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

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Title: Intra-alveolar neutrophil-derived microvesicles are associated with disease severity in COPD
Authors: Soni, S
Garner, J
O'Dea, K
Kohn, M
Finney, L
Tirlapur, N
Srikanthan, K
Aboelhassan, A
Singh, S
Wilson, M
Wedzicha, J
Kemp, S
Usmani, O
Shah, P
Takata, M
Item Type: Journal Article
Abstract: Despite advances in the pathophysiology of Chronic Obstructive Pulmonary Disease (COPD), there is a distinct lack of biochemical markers to aid clinical management. Microvesicles (MVs) have been implicated in the pathophysiology of inflammatory diseases including COPD but their association to COPD disease severity remains unknown. We analysed different MV populations in plasma and bronchoalveolar lavage fluid (BALF) taken from sixty-two patients with mild to very severe COPD (51% male; mean age: 65.9 years). These patients underwent comprehensive clinical evaluation (symptom scores, lung function, exercise testing) and the capacity of MVs to be clinical markers of disease severity was assessed. We successfully identified various MV subtype populations within BALF (leukocyte, PMN (polymorphonuclear leukocyte i.e. neutrophil), monocyte, epithelial and platelet MVs) and plasma (leukocyte, PMN, monocyte and endothelial MVs), and compared each MV population to disease severity. BALF neutrophil MVs were the only population to significantly correlate with the clinical evaluation scores including FEV1, mMRC dyspnoea score, 6-minute walk test, hyperinflation and gas transfer. BALF neutrophil MVs, but not neutrophil cell numbers, also strongly correlated with BODE index. We have undertaken, for the first time, a comprehensive evaluation of MV profiles within BALF/plasma of COPD patients. We demonstrate that BALF levels of neutrophil-derived MVs are unique in correlating with a number of key functional and clinically-relevant disease severity indices. Our results show the potential of BALF neutrophil MVs for a COPD biomarker that tightly links a key pathophysiological mechanism of COPD (intra-alveolar neutrophil activation) with clinical severity/outcome.
Issue Date: 1-Jan-2021
Date of Acceptance: 23-Oct-2020
URI: http://hdl.handle.net/10044/1/85018
DOI: 10.1152/ajplung.00099.2020
ISSN: 1040-0605
Publisher: American Physiological Society
Start Page: L73
End Page: L83
Journal / Book Title: American Journal of Physiology: Lung Cellular and Molecular Physiology
Volume: 320
Issue: 1
Copyright Statement: © 2020, American Journal of Physiology-Lung Cellular and Molecular Physiology. This accepted manuscript is available open access under a CC-BY Licence (https://creativecommons.org/licenses/by/4.0/)
Sponsor/Funder: Medical Research Council/British Journal of Anaesthesia
Medical Research Council (MRC)
CW+
Funder's Grant Number: MR/M018164/1
Award 0096
Keywords: biomarker
chronic obstructive pulmonary disease
extracellular vesicles
microvesicles
neutrophil
Aged
Bronchoalveolar Lavage Fluid
Cell-Derived Microparticles
Cytokines
Female
Forced Expiratory Volume
Humans
Male
Neutrophils
Pulmonary Alveoli
Pulmonary Disease, Chronic Obstructive
Respiratory Function Tests
Severity of Illness Index
Pulmonary Alveoli
Neutrophils
Bronchoalveolar Lavage Fluid
Humans
Pulmonary Disease, Chronic Obstructive
Cytokines
Respiratory Function Tests
Forced Expiratory Volume
Severity of Illness Index
Aged
Female
Male
Cell-Derived Microparticles
Respiratory System
0606 Physiology
1116 Medical Physiology
Publication Status: Published
Online Publication Date: 2021-01-28
Appears in Collections:Department of Surgery and Cancer
National Heart and Lung Institute
Faculty of Medicine



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