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      The impact of long-acting muscarinic antagonists on mucus hypersecretion and cough in chronic obstructive pulmonary disease: a systematic review

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          Abstract

          Patients suffering from chronic obstructive pulmonary disease (COPD) clinically manifest airway mucus hypersecretion as sputum expectoration and cough. Evidence accumulated in the past decade has shown that the cholinergic system not only regulates airway smooth muscle contraction but also the activity of inflammatory and airway epithelial cells, including goblet cells, and submucosal gland activity. Long-acting muscarinic antagonists (LAMAs) with the most favourable M 3/M 2 muscarinic acetylcholine (ACh) receptors residency properties are not only excellent bronchodilators but potentially also mucus-modifying agents, able to positively impact on mucus hypersecretion and cough. The aim of this systematic review was to investigate the impact of LAMAs on mucus hypersecretion and cough in COPD patients. The evidence confirmed that LAMAs, mainly tiotropium and aclidinium, improved sputum production and cough in moderate to severe COPD. Thus, LAMAs not only antagonise the ACh-induced bronchoconstriction of the airways but also appear to limit the production of mucus secreted in response to ACh by airway goblet cells and/or submucosal glands. Further clinical studies are necessary to evaluate the impact of LAMAs exclusively on sputum symptoms and cough as primary end-points and to investigate whether LAMAs have a modulatory action on the rheological properties of mucus.

          Abstract

          This systematic review provides evidence that LAMAs, mainly tiotropium and aclidinium, have a beneficial impact on mucus hypersecretion and mucociliary clearance, with consequent improvement of sputum production and cough in moderate to severe COPD. https://bit.ly/3wHXZiZ

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          Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

          Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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            Assessing the quality of reports of randomized clinical trials: is blinding necessary?

            It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed.
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              Risk‐of‐bias VISualization (robvis): An R package and Shiny web app for visualizing risk‐of‐bias assessments

              Despite a major increase in the range and number of software offerings now available to help researchers produce evidence syntheses, there is currently no generic tool for producing figures to display and explore the risk-of-bias assessments that routinely take place as part of systematic review. However, tools such as the R programming environment and Shiny (an R package for building interactive web apps) have made it straightforward to produce new tools to help in producing evidence syntheses. We present a new tool, robvis (Risk-Of-Bias VISualization), available as an R package and web app, which facilitates rapid production of publication-quality risk-of-bias assessment figures. We present a timeline of the tool's development and its key functionality.
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                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 2022
                04 May 2022
                : 31
                : 164
                : 210196
                Affiliations
                [1 ]Dept of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Parma, Italy
                [2 ]Unit of Respiratory Medicine, Dept of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy
                [3 ]Pulmonology Dept, Sandro Pertini Hospital, Rome, Italy
                [4 ]School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth, UK
                Author notes
                Corresponding author: Luigino Calzetta ( luigino.calzetta@ 123456unipr.it )
                Author information
                https://orcid.org/0000-0003-0456-069X
                https://orcid.org/0000-0002-9071-2006
                https://orcid.org/0000-0002-7162-3956
                https://orcid.org/0000-0001-7801-5040
                Article
                ERR-0196-2021
                10.1183/16000617.0196-2021
                9488979
                35508331
                2f3b59a1-1c2c-4eb6-8b17-b63c29b38a14
                Copyright ©The authors 2022

                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
                : 24 August 2021
                : 20 March 2022
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