Publications
2498 results found
Jenkins CR, Wen F-Q, Martin A, et al., 2021, The effect of low-dose corticosteroids and theophylline on the risk of acute exacerbations of COPD: the TASCS randomised controlled trial, EUROPEAN RESPIRATORY JOURNAL, Vol: 57, ISSN: 0903-1936
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- Citations: 19
Wada H, Nakamura M, Inoue S-I, et al., 2021, Dual interleukin-17A/F deficiency protects against acute and chronic response to cigarette smoke exposure in mice, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322
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- Citations: 2
Singh R, Belchamber K, Fenwick P, et al., 2021, Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD, Respiratory Research, Vol: 22, Pages: 1-11, ISSN: 1465-9921
BackgroundLower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline. Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters.MethodsMonocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR.ResultsPhagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 103 RFU vs. 2.5 × 103 RFU, p < 0.01). There was no correlation for S. pneumoniae. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state.ConclusionImpaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.
FitzGerald JM, O'Byrne PM, Bateman ED, et al., 2021, Safety of As-Needed Budesonide-Formoterol in Mild Asthma: Data from the Two Phase III SYGMA Studies, DRUG SAFETY, Vol: 44, Pages: 467-478, ISSN: 0114-5916
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- Citations: 5
Barnes PJ, Anderson GP, Fageras M, et al., 2021, Chronic lung diseases: prospects for regeneration and repair, EUROPEAN RESPIRATORY REVIEW, Vol: 30, ISSN: 0905-9180
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- Citations: 9
Siddharthan T, Pollard SL, Jackson P, et al., 2021, Effectiveness of low-dose theophylline for the management of biomass-associated COPD (LODOT-BCOPD): study protocol for a randomized controlled trial, TRIALS, Vol: 22
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- Citations: 2
Barnes PJ, 2021, Targeting cellular senescence as a new approach to chronic obstructive pulmonary disease therapy, CURRENT OPINION IN PHARMACOLOGY, Vol: 56, Pages: 68-73, ISSN: 1471-4892
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- Citations: 8
O'Byrne PM, FitzGerald JM, Bateman ED, et al., 2021, Effect of a single day of increased as-needed budesonide-formoterol use on short-term risk of severe exacerbations in patients with mild asthma: a post-hoc analysis of the SYGMA 1 study, LANCET RESPIRATORY MEDICINE, Vol: 9, Pages: 149-158, ISSN: 2213-2600
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- Citations: 39
Wada H, Ikeda A, Maruyama K, et al., 2021, Low BMI and weight loss aggravate COPD mortality in men, findings from a large prospective cohort: the JACC study, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322
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- Citations: 20
Kono Y, Colley T, To M, et al., 2021, Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322
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- Citations: 14
Barnes PJ, 2021, Endo-phenotyping of COPD patients, EXPERT REVIEW OF RESPIRATORY MEDICINE, Vol: 15, Pages: 27-37, ISSN: 1747-6348
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- Citations: 12
Lightley J, Görlitz F, Kumar S, et al., 2021, ROBUST OPTICAL AUTOFOCUS SYSTEM UTILIZING NEURAL NETWORKS APPLIED TO AUTOMATED MULTIWELL PLATE STORM MICROSCOPY, ISSN: 1605-7422
We present a robust, low-cost neural network-based optical autofocus system that can operate over a range of ±100µm with submicron precision, enabling automated high-content super-resolved imaging with a 1.3 NA objective lens.
Clarke S, Barnes P, 2021, Inflammatory and Immune Mechanisms in COPD, Encyclopedia of Respiratory Medicine, Second Edition, Pages: 549-558, ISBN: 9780081027233
Environmental insults, notably cigarette smoke, activate both innate and adaptive immune pathways to drive the inflammation that characterizes chronic obstructive pulmonary disorder (COPD). This article looks at the reasons why, in some individuals, the inflammatory response is exaggerated and persistent, causing irreversible airway and parenchymal damage, as well as the inflammatory cells and mediators that orchestrate this process.
Barnes PJ, 2021, Accelerated Lung Aging and Cellular Senescence in COPD, Encyclopedia of Respiratory Medicine, Second Edition, Pages: 583-593, ISBN: 9780081027233
Cellular senescence, when cells stop dividing, is a key feature of cell aging and may play an important role in the progression of COPD. Senescent cells accumulate in the lungs of COPD patients and release a variety of inflammatory proteins, cause fibrosis of small airways, and defective tissue repair leading to emphysema. The molecular pathways that lead to senescence and a loss of anti-aging molecules, such as sirtuins, are now better understood. Senescence may spread via microRNAs in extracellular vesicles, resulting in comorbidities. Identification of senescence mechanisms may result in new therapies (senotherapies), including senostatics that inhibit these pathways and senolytics that remove senescent cells. Understanding the pathways that lead to cellular senescence in COPD lungs may lead to new treatments that may reduce disease progression, mortality and comorbidities.
Barnes PJ, 2021, Other Drugs for Asthma and COPD, Encyclopedia of Respiratory Medicine, Second Edition, Pages: 729-740, ISBN: 9780081027233
In addition to β2-agonists, anticholinergics and corticosteroids, several other classes of drug are used in the treatment of asthma and COPD. These include cromones in asthma patients, antagonists or inhibitors of various inflammatory mediators (histamine, leukotrienes), theophylline and other methylxanthines, selective phosphodiesterase inhibitors, immunomodulators (such as methotrexate, gold, cyclosporin), specific immunotherapy for allergic asthma and mucoregulators, particularly in COPD. Overall, these drugs are less effective than the major classes of inhaled drug and often have side effects that limit their dose if the drugs are given systemically. Some recent developments of drugs that are close to approval are also discussed.
Barnes PJ, Adcock IM, Mumby S, et al., 2021, Asthmatic patients, Supporting Tobacco Cessation, Publisher: European Respiratory Society, Pages: 136-153
Lightley J, Gorlitz F, Kumar S, et al., 2021, ROBUST OPTICAL AUTOFOCUS SYSTEM UTILIZING NEURAL NETWORKS APPLIED TO AUTOMATED MULTIWELL PLATE STORM MICROSCOPY, European Conferences on Biomedical Optics - Advances in Microscopic Imaging III, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X
Adeloye D, Agarwal D, Barnes PJ, et al., 2021, Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade, JOURNAL OF GLOBAL HEALTH, Vol: 11, ISSN: 2047-2978
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- Citations: 10
Perez E, Baker JR, Di Giandomenico S, et al., 2020, Hepcidin Is Essential for Alveolar Macrophage Function and Is Disrupted by Smoke in a Murine Chronic Obstructive Pulmonary Disease Model, JOURNAL OF IMMUNOLOGY, Vol: 205, Pages: 2489-+, ISSN: 0022-1767
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- Citations: 9
Barnes PJ, 2020, COPD 2020: new directions needed, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 319, Pages: L884-L886, ISSN: 1040-0605
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- Citations: 20
Zhu J, Mallia P, Footitt J, et al., 2020, Bronchial mucosal inflammation and illness severity in response to experimental rhinovirus infection in COPD, Journal of Allergy and Clinical Immunology, Vol: 146, Pages: 840-850.e7, ISSN: 0091-6749
BackgroundRespiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in patients with COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity.ObjectivesWe sought to determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16–induced COPD exacerbations and its relationship to disease severity.MethodsBronchial mucosal inflammatory cell phenotypes were determined at preinfection baseline and following experimental RV infection in 17 Global Initiative for Chronic Obstructive Lung Disease stage II subjects with COPD and as controls 20 smokers and 11 nonsmokers with normal lung function. No subject had a history of asthma/allergic rhinitis: all had negative results for aeroallergen skin prick tests.ResultsRV infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8+ T lymphocytes in patients with COPD and nonsmokers. Monocytes/macrophages, CD4+ T lymphocytes, and CD20+ B lymphocytes were increased in all subjects. At baseline, compared with nonsmokers, subjects with COPD and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8+ T lymphocytes but fewer numbers of CD4+ T lymphocytes and CD20+ B lymphocytes. The virus-induced inflammatory cells in patients with COPD were positively associated with virus load, illness severity, and reductions in lung function.ConclusionsExperimental RV infection induces bronchial mucosal eosinophilia and neutrophilia only in patients with COPD and monocytes/macrophages and lymphocytes in both patients with COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load and illness severity. Antiviral/anti-inflamma
Cloonan SM, Kim K, Esteves P, et al., 2020, Mitochondrial dysfunction in lung ageing and disease, EUROPEAN RESPIRATORY REVIEW, Vol: 29, ISSN: 0905-9180
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- Citations: 39
Delbrel E, Wrench C, Fenwick P, et al., 2020, Endoplasmic reticulum stress implication in senescence of small airway fibroblasts from COPD patients, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Biddiscombe M, Matthews J, Wright M, et al., 2020, No evidence electric charge increases inhaled ultrafine particle deposition in human lungs, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Wysoczanski R, Baker JR, Fenwick P, et al., 2020, Analysis of defective phagocytosis in COPD using super-resolution microscopy and automated bacterial quantification, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Baker JR, Fenwick PS, Donnelly L, et al., 2020, Altered iron metabolism and elevated cellular senescence in COPD small airway epithelial cells, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 2
Bateman ED, Fitzgerald JM, Reddel HK, et al., 2020, Efficacy of as-needed budesonide/formoterol in mild asthma: pooled analysis of SYGMA 1 and 2, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Devulder J, Baker JR, Donnelly LE, et al., 2020, LSC-2020-Extracellular vesicles produced by bronchial epithelial cells in response to oxidative stress contain micro-RNAs associated with senescence, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Mauvais-Jarvis F, Merz NB, Barnes PJ, et al., 2020, Sex and gender: modifiers of health, disease, and medicine, LANCET, Vol: 396, Pages: 565-582, ISSN: 0140-6736
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- Citations: 676
Fukuda Y, Akimoto K, Homma T, et al., 2020, Virus-Induced Asthma Exacerbations: SIRT1 Targeted Approach, JOURNAL OF CLINICAL MEDICINE, Vol: 9
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- Citations: 8
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