The DOI matches its Crossref record; 108 of the 108 references it cites were found in a registry or an index.
The Aging Immune System and Its Relationship to the Development of Chronic Obstructive Pulmonary Disease
Open accessAbstract
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lungs that usually manifests late in life. Physiologic and immunologic changes that occur in COPD often mimic changes seen in the aging lung. This has led some to characterize COPD as an “accelerated aging phenotype.” At the molecular level, COPD and aging share common mechanisms and are associated with significant dysregulation of the immune systems. Aging and COPD are characterized by increases in proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, which are implicated in aging-related inflammatory diseases and correlate with degree of obstruction in COPD. There is an age-dependent decline in naïve T cells with oligoclonal expansion of CD8+ CD28null T cells from chronic antigenic stimulation. The increase in CD8+ CD28 null T regulatory cells inhibits antigen-specific CD4+ T cell responses, leading to a decline in adaptive immune response. To compensate for the decline in the adaptive immune function there is a paradoxical up-regulation of innate immune system resulting in a proinflammatory state. The dysregulated adaptive immune system with activated innate immune responses seen with aging results in recruitment and retention of neutrophils, macrophages, and CD4+ and CD8+ T cells in the lungs of smokers with COPD. Once the inflammation is triggered, there is a self-perpetuating cascade of inflammation and lung parenchymal damage. This review will focus on how the aging immune system may contribute to COPD development later in life in susceptible individuals.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Due to changes in lung function and anatomy as well as lung antioxidant defenses, the aged lung is more susceptible to environmental exposure–induced injury (19, 86).”
From Aging and Lung Disease (2020) · cites this paper as [86]
In the citing paper
“Age-associated immunosenescence and cellular senescence in response to exposure to cigarette smoke can greatly impact COPD pathogenesis (3, 19, 86).”
From Aging and Lung Disease (2020) · cites this paper as [86]
In the citing paper
“Acute exacerbations of COPD (AECOPD) are common in patients with severe and very severe COPD and are characterized by increased dyspnea, purulence, and augmented sputum volume (86, 137).”
From Aging and Lung Disease (2020) · cites this paper as [86]
In the citing paper
“An age-dependent increase in cytotoxic CD8+ and memory CD4+ T cells in the airways of COPD patients may further disease progression (86, 130, 132).”
From Aging and Lung Disease (2020) · cites this paper as [86]
In the citing paper
“Specifically, macrophages, which can produce multiple proinflammatory cytokines and secrete MMPs, are the most abundant cell type in the BAL fluid of COPD patients, and increased numbers correlate with disease severity (85, 86, 104).”
From Aging and Lung Disease (2020) · cites this paper as [86]
Citations
Cites
Fiore, A. E., Shay, D. K., Broder, K. R., Iskander, J. K., Uyeki, T. M., Mootrey, G., Bresee, J. S., & Cox, N. S. (2001) · PsycEXTRA Dataset · doi:10.1037/e548312006-001 · Cited by 5,006
The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease
Hogg, J. C., Chu, F. S. F., Utokaparch, S., Woods, R. R., Elliott, W. M., Buzatu, L., Cherniack, R. M., Rogers, R. M., Sciurba, F. C., Coxson, H. O., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032158 · Cited by 3,828
Buist, A. S., McBurnie, M. A., Vollmer, W. M., Gillespie, S., Burney, P., Mannino, D. M., Menezes, A. M., Sullivan, S. D., Lee, T. A., Weiss, K. B., et al. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61377-4 · Cited by 2,364
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087
Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
Ershler, W. B., & Keller, E. T. (2000) · Annual Review of Medicine · doi:10.1146/annurev.med.51.1.245 · Cited by 1,282
Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age
Rossi, D. J., Bryder, D., Seita, J., Nussenzweig, A., Hoeijmakers, J., & Weissman, I. L. (2007) · Nature · doi:10.1038/nature05862 · Cited by 1,115
Antibody response to influenza vaccination in the elderly: A quantitative review
GOODWIN, K., VIBOUD, C., & SIMONSEN, L. (2006) · Vaccine · doi:10.1016/j.vaccine.2005.08.105 · Cited by 1,064
The Foxp3+ regulatory T cell: a jack of all trades, master of regulation
Tang, Q., & Bluestone, J. A. (2008) · Nature Immunology · doi:10.1038/ni1572 · Cited by 1,045
Inflammatory mediators in the elderly
Krabbe, K. S., Pedersen, M., & Bruunsgaard, H. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.01.009 · Cited by 928
Immunologic Aspects of Chronic Obstructive Pulmonary Disease
Cosío, M. G., Saetta, M. P., & Agustí, A. G. N. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804752 · Cited by 821
Research works printed but not linked: 11
- 2008, Cytokine, 44, 1
- 1999, MMWR Morb Mortal Wkly Rep, 48, 1
- 2007, Blood, 110, 1161
- 2005, Immun Ageing, 2, 1
- 2009, Clin Lab, 55, 31
- 2009, BMC Med Genet, 10, 23
- 2003, Chest, 123, 339S
- 1994, Pneumologie, 48, 57
- 1999, Pneumologie, 53, 400
- 2007, Int J Chron Obstruct Pulmon Dis, 2, 329
- 2005, Int J Mol Med, 15, 443
Cited by
Sorted by citations
Items 101–106 of 106
Cellules Club et susceptibilité respiratoire environnementale
Vernisse, C. (2020) · theses.fr (ABES) · doi:10.70675/a535ee75z19bfz49bdza74fz8707994d6a1d
Assaf, S. M., Adrish, M., & Hanania, N. A. (2026) · Respiratory medicine · doi:10.1007/978-3-032-29861-4_6
Self-citationAllergy and Immunology of the Aging Lung
Pathria, M., Hoyte, F. C. L., & Katial, R. K. (2026) · Respiratory medicine · doi:10.1007/978-3-032-29861-4_2
Predictive Value of Biological Age for All-Cause Mortality in Patients with COPD
Cheng, W., 侯燕群, Zhou, A., Liu, C., Huang, S., Zhao, Y., Li, J., Deng, Z., Zhang, T., Mao, R., et al. (2026) · International Journal of COPD · doi:10.2147/copd.s617907
Liu, X., Fu, Q., Yang, S., Zhang, L., Feng, B., Gao, Y., Zhao, C., Gao, D., Fan, G., Liu, L., et al. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1841730
Metadata
- Authors
- Sharma, G., Hanania, N. A., & Shim, Y. M.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Baylor College of Medicine (US)
- University of Virginia (US)
- Corresponding author
- Sharma, Gulshan
- Venue
- Proceedings of the American Thoracic Society
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-12-01
- Volume
- 6
- Issue
- 7
- Pages
- 573-580
- ISSN
- 1546-3222 (ISSN-L)
- 1943-5665
- PMC
- PMC5820858
- OpenAlex
- W2158912859
- Cited by
- 105
- References
- 106
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 10 · 2023: 4 · 2022: 10 · 2021: 5 · 2020: 2 · 2019: 5 · 2018: 2 · 2017: 7 · 2016: 4 · 2015: 9 · 2014: 7 · 2013: 11 · 2012: 8
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the American Thoracic Society (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K08HL091127)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Keywords
- chronic obstructive pulmonary disease, immunosenescence, inflammatory cytokines, interleukin-6, TNF-α, CD8+CD28- T cells, regulatory T cells, innate immune activation, neutrophil recruitment, macrophages, smoking, lung inflammation
- MeSH terms
- Aging, Humans, Immunity, Tumor Necrosis Factor-alpha, Interleukin-6, 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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
