scholarly journals The elastin peptide VGVAPG increases CD4+ T-cell IL-4 production in patients with chronic obstructive pulmonary disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Flora Lemaire ◽  
Sandra Audonnet ◽  
Jeanne-Marie Perotin ◽  
Pierre Gaudry ◽  
Sandra Dury ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
T Cells ◽  
T Cell ◽  
Pulmonary Disease ◽  
Cytokine Expression ◽  
Chronic Obstructive ◽  
Specific Marker ◽  
Obstructive Pulmonary Disease ◽  
Elastin Degradation ◽  
Copd Patients

Abstract Background In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients. Methods CD4+ and CD8+ T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera. Results Compared with control, the percentage of IL-4 (Th2) producing CD4+ T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p < 0.05), whereas no significant differences were found with IFN-γ (Th1) and IL-17A (Th17). Among COPD patients, two subpopulations were observed based on the percentage of IL-4 (Th2) producing CD4+ T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7). Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4+ T cells expressing IL-4 significantly increased in COPD patients (p < 0.05), but not in controls. The VGVAPG-induced increase in IL-4 was inhibited in the presence of analogous peptide antagonizing VGVAPG/elastin receptor (S-gal) interactions. Conclusions The present study demonstrates that the VGVAPG elastin peptide modulates CD4+ T-cells IL-4 production in COPD. Monitoring IL-4 in circulating CD4+ T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4+ T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients.

scholarly journals Immune checkpoints in chronic obstructive pulmonary disease

2017 ◽  
Vol 26 (144) ◽  
pp. 170045 ◽  
Author(s):  
Tom M.A. Wilkinson
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
T Cells ◽  
T Cell ◽  
Pulmonary Disease ◽  
T Cell Activation ◽  
Acute Infection ◽  
Immune Checkpoints ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Cytotoxic Function

Cell-mediated immune responses are vital to the body's defence against infection and play a key role in tumour immunity. T-cell activation and cytotoxic function is tightly regulated by a series of immune-regulatory receptor–ligand interactions or immune checkpoints. These controls limit immune-mediated damage, particularly in the context of chronic infection. However, prolonged signalling through these axes can lead to progressive loss of T-cell function, termed exhaustion.Understanding of the biology of checkpoints and that exhaustion is reversible has been key to the development of new therapies directed at reversing the dysfunctional status of T-cells, which are dramatically improving outcomes of cancer treatment.Emerging data suggest that immune checkpoint axes are dysregulated in chronic obstructive pulmonary disease (COPD). T-cells from diseased lungs express the key receptor programmed death (PD)1 and demonstrate loss of cytotoxic function. However, the picture is complex with evidence of downregulation of the associated ligand PDL1 on alveolar macrophages. The resulting impact may be excessive T-cell inflammation as a consequence of acute infection, which may contribute to the pattern of exacerbation and lung damage characteristic of COPD. More work is needed to understand these immune controls in COPD before the therapeutic advances seen in lung cancer can be explored.

scholarly journals Low Vitamin K Status Is Associated with Increased Elastin Degradation in Chronic Obstructive Pulmonary Disease

2019 ◽  
Vol 8 (8) ◽  
pp. 1116 ◽  
Author(s):  
Ianthe Piscaer ◽  
Jody M. W. van den Ouweland ◽  
Kristina Vermeersch ◽  
Niki L. Reynaert ◽  
Frits M. E. Franssen ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Vitamin K ◽  
Matrix Gla Protein ◽  
Chronic Obstructive ◽  
Inverse Association ◽  
Obstructive Pulmonary Disease ◽  
Elastin Degradation ◽  
Copd Patients

Elastin degradation is accelerated in chronic obstructive pulmonary disease (COPD) and is partially regulated by Matrix Gla Protein (MGP), via a vitamin K-dependent pathway. The aim was to assess vitamin K status in COPD as well as associations between vitamin K status, elastin degradation, lung function parameters and mortality. A total of 192 COPD patients and 186 age-matched controls were included. In addition to this, 290 COPD patients from a second independent longitudinal cohort were also included. Vitamin K status was assessed by measuring plasma inactive MGP levels and rates of elastin degradation by measuring plasma desmosine levels. Reduced vitamin K status was found in COPD patients compared to smoking controls (p < 0.0005) and controls who had never smoked (p = 0.001). Vitamin K status was inversely associated with desmosine (cohort 1: p = 0.001; cohort 2: p = 0.004). Only few significant associations between vitamin K status and lung function parameters were found. Mortality was higher in COPD patients within the quartile with the lowest vitamin K status compared to those within the other quartiles (hazard ratio 1.85, 95% confidence interval (CI), 1.21–2.83, p = 0.005). In conclusion, we demonstrated reduced vitamin K status in COPD and an inverse association between vitamin K status and elastin degradation rate. Our results therefore suggest a potential role of vitamin K in COPD pathogenesis.

scholarly journals Correlation between level of autophagy and frequency of CD8+ T cells in patients with chronic obstructive pulmonary disease

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095263
Author(s):  
Hong Zhuang ◽  
Na Li ◽  
Sida Chen ◽  
Yan Shen ◽  
Wugen Zhan ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
T Cells ◽  
T Cell ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Normal Lung Function

Objective The pathogenesis of chronic obstructive pulmonary disease (COPD) remains elusive. Here, we assessed the correlation between CD8+ T cell frequencies and autophagy in COPD patients. Methods Subjects were divided into three groups (n = 30 patients/group): (1) COPD patients in the stable phase; (2) smokers with normal lung function; and (3) non-smokers with normal lung function. Flow cytometry was used to enumerate CD8+ T cell subsets (CD8+, CD8+ effector, and CD8+ memory T cells) and quantitate T-cell apoptosis. RT-PCR and western blotting were used to measure levels of LC3 and p62. Results Frequencies of CD8+ T cell subsets and expression of p62 and LC3 II/I were significantly higher in COPD patients compared with the other two groups, while the rate of apoptosis was lower. In COPD patients, LC3 II/I and p62 expression were positively correlated with CD8+ T cell subset frequencies. Moreover, a significant correlation was observed between LC3 II/I and p62 expression and T cell subset frequencies. Conclusion Autophagy level is positively correlated with the frequencies of CD8+ T cells, suggesting that autophagy might be involved in COPD pathogenesis.

Oral and Oropharyngeal Sensory Function in Adults With Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Oral Cavity ◽  
Pulmonary Disease ◽  
Thermal Sensation ◽  
Sensory Function ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Copd Patients

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.

Clinical and functional peculiarities at patients with bronchial asthma, chronic obstructive pulmonary disease and overlap of asthma-chronic obstructive pulmonary disease

2020 ◽  
Vol 24 (4) ◽  
pp. 80-86
Author(s):  
V. I. Trofimov ◽  
D. Z. Baranov
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Bronchial Asthma ◽  
Blood Test ◽  
Chronic Obstructive ◽  
Inflammation Markers ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Functional Features ◽  
Lower Airways

BACKGROUND: a comparative analysis of laboratory and instrumental tests at patients with bronchial obstructive diseases seems very actual due to the wide prevalence of these diseases. THE AIM: to evaluate characteristics of spirometry as well as allergic (total IgE, sputum eosinophils) and infectious (blood and sputum leucocytes, ESR, CRP, fibrinogen) inflammation markers at patients with bronchial obstructive diseases. PATIENTS AND METHODS: 104 case histories of patients with bronchial asthma, chronic obstructive pulmonary disease and overlap were analyzed including age, duration of smoking (pack-years), laboratory (clinical blood test, biochemical blood test, general sputum analysis, sputum culture) and instrumental (spirometry, body plethysmography, echocardiography) tests. Data were processed statistically with non-parametric methods. RESULTS: COPD patients were older than other groups’ patients, had the highest pack-years index. ACO patients were marked with maximal TLC and Raw, minimal FEV1, FEF25-75, FEV1/FVC. Patients with COPD had the highest inflammation markers (leucocyte count, CRP, fibrinogen). CONCLUSION: high active inflammation may cause severe lower airways possibility disorders at patients with COPD. Data related to a possible role of K. pneumoniaе in the pathogenesis of eosinophilic inflammation in lower airways are of significant interest. Patients with ACO occupy an intermediate position between asthma and COPD patients based on clinical and functional features.

scholarly journals LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoman Zhou ◽  
Yunjun Zhang ◽  
Yutian Zhang ◽  
Quanni Li ◽  
Mei Lin ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Polymorphisms ◽  
Chronic Obstructive ◽  
Nucleotide Polymorphisms ◽  
Obstructive Pulmonary Disease ◽  
Logistic Analysis ◽  
Copd Patients ◽  
Increased Risk ◽  
And Gender

Abstract Objective Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. Methods Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. Results LINC01414 rs699467 (OR = 0.73, 95% CI 0.56–0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31–0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31–6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). Conclusion Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

scholarly journals Blood eosinophil count-guided corticosteroid therapy and as a prognostic biomarker of exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204062232110287
Author(s):  
Tao Liu ◽  
Zi-Jian Xiang ◽  
Xiao-Meng Hou ◽  
Jing-Jing Chai ◽  
Yan-Li Yang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Prognostic Biomarker ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
The Stability

Background: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and dyspnea, as well as an increase in the number of leukocytes in the airways, lungs, and pulmonary vessels. A ‘One size fits all’ approach to COPD patients with different clinical features may be considered outdated. The following are the two major objectives of this meta-analysis: the first is to determine if blood eosinophil counts (BEC) can serve as a prognostic biomarker of COPD outcomes, and the second is to determine which level of BEC is effective for inhaled corticosteroid (ICS) treatment. Methods: We searched articles published before 15 May 2021 in the following four electronic databases: Web of Science, Cochrane Library, EMBASE, and PubMed. Results: A total of 42 studies, comprising a sampling of 188,710 subjects, were summarized and compared in this meta-analysis. The rate ratio (RR) of exacerbations of COPD (ECOPD) between ICS and non-ICS treatment was statistically significant for the COPD patients with a baseline BEC ⩾ 2% or ⩾ 200 cells/μl, RR = 0.82 (0.73, 0.93) or 0.79 (0.70, 0.89) respectively, while the RR of ECOPD between ICS and non-ICS treatment was statistically insignificant for the COPD patients with baseline BEC < 2% or <200 cells/μl, RR = 0.97 (0.87, 1.08) or 0.97 (0.86, 1.08), suggested that ICS therapy was beneficial to the improvement of ECOPD in patients with a baseline BEC ⩾ 2% or BEC ⩾ 200 cells/μl. Conclusion: Our research shows that a BEC ⩾ 200 cells/μl or ⩾2% is likely to become the cutoff value of ICS treatment for ECOPD. Moreover, we believe that the baseline BEC can be used as a biomarker for predicting ECOPD. The stability of BEC requires special attention.

Sign in / Sign up

Export Citation Format

Share Document