February 3, 2023International Journal of Molecular SciencesOpen Access

Do Circulating Extracellular Vesicles Strictly Reflect Bronchoalveolar Lavage Extracellular Vesicles in COPD?

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Why the study?

EVs from BAL might be more informative of lung abnormalities than EVs from blood, prompting a comparison of EV characteristics across both sources in smokers with and without COPD.

Are bronchoalveolar lavage extracellular vesicles more informative than blood extracellular vesicles in reflecting lung abnormalities in smokers and COPD patients?

Structured PICO

Are bronchoalveolar lavage extracellular vesicles more informative than blood extracellular vesicles in reflecting lung abnormalities in smokers and COPD patients?

Population

29 subjects including 9 nonsmokers (NS), 11 smokers without COPD (S), and 9 smokers with COPD (SCOPD) (FEV1: 59 ± 3% pred).

Intervention

Measurement of extracellular vesicles (EVs) in bronchoalveolar lavage (BAL) and blood

Comparator

Comparison between nonsmokers, smokers without COPD, and smokers with COPD

Outcome

Characteristics and concentrations of cell-type specific EVs (CD14, CD326, CD146, CD62E) in BAL versus bloodsurrogate

Bronchoalveolar lavage is a better medium than blood to study extracellular vesicles in lung diseases like COPD, as disease-specific EV differences are detectable in BAL but not plasma.

Implication

BAL may be more informative than plasma for EV studies in COPD; hypothesis-generating pending prospective validation.

Abstract

Cell-derived extracellular vesicles (EVs) found in the circulation and body fluids contain biomolecules that could be used as biomarkers for lung and other diseases. EVs from bronchoalveolar lavage (BAL) might be more informative of lung abnormalities than EVs from blood, where information might be diluted. To compare EVs’ characteristics in BAL and blood in smokers with and without COPD. Same-day BAL and blood samples were obtained in 9 nonsmokers (NS), 11 smokers w/o COPD (S), and 9 with COPD (SCOPD) (FEV1: 59 ± 3% pred). After differential centrifugation, EVs (200–500 nm diameter) were identified by flow cytometry and labeled with cell-type specific antigens: CD14 for macrophage-derived EVs, CD326 for epithelial-derived EVs, CD146 for endothelial-derived EVs, and CD62E for activated-endothelial-derived EVs. In BAL, CD14-EVs were increased in S compared to NS [384 (56–567) vs. 172 (115–282) events/μL; p = 0.007] and further increased in SCOPD [619 (224–888)] compared to both S (p = 0.04) and NS (p < 0.001). CD326-EVs were increased in S [760 (48–2856) events/μL, p < 0.001] and in SCOPD [1055 (194–11,491), p < 0.001] when compared to NS [15 (0–68)]. CD146-EVs and CD62E-EVs were similar in the three groups. In BAL, significant differences in macrophage and epithelial-derived EVs can be clearly detected between NS, S and SCOPD, while these differences were not found in plasma. This suggests that BAL is a better medium than blood to study EVs in lung diseases.