scholarly journals Distinct Exosomal miRNA Profiles from BALF and Lung Tissue of COPD and IPF Patients

2021 ◽  
Vol 22 (21) ◽  
pp. 11830
Author(s):  
Gagandeep Kaur ◽  
Krishna Prahlad Maremanda ◽  
Michael Campos ◽  
Hitendra S. Chand ◽  
Feng Li ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Cell Communication ◽  
Lavage Fluid ◽  
Differentially Expressed ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Rna Molecules ◽  
Chronic Lung Diseases ◽  
Copd Patients ◽  
Differentially Expressed Mirnas

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.

scholarly journals Distinct Exosomal miRNA Profiles from BALF and Lung Tissue from COPD and IPF Patients

2021 ◽  
Author(s):  
Gagandeep Kaur ◽  
Krishna Maremanda ◽  
Michael Campos ◽  
Hitendra Singh Chand ◽  
Feng Li ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Cell Communication ◽  
Differentially Expressed ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Copd Patients ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas ◽  
Exosomal Mirna

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.

scholarly journals Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients

2021 ◽  
Author(s):  
Gagandeep Kaur ◽  
Krishna P Maremanda ◽  
Michael Campos ◽  
Hitendra S Chand ◽  
Feng Li ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Cell Communication ◽  
Differentially Expressed ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Copd Patients ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas ◽  
Exosomal Mirna

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.

scholarly journals FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Liu ◽  
Jiawei Xu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Airway Remodeling ◽  
Critical Factor ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

scholarly journals Whole transcriptome analysis of human lung tissue to identify COPD-associated gene

2020 ◽  
Author(s):  
Qiuyu Li ◽  
Yizhang Zhu ◽  
Aiyuan Zhou ◽  
Yuxin Yin
Keyword(s):  
Lung Tissue ◽  
Human Lung ◽  
Tissue Expression ◽  
Chronic Obstructive ◽  
Human Lung Tissue ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Matrix Organization ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome

Abstract Identification of the dysfunctional genes in human lung from patients with Chronic obstructive pulmonary disease (COPD) will help up to understand the pathology of this disease. Here, using transcriptomic data of lung tissue for 91 COPD cases and 182 matched healthy controls from the Genotype-Tissue Expression (GTEx) database. Employing a stringent model controlling for known covariates and hidden confounders, we identified 1,359 significant differentially expressed genes (DEG) with 707 upregulated and 602 downregulated respectively. We evaluated the identified DEGs in an independent microarray cohort of 219 COPD and 108 controls, demonstrating the robustness of our result. Functional annotation of COPD-associated genes highlighted the activation of complement cascade, dysregulation of inflammatory response and extracellular matrix organization in the COPD patients. In addition, we identified several novel key-hub genes involved in the COPD pathogenesis using a network analysis method. In summary, our study represents the comprehensive analysis of gene expression on COPD with the largest sample size providing great resource for the molecular research in the COPD community.

scholarly journals Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma

Metabolites ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 157 ◽  
Author(s):  
Eitan Halper-Stromberg ◽  
Lucas Gillenwater ◽  
Charmion Cruickshank-Quinn ◽  
Wanda Kay O’Neal ◽  
Nichole Reisdorph ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Cell Metabolism ◽  
Lavage Fluid ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
False Discovery ◽  
Copd Patients ◽  
Clinical Covariates

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography–mass spectrometry (LC–MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected 7939 and 10,561 compounds in BAL and paired plasma samples, respectively. FEV1/FVC (Forced Expiratory Volume in One Second/Forced Vital Capacity) ratio, emphysema, FEV1 % predicted, and COPD exacerbations associated with 1230, 792, eight, and one BAL compounds, respectively. Only two plasma compounds associated with a COPD phenotype (emphysema). Three BAL co-expression modules associated with FEV1/FVC and emphysema. K-means BAL metabolomic signature clustering identified two groups, one with more airway obstruction (34% of subjects, median FEV1/FVC 0.67), one with less (66% of subjects, median FEV1/FVC 0.77; p < 2 × 10−4). Associations between metabolites and COPD phenotypes are more robustly represented in BAL compared to plasma.

scholarly journals Different source of sample strains corresponds to different characteristics of patients with non-tuberculous mycobacterium.

2020 ◽  
Author(s):  
Xinling Pan ◽  
Jin Zhao ◽  
Xiaoling Jin ◽  
Songjun Ji
Keyword(s):  
Lavage Fluid ◽  
Smoking History ◽  
Lower Percentage ◽  
Chronic Obstructive ◽  
Symptom Duration ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Different Characteristics ◽  
Different Sources ◽  
Positive Results

Abstract Background: The non-tuberculous mycobacteria (NTM) strains are important in the diagnosis of pulmonary diseases. However, the different source of the sample may correspond to different characteristics of both NTM disease and infected patients and these aspects have not been investigated. Methods: Samples isolated from different sources in inpatients with NTM strains were comprehensively analyzed in this study, including basic information, laboratory examination and coexisting diseases.Results: A total of 242 inpatients with NTM strains were considered in this study. Sputum (n=129) and bronchoalveolar lavage fluid (BALF, n=50) were the most common samples among patients with NTM strains from whom a sample was collected from a single source (n=179). The patients with NTM-positive BALF differed in age, gender, acid fast assay, the percentage of presence of chronic obstructive pulmonary disease (COPD) and bronchiectasis, and symptom duration compared to the patients with NTM-positive sputum. The patients with COPD were older and mainly male, with longer symptom duration, with higher rates of smoking history and prostatic hyperplasia than those without COPD. Patients with bronchiectasis were mainly females, with a lower percentage of them with a tuberculosis history and smoking history compared to patients without bronchiectasis. Excluding the patients with COPD and bronchiectasis, patients with NTM-positive sputum were older, with positive results in acid-fast assay and T. spot assay compared to patients with NTM-positive BALF. Conclusions: The different specimen source in NTM patients was associated with different patients’ characteristics, and its choice could be influenced by presence of COPD and bronchiectasis. Patients with COPD and bronchiectasis differed in gender and smoking history, thus, these aspects should be comprehensively analyzed during the investigation of patients with pulmonary NTM infection.

scholarly journals Increased pulmonary serotonin transporter in patients with chronic obstructive pulmonary disease who developed pulmonary hypertension

2020 ◽  
Author(s):  
Armin Frille ◽  
Michael Rullmann ◽  
Georg-Alexander Becker ◽  
Marianne Patt ◽  
Julia Luthardt ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Hypertension ◽  
Pulmonary Disease ◽  
Serotonin Transporter ◽  
Lung Tissue ◽  
Chronic Obstructive ◽  
Right Heart ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Pet Ct

Abstract Purpose Pulmonary hypertension (PH) is characterized by a progressive remodelling of the pulmonary vasculature resulting in right heart failure and eventually death. The serotonin transporter (SERT) may be involved in the pathogenesis of PH in patients with chronic-obstructive pulmonary disease (COPD). This study investigated for the first time the SERT in vivo availability in the lungs of patients with COPD and PH (COPD+PH). Methods SERT availability was assessed using SERT-selective [11C]DASB and positron emission tomography/computed tomography (PET/CT) with dynamic acquisition over 30 min in 4 groups of 5 participants each: COPD, COPD+PH, pulmonary arterial hypertension, and a healthy control (HC). Time activity curves were generated based on a volume of interest within the middle lobe. Tissue-to-blood concentration ratios after 25 to 30 min (TTBR25–30) served as receptor parameter for group comparison and were corrected for lung tissue attenuation. Participants underwent comprehensive pulmonary workup. Statistical analysis included group comparisons and correlation analysis. Results [11C]DASB uptake peak values did not differ among the cohorts after adjusting for lung tissue attenuation, suggesting equal radiotracer delivery. Both the COPD and COPD+PH cohort showed significantly lower TTBR25–30 values after correction for lung attenuation than HC. Attenuation corrected TTBR25–30 values were significantly higher in the COPD+PH cohort than those in the COPD cohort and higher in non-smokers than in smokers. They positively correlated with invasively measured severity of PH and inversely with airflow limitation and emphysema. Considering all COPD patients ± PH, they positively correlated with right heart strain (NT-proBNP). Conclusion By applying [11C]DASB and PET/CT, semiquantitative measures of SERT availability are demonstrated in the lung vasculature of patients with COPD and/or PH. COPD patients who developed PH show increased pulmonary [11C]DASB uptake compared to COPD patients without PH indicating an implication of pulmonary SERT in the development of PH in COPD patients.

scholarly journals Extracellular Vesicles from Airway Secretions: New Insights in Lung Diseases

2021 ◽  
Vol 22 (2) ◽  
pp. 583
Author(s):  
Laura Pastor ◽  
Elisabeth Vera ◽  
Jose M. Marin ◽  
David Sanz-Rubio
Keyword(s):  
Extracellular Vesicles ◽  
Lung Diseases ◽  
Biomarker Discovery ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Lavage Fluid ◽  
In Vitro Models ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

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.

scholarly journals COPD lungs show an attached stratified mucus layer resembling the protective colonic mucus

2017 ◽  
Author(s):  
Joan Antoni Fernández-Blanco ◽  
Liisa Arike ◽  
Anna Ermund ◽  
Dalia Fakih ◽  
Ana M. Rodríguez-Piñeiro ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cystic Fibrosis ◽  
Bronchoalveolar Lavage Fluid ◽  
Goblet Cells ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Mucus Layer ◽  
Cell Hyperplasia ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

AbstractThe respiratory tract is normally kept essentially free of bacteria by cilia-mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) mucus accumulates due to goblet cell hyperplasia and mucin overexpression. To address mechanisms behind the mucus accumulation, the elastase-induced mouse model was utilized. The proteomes of bronchoalveolar lavage fluid from elastase-induced mice and COPD patients showed similarities to each other and to colonic mucus. Lung mucus showed a striated, laminated appearance in the elastase-induced mice, COPD and CF, resembling that observed for colonic mucus. Less mucus obstruction was observed in mice lacking the Muc5b mucin. The accumulated mucus plugs of the elastase-induced mice were possible to wash out, but a mucus layer covering the epithelium remained attached to the surface goblet cells also after hypertonic saline washings as widely used in CF therapy. The results suggest that the lung can convert its mucus system into an attached mucus layer that protects the epithelium, similarly to the colon.

scholarly journals Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243065 ◽  
Author(s):  
Gagandeep Kaur ◽  
Kameshwar Singh ◽  
Krishna P. Maremanda ◽  
Dongmei Li ◽  
Hitendra S. Chand ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Transcriptional Profiling ◽  
Critical Role ◽  
Cell Communication ◽  
Chronic Obstructive ◽  
Biological Processes ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Non Coding Rnas ◽  
Differentiation And Proliferation

Long non-coding RNAs (lncRNAs) are the varied set of transcripts that play a critical role in biological processes like gene regulation, transcription, post-transcriptional modification, and chromatin remodeling. Recent studies have reported the presence of lncRNAs in the exosomes that are involved in regulating cell-to-cell communication in lung pathologies including lung cancer, chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). In this study, we compared the lncRNA profiles in the plasma-derived exosomes amongst non-smokers (NS), cigarette smokers (CS), E-cig users (E-cig), waterpipe smokers (WP) and dual smokers (CSWP) using GeneChip™ WT Pico kit for transcriptional profiling. We found alterations in a distinct set of lncRNAs among subjects exposed to E-cig vapor, cigarette smoke, waterpipe smoke and dual smoke with some overlaps. Gene enrichment analyses of the differentially expressed lncRNAs demonstrated enrichment in the lncRNAs involved in crucial biological processes including steroid metabolism, cell differentiation and proliferation. Thus, the characterized lncRNA profiles of the plasma-derived exosomes from smokers, vapers, waterpipe users, and dual smokers will help identify the biomarkers relevant to chronic lung diseases such as COPD, asthma or IPF.

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