scholarly journals Mitochondrial dysfunction in airways and quadriceps muscle of patients with chronic obstructive pulmonary disease

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Gulam Haji ◽  
◽  
Coen H. Wiegman ◽  
Charalambos Michaeloudes ◽  
Mehul S. Patel ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Mitochondrial Dysfunction ◽  
Pulmonary Disease ◽  
Quadriceps Muscle ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Bronchial Biopsies ◽  
Gold Grade ◽  
Grade 3

Abstract Background Mitochondrial damage and dysfunction have been reported in airway and quadriceps muscle cells of patients with chronic obstructive pulmonary disease (COPD). We determined the concomitance of mitochondrial dysfunction in these cells in COPD. Methods Bronchial biopsies were obtained from never- and ex-smoker volunteers and COPD patients (GOLD Grade 2) and quadriceps muscle biopsies from the same volunteers in addition to COPD patients at GOLD Grade 3/4 for measurement of mitochondrial function. Results Decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mtROS) and decreased superoxide dismutase 2 (SOD2) levels were observed in mitochondria isolated from bronchial biopsies from Grade 2 patients compared to healthy never- and ex-smokers. There was a significant correlation between ΔΨm and FEV1 (% predicted), transfer factor of the lung for carbon monoxide (TLCOC % predicted), 6-min walk test and maximum oxygen consumption. In addition, ΔΨm was also associated with decreased expression levels of electron transport chain (ETC) complex proteins I and II. In quadriceps muscle of Grade 2 COPD patients, a significant increase in total ROS and mtROS was observed without changes in ΔΨm, SOD2 or ETC complex protein expression. However, quadriceps muscle of GOLD Grade 3/4 COPD patients showed an increased mtROS and decreased SOD2 and ETC complex proteins I, II, III and V expression. Conclusions Mitochondrial dysfunction in the airways, but not in quadriceps muscle, is associated with airflow obstruction and exercise capacity in Grade 2 COPD. Oxidative stress-induced mitochondrial dysfunction in the quadriceps may result from similar disease processes occurring in the lungs.

scholarly journals Quadriceps miR-542-3p and -5p are elevated in COPD and reduce function by inhibiting ribosomal and protein synthesis

2019 ◽  
Vol 126 (6) ◽  
pp. 1514-1524 ◽  
Author(s):  
Roser Farre-Garros ◽  
Jen Y. Lee ◽  
S. Amanda Natanek ◽  
Martin Connolly ◽  
Avan A. Sayer ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Protein Synthesis ◽  
Mitochondrial Dysfunction ◽  
Pulmonary Disease ◽  
Physical Performance ◽  
Quadriceps Muscle ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Reduced physical performance reduces quality of life in patients with chronic obstructive pulmonary disease (COPD). Impaired physical performance is, in part, a consequence of reduced muscle mass and function, which is accompanied by mitochondrial dysfunction. We recently showed that miR-542-3p and miR-542-5p were elevated in a small cohort of COPD patients and more markedly in critical care patients. In mice, these microRNAs (miRNAs) promoted mitochondrial dysfunction suggesting that they would affect physical performance in patients with COPD, but we did not explore the association of these miRNAs with disease severity or physical performance further. We therefore quantified miR-542-3p/5p and mitochondrial rRNA expression in RNA extracted from quadriceps muscle of patients with COPD and determined their association with physical performance. As miR-542-3p inhibits ribosomal protein synthesis its ability to inhibit protein synthesis was also determined in vitro. Both miR-542-3p expression and -5p expression were elevated in patients with COPD (5-fold P < 0.001) and the degree of elevation associated with impaired lung function (transfer capacity of the lung for CO in % and forced expiratory volume in 1 s in %) and physical performance (6-min walk distance in %). In COPD patients, the ratio of 12S rRNA to 16S rRNA was suppressed suggesting mitochondrial ribosomal stress and mitochondrial dysfunction and miR-542-3p/5p expression was inversely associated with mitochondrial gene expression and positively associated with p53 activity. miR-542-3p suppressed RPS23 expression and maximal protein synthesis in vitro. Our data show that miR-542-3p and -5p expression is elevated in COPD patients and may suppress physical performance at least in part by inhibiting mitochondrial and cytoplasmic ribosome synthesis and suppressing protein synthesis. NEW & NOTEWORTHY miR-542-3p and -5p are elevated in the quadriceps muscle of patients with chronic obstructive pulmonary disease (COPD) in proportion to the severity of their lung disease. These microRNAs inhibit mitochondrial and cytoplasmic protein synthesis suggesting that they contribute to impaired exercise performance in COPD.

scholarly journals Association between serum CCL-18 and IL-23 concentrations and disease progression of chronic obstructive pulmonary disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Biaoxue Rong ◽  
Tian Fu ◽  
Congxue Rong ◽  
Wen Liu ◽  
Kai Li ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Disease Progression ◽  
Pulmonary Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chronic Obstructive ◽  
Clinical Parameters ◽  
Serum Concentrations ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Gold Grade

Abstract This study aimed to investigate the association between serum concentrations of chemokine (C–C Motif) ligand 18 (CCL-18) and interleukin 23 (IL-23) and clinical parameters of chronic obstructive pulmonary disease (COPD). The serum concentrations of CCL-18 and IL-23 were tested by enzyme linked immunosorbent assay (ELISA). The association between their concentrations and clinical parameters of COPD patients were analyzed by linear regression, logistic regression and ROC curve. The results showed that the serum concentrations of CCL-18 and IL-23 in COPD patients were increased compared with healthy people (P < 0.001) and that patients with acute exacerbation of COPD (AECOPD) had higher serum CCL-18 and IL-23 concentrations than stable patients (P < 0.001). Synergistic increase of CCL-18 and IL-23 in COPD patients was positively correlated with COPD patients' higher GOLD grade (P < 0.001), higher mMRC score (P < 0.001) and longer medical history (P < 0.001), but negatively correlated with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (P < 0.001) and FEV1% predicted (P < 0.001). The serum concentrations of CCL-18 and IL-23 were most related to the GOLD grade (OR = 2.764 for CCL-18 and OR = 4.215 for IL-23) and detection of both showed considerable sensitivity (72.57% for CCL-18 and 76.92% for IL-23) and specificity (92.50% for CCL-18 and 77.5% for IL-23) in identifying COPD. Increased serum concentrations of CCL-18 and IL-23 correlated with the disease progression of COPD and they could be used as biomarkers for disease evaluation of COPD.

scholarly journals Bufei Jianpi Granules Reduce Quadriceps Muscular Cell Apoptosis by Improving Mitochondrial Function in Rats with Chronic Obstructive Pulmonary Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jing Mao ◽  
Ya Li ◽  
Suyun Li ◽  
Jiansheng Li ◽  
Yange Tian ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Pulmonary Disease ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Smoke Inhalation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Background. Cell apoptosis is an important mechanism underlying skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) patients, and mitochondrial dysfunction is recognized as a central aspect contributing to skeletal muscle deterioration. Bufei Jianpi granules have been confirmed effective for improving motor function in COPD patients, but the specific mechanism for this improved function remains unknown. This study explored the mechanisms by which Bufei Jianpi granules improve cell apoptosis and mitochondrial dysfunction in COPD. Methods. Sprague-Dawley rats were randomized into control, model, Bufei Jianpi, and aminophylline groups. A stable COPD rat model was induced with respective repeated cigarette smoke inhalation and intragastric bacterial infection, and rats were sacrificed after 20 weeks; the quadriceps muscle was harvested from each rat. Skeletal muscle mitochondria were extracted for measurements of mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore openings (mPTPs). ATP levels were determined with a firefly luciferase-based ATP assay kit. The rates of cell apoptosis were determined by the transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method. Cyto C and caspase-3 mRNA and protein levels were measured by qPCR and western blotting. Results. ATP, MMP, and mPTPs were markedly decreased in COPD rats, while cell apoptosis, caspase-3, and Cyto C were increased (P<0.01). All aforementioned parameters were improved in treatment groups (P<0.05). ATP, MMP, and mPTPs were significantly higher in the Bufei Jianpi group than in the aminophylline group, while cell apoptosis, caspase-3, and Cyto C were lower (P<0.05). Conclusions. Bufei Jianpi granules can inhibit mitochondrial dysfunction and cell apoptosis in peripheral muscles, which might be the mechanism involved in improving skeletal muscle function in COPD patients.

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.

Metabolomic profiling of anaerobic and aerobic energy metabolic pathways in chronic obstructive pulmonary disease

2021 ◽  
pp. 153537022110088
Author(s):  
Mingshan Xue ◽  
Yifeng Zeng ◽  
Runpei Lin ◽  
Hui-Qi Qu ◽  
Teng Zhang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Energy Metabolism ◽  
Pulmonary Disease ◽  
Metabolic Pathways ◽  
Energy Supply ◽  
Stable Phase ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Anaerobic Energy

While there is no cure for chronic obstructive pulmonary disease (COPD), its progressive nature and the formidable challenge to manage its symptoms warrant a more extensive study of the pathogenesis and related mechanisms. A new emphasis on COPD study is the change of energy metabolism. For the first time, this study investigated the anaerobic and aerobic energy metabolic pathways in COPD using the metabolomic approach. Metabolomic analysis was used to investigate energy metabolites in 140 COPD patients. The significance of energy metabolism in COPD was comprehensively explored by the Global Initiative for Chronic Obstructive Lung Disease–GOLD grading, acute exacerbation vs. stable phase (either clinical stability or four-week stable phase), age group, smoking index, lung function, and COPD Assessment Test (CAT) score. Through comprehensive evaluation, we found that COPD patients have a significant imbalance in the aerobic and anaerobic energy metabolisms in resting state, and a high tendency of anaerobic energy supply mechanism that correlates positively with disease progression. This study highlighted the significance of anaerobic and low-efficiency energy supply pathways in lung injury and linked it to the energy-inflammation-lung ventilatory function and the motion limitation mechanism in COPD patients, which implies a novel therapeutic direction for this devastating disease.

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