Chest
Volume 140, Issue 2, August 2011, Pages 408-417
Journal home page for Chest

Original Research
Sleep Disorders
Circulating Microparticles in Children With Sleep Disordered Breathing

https://doi.org/10.1378/chest.10-2161Get rights and content

Background

Endothelial dysfunction is a common complication of pediatric obstructive sleep apnea (OSA). Circulating cell-derived microparticles (MPs) have emerged as reliable biomarkers of endothelial dysfunction and atherosclerosis.

Methods

Children underwent blood drawing the morning after a sleep study. Endothelial function was assessed using a modified hyperemic test after cuff-induced occlusion of the brachial artery. Circulating MP levels in plasma, including levels of endothelial MPs, endothelial progenitor MPs, leukocyte MPs, and platelet MPs, were measured using flow cytometry after staining with cell-specific antibodies.

Results

The levels of endothelial MPs, endothelial progenitor MPs, leukocyte MPs, and platelet MPs were significantly different according to the severity of OSA in children. Leukocyte CD11b+ MPs and platelet CD41a+ MPs correlated with the apnea-hypopnea index (AHI) (r = 0.334, P < .001; and r = 0.301, P < .001, respectively), and associations emerged between leukocyte CD11b+ MPs and apolipoprotein B (r = 0.206, P < .05) and between endothelial MPs and low-density lipoprotein cholesterol (r = 0.240, P < .01). In a multivariate regression model, the BMI z score (β ± SE, 0.045 ± 0.020; P = .020) and the CD41a MPs to leukocyte CD45 MPs ratio (β ± SE, 0.074 ± 0.032; P = .021) were independently associated with peak hyperemic responses. After controlling for age, gender, race, BMI z score, and apolipoprotein B levels, endothelial MPs, endothelial progenitor MPs, and leukocyte MPs showed independent associations with the AHI. Complex significant associations emerged between endothelial function, the AHI, and CD41a MPs.

Conclusions

Childhood OSA is associated with higher circulating MP levels that can promote cardiovascular risk. Platelet-derived MPs emerge as being significantly associated with the vascular dysfunction associated with OSA in children and could potentially account for increased risk for altered endothelial function. However, the clinical use of MPs as reliable biomarker indicators of vascular risk will have to await further studies.

Section snippets

Study Subjects

Consecutive, healthy, habitually snoring and nonsnoring prepubertal children (aged 4-12 years) participating in a study on neurocognitive function and sleep in children at the University of Louisville Pediatric Sleep Medicine Center were recruited to investigate endothelial function in the context of OSA. All methods outlined in this study were approved by the University of Louisville Human Research Committee (protocol 474.99), and informed consent was obtained from the legal caregiver of each

Study Population

Based on the presence or absence of habitual snoring and the AHI score, 65 children had mild OSA, 14 children had moderate to severe OSA, and 56 were control subjects. The demographic, polysomnographic, and biochemical characteristics of the three groups are shown in Table 1. Mean age, gender and ethnic BPs and mean arterial pressures were significantly elevated in the children with OSA. The BMI z scores and the log MRP 8/14 and apolipoprotein B levels also showed significant group differences (

Discussion

This study shows that pediatric OSA leads to severity-related increases in the number of cell-derived MPs in the peripheral blood and to increased risk for altered endothelial function,18, 39 particularly in the presence of more severe disease. Furthermore, platelet-derived MPs along with BMI z scores accounted for a significant portion of the variance in postocclusive hyperemic responses in the stepwise multivariate regression model (Table 3), with BMI z scores, an AHI > 1 event per hour of

Acknowledgments

Authors contributions: Dr Gozal had full access to the data and will vouch for the integrity of the data analysis.

Dr Kim: contributed to conducting flow cytometry assays, conducting preliminary data analyses, and initial drafting of the manuscript.

Dr Bhattacharjee: contributed to recruiting subjects, performing vascular function studies, and reviewing the manuscript.

Dr Kheirandish-Gozal: contributed to recruiting subjects, performing vascular function studies, and drafting and revising the

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    Funding/Support: Dr Gozal's work is funded by the National Institutes of Health [Grant HL65270].

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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