2206 results found
Barnes PJ, 2019, Inflammatory Endotypes in COPD., Allergy
Chronic obstructive pulmonary disease (COPD) is a major global health problem that is poorly treated by current therapies as it has proved difficult to treat the underlying inflammation, which is largely corticosteroid-resistant in most patients. Although rare genetic endotypes of COPD have been recognised, despite the clinical heterogeneity of COPD it has proved difficult to identify distinct inflammatory endotypes. Most patients have increased neutrophils and macrophages in sputum, reflecting the increased secretion of neutrophil and monocyte chemotactic mediators in the lungs. However, some patients also have increased eosinophils in sputum and this may be reflected by increased blood eosinophils. Increased blood and sputum eosinophils are associated with more frequent exacerbations and predict a good response to corticosteroids in reducing and treating acute exacerbations. Eosinophilic COPD may represent an overlap with asthma but the mechanism of eosinophilia are uncertain as, although an increase in sputum IL-5 has been detected, anti-IL-5 therapies are not effective in preventing exacerbations. More research is needed to link inflammatory endotypes to clinical manifestations and outcomes in COPD and in particular to predict response to precision medicines. This article is protected by copyright. All rights reserved.
Hakim A, Khan Y, Esteban I, et al., 2019, Low-Dose Budesonide/Formoterol Counteracts Airway Inflammation and Improves Lung Function in Chronic Obstructive Pulmonary Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 199, Pages: 662-664, ISSN: 1073-449X
Jia M, Yan X, Jiang X, et al., 2019, Ezrin, a Membrane Cytoskeleton Cross-Linker Protein, as a Marker of Epithelial Damage in Asthma, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 199, Pages: 496-507, ISSN: 1073-449X
Baker JR, Vuppusetty C, Colley T, et al., 2019, MicroRNA-570 is a novel regulator of cellular senescence and inflammaging, FASEB JOURNAL, Vol: 33, Pages: 1605-1616, ISSN: 0892-6638
Ghosh B, Gaike AH, Pyasi K, et al., 2019, Bacterial load and defective monocyte-derived macrophage bacterial phagocytosis in biomass smoke-related COPD., Eur Respir J, Vol: 53
Lower airway colonisation with species of potentially pathogenic bacteria (PPB) is associated with defective bacterial phagocytosis, in monocyte-derived macrophages (MDMs) and alveolar macrophages, from tobacco smoke-associated chronic obstructive pulmonary disease (S-COPD) subjects. In the developing world, COPD among nonsmokers is largely due to biomass smoke (BMS) exposure; however, little is known about PPB colonisation and its association with impaired innate immunity in these subjects.We investigated the PPB load (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas aeruginosa) in BMS-exposed COPD (BMS-COPD) subjects compared with S-COPD and spirometrically normal subjects. We also examined the association between PPB load and phagocytic activity of MDMs and lung function. Induced sputum and peripheral venous blood samples were collected from 18 healthy nonsmokers, 15 smokers without COPD, 16 BMS-exposed healthy subjects, 19 S-COPD subjects and 23 BMS-COPD subjects. PPB load in induced sputum and MDM phagocytic activity were determined using quantitative PCR and fluorimetry, respectively.Higher bacterial loads of S. pneumoniae, H. influenzae and P. aeruginosa were observed in BMS-COPD subjects. Increased PPB load in BMS-exposed subjects was significantly negatively associated with defective phagocytosis in MDMs and spirometric lung function indices (p<0.05).Increased PPB load in airways of BMS-COPD subjects is inversely associated with defective bacterial phagocytosis and lung function.
Criner GJ, Martinez FJ, Aaron S, et al., 2019, Current Controversies in Chronic Obstructive Pulmonary Disease A Report from the Global Initiative for Chronic Obstructive Lung Disease Scientific Committee, ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 16, Pages: 29-39, ISSN: 1546-3222
Izuhara K, Barnes PJ, 2019, Can We Define Asthma-COPD Overlap (ACO) by Biomarkers?, J Allergy Clin Immunol Pract, Vol: 7, Pages: 146-147
Barnes PJ, 2018, THERAPY FOR ASTHMA AND COPD, Publisher: BMJ PUBLISHING GROUP, Pages: A2-A3, ISSN: 0032-5473
Dunne AE, Kawamatawong T, Fenwick PS, et al., 2018, Direct Inhibitory Effect of the Phosphodiesterase-4 Inhibitor, Roflumilast, on Neutrophil Migration in COPD., Am J Respir Cell Mol Biol
Neutrophilic inflammation is characteristic of COPD, yet there are no effective anti-inflammatory therapies. The phosphodiesterase (PDE)4 inhibitor, roflumilast is approved for use in COPD and suppresses sputum neutrophilia. The mechanism underlying this observation is unclear and therefore this study addressed whether roflumilast directly affected neutrophil migration. Blood-derived neutrophils were isolated from non-smokers, smokers and COPD patients and chemotaxis measured using Boyden chambers. Intracellular calcium ion concentration ([Ca2+]i) was measured by fluorimetry and shape change and CD11b expression by flow cytometry. Neutrophils from COPD patients showed enhanced chemotactic responses towards both CXCL1 and LTB4 compared with control cells. Chemotaxis was inhibited by both the active metabolite, roflumilast-N-oxide, and rolipram in a concentration-dependent manner with no difference in responsiveness between subjects. Roflumilast-N-oxide and rolipram were less efficacious against CXCL1 and LTB4-mediated [Ca2+]i suggesting that inhibition was not via this pathway. Both PDE4 inhibitors attenuated chemoattractant-mediated shape change and CD11b up-regulation suggesting common mechanisms. The stable cAMP analogue, 8-Br-cAMP, inhibited chemotaxis, as did the direct Epac1 activator 8-pCPT-2'-O-Me-cAMP but not the direct PKA activator, 6-Bnz-cAMP. These data suggest that roflumilast inhibits neutrophil chemotaxis directly via a cAMP-mediated mechanism requiring activation of Epac1, and that Epac1 activators could reduce COPD neutrophilic inflammation.
Carpagnano GE, Scioscia G, Lacedonia D, et al., 2018, Looking for Airways Periostin in Severe Asthma Could It Be Useful for Clustering Type 2 Endotype?, CHEST, Vol: 154, Pages: 1083-1090, ISSN: 0012-3692
Devereux G, Cotton S, Fielding S, et al., 2018, Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD A Randomized Clinical Trial, JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, Vol: 320, Pages: 1548-1559, ISSN: 0098-7484
Cazzola M, Calzetta L, Barnes PJ, et al., 2018, Efficacy and safety profile of xanthines in COPD: a network meta-analysis, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
O'Byrne P, Fitzgerald JM, Bateman ED, et al., 2018, Late Breaking Abstract - Risk of a severe exacerbation following higher reliever use: post-hoc analysis of SYGMA 1 in mild asthma, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Bewley MA, Budd RC, Ryan E, et al., 2018, Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease Is Enhanced by Nrf2 Agonists, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 198, Pages: 739-750, ISSN: 1073-449X
Mallia P, Webber J, Gill SK, et al., 2018, Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 142, Pages: 815-+, ISSN: 0091-6749
Maneechotesuwan K, Yao X, Ito K, et al., 2018, Correction: Suppression of GATA-3 Nuclear Import and Phosphorylation: A Novel Mechanism of Corticosteroid Action in Allergic Disease., PLoS Med, Vol: 15
[This corrects the article DOI: 10.1371/journal.pmed.1000076.].
Pelleg A, Schulman ES, Barnes PJ, 2018, Adenosine 5 '-triphosphate's role in bradycardia and syncope associated with pulmonary embolism, RESPIRATORY RESEARCH, Vol: 19, ISSN: 1465-993X
Dai Y, Yeo SCM, Barnes PJ, et al., 2018, Pre-clinical Pharmacokinetic and Metabolomic Analyses of Isorhapontigenin, a Dietary Resveratrol Derivative, FRONTIERS IN PHARMACOLOGY, Vol: 9, ISSN: 1663-9812
Barnes PJ, 2018, Targeting cytokines to treat asthma and chronic obstructive pulmonary disease, NATURE REVIEWS IMMUNOLOGY, Vol: 18, Pages: 454-466, ISSN: 1474-1733
Cazzola M, Calzetta L, Barnes PJ, et al., 2018, Efficacy and safety profile of xanthines in COPD: a network meta-analysis, EUROPEAN RESPIRATORY REVIEW, Vol: 27, ISSN: 0905-9180
O'Byrne PM, FitzGerald JM, Bateman ED, et al., 2018, Inhaled Combined Budesonide-Formoterol as Needed in Mild Asthma, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 378, Pages: 1865-1876, ISSN: 0028-4793
Bateman ED, Reddel HK, O'Byrne PM, et al., 2018, As-Needed Budesonide-Formoterol versus Maintenance Budesonide in Mild Asthma, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 378, Pages: 1877-1887, ISSN: 0028-4793
Montuschi P, Santini G, Mores N, et al., 2018, Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD, FRONTIERS IN PHARMACOLOGY, Vol: 9, ISSN: 1663-9812
Singh D, Barnes PJ, Stockley R, et al., 2018, Pharmacological treatment of COPD: the devil is always in the detail, EUROPEAN RESPIRATORY JOURNAL, Vol: 51, ISSN: 0903-1936
Wang Z, Singh R, Miller BE, et al., 2018, Sputum microbiome temporal variability and dysbiosis in chronic obstructive pulmonary disease exacerbations: an analysis of the COPDMAP study, THORAX, Vol: 73, Pages: 331-338, ISSN: 0040-6376
Di Stefano A, Sangiorgi C, Gnemmi I, et al., 2018, TGF-beta Signaling Pathways in Different Compartments of the Lower Airways of Patients With Stable COPD, CHEST, Vol: 153, Pages: 851-862, ISSN: 0012-3692
Hashemian SM, Mortaz E, Jamaati H, et al., 2018, Budesonide facilitates weaning from mechanical ventilation in difficult-to-wean very severe COPD patients: Association with inflammatory mediators and cells, JOURNAL OF CRITICAL CARE, Vol: 44, Pages: 161-167, ISSN: 0883-9441
Yanagisawa S, Baker JR, Vuppusetty C, et al., 2018, The dynamic shuttling of SIRT1 between cytoplasm and nuclei in bronchial epithelial cells by single and repeated cigarette smoke exposure, PLOS ONE, Vol: 13, ISSN: 1932-6203
Paschalaki KE, Zampetaki A, Baker JR, et al., 2018, Downregulation of MicroRNA-126 Augments DNA Damage Response in Cigarette Smokers and Patients with Chronic Obstructive Pulmonary Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 197, Pages: 665-668, ISSN: 1073-449X
Birch J, Barnes PJ, Passos JF, 2018, Mitochondria, telomeres and cell senescence: Implications for lung ageing and disease, PHARMACOLOGY & THERAPEUTICS, Vol: 183, Pages: 34-49, ISSN: 0163-7258
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.