PracticeUpdate Conference Series: ERS 2018

Numbers of BALF Neutrophil-Derived

Microvesicles Correlate With Severity of COPD These numbers appear to be a biomarker of COPD disease severity.

F or the first time, comprehensive evaluation of microvesicles within bronchoalveolar lav- age fluid and plasma of patients with chronic obstructive pulmonary disease (COPD) demon- strated that numbers of neutrophil-derived microvesicles in the fluid correlate with functional and clinically relevant indexes of disease severity. This outcome of a flow cytometric study was reported at ERS 2018. Justin M. Garner, MD, of Baptist Memorial Healthcare Corporation in Memphis, Tennessee, and colleagues investigated the profile of microve- sicles present within bronchoalveolar lavage fluid and plasma in patients with another inflammatory disease, COPD, and assessed their relationship to disease severity. A total of 30 patients with moderate to severe COPD underwent clinical evaluation (symptom scores, lung function, exercise testing) and bronchoscopy. Paired samples of plasma and bronchoalveolar lavage fluid were analyzed by flow cytometry for microvesicles derived from: ƒ ƒ Leukocytes (CD45+) ƒ ƒ Neutrophils (CD66b+/CD11b+) ƒ ƒ Monocytes (CD45+/CD14+) ƒ ƒ Alveolar macrophages (CD206+/CD71+) ƒ ƒ Platelets (CD31+/42b+) ƒ ƒ Epithelial cells (EpCAM+/T1α+) ƒ ƒ Endothelial cells (CD146+/CD62E+/CD144+) Microvesicle subpopulations were identified within samples of bronchoalveolar lavage fluid

(leukocytes, neutrophils, monocytes, alveolar mac- rophages, epithelial cells, platelets) and plasma (leukocyte, neutrophil, monocyte, endothelial). Neutrophil-derived microvesicle numbers from bronchoalveolar lavage fluid correlated with: ƒ ƒ Modified Medical Research Council dyspnea scale (P < .001) ƒ ƒ St. George’s Respiratory Questionnaire (P < .05) ƒ ƒ Forced expiratory volume in 1 s (P < .05) ƒ ƒ 6-minute walk test (P < .01) ƒ ƒ Body mass index, airflow obstruction, dyspnea, and exercise capacity mortality index (P < .001) Neutrophil numbers in bronchoalveolar lavage fluid and plasma did not correlate with any indexes. Dr. Garner explained that in 2016, Soni et al showed that microvesicles play an important role in mediating intra-alveolar inflammation during acute lung injury. Soni et al showed, for the first time, that microvesi- cles from different intra-alveolar precursor cells are sequentially produced within the alveolar space early in the course of acute lung injury. They showed that these intra-alveolar microve- sicles, principally alveolar macrophage-derived microvesicles, are potent initiators of inflammation, mediated by their molecular cargo, in particular, tumor necrosis factor.

" Usingmicrovesicles as novel therapeutic tools in inflammatory diseases is a promising clinical approach becausemicrovesicles can be enriched with proteins or bioactive lipidmediators and their precursors. " PRACTICEUPDATE CONFERENCE SERIES • ERS 2018 14