Lymphocytes Apoptosis in Patients with Acute Exacerbation of Asthma

Asthma is characterized by airway inflammation, which can be now assessed by the analysis of induced sputum . Ten patients with asthma were investigated during acute exacerbation for the quantification of apoptosis, for Bcl-2 and Fas expression, in induced sputum lymphocytes. They were compared to 12 patients with chronic obstructive pulmonary disease (COPD), and 10 healthy controls. Spontaneous apoptosis was determined by staining nuclei with propidium iodide, and analyzed with a FACScan. Bcl-2 was measured by Western blotting, and results were obtained by densitometric scanning, done by the gel proanalyser. The investigation of Fas was performed using the streptavidin-biotin preroxidase-complex method. Patients with asthma and patients with COPD exhibited a significant increase of cellularity, percentage of neutrophils, eosinophils and lymphocytes when compared to healthy controls. Apoptosis in induced sputum mononuclear cells was found decreased in patients with asthma compared to COPD patients and healthy controls. The quantification of apoptosis was measured after exposure to anticytokine antibodies. Anti-TNF-α antibody blocked the apoptosis in both patients groups and healthy controls, suggesting that TNF-α acted as an inducer of apoptosis. Anti-IL-10 blocked apoptosis completely exclusively in patients with asthma. Bcl-2 expression was found to be increased in induced sputum mononuclear cells from patients with asthma, compared to healthy controls and patients with COPD. Expression of Fas could be detected in patients with asthma, at a lower level than COPD patients and healthy controls. Distinct mechanisms of apoptosis were found in patients with asthma and patients with COPD, characterized by different levels of Bcl-2 and Fas expression. Induction of apoptosis should be a beneficial process in allergic inflammation traduced in induced sputum mononuclear cells. The apoptosis process is assumed by two different mechanisms in asthma and COPD. Our findings indicated that in asthmatic patients, activated lymphocytes accumulate in the bronchi; because of their prolonged survival that maintains inflammation.

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Chronic Obstructive Pulmonary Disease Patients Have Increased Levels of Plasma Inflammatory Mediators Reported Upregulated in Severe COVID-19

Frontiers in Immunology ◽

10.3389/fimmu.2021.678661 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nathalie Acevedo ◽

Jose Miguel Escamilla-Gil ◽

Héctor Espinoza ◽

Ronald Regino ◽

Jonathan Ramírez ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Plasma Proteins ◽

Viral Infections ◽

Chronic Obstructive ◽

Healthy Controls ◽

Obstructive Pulmonary Disease ◽

Asthmatic Patients ◽

Copd Patients ◽

Increased Risk

BackgroundChronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear. Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators.MethodsNinety-two proteins were quantified in 315 plasma samples from 118 asthmatics, 99 COPD patients and 98 healthy controls (age 40-90 years), who were recruited in Colombia before the COVID-19 pandemic. Protein levels were compared between each disease group and healthy controls. Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the “COVID-19 Drug and Gene Set Library” and with experimentally tested protein biomarkers of severe COVID-19.ResultsForty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database. An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been experimentally detected in patients with severe COVID-19.ConclusionsCOPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19. Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19. Also, that IL-6 levels are increased in some asthmatic patients (especially in females) and this may influence their response to COVID-19. The findings in this study depict a novel panel of inflammatory plasma proteins in COPD patients that may potentially associate with increased susceptibility to severe COVID-19 and might be useful as a biomarker signature after future experimental validation.

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Lipoxygenase-Derived Arachidonic Acid Metabolites in Chronic Obstructive Pulmonary Disease

Medicina ◽

10.3390/medicina48060043 ◽

2011 ◽

Vol 48 (6) ◽

pp. 43

Author(s):

Līga Balode ◽

Gunta Strazda ◽

Normunds Jurka ◽

Uldis Kopeika ◽

Agnese Kislina ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Arachidonic Acid ◽

Pulmonary Disease ◽

Inflammatory Cell ◽

Induced Sputum ◽

Chronic Obstructive ◽

Healthy Controls ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Anti Inflammatory

Background and Objective. Chronic obstructive pulmonary disease (COPD) is characterized by a persistence of inflammation in large and small airways. We hypothesized that this could be caused by the inability of an inflammatory process to resolve. In the resolution of inflammation, a switching of arachidonic acid metabolism from the production of proinflammatory leukotriene B4 (LtB4) to the synthesis of anti-inflammatory lipoxins plays an important role. The aim of our study was to determine the content of lipoxin A4 (LXA4) and LtB4 in induced sputum of patients with exacerbated COPD and to compare it to healthy controls, as well as to analyze the relationship between proinflammatory and anti-inflammatory mediators and an inflammatory cell spectrum in induced sputum. Material and Methods. Induced sputum from 17 COPD patients and 7 healthy controls were analyzed for LXA4 and LtB4 content and inflammatory cell spectrum. Results. COPD patients had a significantly lower sputum LXA4 concentration and LtB4/LXA4 ratio compared with healthy controls. A significant negative correlation was found between the LXA4 concentration and the relative neutrophil count and between the LtB4/LXA4 ratio and the relative macrophage count. Conclusions. COPD patients during the late phase of exacerbation had a suppressed production of LXA4 and an elevated LtB4/LXA4 ratio in induced sputum demonstrating a proinflammatory imbalance. The correction of a balance between proinflammatory and anti-inflammatory eicosanoids by the administration of stable analogues of lipoxins could improve the treatment of chronic obstructive pulmonary disease in the future.

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Inflammatory response in induced sputum mononuclear cells from patients with acute exacerbation of asthma

Mediators of Inflammation ◽

10.1080/09629350020002886 ◽

2000 ◽

Vol 9 (3-4) ◽

pp. 147-153 ◽

Cited By ~ 9

Author(s):

A. Hamzaoui ◽

M. Ben Brahim ◽

A. Zhioua ◽

Kh. Ayed ◽

K. Hamzaoui

Keyword(s):

Mrna Expression ◽

Mononuclear Cells ◽

Cytokine Production ◽

Induced Sputum ◽

Healthy Controls ◽

Rt Pcr ◽

Sputum Induction ◽

Asthmatic Patients ◽

Ifn Γ ◽

Pcr Techniques

Examination of sputum provides a direct method to investigate airway inflam mation non-invasively in particular Th1 (IL-2, IFN–γ) and Th2 (IL–4, IL–10) cytokine production.IL–2, IL–4, IL–10 and IFN–γ cytokine were studied in induced sputum mononuclear cells of asthmatic patients.Sputum induction was performed on 10 patients and 10 normal controls. Basal and mitogen-stimulated cytokine production was determined in induced sputum T-cell culture. Supernatants were collected and assayed not only with specific ELISA but also with polymerase chain reaction (PCR) techniques.Data showed a significantly higher production of IL–10 by both the ELISA and the RT-PCR techniques in asthmatic patients compared with sputum mononuclear cells from healthy controls. IL–4 production was detected at a low level using the ELISA method in asthmatic patients. The RT-PCR analysis detected a significantly IL–4-mRNA expression in all asthmatic patients, compared with controls. Results of IL–10 and IL–4 mRNA expression were reproducible. We did not find any alteration in the expression of the type 1 derived cytokines (IL–2 and IFN–γ) in asthmatic patients or in healthy controls.Our study showed a tendency of induced sputum mononuclear cells to express a Th2-like cytokine pattern in acute exacerbation of asthmatic patients, where IL–10 and IL–4 are synthesized in larger amounts. The combination of sputum induction as a non-invasive tool to explore the lung and the identification of disease-associated cytokine expression and of specific cytokine mRNA should help elucidate mechanisms of the immunologically mediated inflammatory responses in asthma.

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Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

Journal of Clinical Medicine ◽

10.3390/jcm10040875 ◽

2021 ◽

Vol 10 (4) ◽

pp. 875

Author(s):

Kawaljit Kaur ◽

Shahram Vaziri ◽

Marcela Romero-Reyes ◽

Avina Paranjpe ◽

Anahid Jewett

Keyword(s):

Periodontal Disease ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Oral Disease ◽

Healthy Controls ◽

Healthy Individuals ◽

Tnf Α ◽

Blood Mononuclear Cells ◽

Ifn Γ ◽

And Function

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood.

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Effects of Mangosteen pericarp Extract to Clinical Improvements, The Plasma Level of IL-6 and Malondialdehyde in Acute Exacerbation of COPD Patients

Jurnal Respirologi Indonesia ◽

10.36497/jri.v38i3.6 ◽

2018 ◽

Vol 38 (3) ◽

pp. 164-172

Author(s):

Khilyatul Baroroh ◽

Suradi Suradi ◽

Ade Rima

Keyword(s):

Treatment Group ◽

Plasma Level ◽

Length Of Stay ◽

Acute Exacerbation ◽

Clinical Symptoms ◽

Control Group ◽

Chronic Obstructive ◽

Copd Patients ◽

Significant Difference ◽

And Control

Background: Amplification of inflammation in acute exacerbation of chronic obstructive pulmonary disease (COPD) increases inflammatory mediators and oxidative stress in the airways, pulmonary and systemic circulation that are characterized by increased plasma level of IL-6 and MDA, resulting in worsening of clinical symptoms. Xanthones in mangosteen pericarp have anti-inflammatory and antioxidant effects, potentially as an adjuntive therapy in acute exacerbations of COPD. Methods: The aim of this study was to determine the effect of mangosteen pericarp extract to clinical improvements, plasma level of IL-6 and MDA of acute exacerbation COPD patients. A clinical trial of experimental with pretest and posttest was conducted on 34 acute exacerbation of COPD patients in Dr. Moewardi Hospital Surakarta and Dr. Ario Wirawan Lung Hospital Salatiga from April until May 2016. The sample was taken by consecutive sampling. Subjects were divided by randomized double blind technique into the treatment group (n=17) received mangosteen pericarp extract 2x1100mg/day and control group (n = 17) received placebo. Clinical improvements were measured in CAT score and length of stay. CAT score, plasma level of IL-6 and MDA were measured on admission and at discharge. Length of stay based on the number of days of care in hospitals. Results: There was significant difference (p=0,011) towards decreased of IL-6 plasma level between treatment group (-2,17 ± 3,46 pg/ mL) and control group (+1,67 ± 6,81 pg/mL). There were no significant difference towards decreased of length of stay (p=0,34) between treatment group (4,12 ± 1,54 days) and control group (5,24 ± 2,49 days), towards decreased of CAT score (p=0,252) between treatment group (-19,18 ± 3,96) and control group (-18,24 ± 2,75), and towards decreased of MDA plasma level (p=0,986) between treatment group (+0,03 ± 0,36μmol/L) and control group (+0,35 ± 1,58). Conclusions: The addition of mangosteen pericarp extract 2x1100mg/day during hospitalization was significantly lowered plasma levels of IL-6, but were not significant in lowering the CAT score, shortening the length of stay, and reducing the increase in plasma level of MDA.

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Suppressor of Variegation 3-9 Homologue 1 Impairment and Neutrophil-skewed Systemic Inflammation Are Associated with Comorbidities in COPD

10.21203/rs.3.rs-45674/v2 ◽

2020 ◽

Author(s):

Tzu-Tao Chen ◽

Sheng-Ming Wu ◽

Kuan-Yuan Chen ◽

Chien-Hua Tseng ◽

Shu-Chuan Ho ◽

...

Keyword(s):

Blood Cell ◽

Clinical Outcomes ◽

Systemic Inflammation ◽

Mononuclear Cells ◽

Chronic Obstructive ◽

Th2 Response ◽

Neutrophilic Inflammation ◽

Cell Counts ◽

Blood Cell Counts ◽

Copd Patients

Abstract BACKGROUND: Systemic manifestations and comorbidities are characteristics of chronic obstructive pulmonary disease (COPD) and are probably due to systemic inflammation. The histone methyltransferase SUV39H1 controls the Th1/Th2 balance. We previously reported that reduced SUV39H1 expression contributed to abnormal inflammation in COPD.METHODS: To assess whether impaired SUV39H1 expression in COPD patients leads to neutrophilic inflammation, downstream responses to IL-8 and suppression of Th2 responses, the SUV39H1 levels in peripheral blood mononuclear cells (PBMCs) from 13 healthy subjects and 30 COPD patients were measured by immunoblotting. Clinical outcomes associated with SUV39H1-related inflammation were also studied. The relationships between SUV39H1 and neutrophil or eosinophil (Th2 response) counts and clinical outcomes were evaluated. In an extended COPD cohort (213 patients), association analyses of blood cell counts with comorbidities and exacerbations were performed.RESULTS: Low SUV39H1 expression was associated with high neutrophil counts and a trend towards low eosinophil counts. In the extended cohort, the high comorbidity group had higher neutrophil counts than the low comorbidity group but similar whole white blood cell counts. The eosinophil percentage and eosinophil/neutrophil ratio displayed contrasting results. The proportion of neutrophils was correlated with COPD comorbidities. Patients with 0-1 moderate to severe exacerbations in the past year had numbers of neutrophils and eosinophils similar to those of patients who experienced more than an exacerbation. Finally, patients with high comorbidities had lower SUV39H1 levels in their PBMCs than did those with low comorbidities.CONCLUSION: Blood neutrophil counts are associated with comorbidities in COPD patients. Impaired SUV39H1 expression in PBMCs from COPD patients are correlated with neutrophilic inflammation and comorbidities.

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RELATIONSHIP OF MEAN PLATELET VOLUME WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ITS SEVERITY- AN OBSERVATIONAL STUDY

International Journal of Advanced Research ◽

10.21474/ijar01/13561 ◽

2021 ◽

Vol 9 (10) ◽

pp. 423-428

Author(s):

Kishore Kumar Sharma ◽

Mani Ram Kumhar ◽

Mayank Shrivastav ◽

Harsh Tak

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Body Mass Index ◽

Acute Exacerbation ◽

Mean Platelet Volume ◽

Chronic Obstructive ◽

Platelet Volume ◽

Obstructive Pulmonary Disease ◽

Bode Index ◽

Copd Patients ◽

Relationship Of

Background & Objectives: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and inflammation. Mean platelet volume (MPV) may be used as a marker of inflammation. We aimed to study the association between MPV and COPD patients during acute attack and relationship of MPV with severity of COPD by FEV1 (%predicted), BODE Index, PaO2, mMRC grade and 6MWD test. Methods: 100 patients with COPD (50 with acute exacerbation and 50 with stable COPD) and 30 healthy controls were enrolled in the study. Mean platelet volume (MPV), spirometry, arterial blood gases, body mass index, renal function tests and BODE index (body mass index, airflow obstruction,dyspnoea and exercise) were assessed. Level of MPV was compared between cases and controls. Results: Of 100 COPD patients, 87(87%) were male and 13(13%)were female.MPV was significantly higher in COPD patients than control and also higher in acute exacerbation group than stable COPD (p=0.001). Interpretation & Conclusions: In the present study,MPV remain in normal range in all COPD patients, but MPV values were significantly higher in COPD cases compared with control.Increased MPV was associated with acute exacerbation and also increasing with severity of COPD.

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Sleep Quality in Chronic Obstructive Pulmonary Disease With High Risk of Acute Exacerbation

10.21203/rs.3.rs-446799/v1 ◽

2021 ◽

Author(s):

Chong Xing ◽

Hui Shen ◽

Wenyang Li ◽

Wei Wang

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

High Risk ◽

Sleep Quality ◽

Acute Exacerbation ◽

Overlap Syndrome ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Sleep Parameters

Abstract This was a prospective case-control study aimed to explore the sleep quality, especially sleep-related disorders, among chronic obstructive pulmonary disease (COPD) patients with high risk of acute exacerbation, and to determine the risk factors. We enrolled COPD patients with acute exacerbation or health control visited the first hospital of China Medical University from October 1st, 2017 to October 28th, 2018. The subjective and objective sleep parameters were compared among them, and then the stepwise multiple regression analysis were performed. We found that COPD patients with high risk of acute exacerbation had decreased subjective and objective sleep quality. Patients with COPD-obstructive sleep apnea overlap syndrome revealed decreased slow wave sleep than patients with COPD alone. The subjective sleep parameters were correlated with the frequency of acute exacerbation, dyspnea index and Epworth sleepiness score. The objective sleep parameters were related to the degree of airflow obstruction, COPD Assessment Test score and the Modified British Medical Research Council dyspena score. So, we believe that the subjective and objective sleep quality of patients with high risk of acute exacerbations of COPD was poor, and the sleep quality of patients with overlap syndrome was worse than that of patients with COPD alone.

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A NEW PERSPECTIVE ON BRONCHIAL ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE OVERLAP: POTENTIAL DIAGNOSTIC CRITERIA

Wiadomości Lekarskie ◽

10.36740/wlek202007131 ◽

2020 ◽

Vol 73 (7) ◽

pp. 1480-1483

Author(s):

Tetyana O. Pertseva ◽

Lyudmyla I. Konopkina ◽

Alina O. Babenko

Keyword(s):

Allergic Inflammation ◽

Chronic Obstructive ◽

Bronchial Obstruction ◽

Obstructive Pulmonary Disease ◽

Total Ige ◽

Copd Patients ◽

Group 2 ◽

New Perspective ◽

High Level ◽

Blood Eosinophils

The aim: The aim of the research was to analyze the results of observation and examination of COPD patients in order to identify a group of individuals with potential asthma overlap. Materials and methods: We have conducted a two-stage dynamic investigation of 43 COPD patients during 3–8 years. The patients were divided into two groups: group 1 counted 30 individuals who presented with at least one episode of reversible bronchial obstruction (RBO) during the observation; group 2 – 13 individuals who presented with nonreversible bronchial obstruction (nonRBO). At the first stage, we conducted a clinical observations analysis and studied lung function examination records; at the second stage, we calculated the markers of allergic inflammation. Results: It was revealed that around 70% of COPD patients have occasional episodes of RBO. It was established that the level of blood eosinophils in these patients on the whole is rather low even in people with intermittent RBO, and the total IgE level appeared to be significantly higher in patients with intermittent RBO comparing to the level of this marker in patients who have nonRBO. Conclusions: COPD patients with intermittent RBO and high level of total IgE level form a group with potential asthma overlap.

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Neuromorphic on-chip recognition of saliva samples of COPD and healthy controls using memristive devices

Scientific Reports ◽

10.1038/s41598-020-76823-7 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Pouya Soltani Zarrin ◽

Finn Zahari ◽

Mamathamba K. Mahadevaiah ◽

Eduardo Perez ◽

Hermann Kohlstedt ◽

...

Keyword(s):

Medical Devices ◽

Energy Efficient ◽

Performance Evaluations ◽

Chronic Obstructive ◽

Healthy Controls ◽

Effective Management ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Life Threatening ◽

On Chip

AbstractChronic Obstructive Pulmonary Disease (COPD) is a life-threatening lung disease, affecting millions of people worldwide. Implementation of Machine Learning (ML) techniques is crucial for the effective management of COPD in home-care environments. However, shortcomings of cloud-based ML tools in terms of data safety and energy efficiency limit their integration with low-power medical devices. To address this, energy efficient neuromorphic platforms can be used for the hardware-based implementation of ML methods. Therefore, a memristive neuromorphic platform is presented in this paper for the on-chip recognition of saliva samples of COPD patients and healthy controls. Results of its performance evaluations showed that the digital neuromorphic chip is capable of recognizing unseen COPD samples with accuracy and sensitivity values of 89% and 86%, respectively. Integration of this technology into personalized healthcare devices will enable the better management of chronic diseases such as COPD.

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