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      COPD immunopathology

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          Abstract

          The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking. In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations. This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways. This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function.

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          New insights into the immunology of chronic obstructive pulmonary disease.

          Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome associated with abnormal inflammatory immune responses of the lung to noxious particles and gases. Cigarette smoke activates innate immune cells such as epithelial cells and macrophages by triggering pattern recognition receptors, either directly or indirectly via the release of damage-associated molecular patterns from stressed or dying cells. Activated dendritic cells induce adaptive immune responses encompassing T helper (Th1 and Th17) CD4+ T cells, CD8+ cytotoxicity, and B-cell responses, which lead to the development of lymphoid follicles on chronic inflammation. Viral and bacterial infections not only cause acute exacerbations of COPD, but also amplify and perpetuate chronic inflammation in stable COPD via pathogen-associated molecular patterns. We discuss the role of autoimmunity (autoantibodies), remodelling, extracellular matrix-derived fragments, impaired innate lung defences, oxidative stress, hypoxia, and dysregulation of microRNAs in the persistence of the pulmonary inflammation despite smoking cessation. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Oxidative stress in COPD.

            Oxidative stress is now recognized as a major predisposing factor in the pathogenesis of COPD. Existing therapies for COPD are ineffective at halting disease progression, with bronchodilators being the mainstay of pharmacotherapy, providing symptomatic relief only. It is, therefore, important for a better understanding of the underlying mechanisms by which oxidative stress drives disease pathogenesis to develop novel and more effective therapies. Antioxidant capacity in COPD is substantially reduced as a result of cigarette smoking and exacerbations, with oxidative stress persisting long after the cessation of cigarette smoking or exacerbation, due to the continued production of reactive oxygen species from endogenous sources. We discuss (1) how oxidative stress arises in the lung, (2) how it is neutralized, (3) what genetic factors may predispose to the development of COPD, and (4) how this impacts inflammation and autoimmunity in the development of emphysema and small airways disease. Finally, various strategies have been considered to neutralize the increased oxidative burden present in COPD. This review highlights why current antioxidant strategies have so far failed and what promising alternatives are on the horizon. Moreover, a number of studies have shown that there is no single "magic bullet" to combat oxidative stress, but instead a combination therapy, targeting oxidative stress in the various subcellular compartments, may prove to be more effective in COPD.
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              Chronic obstructive pulmonary disease.

              P Barnes (2000)
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                Author and article information

                Contributors
                +39-0532-210420 , +39-0532-210297 , gaetano.caramori@unife.it
                Journal
                Semin Immunopathol
                Semin Immunopathol
                Seminars in Immunopathology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1863-2297
                1863-2300
                13 May 2016
                13 May 2016
                2016
                : 38
                : 497-515
                Affiliations
                [ ]Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly named Centro di Ricerca su Asma e BPCO), Sezione di Medicina Interna e Cardiorespiratoria, Università di Ferrara, Via Savonarola 9, 44121 Ferrara, Italy
                [ ]Katedra i Klinika Pneumonologii, Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland
                [ ]Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
                [ ]Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell’Apparato Cardio Respiratorio, Salvatore Maugeri Foundation, IRCCS, Veruno, NO Italy
                Article
                561
                10.1007/s00281-016-0561-5
                4897000
                27178410
                9a528e28-ceb7-4b66-a3ae-d6fc80c17d6e
                © The Author(s) 2016

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 26 February 2016
                : 20 April 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 093080/z/10/z
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/100004325, AstraZeneca;
                Funded by: Boehringer Ingelheim Italy
                Funded by: GSK Italy
                Funded by: Menarini
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/501100000351, British Lung Foundation;
                Categories
                Review
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2016

                Pathology
                Pathology

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