrophages Is Improved by Mitochondrial Antioxidants Without Alteration in Mitochondrial Function, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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- Citations: 1
Ho V, Baker JR, Willison KR, et al., 2022, Novel Single Cell Analysis of microRNA Levels in Response to Oxidative Stress and in COPD Using Microfluidic Technology, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Barnes PJ, Baker J, Donnelly LE, 2022, Autophagy in asthma and chronic obstructive pulmonary disease, CLINICAL SCIENCE, Vol: 136, Pages: 733-746, ISSN: 0143-5221
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- Citations: 13
Barnes PJ, 2022, Oxidative Stress in Chronic Obstructive Pulmonary Disease, ANTIOXIDANTS, Vol: 11
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- Citations: 36
Baker JR, Mahdi M, Nicolau DV, et al., 2022, Early Th2 inflammation in the upper respiratory mucosa as a predictor of severe COVID-19 and modulation by early treatment with inhaled corticosteroids: a mechanistic analysis., The Lancet Respiratory Medicine, ISSN: 2213-2600
BACKGROUND: Community-based clinical trials of the inhaled corticosteroid budesonide in early COVID-19 have shown improved patient outcomes. We aimed to understand the inflammatory mechanism of budesonide in the treatment of early COVID-19. METHODS: The STOIC trial was a randomised, open label, parallel group, phase 2 clinical intervention trial where patients were randomly assigned (1:1) to receive usual care (as needed antipyretics were only available treatment) or inhaled budesonide at a dose of 800 μg twice a day plus usual care. For this experimental analysis, we investigated the nasal mucosal inflammatory response in patients recruited to the STOIC trial and in a cohort of SARS-CoV-2-negative healthy controls, recruited from a long-term observational data collection study at the University of Oxford. In patients with SARS-CoV-2 who entered the STOIC study, nasal epithelial lining fluid was sampled at day of randomisation (day 0) and at day 14 following randomisation, blood samples were also collected at day 28 after randomisation. Nasal epithelial lining fluid and blood samples were collected from the SARS-CoV-2 negative control cohort. Inflammatory mediators in the nasal epithelial lining fluid and blood were assessed for a range of viral response proteins, and innate and adaptive response markers using Meso Scale Discovery enzyme linked immunoassay panels. These samples were used to investigate the evolution of inflammation in the early COVID-19 disease course and assess the effect of budesonide on inflammation. FINDINGS: 146 participants were recruited in the STOIC trial (n=73 in the usual care group; n=73 in the budesonide group). 140 nasal mucosal samples were available at day 0 (randomisation) and 122 samples at day 14. At day 28, whole blood was collected from 123 participants (62 in the budesonide group and 61 in the usual care group). 20 blood or nasal samples were collected from healthy controls. In early COVID-19 disease, there was an enhanced in
Barnes PJ, 2022, INHALED THERAPIES FOR COVID-19, Publisher: MARY ANN LIEBERT, INC, Pages: A2-A2, ISSN: 1941-2711
Paschalaki K, Rossios C, Pericleous C, et al., 2022, Inhaled corticosteroids reduce senescence in endothelial progenitor cells from COPD patients, Thorax, Vol: 77, ISSN: 0040-6376
Cellular senescence contributes to the pathophysiology of chronic obstructive pulmonarydisease (COPD) and cardiovascular disease. Using endothelial-colony-forming-cells (ECFC),we have demonstrated accelerated senescence in smokers and COPD patients compared tonon-smokers. Subgroup analysis suggests that ECFC from COPD patients on inhaledcorticosteroids (ICS) (n=14; 8 on ICS) exhibited significantly reduced senescence(Senescence-associated-beta galactosidase activity, p21CIP1), markers of DNA damageresponse (DDR) and IFN-γ-inducible-protein-10 compared to COPD patients not on ICS. Invitro studies using human-umbilical-vein-endothelial-cells showed a protective effect of ICSon the DDR, senescence and apoptosis caused by oxidative-stress, suggesting a protectivemolecular mechanism of action of corticosteroids on endothelium.
Bradbury T, Di Tanna GL, Scaria A, et al., 2022, Blood Eosinophils in Chinese COPD Participants and Response to Treatment with Combination Low-Dose Theophylline and Prednisone: A Post-Hoc Analysis of the TASCS Trial, INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Vol: 17, Pages: 273-282, ISSN: 1178-2005
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- Citations: 1
Koss CK, Wohnhaas CT, Baker JR, et al., 2021, IL36 is a critical upstream amplifier of neutrophilic lung inflammation in mice, Communications Biology, Vol: 4, Pages: 1-15, ISSN: 2399-3642
IL-36, which belongs to the IL-1 superfamily, is increasingly linked to neutrophilic inflammation. Here, we combined in vivo and in vitro approaches using primary mouse and human cells, as well as, acute and chronic mouse models of lung inflammation to provide mechanistic insight into the intercellular signaling pathways and mechanisms through which IL-36 promotes lung inflammation. IL-36 receptor deficient mice exposed to cigarette smoke or cigarette smoke and H1N1 influenza virus had attenuated lung inflammation compared with wild-type controls. We identified neutrophils as a source of IL-36 and show that IL-36 is a key upstream amplifier of lung inflammation by promoting activation of neutrophils, macrophages and fibroblasts through cooperation with GM-CSF and the viral mimic poly(I:C). Our data implicate IL-36, independent of other IL-1 family members, as a key upstream amplifier of neutrophilic lung inflammation, providing a rationale for targeting IL-36 to improve treatment of a variety of neutrophilic lung diseases.
Bateman ED, O'Byrne PM, FitzGerald JM, et al., 2021, Positioning As-needed Budesonide-Formoterol for Mild Asthma Effect of Prestudy Treatment in Pooled Analysis of SYGMA 1 and 2, ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 18, Pages: 2007-2017, ISSN: 1546-3222
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- Citations: 9
Maneechotesuwan K, Kasetsinsombat K, Wongkajornsilp A, et al., 2021, Role of autophagy in regulating interleukin-10 and the responses to corticosteroids and statins in asthma, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 1553-1565, ISSN: 0954-7894
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- Citations: 18
Adeloye D, Elneima O, Daines L, et al., 2021, The long-term sequelae of COVID-19: an international consensus on research priorities for patients with pre-existing and new-onset airways disease, LANCET RESPIRATORY MEDICINE, Vol: 9, Pages: 1467-1478, ISSN: 2213-2600
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- Citations: 62
Reddel HK, O'Byrne PM, FitzGerald JM, et al., 2021, Reply to "As-needed budesonideformoterol for adolescents with mild asthma: importance of lung function'', JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 9, Pages: 4179-4180, ISSN: 2213-2198
Baker JR, Mahdi M, Nicolau DV, et al., 2021, Dampening of the respiratory cytokine storm is promoted by inhaled budesonide in patients with early COVID-19
<jats:title>Summary</jats:title><jats:p>Vaccinations against SARS-CoV-2 are effective in COVID-19. However, with limited vaccine access, vaccine hesitancy and variant breakthroughs, there is still a need for effective and safe early treatments. Two community-based clinical trials of the inhaled corticosteroid, budesonide, have recently been published showing and improvement in patients with COVID-19 treated early with budesonide<jats:sup>1,2</jats:sup>. To understand mechanistically how budesonide was beneficial, inflammatory mediators were assessed in the nasal mucosa of patients recruited to the Steroids in COVID (STOIC<jats:sup>1</jats:sup>) trial and a cohort of SARS-CoV-2 negative individuals. Here we show that in early COVID-19, elevation in viral response proteins and Th1 and Th2 inflammation occurs. Longitudinal sampling in the natural course of COVID-19 showed persistently high interferon levels and elevated concentrations of the eosinophil chemokine, CCL11. In patients who deteriorate, the initial nasal mucosal signal is characterised by a marked suppression of the early inflammatory response, with reduced concentrations of interferon and inflammatory cytokines, but elevated eosinophil chemokines. Systemic inflammation remained altered in COVID-19 patients, implying that even after symptom resolution, changes in immunological mediators do not resolve. Budesonide treatment decreased IL-33 and IFN-γ, implying a reduction in epithelial damage and dampening of the interferon response. Budesonide treatment also increased CCL17 concentrations, suggesting an improved T-cell response; and significantly alters inflammatory pathways giving further insight into how this treatment can accelerate patient recovery.</jats:p><jats:sec><jats:title>Abstract Figure</jats:title><jats:fig id="ufig1" position="float" fig-type="figure" orientation="portrait"><
Hassibi S, Baker J, Barnes P, et al., 2021, Generating senescent airway epithelial cell populations using low-concentration doxorubicin or etoposide, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Paschalaki K, Evangelou K, Veroutis D, et al., 2021, Alveolar type II cells harbouring SARS-CoV-2 show senescence with a proinflammatory phenotype, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Baker JR, Fenwick PS, Owles HB, et al., 2021, IL-36? - a key mediator of neutrophilic inflammation in chronic obstructive pulmonary disease, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Ho V, Willison K, Baker J, et al., 2021, Microfluidic single cell analysis of microRNA levels in small airway epithelial cells and fibroblasts from COPD patients, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Devulder J, Baker JR, Donnelly LE, et al., 2021, Extracellular vesicles produced by airway epithelial cells in response to oxidative stress contain microRNAs associated with cellular senescence, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Ramakrishnan S, Nicolau DV, Langford B, et al., 2021, Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Wysoczanski R, Baker J, Fenwick P, et al., 2021, Image analysis of tissue macrophages to confirm differential phagocytosis between groups by microscopy and automated bacterial quantification, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Yu L-M, Bafadhel M, Dorward J, et al., 2021, Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial, LANCET, Vol: 398, Pages: 843-855, ISSN: 0140-6736
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- Citations: 114
Reddel HK, O'Byrne PM, FitzGerald JM, et al., 2021, Efficacy and Safety of As-Needed Budesonide-Formoterol in Adolescents with Mild Asthma, International Conference of the American-Thoracic-Society, Publisher: ELSEVIER, Pages: 3069-+, ISSN: 2213-2198
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- Citations: 13
Norwitz NG, Winwood R, Stubbs BJ, et al., 2021, Case Report: Ketogenic Diet Is Associated With Improvements in Chronic Obstructive Pulmonary Disease, FRONTIERS IN MEDICINE, Vol: 8
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- Citations: 1
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