Circulating Extracellular Vesicles Are Associated with Disease Severity and Interleukin-6 Levels in COPD: A Pilot Study.

Dario Nieri,Sabrina Santerini,Erica Bazzan,Alessandro Celi,Stefania Lombardi,Giovanna De Cusatis,Marta Daniele,Marina Saetta,Pierluigi Paggiaro,Manuel G Cosio,Tommaso Neri,Barbara Vagaggini

doi:10.3390/jcm10215014

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex condition in which systemic inflammation plays a role in extrapulmonary manifestations, including cardiovascular diseases: interleukin (IL)-6 has a role in both COPD and atherogenesis. The 2011 GOLD document classified patients according to FEV1, symptoms, and exacerbations history, creating four groups, from A (less symptoms/low risk) to D (more symptoms/high risk). Extracellular vesicles (EV) represent potential markers in COPD: nevertheless, no studies have explored their value in association to both disease severity and inflammation. We conducted a pilot study to analyze circulating endothelial-(E) and monocyte-derived (M) EV levels in 35 COPD patients, who were grouped according to the 2011 GOLD document; the relationship between EV and plasmatic markers of inflammation was analyzed. We found a statistically significant trend for increasing EEV, MEV, IL-6, from group A to D, and a significant correlation between EEV and IL-6. The associations between both EEV and MEV and disease severity, and between EEV and IL-6, suggest a significant interplay between pulmonary disease and inflammation, with non-respiratory cells (endothelial cells and monocytes) involvement, along with the progression of the disease. Thus, EV might help identify a high-risk population for extrapulmonary events, especially in the most severe patients.

Highlights

No statistically significant differences were observed among the four groups; we have not performed statistical analysis on FEV1 values, mMRC, and COPD Assessment Test (CAT) scores, because they differ by definition among the four groups, since the 2011 GOLD
Our results show for the first time a significant increase in circulating endothelial- and monocyte-derived extracellular vesicles (EEV and MEV, respectively) levels along with Chronic obstructive pulmonary disease (COPD) progressive stages, defined by a multidimensional approach, including airflow limitation, symptoms, and exacerbations history [5]
We decided to divide patients according to the 2011 GOLD document, since it probably represents a reasonable compromise for COPD evaluation in clinical practice, with respect to both previous and subsequent versions

Summary

Introduction

Irreversible airflow limitation represents the defining characteristic of chronic obstructive pulmonary disease (COPD) [1]. This functional abnormality is no longer regarded as the sole component of the disease, and COPD is considered a complex condition that involves several manifestations, both pulmonary and extrapulmonary, besides airflow limitation. In this case, “complex” means that these different elements display nonlinear interactions [2], and the final result has been considered a syndrome rather than a disease [3]. Lung function measurement is essential for diagnosis, and Forced Expiratory

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Conclusion