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      International Journal of COPD (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

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      A Proteomics-Based Analysis of Blood Biomarkers for the Diagnosis of COPD Acute Exacerbation

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          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

          Purpose

          The identification of blood biomarkers to diagnose acute exacerbation of chronic obstructive pulmonary disease (AECOPD) will have clinical utility. Here, we used a proteomics-based approach to identify biomarkers capable of identifying AECOPD.

          Patients and Methods

          This prospective, single-center pilot study enrolled 12 patients who came to Asan Medical Center (South Korea) via the outpatient clinic or emergency department with symptoms of AECOPD and were follow-up in the outpatient clinic during convalescence between 2015 and 2017. Paired blood samples collected from each patient during the treatment naïve AECOPD and convalescence stages were analyzed. A sequential window acquisition of all theoretical fragmentation spectra-mass spectrometry (SWATH-MS)-based proteome analysis was performed and a subset of the data were verified by ELISA.

          Results

          The SWATH-MS analysis identified 226 plasma proteins across all samples examined. The median coefficient of variation for triplicate technical replicates of each sample was 1.13 ± 1.38%, indicating high precision of the technique. Fold-change and paired t-test analyses revealed that 14 proteins were present at higher levels in the AECOPD samples than in the convalescence samples. A gene ontology analysis revealed that these proteins are involved in the acute-phase response. A total of 15 proteins were present at higher levels during the recovery (convalescence) stage than during the acute exacerbation phase, and gene ontology analysis revealed that these proteins are related to lipid metabolism and transport. Verification of the SWATH-MS data was performed using ELISAs for three proteins that were up-regulated in AECOPD, namely, LBP, ORM2, and SERPINA3. Among them, SERPINA3 (p = 0.005) was up-regulated significantly in AECOPD compared with the convalescence state.

          Conclusion

          Potential plasma biomarkers of AECOPD were discovered using the SWATH-MS proteomics method, and functional molecular associations were investigated. SERPINA3 could be a promising diagnostic biomarker for the early identification and tracking of AECOPD.

          Most cited references46

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          Chronic obstructive pulmonary disease

          Summary Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease.
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            Data‐independent acquisition‐based SWATH ‐ MS for quantitative proteomics: a tutorial

            Abstract Many research questions in fields such as personalized medicine, drug screens or systems biology depend on obtaining consistent and quantitatively accurate proteomics data from many samples. SWATH‐MS is a specific variant of data‐independent acquisition (DIA) methods and is emerging as a technology that combines deep proteome coverage capabilities with quantitative consistency and accuracy. In a SWATH‐MS measurement, all ionized peptides of a given sample that fall within a specified mass range are fragmented in a systematic and unbiased fashion using rather large precursor isolation windows. To analyse SWATH‐MS data, a strategy based on peptide‐centric scoring has been established, which typically requires prior knowledge about the chromatographic and mass spectrometric behaviour of peptides of interest in the form of spectral libraries and peptide query parameters. This tutorial provides guidelines on how to set up and plan a SWATH‐MS experiment, how to perform the mass spectrometric measurement and how to analyse SWATH‐MS data using peptide‐centric scoring. Furthermore, concepts on how to improve SWATH‐MS data acquisition, potential trade‐offs of parameter settings and alternative data analysis strategies are discussed.
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              Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

              Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                copd
                copd
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove
                1176-9106
                1178-2005
                01 June 2021
                2021
                : 16
                : 1497-1508
                Affiliations
                [1 ]Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital , Busan, 49241, Korea
                [2 ]Asan Institute for Life Science, Asan Medical Center , Seoul, Korea
                [3 ]Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center , Seoul, Korea
                [4 ]Department of Biomedical Sciences, University of Ulsan College of Medicine , Seoul, Korea
                [5 ]Clinical Proteomics Core Laboratory, Convergence Medicine Research Center, Asan Medical Center , Seoul, Korea
                [6 ]Bio-Medical Institute of Technology, Asan Medical Center , Seoul, Korea
                [7 ]Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center , Seoul, Korea
                Author notes
                Correspondence: Kyunggon Kim Department of Biomedical Sciences, University of Ulsan College of Medicine , 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of KoreaTel +82-2-3010-4633 Email kkkon1@amc.seoul.kr
                Yeon-Mok Oh Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center , 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of KoreaTel +82-2-3010-3136 Email ymoh55@amc.seoul.kr
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0003-2241-6536
                http://orcid.org/0000-0003-0116-4683
                Article
                308305
                10.2147/COPD.S308305
                8183188
                59e661ff-055b-4fce-8e6c-1ea9ee34039a
                © 2021 Kim et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 24 February 2021
                : 19 April 2021
                Page count
                Figures: 5, Tables: 3, References: 46, Pages: 12
                Categories
                Original Research

                Respiratory medicine
                copd,plasma,biomarker,elisa,swath,mass spectrometry
                Respiratory medicine
                copd, plasma, biomarker, elisa, swath, mass spectrometry

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