Table 1. Key COPD EV studies over the past ten years.
| Reference | EV type | Cohort | Main findings |
|---|---|---|---|
| (28) | Plasma endothelial microparticles | N=32 healthy non smokers, N=41 healthy smokers with normal spirometry and DLco, N=19 healthy smokers with normal spirometry and low DLco | This study found that smokers with emphysema have increased circulating EMPs, highlighting that monitoring plasma EMP levels would be useful for identifying early emphysema development |
| (29) | Plasma endothelial microparticles | N=80 stable COPD patients, N=27 exacerbation COPD patients, N=20 healthy non-COPD controls | This study showed that EMPs CD144+, CD31+ and CD62E+ were significantly elevated in stable COPD patients than healthy controls, further highlighting EMPs biomarker potential for COPD exacerbations |
| (30) | Macrophage microparticles | THP-1 macrophages or hMDMs with or without tobacco smoke extract exposure | Macrophage-derived EVs attributed to MMP14 were released in response to tobacco smoke extract exposure. Further these EVs may contribute to emphysema in smokers |
| (31) | Plasma endothelial microparticles | N=104 stable COPD patients, N=76 non-COPD patients | CD31+ EMPs were significantly elevated in mild COPD and emphysema patients compared to controls, while CD62E+ EMPs were significantly elevated in hyperinflation and severe COPD |
| (32) | Human mononuclear cell microparticles | Human mononuclear cells exposed to cigarette smoke extract with microparticles isolated | Macrophage EV release is increased by cigarette smoke extract through the activation of mononuclear cells via intracellular calcium mobilisation. These microparticles contain proinflammatory mediators |
| Human bronchial epithelial cells and A549 alveolar cells were then incubated with cigarette smoke extract induced microparticles | |||
| (33) | BALF EVs | N=8 mice (C57bl/6) per treatment group, saline control, LPS challenged, air exposed or smoke exposed | The results from this study support that infective agents (bacterial or viral) can trigger EV release in the airways of mice and humans and that ATP drives EVs to release IL-1b and IL-18 through a P2X7/caspase-1-dependent manner |
| BALF and lung tissue were collected | |||
| (34) | Plasma endothelial microparticles | N=60 rats divided into six groups, containing 10 rats each. 3 groups of 10 rats were exposed to cigarettes for 2, 4 or 6 months, while the other 3 groups of 10 rats were control groups who were sham-smoked | Plasma CD42b-/CD31+ EMPs were significantly increased in rats exposed to cigarette smoke, highlighting their biomarker potential for pulmonary function impairment, which would be useful for evaluating COPD progression |
| (35) | Lung epithelial derived EVs | BEAS-2B human bronchial epithelial cells | BEAS-2B EVs increased in response to cigarette smoke extract, further inducing RAB27A, further inducing full length flCCN1 enriched EVs |
| Primary human bronchial epithelial cells | |||
| C57BL/6 mice (BALF fluid, lung tissue) | |||
| Human lung tissue | |||
| (36) | Primary human bronchial epithelial cells (HBECs) EVs | BEAS-2B human bronchial epithelial cells EVs | HBEC-derived EVs promoted myofibroblast differentiation in lung fibroblasts in response to cigarette smoke extract. Further miR-210 derived from bronchial epithelial cells targeting ATG7 in lung fibroblasts leads to modulated autophagy |
| HBEC EVs | |||
| Lung Fibroblasts used to assess EV uptake | |||
| (37) | E.coli and dust derived EVs | WT C57BL/6, IFN-γ–deficient, IL-17A–deficient, or TNF-α–deficient mice | Neutrophilic inflammation and emphysema can be induced in a IL-17A dependent manner by E. coli-derived EVs, highlighting a novel target for COPD control |
| BAL fluid and lung tissue were used to evaluate COPD phenotypes | |||
| (38) | Plasma endothelial microparticles (EMPs) | N=28 non smokers, N=61 healthy smokers, N= 49 COPD smokers | COPD smokers and healthy smokers had elevated circulating EMPs compared to non smokers, which remained elevated over 12 months, but returned to non smoker levels for healthy smokers only who quit, unlike COPD smokers who quit with EMP levels still remaining significantly abnormal |
| (39) | Sputum microparticles | N=18 male COPD patients | Microparticles were able to be identified from sputum from COPD patients, with a negative correlation identified between FEV1 and CD31 MPs |
| (40) | Plasma endothelial microparticles | N=8 healthy non-smokers, N=17 COPD patients | miRNAs let-7d, miR-191; miR-126; and miR125a were significantly enriched in EMPs exposed to cigarette smoke, through the enzyme aSMase, which is significantly higher in COPD patient plasma |
| (41) | BAL EVs | N=10 smokers, N=10 non-smokers | BALs EVs from smokers and non-smokers were isolated, characterised and extracted for small RNAs containing miRNAs. RT-qPCR compared miRNA expression between the two groups. BEAS-2B cells were then exposed to BAL EVs to assess different miRNA expression between the two smoking groups. This is one of the first studies to show that smoking alters lung EV profiles in human samples, influencing surrounding bronchial epithelial cells |
| (42) | Lung tissue EVs | N=13 non smokers, N=13 healthy smokers, N=13 COPD patients | This study showed that lung tissue EVs contained more operational taxonomic units (OTUs) than lung tissue. Lung tissue EVs in healthy smoker and COPD groups contained higher Shannon index and lower Simpson index compared to lung tissue. Firmicutes in the EV COPD group compared to other groups was highly present |
| (43) | Plasma exosomes | N=20 Exacerbation COPD patients | Circulating plasma exosome levels (CD9+) were significantly higher in COPD patients compared to healthy controls, with the level of exosomes correlating with systemic inflammatory markers CRP, sTNFR1 and IL-6. This study highlights exosomes involvement in COPD and that they may mediate inflammatory processes |
| N=20 Stable COPD patients | |||
| N=20 Healthy aged matched controls | |||
| (44) | Bronchial epithelial cell EVs | N=5 COPD stable patients, N=5 healthy controls—serum was collected | Serum EVs had elevated miR-21 in COPD patients. Further BEAS-2B EVs when exposed to cigarette smoke extract produced less miR-21, having a reduced impact on M2-directed macrophage polarisation in comparison to control EVs |
| Human serum EVs | N=20 C57Bl/6 mice—split into cigarette smoke exposure and control groups—lung tissue was used for further analyses |
EV, extracellular vesicle; COPD, chronic obstructive pulmonary disease.