SESSION TITLE: Biomarkers for COPD
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Wednesday, October 30, 2013 at 07:30 AM - 09:00 AM
PURPOSE: Chronic exposure to cigarette smoke (CS) is the main risk factor for the development of COPD main phenotypes: chronic bronchitis and emphysema. Patients with emphysema display systemic and pulmonary endothelial cell (EC) dysfunction. CS induces EC dysfunction through apoptosis and release of membrane-bound microparticles (EC-MPs) which can be detected in high number in the plasma of COPD individuals. We aimed to compare the effect of AC and other systemic comorbidities on the MPs number in COPD individuals.
METHODS: Clinical and functional parameters were collected from 5 non-smokers, 2 non-diseased smokers, and 10 COPD individuals using a simplified LTRC questionnaire. Exclusion criteria were: history of angina, polysubstance abuse, pulmonary hypertension, cancer, and anemia. Blood samples were collected in BD-CPT tubes for the separation of plasma and mononuclear cells. MPs were isolated by ultra-centrifugation at 100,000g (2 h, 4C). Labeled EC-MPs (CD31+/CD42b-) were measured by flow-cytometry. The study was approved by the institutional IRB committee.
RESULTS: Total number of circulating MPs and EC-MPs was significantly higher in smokers and active smoker COPD compared with non-smokers (113±0.2/mL vs. 29±9/mL,p=0.002; 64±12/mL vs. 3±2/mL,p=0.0003, respectively) and ex-smoker COPD individuals (113±0.2/mL vs. 17±3/mL,p=0.0001; 64±12/mL vs. 2±2/mL,p=0.007, respectively). In smokers and smoker COPD patients 56.2% MPs were CD31+/CD42b- compared with 16% in non-smokers and 21% in ex-smoker COPD. Patients with combined pulmonary fibrosis emphysema syndrome (CPFE), COPD and pulmonary embolism, and COPD with AC treated with systemic corticosteroids had a lower number of total (21±17/ml) and EC-MPs (<5%) and higher number of CD31+/CD42b+ platelet-derived MPs (28.4%) and un-labeled MPs (71.4%), independent of the smoking status.
CONCLUSIONS: Increased plasma level of total MPs and EC-MPs is a useful biomarker of endothelial damage in smokers and smoker COPD individuals. Systemic co-morbidities and corticosteroid treatment modulate the total number and the source of circulating MPs. Concomitant pulmonary embolism, CPFE, and systemic corticosteroid treatment are characterized by increased number of platelet-derived and un-labeled MPs.
CLINICAL IMPLICATIONS: Total, EC-MPs, and platelet-derived MPs are useful biomarkers of COPD phenotypes and associated comorbidities.
DISCLOSURE: The following authors have nothing to disclose: Karina Serban, Khalil Diab, Daniela Petrusca, Angelia Lockett, Irina Petrache
The isolation of circulating microparticles from plasma of human subjects is a technique available in Dr. Petrache lab at Indiana University. It is considered research and not approved for clinical purposes.