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Circulating microparticle levels are reduced in patients with ARDS
Ciara M Shaver1, Justin Woods1, Jennifer K Clune1
1Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, 1161 21st Ave South, Medical Center North T-1218, Nashville, 37232, Tennessee, USA.
Background:
It is unclear how to identify which patients at risk for acute respiratory distress syndrome (ARDS) will develop this condition during critical illness. Elevated microparticle (MP) concentrations in the airspace during ARDS are associated with activation of coagulation and in vitro studies have demonstrated that MPs contribute to acute lung injury, but the significance of MPs in the circulation during ARDS has not been well studied. The goal of the present study was to test the hypothesis that elevated levels of circulating MPs could prospectively identify critically ill patients who will develop ARDS and that elevated circulating MPs are associated with poor clinical outcomes.
Methods:
A total of 280 patients with platelet-poor plasma samples from the prospective Validating Acute Lung Injury biomarkers for Diagnosis (VALID) cohort study were selected for this analysis. Demographics and clinical data were obtained by chart review. MP concentrations in plasma were measured at study enrollment on intensive care unit (ICU) day 2 and on ICU day 4 by MP capture assay. Activation of coagulation was measured by plasma recalcification (clot) times.
Results:
ARDS developed in 90 of 280 patients (32%) in the study. Elevated plasma MP concentrations were associated with reduced risk of developing ARDS (odds ratio (OR) 0.70 per 10 μM increase in MP concentration, 95% CI 0.50-0.98, p = 0.042), but had no significant effect on hospital mortality. MP concentration was greatest in patients with sepsis, pneumonia, or aspiration as compared with those with trauma or receiving multiple blood transfusions. MP levels did not significantly change over time. The inverse association of MP levels with ARDS development was most striking in patients with sepsis. After controlling for age, presence of sepsis, and severity of illness, higher MP concentrations were independently associated with a reduced risk of developing ARDS (OR 0.69, 95% CI 0.49-0.98, p = 0.038). MP concentration was associated with reduced plasma recalcification time.
Conclusions:
Elevated levels of circulating MPs are independently associated with a reduced risk of ARDS in critically ill patients. Whether this is due to MP effects on systemic coagulation warrants further investigation.
Insights
Elevated circulating microparticles (MPs) were found to be associated with a reduced risk of developing acute respiratory distress syndrome (ARDS) in critically ill patients. This finding suggests MPs may play a protective role, contrary to previous hypotheses.
Area of Science:
- Critical Care Medicine
- Pulmonary Medicine
- Biomarker Discovery
Background:
- Identifying patients at risk for acute respiratory distress syndrome (ARDS) during critical illness remains challenging.
- Elevated airspace microparticle (MP) concentrations are linked to coagulation activation in ARDS, but circulating MP significance is understudied.
Purpose of the Study:
- To test if elevated circulating MPs prospectively identify critically ill patients who will develop ARDS.
- To determine if elevated circulating MPs correlate with poor clinical outcomes.
Main Methods:
- Analysis of 280 patients from the prospective VALID cohort study with platelet-poor plasma samples.
- Measurement of MP concentrations in plasma on ICU days 2 and 4 using MP capture assay.
- Assessment of coagulation activation via plasma recalcification times.
Main Results:
- ARDS developed in 32% of patients; elevated plasma MP concentrations were associated with a reduced risk of ARDS (OR 0.70, p=0.042).
- MP levels were highest in patients with sepsis, pneumonia, or aspiration.
- Higher MP concentrations were independently associated with reduced ARDS risk after controlling for confounders (OR 0.69, p=0.038).
Conclusions:
- Elevated circulating MPs are independently associated with a decreased risk of ARDS in critically ill patients.
- The inverse association was most pronounced in septic patients.
- Further research is needed to understand the role of MPs in systemic coagulation and ARDS development.
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