scholarly journals Expression Analysis of Muscle-Specific miRNAs in Plasma-Derived Extracellular Vesicles from Patients with Chronic Obstructive Pulmonary Disease

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 502
Author(s):  
Sara Carpi ◽  
Beatrice Polini ◽  
Dario Nieri ◽  
Nevio Dubbini ◽  
Alessandro Celi ◽  
...  

MicroRNAs (miRNAs) are a class of short non-coding RNAs involved in the regulation of gene expression and the control of several cellular processes at physiological and pathological levels. Furthermore, extracellular vesicles (EV), which are small membrane-bound vesicles secreted by cells in the extracellular environment, contain functional miRNAs. The remarkable deregulation of many miRNAs has been demonstrated in respiratory diseases. Among them, miR-206, miR-133a-5p, and miR-133a-3p are striated muscle-specific miRNAs (myo-miRNA), related to skeletal muscle dysfunction, one of the commonest systemic manifestations in patients with chronic obstructive pulmonary disease (COPD). Nevertheless, their circulating expression in COPD patients is not demonstrated. For these reasons, we performed a pilot study to analyze the expression profiles of myo-miRNAs in plasma-derived EV from patients with COPD. We analyzed the expression profiles of selected myo-miRNAs in plasma-derived EV from COPD. Receiver operating characteristic analyses were carried out to evaluate whether selected plasma miRNAs were able to discriminate between different groups of COPD patients. We found EV-embedded myo-miRNAs in the bloodstream of COPD patients. Specifically, miR-206, miR-133a-5p and miR-133a-3p were significantly upregulated in group B patients. Receiver operating characteristic analyses of the combination of these selected miRNAs showed their high capacity to discriminate group B from other COPD patients. Our data provide evidence that myo-miRNA are present in EV in the plasma of COPD patients and their expression (miR-206, miR-133a-5p, and miR-133a-3p) can discriminate group B from group C patients. The future analysis of a larger number of patients should allow us to obtain more refined correlations.

2020 ◽  
Author(s):  
Fuqiang Wen ◽  
Xiaoou Li ◽  
Yongchun Shen ◽  
Jiahan Cheng ◽  
Jun Chen ◽  
...  

Abstract Background: Lung cancer complicated with chronic obstructive pulmonary disease (COPD) are major causes of mortality worldwide, and the incidence of lung cancer and COPD increasing significantly. Circular RNAs (circRNAs), have been reported to participate in various biological processes, whereas the role of circRNAs in lung cancer complicated with COPD remains unclear. We aims to identify differentially expressed circRNAs (DEcircRNAs) between lung cancer complicated with COPD and lung cancer without COPD. Method: The circRNAs expression profiles were identified using a high-throughput circRNA microarray in cancer adjacent tissues from 6 lung cancer without COPD patients and 8 lung cancer complicated with COPD patients. Bioinformatic analyses were conducted to identify the functions of DEcircRNAs. Result: A total of 115 up- and 128 down-regulated circRNAs were screened in lung cancer complicated with COPD patients compared with lung cancer without COPD patients. The myD88-dependent toll-like receptor signaling pathway and positive regulation of nitric oxide biosynthetic process ranked the top 2 enriched biological processes in Gene Ontology analysis. Signaling transduction and infectious diseases were the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways in both up- and down-regulated circRNAs. Compared with lung cancer without COPD, circRNAs are dysregulated in the adjacent tissues of lung cancer with COPD. Conclusion: The DEcircRNAs might act as potential targets for the diagnosis of lung cancer with COPD.


2021 ◽  
Author(s):  
Tai Joon An ◽  
Yeun Jie Yoo ◽  
Jeong Uk Lim ◽  
Wan Seo ◽  
Chan Kwon Park ◽  
...  

Abstract Background: The importance of evaluating the diaphragm muscle in chronic obstructive pulmonary disease (COPD) is widely accepted. However, the role of diaphragm ultrasound (DUS) in COPD is not fully understood. We set this study to evaluate the role of DUS for distinguishing the status of COPD. Methods: COPD patients who underwent DUS were enrolled between March 2020 and November 2020. The diaphragm thickening fraction (TFmax) and diaphragm excursion (DEmax) during maximal deep breathing were measured. Patients were divided into exacerbation and stable groups. Demographics, lung function, and DUS findings were compared between the two groups. Receiver operating characteristic (ROC) curve and univariate/multivariate logistic regression analyses were performed.Results: Fifty-five patients were enrolled. The exacerbation group had a lower body mass index (BMI) (20.9 vs. 24.2, p = 0.003), lower TFmax (94.8 ± 8.2% vs. 158.4 ± 83.5%, p = 0.010), and lower DEmax (30.8 ± 11.1 mm vs. 40.5 ± 12.5 mm, p = 0.007) compared to stable group. The areas under the TFmax (0.745) and DEmax (0.721) curves indicated fair results for distinguishing exacerbation. The patients were divided into low and high TFmax and DEmax groups based on calculated cut-off values. Low TFmax (odds ratio [OR] 8.40; 95% confidence interval [CI] 1.55–45.56) and low DEmax (OR 11.51; 95% CI 1.15–115.56) were associated with exacerbation after adjusting for age, sex, BMI, forced vital capacity and forced expiratory volume in 1 sec.Conclusion: TFmax and DEmax distinguished exacerbation from stable status. We describe the DUS cut-off values for determining an exacerbation status in this study.


Author(s):  
Kavitha Devi M ◽  
Sarumathy S ◽  
Sarath Lal Sasidharan ◽  
Sarumathy S ◽  
Mehanaz Shaik ◽  
...  

 Objectives: The objective of this study is to assess the safety and efficacy of formoterol and tiotropium combination compared to formoterol and tiotropium with roflumilast combination in treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD) patients on inhaled combination therapy. Methods: A comparative prospective interventional study was carried out in 61 COPD patients who were visiting the pulmonary medicine ward during 6 months (October 2016 to March 2017). The patients were randomized into two groups. Group A patients received a combination of formoterol and tiotropium, whereas Group B patients received roflumilast along with formoterol and tiotropium combination. Spirometry tests were done to both the study population. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were noted at the initial visit and after the treatment. All the statistical analyses such as mean and p values were calculated using SPSS 14.0 version software. Results: The average age group of the study population was 57.63±8.3 years. Comorbid condition such as diabetes mellitus was higher in the study groups. Comparison of spirometry reports before and after drug administration in both groups was done. FEV1 and FVC were found to be statistically significant between the study group (0.001, p<0.05).The average mean change of FEV1 before and after treatment in Group B was found to be improved as compared to Group B (0.66). Conclusion: Tiotropium and formoterol with roflumilast combination were found to be safe and effective in moderate-to-severe COPD patients.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ding Liu ◽  
Maureen Meister ◽  
Shiying Zhang ◽  
Chi-In Vong ◽  
Shuaishuai Wang ◽  
...  

Abstract Background Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with no effective treatment. The current diagnostic method, spirometry, does not accurately reflect the severity of COPD disease status. Therefore, there is a pressing unmet medical need to develop noninvasive methods and reliable biomarkers to detect early stages of COPD. Lipids are the fundamental components of cell membranes, and dysregulation of lipids was proven to be associated with COPD. Lipidomics is a comprehensive approach to all the pathways and networks of cellular lipids in biological systems. It is widely used for disease diagnosis, biomarker identification, and pathology disorders detection relating to lipid metabolism. Methods In the current study, a total of 25 serum samples were collected from 5 normal control subjects and 20 patients with different stages of COPD according to the global initiative for chronic obstructive lung disease (GOLD) (GOLD stages I ~ IV, 5 patients per group). After metabolite extraction, lipidomic analysis was performed using electrospray ionization mass spectrometry (ESI-MS) to detect the serum lipid species. Later, the comparisons of individual lipids were performed between controls and patients with COPD. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) analysis were utilized to test the potential biomarkers. Finally, correlations between the validated lipidomic biomarkers and disease stages, age, FEV1% pack years and BMI were evaluated. Results Our results indicate that a panel of 50 lipid metabolites including phospholipids, sphingolipids, glycerolipids, and cholesterol esters can be used to differentiate the presence of COPD. Among them, 10 individual lipid species showed significance (p < 0.05) with a two-fold change. In addition, lipid ratios between every two lipid species were also evaluated as potential biomarkers. Further multivariate data analysis and receiver operating characteristic (ROC: 0.83 ~ 0.99) analysis suggest that four lipid species (AUC:0.86 ~ 0.95) and ten lipid ratios could be potential biomarkers for COPD (AUC:0.94 ~ 1) with higher sensitivity and specificity. Further correlation analyses indicate these potential biomarkers were not affected age, BMI, stages and FEV1%, but were associated with smoking pack years. Conclusion Using lipidomics and statistical methods, we identified unique lipid signatures as potential biomarkers for diagnosis of COPD. Further validation studies of these potential biomarkers with large population may elucidate their roles in the development of COPD.


2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes

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.


2020 ◽  
Vol 24 (4) ◽  
pp. 80-86
Author(s):  
V. I. Trofimov ◽  
D. Z. Baranov

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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoman Zhou ◽  
Yunjun Zhang ◽  
Yutian Zhang ◽  
Quanni Li ◽  
Mei Lin ◽  
...  

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.


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