Publications
2425 results found
Chiarella SE, Barnes PJ, 2023, Endogenous inhibitory mechanisms in asthma, Journal of Allergy and Clinical Immunology: Global, Vol: 2
Endogenous inhibitory mechanisms promote resolution of inflammation, enhance tissue repair and integrity, and promote homeostasis in the lung. These mechanisms include steroid hormones, regulatory T cells, IL-10, prostaglandin E2, prostaglandin I2, lipoxins, resolvins, protectins, maresins, glucagon-like peptide-1 receptor, adrenomedullin, nitric oxide, and carbon monoxide. Here we review the most recent literature regarding these endogenous inhibitory mechanisms in asthma, which remain a promising target for the prevention and treatment of asthma.
Jia M, Fu H, Jiang X, et al., 2023, DEL-1, as an anti-neutrophil transepithelial migration molecule, inhibits airway neutrophilic inflammation in asthma., Allergy
BACKGROUND: Neutrophil migration into the airways is a key process in neutrophilic asthma. Developmental endothelial locus-1 (DEL-1), an extracellular matrix protein, is a neutrophil adhesion inhibitor that attenuates neutrophilic inflammation. METHODS: Levels of DEL-1 were measured in exhaled breath condensate (EBC) and serum in asthma patients by ELISA. DEL-1 modulation of neutrophil adhesion and transepithelial migration was examined in a co-culture model in vitro. The effects of DEL-1-adenoviral vector-mediated overexpression on ovalbumin/lipopolysaccharide (OVA/LPS)-induced neutrophilic asthma were studied in mice in vivo. RESULTS: DEL-1 was primarily expressed in human bronchial epithelial cells and was decreased in asthma patients. Serum DEL-1 concentrations were reduced in patients with severe asthma compared with normal subjects (567.1 ± 75.3 vs. 276.8 ± 29.36 pg/mL, p < .001) and were negatively correlated to blood neutrophils (r = -0.2881, p = .0384) and neutrophil-to-lymphocyte ratio (NLR) (r = -0.5469, p < .0001). DEL-1 concentrations in the EBC of severe asthmatic patients (113.2 ± 8.09 pg/mL) were also lower than normal subjects (193.0 ± 7.61 pg/mL, p < .001) and were positively correlated with the asthma control test (ACT) score (r = 0.3678, p = .0035) and negatively related to EBC IL-17 (r = -0.3756, p = .0131), myeloperoxidase (MPO) (r = -0.5967, p = .0055), and neutrophil elastase (NE) (r = -0.5488, p = .0009) expression in asthma patients. Neutrophil adhesion and transepithelial migration in asthma patients were associated with LFA-1 binding to ICAM-1 and inhibited by DEL-1. DEL-1 mRNA and protein expression in human bronchial epithelial cell
Cazzola M, Rogliani P, Barnes PJ, et al., 2023, An Update on Outcomes for COPD Pharmacological Trials: A COPD Investigators Report - Reassessment of the 2008 American Thoracic Society/European Respiratory Society Statement on Outcomes for COPD Pharmacological Trials., Am J Respir Crit Care Med, Vol: 208, Pages: 374-394
Background: In 2008, a dedicated American Thoracic Society/European Respiratory Society task force published a paper on the possible use and limitations of clinical outcomes and biomarkers to evaluate the impact of pharmacological therapy in patients with chronic obstructive pulmonary disease. Since then, our scientific understanding of chronic obstructive pulmonary disease has increased considerably; there has been a progressive shift from a one-size-fits-all diagnostic and therapeutic approach to a personalized approach; and many new treatments currently in development will require new endpoints to evaluate their efficacy adequately. Objectives: The emergence of several new relevant outcome measures motivated the authors to review advances in the field and highlight the need to update the content of the original report. Methods: The authors separately created search strategies for the literature, primarily based on their opinions and assessments supported by carefully chosen references. No centralized examination of the literature or uniform criteria for including or excluding evidence were used. Measurements and Main Results: Endpoints, outcomes, and biomarkers have been revisited. The limitations of some of those reported in the American Thoracic Society/European Respiratory Society task force document have been highlighted. In addition, new tools that may be useful, especially in evaluating personalized therapy, have been described. Conclusions: Because the "label-free" treatable traits approach is becoming an important step toward precision medicine, future clinical trials should focus on highly prevalent treatable traits, and this will influence the choice of outcomes and markers to be considered. The use of the new tools, particularly combination endpoints, could help better identify the right patients to be treated with the new drugs.
Quint JK, Ariel A, Barnes PJ, 2023, Rational use of inhaled corticosteroids for the treatment of COPD., NPJ Prim Care Respir Med, Vol: 33
Inhaled corticosteroids (ICS) are the mainstay of treatment for asthma, but their role in chronic obstructive pulmonary disease (COPD) is debated. Recent randomised controlled trials (RCTs) conducted in patients with COPD and frequent or severe exacerbations demonstrated a significant reduction (~25%) in exacerbations with ICS in combination with dual bronchodilator therapy (triple therapy). However, the suggestion of a mortality benefit associated with ICS in these trials has since been rejected by the European Medicines Agency and US Food and Drug Administration. Observational evidence from routine clinical practice demonstrates that dual bronchodilation is associated with better clinical outcomes than triple therapy in a broad population of patients with COPD and infrequent exacerbations. This reinforces guideline recommendations that ICS-containing maintenance therapy should be reserved for patients with frequent or severe exacerbations and high blood eosinophils (~10% of the COPD population), or those with concomitant asthma. However, data from routine clinical practice indicate ICS overuse, with up to 50-80% of patients prescribed ICS. Prescription of ICS in patients not fulfilling guideline criteria puts patients at unnecessary risk of pneumonia and other long-term adverse events and also has cost implications, without any clear benefit in disease control. In this article, we review the benefits and risks of ICS use in COPD, drawing on evidence from RCTs and observational studies conducted in primary care. We also provide a practical guide to prescribing ICS, based on the latest global treatment guidelines, to help primary care providers identify patients for whom the benefits of ICS outweigh the risks.
Sin DD, Doiron D, Agusti A, et al., 2023, Air pollution and COPD: GOLD 2023 committee report., Eur Respir J, Vol: 61
Exposure to air pollution is a major contributor to the pathogenesis of COPD worldwide. Indeed, most recent estimates suggest that 50% of the total attributable risk of COPD may be related to air pollution. In response, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Scientific Committee performed a comprehensive review on this topic, qualitatively synthesised the evidence to date and proffered recommendations to mitigate the risk. The review found that both gaseous and particulate components of air pollution are likely contributors to COPD. There are no absolutely safe levels of ambient air pollution and the relationship between air pollution levels and respiratory events is supra-linear. Wildfires and extreme weather events such as heat waves, which are becoming more common owing to climate change, are major threats to COPD patients and acutely increase their risk of morbidity and mortality. Exposure to air pollution also impairs lung growth in children and as such may lead to developmental COPD. GOLD recommends strong public health policies around the world to reduce ambient air pollution and for implementation of public warning systems and advisories, including where possible the use of personalised apps, to alert patients when ambient air pollution levels exceed acceptable minimal thresholds. When household particulate content exceeds acceptable thresholds, patients should consider using air cleaners and filters where feasible. Air pollution is a major health threat to patients living with COPD and actions are urgently required to reduce the morbidity and mortality related to poor air quality around the world.
Ho V, Baker J, Willison K, et al., 2023, Single cell quantification of microRNA from small numbers of non-invasively sampled primary human cells, Communications Biology, Vol: 6, Pages: 1-11, ISSN: 2399-3642
Expression levels of microRNAs (miRNAs) in single cells are low and conventional miRNA detection methods require amplification that can be complex, time-consuming, costly and may bias results. Single cell microfluidic platforms have been developed; however, current approaches are unable to absolutely quantify single miRNA molecules expressed in single cells. Herein, we present an amplification-free sandwich hybridisation assay to detect single miRNA molecules in single cells using a microfluidic platform that optically traps and lyses individual cells. Absolute quantification of miR-21 and miR-34a molecules was achieved at a single cell level in human cell lines and validated using real-time qPCR. The sensitivity of the assay was demonstrated by quantifying single miRNA molecules in nasal epithelial cells and CD3+ T-cells, as well as nasal fluid collected non-invasively from healthy individuals. This platform requires ~50 cells or ~30 µL biofluid and can be extended for other miRNA targets therefore it could monitor miRNA levels in disease progression or clinical studies.
Agustí A, Celli BR, Criner GJ, et al., 2023, Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary., Am J Respir Crit Care Med, Vol: 207, Pages: 819-837
Agustí A, Celli BR, Criner GJ, et al., 2023, Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary., Eur Respir J, Vol: 61
Executive summary of the Global Strategy for Prevention, Diagnosis and Management of COPD 2023: the latest evidence-based strategy document from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) https://bit.ly/3KCaTGe
Agustí A, Celli BR, Criner GJ, et al., 2023, Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary., Respirology, Vol: 28, Pages: 316-338
Agustí A, Celli BR, Criner GJ, et al., 2023, Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary., Arch Bronconeumol, Vol: 59, Pages: 232-248
Ombredane HCJ, Fenwick PS, Barnes PJ, et al., 2023, Temporal Release of IL-1 Family Members from Virally Infected Airway Epithelial Cells Suggests IL-36 gamma Is the Early Responder, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 68, Pages: 339-341, ISSN: 1044-1549
Ahmad S, Noor NM, Syafirah EAREN, et al., 2023, Anti-Tumor Necrosis Factor for Supplementary Management in Severe Asthma: A Systematic Review and Meta-analysis, JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, Vol: 43, Pages: 77-85, ISSN: 1079-9907
Pavord ID, Barnes PJ, Lemiere C, et al., 2023, Developing the water paucity index using dimensional homogeneity, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 11, Pages: 1-8, ISSN: 2213-2198
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- Citations: 1
Barnes PJ, Godfrey S, 2023, Chronic obstrudive pulmonary disease, Second Edition, ISBN: 9781003420316
This book provides an up-to-date perspective on the inflammatory cells, mediators, and molecular pathology of Chronic obstructive pulmonary disease (COPD), emphasizing the urgent need to clearly understand the underlying cellular and molecular mechanisms involved in COPD.
Barnes PJ, 2023, Senotherapy for lung diseases., Pages: 249-271
Increasing evidence suggests that there is acceleration of lung ageing in chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), with the accumulation of senescent cells in the lung. Senescent cells fail to repair tissue damage and release an array of inflammatory proteins, known as the senescence-associated secretory phenotype, which drive further senescence and disease progression. This suggests that targeting cellular senescence with senotherapies may treat the underlying disease process in COPD and IPF and thus reduce disease progression and mortality. Several existing or future drugs may inhibit the development of cellular senescence which is driven by chronic oxidative stress (senostatics), including inhibitors of PI3K-mTOR signalling pathways, antagomirs of critical microRNAs and novel antioxidants. Other drugs (senolytics) selectively remove senescent cells by promoting apoptosis. Clinical studies with senotherapies are already underway in chronic lung diseases.
Bafadhel M, Faner R, Taille C, et al., 2022, Inhaled corticosteroids for the treatment of COVID-19, EUROPEAN RESPIRATORY REVIEW, Vol: 31, ISSN: 0905-9180
Casale TB, Barnes PJ, 2022, Smoke and the Lungs, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 10, Pages: 2852-2853, ISSN: 2213-2198
Devulder J, Baker JR, Odqvist L, et al., 2022, Extracellular vesicles propagate cellular senescence by transferring miR34a in airway epithelial cells, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Ho V, Baker JR, Willison KR, et al., 2022, An amplification-free, innovative, multiplex assay to quantify microRNAs in single cells from COPD patients, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Havaki S, Evangelou K, Paschalaki K, et al., 2022, Reply: Identification of coronavirus particles by electron microscopy: a complementary tool for deciphering COVID-19, EUROPEAN RESPIRATORY JOURNAL, Vol: 60, ISSN: 0903-1936
Havaki S, Evangelou K, Paschalaki K, et al., 2022, Reply: Identification of coronavirus particles by electron microscopy: a complementary tool for deciphering COVID-19, EUROPEAN RESPIRATORY JOURNAL, Vol: 60, ISSN: 0903-1936
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- Citations: 1
Iemoli E, Ortolani VGR, Preziosi D, et al., 2022, Failure of desensitization with Pfizer-BioNTech COVID-19 vaccine in two asthmatic patients., Eur Ann Allergy Clin Immunol, Vol: 54, Pages: 240-241, ISSN: 1764-1489
Since December 2020, in various countries of the world, many cases of severe allergic reactions after administration of PfizerBioNTech COVID-19 vaccine, were reported. A great concern has arisen among the doctors who administer the vaccine and the allergic patients who undergo vaccinations. In Italy guidelines were published in order to stratify the risk in the allergic population. In mRNA vaccines, the component currently suspected of causing allergic reactions is the polyethylene glycol excipient (PEG or macrogol). In patients who have shown an immediate allergic reaction to vaccine and who are negative to skin tests for PEG, desensitization with the same vaccine is proposed. In this paper we describe two cases of asthma after the first COVID vaccine administration in which desensitization has failed.
Baker JR, Fenwick PS, Koss CK, et al., 2022, Imbalance between IL-36 receptor agonist and antagonist drives neutrophilic inflammation in COPD, JCI Insight, Vol: 7, ISSN: 2379-3708
Current treatments fail to modify the underlying pathophysiology and disease progression of chronic obstructive pulmonary disease (COPD), necessitating alternative therapies. Here, we show that COPD subjects have increased IL-36γ and decreased IL-36 receptor antagonist (IL-36Ra) in bronchoalveolar and nasal fluid compared to control subjects. IL-36γ is derived from small airway epithelial cells (SAEC) and further induced by a viral mimetic, whereas IL-36RA is derived from macrophages. IL-36γ stimulates release of the neutrophil chemoattractants CXCL1 and CXCL8, as well as elastolytic matrix metalloproteinases (MMPs) from small airway fibroblasts (SAF). Proteases released from COPD neutrophils cleave and activate IL-36γ thereby perpetuating IL-36 inflammation. Transfer of culture media from SAEC to SAF stimulated release of CXCL1, that was inhibited by exogenous IL-36RA. The use of a therapeutic antibody that inhibits binding to the IL-36 receptor (IL-36R) attenuated IL-36γ driven inflammation and cellular cross talk. We have demonstrated a mechanism for the amplification and propagation of neutrophilic inflammation in COPD and that blocking this cytokine family via a IL-36R neutralizing antibody could be a promising new therapeutic strategy in the treatment of COPD.
Evangelou K, Veroutis D, Paschalaki K, et al., 2022, Pulmonary infection by SARS-CoV-2 induces senescence accompanied by an inflammatory phenotype in severe COVID-19: possible implications for viral mutagenesis, EUROPEAN RESPIRATORY JOURNAL, Vol: 60, ISSN: 0903-1936
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- Citations: 18
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
Barnes PJ, 2022, Chemokine receptor CCR1: new target for asthma therapy, TRENDS IN PHARMACOLOGICAL SCIENCES, Vol: 43, Pages: 539-541, ISSN: 0165-6147
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
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
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
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
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