Endothelial Microparticles as Predictive Biomarkers for COPD Exacerbations

Microparticles (MPs) are shedding-membrane vesicles released from activated blood and endothelial cells (eg, platelets, red blood cells, and leukocytes) under inflammatory conditions. Endothelial microparticles (EMPs) have received attention as potential biomarkers for chronic obstructive pulmonary disease (COPD), potentially predicting the presence, progression, and degree of endothelial damage in patients with COPD. However, not enough is known about whether MPs of other origins play a pivotal role in COPD. Now a new study, published in the International Journal of COPD, concludes that the increase in EMPs and various MPs in the systemic circulation that accompanies COPD can lead to disease exacerbation and could be used as early biomarkers on disease progression.

The researchers used flow cytometry to measure EMPs and other cell-derived circulating MPs in 50 patients with COPD, both with stable disease and disease exacerbation. Patients were excluded if they had factors that could significantly alter MP amounts. Including:

• Hematologic diseases
• Kidney diseases
• Cytostatic treatment in the past 30 days
• Disseminated intravascular coagulation scores ≥5
• Antiphospholipid syndrome.

Clinical factors that could alter MP values, such as smoking habits and medications, were also recorded. COPD exacerbations were defined as hospital admissions and intravenous corticosteroid therapy urgently initiated based on worsening of symptoms such as increased sputum, cough, and signs of respiratory distress. Patients presenting for yearly checkup without novel symptoms were deemed stable. Data were compared with 19 healthy individuals in an age-matched control group. Exclusion criteria were the same for controls and patients.

In the absence of a standardized method for MP analysis and lack of consensus on the use of MP-labeling antibodies, the investigators successfully developed a reliable cytometric method for MP isolation that avoids false-positive MP results, which they describe in detail in the publication. They selected EMPs (CD31+, CD62E+) and platelet-derived (CD61+, CD41+, CD42a+, PAC1+), red blood cell—derived (GlyA+), and leukocyte-derived (CD45+, CD13+, CD14+, CD56+) MPs, and conducted flow cytometric measurements along with statistical analysis to investigate differences between patient groups.

All the measured MPs—including CD31+ and CD62E+ with endothelial origin; CD61+, CD41+, CD42a+, and PAC1+ with platelet origin; GlyA+ with red blood cell origin; CD45+ and CD13+ with leukocyte origin; CD14+ with monocyte origin; and CD56+ with lymphocyte origin&mdash;showed significant (P <.001) elevation in patients with stable COPD compared with controls. The researchers detected statistically significant differences in patients with acute exacerbation of COPD (AECOPD) versus those who were stable: the number of CD62E+, CD42a+, and CD14+ MPs was significantly (P <.05) higher in the AECOPD group.

“These endothelial-, platelet-, and monocyte-derived MP numbers showed a remarkable elevation in acute exacerbation of COPD patients,” the investigators conclude. In addition, analyses showed that CD62E+, CD42a+, and CD14+ MPs correlate inversely with measures of lung function (FEV₁/FVC): (-0.406, -0.473, -0.440; P <.001, respectively).

In addition to providing a reliable method for MP analysis, the authors highlight their novel observation that not only are EMPs elevated in exacerbated COPD, but also that platelet-derived CD41+ and CD42a+ and monocyte-derived CD14+ MPs have a significant impact on COPD exacerbations.

An inverse correlation with lung function and elevation in patients with disease exacerbation means that EMPs and MPs could be used as predictive biomarkers in COPD pathophysiology and would allow appropriate treatment to start early. However, the authors point to the need for further research to understand the causative role of specific MPs in the pathophysiology of COPD exacerbations so they can be used as potential predictive biomarkers of COPD worsening and outcome.

Reference

1. To&#779;ke&#769;s-Fu&#776;zesi M, Ruzsics I, Rideg O, Kustán P, Kovács GL, Molnár T. Role of microparticles derived from monocytes, endothelial cells and platelets in the exacerbation of COPD. Intern J COPD. 2018;13:3749-3757. doi: https://doi.org/10.2147/COPD.S175607.