Table 6.

Summary of studies on EVs in COPD exacerbation

COPD exacerbation
Author, year [Ref.]	Title	Aim	Type	Conclusion
Takahashi et al., 2012 [45]	Increased circulating endothelial microparticles in COPD patients: a potential biomarker for COPD exacerbation susceptibility	To compare EMP numbers in stable COPD patients with those during and after exacerbation	Ex vivo Human	VE-cadherin (CD144 +), PECAM (CD31+/41−) and E-selectin (CD62E+) EMPs of pulmonary capillary origin were significantly more numerous in the stable COPD patients than in the healthy non-COPD volunteers, with further increase in the exacerbated phase. Baseline E-selectin EMP levels were significantly higher in COPD patients with frequent exacerbations than patients without, indicative of endothelial damage during exacerbation
Eltom et al., 2014 [46]	Respiratory infections cause the release of extracellular vesicles: implication in exacerbation of asthma/COPD	Investigate whether respiratory infections cause the release of EVs in the airway and that the raised ATP levels, present in respiratory disease, triggers the release of IL-1b/IL-18, neutrophilia and subsequent disease exacerbations	In vitro In vivo/ex vivo Mice Ex vivo Human	Respiratory infections, bacterial and viral, can trigger the release of functional EVs in mice and man. Upon ATP activation, the EVs released IL-1b and IL-18 in a P2X7/caspase-1 axis dependent manner resulting in exacerbated neutrophilia
Tan et al., 2017 [47]	Elevated levels of circulating exosomes in COPD patients are associated with systemic inflammation	Investigate whether the levels of circulating exosomes (CD9+ microvesicles) are abnormally elevated in individuals who experienced acute exacerbations of COPD (AECOPD) and whether exosomes are associated with systemic inflammation	Ex vivo Human	Exosomes (CD9 microvesicles) are elevated in COPD and AECOPD. Level of exosomes correlated with an increase in plasma CRP, sTNFR1 and IL-6, which are well-established markers of systemic inflammation and associated with COPD, with AECOPD group having the highest elevation when compared to sCOPD and healthy controls
Tokes-Fuzesi et al., 2018 [48]	Role of microparticles derived from monocytes, endothelial cells and platelets in the exacerbation of COPD	Measure EMPs and other cell-derived circulating MPs in stable and exacerbated COPD patients	Ex vivo Human	Highly elevated MP levels were found in COPD patients compared to controls, and in particular, CD62E+, CD41+, CD42a+ and CD14+ MPs were significantly increased in exacerbated COPD versus stable COPD, indicative of endothelial activity and vascular injury in the lungs. CD62E+, CD42a+ and CD14+ MPs correlated inversely with FEV1/FVC