scholarly journals COPD is associated with increased pro-inflammatory CD28null CD8 T and NKT-like cells in the small airways

2022 ◽  
Author(s):  
Greg Hodge ◽  
Hubertus Jersmann ◽  
Hai B Tran ◽  
Patrick F Asare ◽  
Minnu Jayapal ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Lymphocyte Subsets ◽  
Granzyme B ◽  
Small Airways ◽  
Steroid Resistant ◽  
Inflammatory Cytokine Production ◽  
Copd Patients ◽  
Distal Airway ◽  
Before And After ◽  
Lymphocytes Subsets

Abstract We previously showed increased steroid resistant CD28null CD8+ senescent lymphocyte subsets in peripheral blood from COPD patients. These cells expressed decreased levels of the glucocorticoid receptor (GCR), suggesting their contribution to the steroid resistant property of these cells. COPD is a disease of the small airways. We therefore hypothesized that there would be a further increase in these steroid resistant lymphocytes in the lung, particularly in the small airways. We further hypothesized that the pro-inflammatory/cytotoxic potential of these cells could be negated using prednisolone with low-dose cyclosporin A. Blood, bronchoalveolar lavage, large proximal and small distal airway brushings were collected from 11 COPD patients and 10 healthy aged-matched controls. The cytotoxic mediator granzyme b, pro-inflammatory cytokines IFNγ/TNFα, and GCR were determined in lymphocytes subsets before and after their exposure to 1µM prednisolone and/or 2.5ng/mL cyclosporin A. Particularly in the small airways, COPD subjects showed an increased percentage of CD28null CD8 T-cells and NKT-like cells, with increased expression of granzyme b, IFNγ and TNFα and a loss of GCR, compared with controls. Significant negative correlations between small airway GCR expression and IFNγ/TNFα production by T and NKT-like cells (eg, T-cell IFNγ R= -.834, p=.031) and with FEV1 (R= -890) were shown. Cyclosporine A and prednisolone synergistically increased GCR expression and inhibited pro-inflammatory cytokine production by CD28null CD8- T and NKT-like cells. COPD is associated with increased pro-inflammatory CD28null CD8+ T and NKT-like cells in the small airways. Treatments that increase GCR in these lymphocyte subsets may improve efficacy of clinical treatment.

scholarly journals COPD is associated with increased pro-inflammatory CD28null CD8 T and NKT-like cells in the small airways 

2021 ◽  
Author(s):  
Greg Hodge et al
Keyword(s):  
Cyclosporin A ◽  
Lymphocyte Subsets ◽  
Granzyme B ◽  
Small Airways ◽  
Steroid Resistant ◽  
Inflammatory Cytokine Production ◽  
Copd Patients ◽  
Distal Airway ◽  
Before And After ◽  
Lymphocytes Subsets

We previously showed increased steroid resistant CD28null CD8+ senescent lymphocyte subsets in peripheral blood from COPD patients. These cells expressed decreased levels of the glucocorticoid receptor (GCR), suggesting their contribution to the steroid resistant property of these cells. COPD is a disease of the small airways. We therefore hypothesized that there would be a further increase in these steroid resistant lymphocytes in the lung, particularly in the small airways. We further hypothesized that the pro-inflammatory/cytotoxic potential of these cells could be negated using prednisolone with low-dose cyclosporin A. Blood, bronchoalveolar lavage, large proximal and small distal airway brushings were collected from 11 COPD patients and 10 healthy aged-matched controls. The cytotoxic mediator granzyme b, pro-inflammatory cytokines IFNγ/TNFα, and GCR were determined in lymphocytes subsets before and after their exposure to 1µM prednisolone and/or 2.5ng/mL cyclosporin A. Particularly in the small airways, COPD subjects showed an increased percentage of CD28null CD8 T-cells and NKT-like cells, with increased expression of granzyme b, IFNγ and TNFα and a loss of GCR, compared with controls. Significant negative correlations between small airway GCR expression and IFNγ/TNFα production by T and NKT-like cells (eg, T-cell IFNγ R= -.834, p=.031) and with FEV (R= -890) were shown. Cyclosporine A and prednisolone synergistically increased GCR expression and inhibited pro-inflammatory cytokine production by CD28null CD8- T and NKT-like cells. COPD is associated with increased pro-inflammatory CD28null CD8+ T and NKT-like cells in the small airways. Treatments that increase GCR in these lymphocyte subsets may improve morbidity in COPD patients.

Effects of use of an eHealth platform e-Vita for COPD patients on disease specific quality of life domains

2020 ◽  
Keyword(s):  
Quality Of Life ◽  
Functional State ◽  
Mental State ◽  
Self Management ◽  
Copd Patients ◽  
Before And After ◽  
Ehealth Intervention ◽  
The Impact ◽  
Disease Specific

Background: Integrated disease management with self-management for Chronic Obstructive Pulmonary Disease (COPD) is effective to improve clinical outcomes. eHealth can improve patients’ involvement to be able to accept and maintain a healthier lifestyle. Eventhough there is mixed evidence of the impact of eHealth on quality of life (QoL) in different settings. Aim: The primary aim of the e-Vita-COPD-study was to investigate the effect of use of eHealth patient platforms on disease specific QoL of COPD patients. Methods: We evaluated the impact of an eHealth platform on disease specific QoL measured with the clinical COPD questionnaire (CCQ), including subscales of symptoms, functional state and mental state. Interrupted time series (ITS) design was used to collect CCQ data at multiple time points. Multilevel linear regression modelling was used to compare trends in CCQ before and after the eHealth intervention. Results: Of 742 invited COPD patients, 244 signed informed consent. For the analyses, we only included patients who actually used the eHealth platform (n = 123). The decrease of CCQ-symptoms was 0,20% before the intervention and 0,27% after the intervention; this difference was statistically significant (P=0.027). The decrease of CCQ-mental was 0,97% before the intervention and after the intervention there was an increase of 0,017%; this difference was statistically significant (P=0,01). No significant difference was found in the slopes of CCQ (P=0,12) and CCQ-function (P=0,11) before and after the intervention. Conclusion: The e-Vita eHealth platform had a potential beneficial impact on the CCQ-symptoms of COPD patients, but not on functional state. The CCQ-mental state remained stable after the intervention, but this was a deterioration compared to the improving situation before the start of the eHealth platform. In conclusion, this study shows that after the introduction of the COPD platform, patients experienced fewer symptoms, but their mental state deteriorated slightly at the same time. Therefore, health care providers should be aware that, although symptoms improve, there might be a slight increase in anxiety and depression after introducing an eHealth intervention to support self-management.

scholarly journals Lung macrophages drive mucus production and steroid-resistant inflammation in chronic bronchitis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kristina Andelid ◽  
Karolina Öst ◽  
Anders Andersson ◽  
Esha Mohamed ◽  
Zala Jevnikar ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Chronic Bronchitis ◽  
Cross Talk ◽  
Alveolar Macrophages ◽  
Ex Vivo ◽  
Bronchial Epithelial Cells ◽  
Steroid Resistance ◽  
Bronchial Epithelial ◽  
Steroid Resistant ◽  
Copd Patients

Abstract Background Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from chronic bronchitis (CB) and display steroid-resistant inflammation with increased sputum neutrophils and macrophages. Recently, a causal link between mucus hyper-concentration and disease progression of CB has been suggested. Methods In this study, we have evaluated the steroid sensitivity of purified, patient-derived sputum and alveolar macrophages and used a novel mechanistic cross-talk assay to examine how macrophages and bronchial epithelial cells cross-talk to regulate MUC5B production. Results We demonstrate that sputum plug macrophages isolated from COPD patients with chronic bronchitis (COPD/CB) are chronically activated and only partially respond to ex vivo corticosteroid treatment compared to alveolar macrophages isolated from lung resections. Further, we show that pseudo-stratified bronchial epithelial cells grown in air–liquid-interface are inert to direct bacterial lipopolysaccharide stimulation and that macrophages are able to relay this signal and activate the CREB/AP-1 transcription factor complex and subsequent MUC5B expression in epithelial cells through a soluble mediator. Using recombinant protein and neutralizing antibodies, we identified a key role for TNFα in this cross-talk. Conclusions For the first time, we describe ex vivo pharmacology in purified human sputum macrophages isolated from chronic bronchitis COPD patients and identify a possible basis for the steroid resistance frequently seen in this population. Our data pinpoint a critical role for chronically activated sputum macrophages in perpetuating TNFα-dependent signals driving mucus hyper-production. Targeting the chronically activated mucus plug macrophage phenotype and interfering with aberrant macrophage-epithelial cross-talk may provide a novel strategy to resolve chronic inflammatory lung disease.

Lymphocyte subsets are influenced by positivity levels in healthy subjects before and after mild acute stress

2017 ◽  
Vol 188 ◽  
pp. 13-20 ◽  
Author(s):  
Gian Vittorio Caprara ◽  
Roberto Nisini ◽  
Valeria Castellani ◽  
Pasquali Vittorio ◽  
Guido Alessandri ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Lymphocyte Subsets ◽  
Acute Stress ◽  
Before And After

Changes of lymphocyte subsets in peripheral blood before and after operation of patients with advanced ovarian carcinoma

1990 ◽  
Vol 116 (3) ◽  
pp. 283-287 ◽  
Author(s):  
Yoshihiro Kikuchi ◽  
Ichiro Iwano ◽  
Tsunekazu Kita ◽  
Munenori Miyauchi ◽  
Eiichi Kuki ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Peripheral Blood ◽  
Lymphocyte Subsets ◽  
Advanced Ovarian Carcinoma ◽  
Before And After

scholarly journals Lymphocyte subset reference intervals in blood donors from northeastern Brazil

2015 ◽  
Vol 87 (2) ◽  
pp. 1019-1025
Author(s):  
ALEX J.L. TORRES ◽  
PATRÍCIA CISNEIROS ◽  
ROSA GUEDES ◽  
MARIA FERNANDA R. GRASSI ◽  
ROBERTO MEYER ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Blood Donors ◽  
Lymphocyte Subsets ◽  
Reference Intervals ◽  
Northeastern Brazil ◽  
Significant Finding ◽  
T Lymphocyte Subsets ◽  
European Origin ◽  
Male Subjects ◽  
Lymphocytes Subsets

The reference intervals for leukocytes and lymphocytes currently used by most clinical laboratories present limitations as they are primarily derived from individuals of North American and European origin. The objective this study was to determine reference values for peripheral blood B lymphocytes, T lymphocyte subsets (CD4+, CD8+, naïve, memory, regulatory, TCRαβ and TCRγδ+) and NK cells from blood donors in Salvador-Bahia, Brazil. Results: The proportion of included male subjects was 73.7% and the median ages of males (34) and females (35) were found to be similar. Absolute counts total lymphocytes subsets to both gender was 1,956 (1,060-4,186) cells and relative values 34%. The T CD4+ and T CD8+ lymphocytes relative values was 51% (20-62) and 24% (9-28), respectively. The most statistically significant finding observed was a higher percentage of B lymphocytes (p=0.03) in females. Commonly cited subset reference intervals were found to be consistent with values in several populations from different geographic areas.

scholarly journals Comprehensive exercise training improves ventilatory muscle function and reduces dyspnea perception in patients with COPD

2016 ◽  
Vol 71 (3) ◽  
Author(s):  
F. Cortopassi ◽  
A.A.M. Castro ◽  
E.F. Porto ◽  
M. Colucci ◽  
G. Fonseca ◽  
...  
Keyword(s):  
Exercise Training ◽  
Respiratory Muscles ◽  
Exercise Programme ◽  
Lower Limbs ◽  
Test Time ◽  
Chronic Obstructive ◽  
Endurance Test ◽  
Incremental Test ◽  
Copd Patients ◽  
Before And After

Background. Comprehensive exercise training (CET) is an efficient strategy to decrease dyspnea perception in chronic obstructive pulmonary disease (COPD) and may result in significant improvement in ventilatory muscles function. Our aim was to evaluate the effects of general exercise training on dyspnea perception and on respiratory muscles strength in COPD patients. Methods. Consecutive COPD patients were enrolled to complete a CET programme. The patients underwent a routine that included a global warm up, upper and lower limbs endurance exercise as well as stretching and relaxation. Before and after the CET programme, patients completed maximal inspiratory (PImax) and expiratory (PEmax) pressures measurements, maximal incremental test, endurance test, and 6-min walk distance (6MWD). Results. 71 patients (52 male). Mean age 67.6±8.6 years, FEV1 (%) 44.2±16.2 and Mahler dyspnea scale 6.4±1.8. The results before and after the exercise programme were: PImax 64.7±22.9 vs. 75.5±23.7 cmH2O (p=0.001), PEmax 110.8±28.1 vs. 120.4±28.1 cmH2O (p=0.004), 6MWD 510.6±90.3 vs. 528.2±99.7 metres (p=0.88), time of incremental test 672±135 vs. 856±226 sec (p<0.0001). Compared with the pre exercise programme, we observed a significant reduction on Borg dyspnea scale (6.1±2.8 to 3.6±2.3, p<0.0001) as well as a longer test time (504±218 to 1.038±841, p<0.0001) at the end of the endurance test after CET programme. Improvement of PImax correlated negatively with dyspnea perception at iso-time during the endurance test (r= -0.33, p=0.03). Conclusions. Our results confirm that CET is associated with significant improvement in PImax, PEmax and provide evidence demonstrating that CET reduces dyspnea perception in patients with COPD.

scholarly journals BOS is associated with decreased HDAC2 from steroid resistant lymphocytes in the small airways

2018 ◽  
Vol 195 (2) ◽  
pp. 277-285 ◽  
Author(s):  
G. Hodge ◽  
S. Hodge ◽  
A. Yeo ◽  
P. Nguyen ◽  
E. Hopkins ◽  
...  
Keyword(s):  
Small Airways ◽  
Steroid Resistant

scholarly journals The Effect of Opiocephalus striatus Extract on Leptin, Adiponectin and COPD Assessment Test Scores on Stable COPD Patients Experiencing Muscle Wasting

2018 ◽  
Vol 38 (3) ◽  
pp. 158-163
Author(s):  
Komang Sri Rahayu Widiasari ◽  
Susanthy Djajalaksana ◽  
Harun Al Rasyid
Keyword(s):  
Quality Of Life ◽  
Muscle Wasting ◽  
Nutrition Therapy ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Before And After ◽  
Quasi Experimental ◽  
Physiology Laboratory

Background: Muscle wasting is one of extrapulmonary manifestations that occur in 20-40% of patients with COPD as a result of an imbalance of protein synthesis and degradation, where it is thought to be a consequence of chronic inflammation. One of the factor that affect muscle wasting is nutritional factor. The purpose of this study is to prove that nutrition therapy can improve inflammation (measured by levels of leptin, adiponectin) further improve muscle wasting and improve the quality of life of patients COPD with muscle wasting. Method: The clinical study design is pre and post auto control quasi experimental in stable COPD patients with comorbid muscle wasting. The experiment was conducted in Pulmonary Outpatient Clinic Dr. Saiful Anwar Hospital and Physiology Laboratory of Medical Faculty Brawijaya University. Chronic obstructive pulmonary disease was diagnosed based on 2014 GOLD criteria. Muscle wasting was diagnosed through examination of the BIA. Levels of leptin and adiponectin was measured using ELISA method, and quality of life was assessed using CAT score. We measured BIA, Leptin, Adiponectin and CAT in 32 COPD patients with muscle wasting, before and after 12 weeks supplementation of Opiocephalus striatus extract 3x1000mg/day. Results: There were significant increased of BMI (p = 0.046), no significant increase of FFMI (p = 0506), a significant decrease in leptin levels (p = 0.000) and a significant increase in adiponectin levels (p = 0.048) and improvement of quality of life (score CAT) (p = 0.000) ) after administration of opiocephalus striatus extract for 12 weeks. Conclusion: Suplementation of Opiocephalus striatus extract for 12 weeks can improve BMI, decrease levels of leptin and increase level of adiponectin resulting in improvement of quality of life in stable COPD patients with muscle wasting.

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