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Airway regulatory T cells are decreased in COPD with a rapid decline in lung function

Eriksson Ström, Jonas ; Pourazar, Jamshid ; Linder, Robert LU orcid ; Blomberg, Anders ; Lindberg, Anne ; Bucht, Anders and Behndig, Annelie F. (2020) In Respiratory Research 21. p.1-9
Abstract

Background: Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not. Upregulation of Tregs in response to smoking would restrain airway inflammation and thus the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD. We hypothesized that—among COPD patients—the same mechanism would affect rate of decline in lung function; specifically, that a decreased expression of Tregs would be associated with a more rapid decline in FEV1. Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study; 12 with COPD and a rapid decline in lung function (loss... (More)

Background: Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not. Upregulation of Tregs in response to smoking would restrain airway inflammation and thus the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD. We hypothesized that—among COPD patients—the same mechanism would affect rate of decline in lung function; specifically, that a decreased expression of Tregs would be associated with a more rapid decline in FEV1. Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry. Results: The proportions of Tregs with regulatory function (FoxP3+/CD4+CD25bright) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline (p = 0.019). This result was confirmed in a mixed model regression analysis in which adjustments for inhaled corticosteroid usage, smoking, sex and age were evaluated. No significant difference was found between COPD subjects and smokers or non-smokers with normal lung function. Conclusions: COPD subjects with a rapid decline in lung function had lower proportions of T cells with regulatory function in BAL fluid, suggesting that an inability to suppress the inflammatory response following smoking might lead to a more rapid decline in FEV1. Trial registration Clinicaltrials.gov identifier NCT02729220.

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bronchoalveolar lavage, Chronic obstructive pulmonary disease, Disease mechanisms, Lung function decline, Regulatory T cells, Smoking habits, Chronic obstructive pulmonary disease (COPD), KOL, Disease mechanisms, sjukdomsmekanismer, Lung function decline, lungfunktionsförsämring, Smoking habits, rökvanor, Bronchoalveolar lavage (BAL), bronkoalveolärt lavage (BAL), Regulatory T (Treg) cells, regulatoriska T-celler (T-reg)
in
Respiratory Research
volume
21
article number
330
pages
1 - 9
publisher
BioMed Central (BMC)
external identifiers
  • pmid:33317530
  • scopus:85098475514
ISSN
1465-9921
DOI
10.1186/s12931-020-01593-9
language
English
LU publication?
no
additional info
Publisher Copyright: © 2020, The Author(s).
id
196b7f39-3072-4912-a690-6029517d94b3
date added to LUP
2025-05-16 10:20:09
date last changed
2025-07-12 00:33:19
@article{196b7f39-3072-4912-a690-6029517d94b3,
  abstract     = {{<p>Background: Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not. Upregulation of Tregs in response to smoking would restrain airway inflammation and thus the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD. We hypothesized that—among COPD patients—the same mechanism would affect rate of decline in lung function; specifically, that a decreased expression of Tregs would be associated with a more rapid decline in FEV<sub>1</sub>. Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study; 12 with COPD and a rapid decline in lung function (loss of FEV<sub>1</sub> ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV<sub>1</sub> ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry. Results: The proportions of Tregs with regulatory function (FoxP3<sup>+</sup>/CD4<sup>+</sup>CD25<sup>bright</sup>) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline (p = 0.019). This result was confirmed in a mixed model regression analysis in which adjustments for inhaled corticosteroid usage, smoking, sex and age were evaluated. No significant difference was found between COPD subjects and smokers or non-smokers with normal lung function. Conclusions: COPD subjects with a rapid decline in lung function had lower proportions of T cells with regulatory function in BAL fluid, suggesting that an inability to suppress the inflammatory response following smoking might lead to a more rapid decline in FEV<sub>1</sub>. Trial registration Clinicaltrials.gov identifier NCT02729220.</p>}},
  author       = {{Eriksson Ström, Jonas and Pourazar, Jamshid and Linder, Robert and Blomberg, Anders and Lindberg, Anne and Bucht, Anders and Behndig, Annelie F.}},
  issn         = {{1465-9921}},
  keywords     = {{Bronchoalveolar lavage; Chronic obstructive pulmonary disease; Disease mechanisms; Lung function decline; Regulatory T cells; Smoking habits; Chronic obstructive pulmonary disease (COPD); KOL; Disease mechanisms; sjukdomsmekanismer; Lung function decline; lungfunktionsförsämring; Smoking habits; rökvanor; Bronchoalveolar lavage (BAL); bronkoalveolärt lavage (BAL); Regulatory T (Treg) cells; regulatoriska T-celler (T-reg)}},
  language     = {{eng}},
  month        = {{12}},
  pages        = {{1--9}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Respiratory Research}},
  title        = {{Airway regulatory T cells are decreased in COPD with a rapid decline in lung function}},
  url          = {{http://dx.doi.org/10.1186/s12931-020-01593-9}},
  doi          = {{10.1186/s12931-020-01593-9}},
  volume       = {{21}},
  year         = {{2020}},
}