scholarly journals The Role of Extracellular Vesicles as a Shared Disease Mechanism Contributing to Multimorbidity in Patients With COPD

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura V. Reid ◽  
C. Mirella Spalluto ◽  
Alastair Watson ◽  
Karl J. Staples ◽  
Tom M. A. Wilkinson

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Individuals with COPD typically experience a progressive, debilitating decline in lung function as well as systemic manifestations of the disease. Multimorbidity, is common in COPD patients and increases the risk of hospitalisation and mortality. Central to the genesis of multimorbidity in COPD patients is a self-perpetuating, abnormal immune and inflammatory response driven by factors including ageing, pollutant inhalation (including smoking) and infection. As many patients with COPD have multiple concurrent chronic conditions, which require an integrative management approach, there is a need to greater understand the shared disease mechanisms contributing to multimorbidity. The intercellular transfer of extracellular vesicles (EVs) has recently been proposed as an important method of local and distal cell-to-cell communication mediating both homeostatic and pathological conditions. EVs have been identified in many biological fluids and provide a stable capsule for the transfer of cargo including proteins, lipids and nucleic acids. Of these cargo, microRNAs (miRNAs), which are short 17-24 nucleotide non-coding RNA molecules, have been amongst the most extensively studied. There is evidence to support that miRNA are selectively packaged into EVs and can regulate recipient cell gene expression including major pathways involved in inflammation, apoptosis and fibrosis. Furthermore changes in EV cargo including miRNA have been reported in many chronic diseases and in response to risk factors including respiratory infections, noxious stimuli and ageing. In this review, we discuss the potential of EVs and EV-associated miRNA to modulate shared pathological processes in chronic diseases. Further delineating these may lead to the identification of novel biomarkers and therapeutic targets for patients with COPD and multimorbidities.

2015 ◽  
Vol 3 (2) ◽  
pp. 67-70
Author(s):  
Rawshan Arra Khanam ◽  
Md Ashraful Haque ◽  
Mohammad Omar Faruq

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable, but progressive disease. Hospital admissions of patients with COPD are frequently due to acute exacerbations of COPD (AECOPD). AECOPD are very common, affecting about 20% of COPD patients. The bacterial infection plays an important role in the exacerbation of COPD patients. In addition, recent studies using molecular diagnostics indicate that a substantial proportion of AECOPD are associated with viral infection. Accurate methods to differentiate viral and bacterial respiratory infections to allow targeted antibiotic therapy would be beneficial. Acute phase reactants are capable of demonstrating the inflammation; however, they cannot be employed to make a difference between bacterial and nonbacterial causes of the inflammation. Recently, measurement of procalcitonin (PCT) levels appears to be useful in order to minimize this problem.Bangladesh Crit Care J September 2015; 3 (2): 67-70


2021 ◽  
Vol 22 (2) ◽  
pp. 583
Author(s):  
Laura Pastor ◽  
Elisabeth Vera ◽  
Jose M. Marin ◽  
David Sanz-Rubio

Lung diseases (LD) are one of the most common causes of death worldwide. Although it is known that chronic airway inflammation and excessive tissue repair are processes associated with LD such as asthma, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), their specific pathways remain unclear. Extracellular vesicles (EVs) are heterogeneous nanoscale membrane vesicles with an important role in cell-to-cell communication. EVs are present in general biofluids as plasma or urine but also in secretions of the airway as bronchoalveolar lavage fluid (BALF), induced sputum (IS), nasal lavage (NL) or pharyngeal lavage. Alterations of airway EV cargo could be crucial for understanding LD. Airway EVs have shown a role in the pathogenesis of some LD such as eosinophil increase in asthma, the promotion of lung cancer in vitro models in COPD and as biomarkers to distinguishing IPF in patients with diffuse lung diseases. In addition, they also have a promising future as therapeutics for LD. In this review, we focus on the importance of airway secretions in LD, the pivotal role of EVs from those secretions on their pathophysiology and their potential for biomarker discovery.


2021 ◽  
Vol 22 (21) ◽  
pp. 11830
Author(s):  
Gagandeep Kaur ◽  
Krishna Prahlad Maremanda ◽  
Michael Campos ◽  
Hitendra S. Chand ◽  
Feng Li ◽  
...  

Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic, progressive lung ailments that are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Extracellular vesicles (EVs), including exosomes, are small, lipid-bound vesicles attributed to carry proteins, lipids, and RNA molecules to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of bronchoalveolar lavage fluid (BALF) or the lung-tissue-derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF- and lung-tissue-derived exosomes of healthy non-smokers, smokers, and patients with COPD or IPF in independent cohorts. Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were ~89.85 nm in size with a yield of ~2.95 × 1010 particles/mL in concentration. Lung-derived exosomes were larger in size (~146.04 nm) with a higher yield of ~2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while there was one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, miR-122-5p was three- or five-fold downregulated among the lung-tissue-derived exosomes of COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were a large number (55) of differentially expressed miRNAs in the lung-tissue-derived exosomes of IPF patients compared to non-smoking controls. Conclusions: Overall, we identified lung-specific miRNAs associated with chronic lung diseases that can serve as potential biomarkers or therapeutic targets.


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.


2019 ◽  
Vol 77 (4) ◽  
Author(s):  
Kelei Zhao ◽  
Yang Yuan ◽  
Jing Li ◽  
Wenjuan Pan ◽  
Chaochao Yan ◽  
...  

ABSTRACT Pseudomonas aeruginosa is an important opportunistic pathogen normally associated with increasing morbidity and mortality of immunocompromised hosts with respiratory infections. The phenotypic and genetic features of P. aeruginosa from patients with chronic obstructive pulmonary disease (COPD) remain poorly understood. By using the sputum samples of 25 hospitalized COPD patients from the affiliated hospital of Southwest Medical University (China), we identified a P. aeruginosa isolate, COP2, which showed multiple antibiotic resistance and enhanced Pseudomonas quinolone signal (PQS) production but decreased motility, biofilm formation and virulence compared with the model strain PAO1. Importantly, COP2 harbored a substantial amount of mutations that might influence the functions of 1771 genes in the genome and the evolutionary status of this isolate was clearly distinct from the PAO1 lineage. Accordingly, COP2 had a discrepant transcriptional pattern relating to flagellar assembly, antibiotic resistance, biofilm and PQS production, and can increase the capacities of compound degradation in response to resource/space stresses. Therefore, the identification of COP2 in this study provides preliminary information regarding the genetic features and survival strategy of P. aeruginosa in colonizing COPD lungs and lays the foundations for further understanding of the pathogenic mechanisms of pseudomonal infections.


2020 ◽  
Vol 8 (2) ◽  
pp. 82-83
Author(s):  
Susanne M. Lang

Background: Chronic obstructive pulmonary disease (COPD) affects up to 65 million people worldwide, and COPD exacerbation causes tissue damage and subsequent loss of lung function. It is a multifactorial event in which respiratory infections are involved, but little is known about its dynamics. Objectives: The objective of our study was to determine the microbiome composition during an exacerbation event and post-stabilization. Methods: We conducted an observational analytical study of a cohort of 55 COPD patients in which 2 sputum samples (the first taken during an exacerbation event and the second during clinical post-stabilization) were submitted to 16s RNA ribosomal analysis by Illumina Miseq Next Generation Sequencing (NGS). The presence of respiratory viruses was also determined. Results: Our study found a stable microbiome composition in the post-stabilization sputum samples of COPD patients, and 4 additional microbiomes in samples taken during the exacerbation, 3 of which showed a marked dysbiosis by Haemophilus, Pseudomonas, and Serratia. The fourth exacerbation microbiome had a very similar composition to post-stabilization samples, but some pathogens such as Moraxella and respiratory viruses were also found. Conclusions: Our study reveals the main protagonists involved in lung microbiome dynamics during an exacerbation event and post-stabilization in COPD patients by NGS analysis.


Author(s):  
Gagandeep Kaur ◽  
Krishna Maremanda ◽  
Michael Campos ◽  
Hitendra Singh Chand ◽  
Feng Li ◽  
...  

Background: Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic, progressive lung ailments which are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Exosomes are small extracellular vesicles attributed to carry proteins, mRNA, miRNA and sncRNA to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF in independent cohorts. Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were approximately 89.85 nm in size and ~2.95 X 1010 particles/mL. Lung-derived exosomes were ~146.04 nm in size and ~2.38 X 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls. Conclusions: Overall, we identified specific miRNAs to develop as biomarkers or targets for pathogenesis of these chronic lung diseases.


2021 ◽  
Author(s):  
Gagandeep Kaur ◽  
Krishna P Maremanda ◽  
Michael Campos ◽  
Hitendra S Chand ◽  
Feng Li ◽  
...  

AbstractBackgroundChronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic, progressive lung ailments which are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Exosomes are small extracellular vesicles attributed to carry proteins, mRNA, miRNA and sncRNA to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF in independent cohorts.ResultsExosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were approximately 89.85 nm in size and ∼2.95 × 1010 particles/mL. Lung-derived exosomes were ∼146.04 nm in size and ∼2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls.ConclusionsOverall, we identified specific miRNAs to develop as biomarkers or targets for pathogenesis of these chronic lung diseases.


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.


Author(s):  
Melvin K Mathews ◽  
Abubaker Siddiq ◽  
Bharathi D R

Background: Chronic obstructive pulmonary disease (COPD) is preventable and treatable disease state characterized by air flow limitation that is not fully reversible. Severity of the symptoms is increased during exacerbations. Objectives: The purpose of the study is to assess and improve the knowledge regarding COPD among study subjects. Materials and Methods: A Cross-sectional interventional study was carried out among the peoples in selected areas of the Chitradurga city for a period of six months. Result: A total 207 subjects enrolled in the study in that 155 male and 52 females. In our study mean score of post test was more (5.87±1.68) when compare to pre-test (2.63±1.46) which show significant increase in their knowledge after educating them (p=0.000). A total of 207 subjects were enrolled into the study. SPSS Software was used to calculate the statistical estimation. Paired t-test was used to detect the association status of different variables. Conclusion: The relatively good level of COPD awareness needs to be maintained to facilitate future prevention and control of the disease. This study had identified that negative illness perceptions should be targeted, so that they will not avoid patients from seeking for COPD treatment and adhere to it. Key words: Cross sectional study, Knowledge, practice, COPD.


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