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Table 7 Summary of studies on EVs in COPD diagnosis

From: Extracellular vesicles and chronic obstructive pulmonary disease (COPD): a systematic review

Diagnostic

Author, year [Ref.]

Title

Aim

Type

Conclusion

Lacedonia et al., 2016 [50]

Microparticles in sputum of COPD patients: a potential biomarker of the disease?

Investigate the presence and source of sputum MPs in COPD patients and to correlate the number and source of MPs to the clinical picture

Ex vivo

Human

CD31-MPs, CD66b-MPs, and CD235ab-MPs were upregulated in all COPD patients. High levels of CD31-MPs in COPD sputum negatively correlated with FEV1% and could be a new noninvasive method to monitor disease course

Gordon et al., 2011 [51]

Circulating endothelial microparticles as a measure of early lung destruction in cigarette smokers

Evaluate whether plasma EMP levels are elevated in smokers with early lung destruction as assessed by normal spirometry but reduced diffusing capacity of the lung for carbon monoxide (DLCO)

Ex vivo

Human

Plasma EMPs with apoptotic characteristics are elevated in smokers with normal spirometry but reduced DLCO

Takahashi et al., 2014 [52]

Annual FEV1 changes and numbers of circulating endothelial microparticles in patients with COPD: a prospective study

Examine the relationship between EMP number and changes in forced expiratory volume in 1 s (FEV1) in patients with COPD

Ex vivo

Human

High E-selectin (CD62E +) EMP level under a stable condition predicted rapid FEV1 decline after a year in patients with COPD. E-selectin EMP number under a stable condition could be a good biomarker to predict the prognosis of patients with COPD

Sundar et al., 2019 [53]

Small RNA-sequence analysis of plasma-derived extracellular vesicle miRNAs in smokers and patients with chronic obstructive pulmonary disease as circulating biomarkers

Investigate whether smoking and progression of chronic lung disease (i.e. COPD) can alter the composition and packaging of proteins, mRNA and ncRNAs in EVs/exosomes

Ex vivo

Human

In vitro

RNA-seq analysis carried out on EVs from plasma samples of human subjects showed significant miRNAs up- or down-regulated in smokers vs. COPD and non-smokers vs. COPD pairwise comparisons

Jung et al., 2020 [54]

Surface proteome of plasma extracellular vesicles as biomarkers for pneumonia and acute exacerbation of chronic obstructive pulmonary disease

Identify surface proteins of plasma small EVs (ssEVs) as biomarkers for diagnosis and differentiation of AECOPD to CAP (community acquired pneumonia)

Ex vivo

Human

There was a significantly higher expression in plasma sEVs (CD45, CD28, CTLA4, TNF-R-II, and CD16) from patients with AECOPD when compared to CAP patients, allowing for discrimination between the two

Koba et al., 2021 [55]

Proteomics of serum extracellular vesicles identifies a novel COPD biomarker, fibulin-3 from elastic fibres

Assess serum EVs to find novel biomarkers for personalised medicine in COPD using the latest proteomic strategies

Ex vivo

Human

In vivo

Mice

This study identified novel biomarkers for COPD using next-generation proteomics of serum extracellular vesicles. Notably, the expression of fibulin-3 is correlated with lung function and emphysema

Soni et al., 2021 [56]

Intra-alveolar neutrophil-derived microvesicles are associated with disease severity in COPD

Evaluate the profiles of intra-alveolar (within BALF) and circulating (within plasma) MVs in COPD patients, characterizing a variety of MV subtype populations

Ex vivo

Human

This study identified a variety of MV subtype populations within the BALF and plasma of COPD patients with a spectrum of disease severity. In this heterogeneous patient cohort ranging from mild to very severe COPD, BALF PMN (i.e., neutrophil) MVs strongly correlate with the BODE index as well as multiple other markers of COPD severity: worsening dyspnea score, degree of airway obstruction and hyperinflation, lung parenchymal damage, and exercise tolerance

Lucchetti et al., 2021 [57]

Detection and characterisation of extracellular vesicles in exhaled breath condensate and sputum of COPD and severe asthma patients

Investigate whether extracellular vesicles are present and detectable in exhaled breathe condensate (EBC) and to perform a preliminary comparison of their concentrations in COPD and healthy control subjects

Ex vivo

Human

Extracellular vesicles are detectable in EBC and sputum and measurement of EBC mEV concentrations might be more informative in COPD patients

Bazzan et al., 2021 [58]

Microvesicles in bronchoalveolar lavage as a potential biomarker of COPD

investigate the presence and source of MVs in bronchoalveolar lavage (BAL) of smokers with and without COPD compared with nonsmoking controls

Ex vivo

Human

MVs obtained directly from the lung BAL show that, in response to smoking and to the development of COPD, measurable inflammatory signals in alveolar macrophages can be quantified and that their numbers are related to the pack-years and the decrease in lung function

Carpi et al., 2020 [59]

Expression analysis of muscle-specific miRNAs in plasma-derived extracellular vesicles from patients with chronic obstructive pulmonary disease

Analyse the expression profiles of EV-derived myo-miRNAs (specifically miR-206, miR-133a-5p, and miR-133a-3p) in plasma samples collected from patients with COPD

Ex vivo

Human

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 between COPD patients

Shen et al., 2021 [60]

A novel diagnostic signature based on three circulating exosomal mircoRNAs for chronic obstructive pulmonary disease

Evaluate differentially expressed exo-miRNAs in the plasma of patients with COPD and healthy individuals for their potential diagnostic value in COPD

Ex vivo

Human

The expression levels of three exo-miRNAs (miR-23a, miR-221 and miR-574) were found to be negatively associated with the forced expiratory volume in the 1st second/forced vital capacity. The three circulating exosomal miRNAs may serve as novel circulating biomarkers for the diagnosis of COPD

Kaur et al., 2021 [61]

Distinct exosomal miRNA Profiles from BALF and lung tissue of COPD and IPF patients

Compare the miRNA population in the BALF and lung-tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD in several independent cohorts to identify potential biomarkers to determine the extent of any pulmonary damage at an early stage

Ex vivo

Human

Next generation sequencing results identified three differentially expressed miRNAs in the BALF and one in the lung-derived exosomes from COPD patients, compared to healthy non-smokers. Of these, miR-122-5p was three- or fivefold downregulated among the lung-tissue-derived exosomes of COPD patients compared to healthy non-smokers and smokers, respectively. The identified lung-specific miRNAs associated with COPD can serve as potential biomarkers or therapeutic targets