Oxidative Stress in COPD
Abstract
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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Oxidative stress appears to be a key factor in the pathophysiology of COPD via several distinct mechanisms.
“Oxidative stress appears to be a key factor in the pathophysiology of COPD via several distinct mechanisms (Kirkham and Barnes 2013; McGuinness and Sapey 2017).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Kirkham and Barnes 2013
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Non-heme (Fe3+) in the lung increases with age in both humans and rats
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Dietary modulation of oxidative stress in chronic obstructive pulmonary disease patients
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New treatments for chronic obstructive pulmonary disease
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Self-citation3-chlorotyrosine in Sputum of COPD Patients: Relationship with Airway Inflammation
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Could problems with bardoxolone methyl have been predicted?
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Self-citationDefective Antioxidant Gene Regulation in COPD: A Case for Broccoli
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
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Cellular Metabolism in Lung Health and Disease
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SIRT1 protects against cigarette smoke-induced lung oxidative stress via a FOXO3-dependent mechanism
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Neutrophil targeted nano-drug delivery system for chronic obstructive lung diseases
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New Insights into Endothelial Cell Physiology and Pathophysiology
Józkowiak, M., Niebora, J., Domagała, D., Data, K., Partyńska, A., Kulus, M., Kotrych, K., Podralska, M., Górska, A., Chwiłkowska, A., et al. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118415 · Cited by 26 · see citing works
- Authors
- Kirkham, P. A., & Barnes, P. J.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Kirkham, Paul A.
- Venue
- Chest
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 144
- Issue
- 1
- Pages
- 266-273
- ISSN
- 0012-3692 (ISSN-L)
- OpenAlex
- W2134160513
- Cited by
- 685
- References
- 203
- Citations by year
- 2026: 28 · 2025: 44 · 2024: 44 · 2023: 64 · 2022: 77 · 2021: 77 · 2020: 68 · 2019: 66 · 2018: 48 · 2017: 52 · 2016: 48 · 2015: 30 · 2014: 27 · 2013: 6
- FWCI
- 5.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CHEST Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- GlaxoSmithKline
- Chiesi Farmaceutici
- Wellcome Trust
- National Institute for Health and Care Research (NF-SI-0611-10148)
- Royal Society
- Engineering and Physical Sciences Research Council
- UCB Celltech
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- oxidative stress, chronic obstructive pulmonary disease, reactive oxygen species, antioxidant capacity, cigarette smoking, COPD exacerbations, emphysema, small airway disease, genetic susceptibility, lung inflammation, autoimmunity, antioxidant therapy, combination therapy
- MeSH terms
- Antioxidants, Humans, Lung, Reactive Oxygen Species, Oxidative Stress, Disease Progression, Genetic Predisposition to Disease, Pulmonary Disease, Chronic Obstructive
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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