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

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 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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Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function

PLoS ONE ◽

10.1371/journal.pone.0164751 ◽

2016 ◽

Vol 11 (10) ◽

pp. e0164751 ◽

Cited By ~ 1

Author(s):

Mahyar Ostadkarampour ◽

Malin Müller ◽

Johan Öckinger ◽

Susanna Kullberg ◽

Anders Lindén ◽

...

Keyword(s):

T Cells ◽

Lung Function ◽

Regulatory T Cells ◽

Cytokine Profile ◽

Normal Lung ◽

Normal Lung Function ◽

Young Smokers

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Correlation between Level of Autophagy and Amount of CD8+T Cells in Chronic Obstructive Pulmonary Disease

10.21203/rs.3.rs-36595/v1 ◽

2020 ◽

Author(s):

Songming Zhuo ◽

Hong Zhuang ◽

Na Li ◽

Sida Chen ◽

Wugen Zhan ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Lung Function ◽

Normal Lung ◽

Stable Phase ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Normal Lung Function ◽

Healthy Control ◽

Function Group

Abstract Background: This study aimed to shed light on the correlation between the amounts of CD8+ T cells and autophagy level in COPD. Results: The objects (n = 90) were divided into three groups: COPD group (patients in the stable phase; n = 30), SN group (healthy control of smoking with normal lung function group; n = 30), and NSN groups (healthy control of non-smoking with normal lung function group; n = 30). The amounts of CD8+ (32.33 ± 4.23%), CD8+ effector (25.63 ± 8.57%) and CD8+memory (11.94 ± 5.77%) T cell in the COPD group were significantly higher those in the other two groups, while the apoptotic rate was lower in the COPD group (P < 0.05). Significant linear correlations were found of P62/GAPDH (‰) with CD8+, CD8+effector, and CD8+ memory- T cell amounts (P<0.001). Conclusions: Autophagy level is positively and linearly associated with the amounts of CD8+ T cells, suggesting that cell autophagy might be involved in COPD pathogenesis.

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Rapid decline in lung function in COPD is associated with decreased CD25brightFoxP3 regulatory T cells in BAL

10.1183/13993003.congress-2019.pa4383 ◽

2019 ◽

Author(s):

Jonas Eriksson Ström ◽

Jamshid Pourazar ◽

Robert Linder ◽

Anders Blomberg ◽

Anne Lindberg ◽

...

Keyword(s):

T Cells ◽

Lung Function ◽

Regulatory T Cells ◽

Rapid Decline

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Increasing CD28-FOXP3+CD8+ Treg and Senescent CD8+NK2GA+Eomes+ NK-like T Cells in Peripheral Blood of Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-118088 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1125-1125 ◽

Cited By ~ 1

Author(s):

Dimitri Kasakovski ◽

Xiangbo Zeng ◽

Ling Xu ◽

Yangqiu Li

Keyword(s):

Multiple Myeloma ◽

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Cd8 T Cell ◽

Regulatory Function ◽

Effector Memory ◽

Significant Difference ◽

Hematological Cancers

Abstract Immune dysfunction in patients with multiple myeloma (MM) includes TGF-β induced dendritic cell dysfunction, regulatory T cell (Tregs)/Th17 cell imbalance, accumulation of Tregs and myeloid derived suppressor cells. These tumor-induced dysfunctions may contribute to immune escape and even suppress immune cells introduced in adoptive cellular immunotherapy. CD28 independent T cells of the effector memory (TEM) and CD45RA+ effector memory (TEMRA) population were shown to accumulate with age and contribute to the immunosuppressive tumor microenvironment in several solid tumors and hematological cancers. Especially in the CD8+ population, the loss of CD28 is associated with high cytotoxicity and regulatory function while showing high diversity and defective antigen-induced proliferation. In the CD4 subset, regulatory and senescent T cells were studied extensively, while in the CD8 positive subset their heterogeneity is still not clearly defined. Their potential immunosuppressive role and distribution in healthy individuals (HI) as well as patients with multiple myeloma (MM) remains to be observed. Furthermore, a recently characterized CD8+CD28- NK-like T cell subset showing expression of NK-related inhibitory receptors and TCR independent effector function is potentially of interest in the progression of MM. In the present study, we compared the changes of distribution of CD8+CD25+ and CD8+FOXP3+ regulatory T cells (Treg), CD28-CD57+ senescent T cells (Tsen), and CD8+KIR/NK2GA+EOMES+ NK-like T in peripheral blood (PB) between HI and patients with MM by multicolour flow cytometry (Gating strategy shown in Figure 1A). When comparing 35 HIs (Median age is 54) and 14 MM patients (Median age is 52), it was shown that there is no significant change in the proportion of senescent T cells in CD8 (P = 0.2452), TEM/CD8 (P = 0.1686) and TEMRA/CD8 (P = 0.4861) between HIs and the MM group, while both the CD25+FOXP3+ regulatory T cells of the CD4 population (P = 0.0031) and CD28-FOXP3+ regulatory T cells of the CD8 population (P = 0.0014) were shown to increase. There is no significant difference in the percentages of KIR/NK2GA+EOMES+ in the CD8 T cell and TEMRA/CD8 T cell population between HIs and the MM group. Remarkably, although there was no overall increase in senescent T cell in MM patients, senescent CD8+NK2GA+EOMES+ NK-like T cells increased in MM patients in comparison to HIs (P = 0.0068) (Figure 1B). In conclusion, the increase of regulatory T cells of both the CD4 and CD8 population as well as the increase of senescent NK-like T cells in the CD8 population potentially contributes to cancer progression through creation of suppressive microenvironments. Moreover, we found that regulatory CD8 T cells and CD8 NK-like T cells only contribute to a small part of the overall CD28- senescent T cell pool. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Poor Cognitive Function Is Associated with Obstructive Lung Diseases in Taiwanese Adults

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052344 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2344

Author(s):

Sun-Wung Hsieh ◽

Da-Wei Wu ◽

Chih-Wen Wang ◽

Szu-Chia Chen ◽

Chih-Hsing Hung ◽

...

Keyword(s):

Cognitive Function ◽

Lung Function ◽

Lung Diseases ◽

Mmse Score ◽

Multivariable Analysis ◽

Forced Expiratory Volume ◽

Normal Lung ◽

Obstructive Lung Diseases ◽

Normal Lung Function ◽

Function Group

Previous studies have reported an association between the impairment of cognitive performance and lung diseases. However, whether obstructive or restrictive lung diseases have an impact on cognitive function is still inconclusive. We aimed to investigate the association between cognitive function and obstructive or restrictive lung diseases in Taiwanese adults using the Mini-Mental State Examination (MMSE). In this study, we used data from the Taiwan Biobank. Cognitive function was evaluated using the MMSE. Spirometry measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained to assess lung function. Participants were classified into three groups according to lung function, namely, normal, restrictive, and obstructive lung function. In total, 683 patients enrolled, of whom 357 participants had normal lung function (52.3%), 95 had restrictive lung function (13.9%), and 231 had obstructive lung function (33.8%). Compared to the normal lung function group, the obstructive lung function group was associated with a higher percentage of cognitive impairment (MMSE < 24). In multivariable analysis, a low MMSE score was significantly associated with low FVC, low FEV1, and low FEV1/FVC. Furthermore, a low MMSE score was significantly associated with low FEV1 in the participants with FEV1/FVC < 70%, whereas MMSE was not significantly associated with FVC in the participants with FEV1/FVC ≥ 70%. Our results showed that a low MMSE score was associated with low FEV1, low FVC and low FEV1/FVC. Furthermore, a low MMSE score was associated with obstructive lung diseases but not with restrictive lung diseases.

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Asthma‐chronic obstructive pulmonary disease overlap: A clinical entity?

Journal of Precision Respiratory Medicine ◽

10.2500/jprm.2020.3.200003 ◽

2020 ◽

Vol 3 (1) ◽

pp. 2-8

Author(s):

Robert A. Wise

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Lung Function ◽

Middle Age ◽

Clinical Manifestations ◽

Normal Lung ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Neutrophilic Inflammation ◽

Normal Lung Function

Asthma and COPD are easily recognizable clinical entities in their characteristic presentations. Asthma is an early-onset disorder characterized by Type 2, eosinophil-predominant, inflammation of the airways and is associated with atopy. COPD presents in middle age and is characterized by neutrophilic inflammation of the airways and is associated with cigarette smoking or biomass fuel exposure. Between exacerbations, asthma typically has normal lung function whereas COPD has incompletely reversible lung function. Approximately one in five patients with either of these disorders will show some features of both COPD and Asthma. This overlap is far more common than can be accounted for by chance concurrence of two common diseases. There are likely genetic and environmental susceptibilities to both disorders, but there is no single pathobiological mechanism that identifies all such overlap patients. Most likely there are numerous predispositions that lead to Asthma-COPD overlap that may be grounded in early childhood or even pre-natal events. Thus, Asthma-COPD overlap is best considered a family of diseases with overlapping clinical manifestations. The future elucidation of these different pathways to Asthma-COPD overlap, in conjunction with highly targeted therapies will aid clinicians in treating these patients.

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Predicted Values for Spirometry may Underestimate Long-Standing Asthma Severity

The Open Respiratory Medicine Journal ◽

10.2174/1874306401610010070 ◽

2016 ◽

Vol 10 (1) ◽

pp. 70-78 ◽

Cited By ~ 1

Author(s):

Bruno Sposato

Keyword(s):

Lung Function ◽

Reference Point ◽

Asthma Severity ◽

Normal Lung ◽

Bronchial Obstruction ◽

Z Score ◽

Lung Function Decline ◽

Normal Lung Function ◽

Z Scores ◽

Predicted Values

Background: Asthma may show an accelerated lung function decline. Asthmatics, although having FEV1 and FEV1/VC (and z-scores) higher than the lower limit of normality, may show a significant FEV1 decline when compared to previous measurements. We assessed how many asymptomatic long-standing asthmatics (LSA) with normal lung function showed a significant FEV1 decline when an older FEV1 was taken as reference point. Methods: 46 well-controlled LSA (age: 48.8±12.1; 23 females) with normal FEV1 and FEV1/VC according to GLI2012 references (FEV1: 94.8±10.1%, z-score:-0.38±0.79; FEV1/VC: 79.3±5.2, z-score:-0.15±0.77) were selected. We considered FEV1 decline, calculated by comparing the latest value to one at least five years older or to the highest predicted value measured at 21 years for females and 23 for males. A FEV1 decline >15% or 30 ml/years was regarded as pathological. Results: When comparing the latest FEV1 to an at least 5-year-older one (mean 8.1±1.4 years between 2 measurements), 14 subjects (30.4%) showed a FEV1 decline <5% (mean: -2.2±2.6%), 19 (41.3%) had a FEV1 5-15% change (mean: -9.2±2.5%) and 13 (28.3%) a FEV1 decrease>15% (mean: -18.3±2.4). Subjects with a FEV1 decline>30 ml/year were 28 (60.8%). When using the highest predicted FEV1 as reference point and declines were corrected by subtracting the physiological decrease, 6 (13%) patients showed a FEV1 decline higher than 15%, whereas asthmatics with a FEV1 loss>30 ml/year were 17 (37%). Conclusion: FEV1 decline calculation may show how severe asthma actually is, avoiding a bronchial obstruction underestimation and a possible under-treatment in lots of apparent “well-controlled” LSA with GLI2012-normal-range lung function values.

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