1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Cytokine-targeted therapies for asthma and COPD

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Asthma affects over 300 million people worldwide and its prevalence is increasing. COPD is the third leading cause of death globally. Asthma and COPD are complex inflammatory diseases of the airways in which impaired host defences lead to increased susceptibility to pathogens, pollutants and allergens. There is a constant interplay between host and the environment. Environmental exposures can alter the lung microbiome and influence the development of sensitisation by disrupting normal immunoregulation. The underlying airway inflammation in severe asthma is heterogeneous, with upregulation of type 2 cytokines in most cases but increased neutrophilic inflammation and activated T-helper 17 mediated immunity in others. COPD may also comprise several different phentoypes that are driven by different molecular mechanisms or endotypes. This disease heterogeneity is affected by comorbidities, treatments and environmental exposures. Recent intervention trials have shed light on the pathways beyond type 2 inflammation that can lead to beneficial outcomes versus potentially deleterious effects. We have made a great deal of progress over the last 10 years in terms of immunology and the pathophysiology of asthma and this has led to the development of novel treatments and major improvements in severe asthma outcomes. In COPD, however, no targeted treatments have demonstrated great improvements. This article reviews the mechanism of action and efficacy of the available biologics in asthma and COPD.

          Abstract

          Asthma and COPD are complex inflammatory diseases of the airways. Targeted treatments have drastically improved severe asthma outcomes, but in COPD no targeted treatments have at present demonstrated great improvement. https://bit.ly/40ebm6H

          Related collections

          Most cited references120

          • Record: found
          • Abstract: found
          • Article: not found

          International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma.

          Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming "uncontrolled" or that remains "uncontrolled" despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial.

            Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab. We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophilic inflammation. They were randomly assigned (in a 1:1:1:1 ratio) to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg) or matched placebo (100 mL 0·9% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratified by whether treatment with oral corticosteroids was required. Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically significant asthma exacerbations, which were defined as validated episodes of acute asthma requiring treatment with oral corticosteroids, admission, or a visit to an emergency department. Patients, clinicians, and data analysts were masked to treatment assignment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01000506. 621 patients were randomised: 159 were assigned to placebo, 154 to 75 mg mepolizumab, 152 to 250 mg mepolizumab, and 156 to 750 mg mepolizumab. 776 exacerbations were deemed to be clinically significant. The rate of clinically significant exacerbations was 2·40 per patient per year in the placebo group, 1·24 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p<0·0001), 1·46 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=0·0005), and 1·15 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<0·0001). Three patients died during the study, but the deaths were not deemed to be related to treatment. Mepolizumab is an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma. GlaxoSmithKline. Copyright © 2012 Elsevier Ltd. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma

              Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma.
                Bookmark

                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                30 June 2023
                19 April 2023
                : 32
                : 168
                : 220193
                Affiliations
                [1 ]Respiratory Medicine, CHU of Liege, Belgium
                [2 ]GIGA I3, University of Liege, Belgium
                Author notes
                Correspondence: Florence Schleich ( fschleich@ 123456chuliege.be )
                Author information
                https://orcid.org/0000-0002-2678-1373
                https://orcid.org/0000-0002-9558-5878
                Article
                ERR-0193-2022
                10.1183/16000617.0193-2022
                10113955
                37076177
                dd51be2b-5b44-4a70-811a-cd204ff6cc4b
                Copyright ©The authors 2023

                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org

                History
                : 12 October 2022
                : 23 January 2023
                Categories
                Lung Science Conference reviews
                1
                2

                Comments

                Comment on this article

                scite_
                0
                0
                0
                0
                Smart Citations
                0
                0
                0
                0
                Citing PublicationsSupportingMentioningContrasting
                View Citations

                See how this article has been cited at scite.ai

                scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

                Similar content382

                Cited by12

                Most referenced authors2,306