Plasma Adhesion Molecules in Children With Sleep-Disordered Breathing

doi:10.1378/chest.129.4.947

Chest

Volume 129, Issue 4, April 2006, Pages 947-953

https://doi.org/10.1378/chest.129.4.947 Get rights and content

Study objectives

To determine whether childhood sleep-disordered breathing (SDB) is associated with elevated levels of plasma adhesion molecules.

Design

Prospective, observational study.

Setting

Sleep Medicine Center of Kosair Children's Hospital.

Participants

Thirty-nine children with SDB (apnea-hypopnea index [AHI] > 5/h), 47 children with mild SDB (AHI 1 to 5/h), and 42 healthy control subjects (AHI < 1/h).

Measurements and results

One hundred twenty-eight children underwent a standard polysomnographic assessment with a blood draw the following morning. Plasma levels of CRP and the adhesion molecules intercellular adhesion molecule (ICAM)-1 and P-selectin were measured. No differences were observed in ICAM-1 levels among the groups; however, obese children had higher ICAM-1 levels than nonobese children (425.0 ± 123.0 ng/mL vs 375.6 ± 107.1 ng/mL, p = 0.04) [mean ± SD]. P-selectin levels were significantly higher in the SDB group (84.0 ± 52.2 ng/mL) and the mild SDB group (89.3 ± 49.9 ng/mL) when compared to control subjects (49.5 ± 22.3 ng/mL; p < 0.001 for both groups). Furthermore, P-selectin correlated with AHI (r = 0.32, p < 0.001), respiratory arousal index (r = 0.27, p = 0.002), and nadir of oxygen saturation as measured by pulse oximetry (r = − 0.19, p = 0.038). Plasma CRP levels were found to correlate with P-selectin even after controlling for BMI (r = 0.20, p = 0.05). No correlations were found between CRP and ICAM-1.

Conclusions

Children with SDB have plasma elevations of P-selectin, a marker of platelet activation, lending support to the premise that inflammatory processes are elicited by SDB in children, and may contribute to accelerated risk for cardiovascular morbidity. In contrast, elevations in ICAM-1 are primarily associated with obesity rather than SDB.

Section snippets

Materials and Methods

Children were recruited to this study from two sources: children undergoing clinical evaluation for suspected SDB who were referred to the Kosair Children's Hospital Sleep Medicine and Apnea Center in Louisville, KY, and those children participating in a larger community-based study in Louisville, KY. The latter community group provided control children. All children were recruited between January and August of 2004. All subjects underwent a standard overnight polysomnographic evaluation and a

Results

A total of 128 children (51% male) underwent polysomnographic evaluation with a morning blood draw. The mean age of the population was 6.9 ± 1.2 years (range, 4.0 to 10.0 years). Sixty percent of the samples were white, 37% were African American, and 4% were of other ethnic backgrounds. A total of 39 children were found to have SDB (AHI > 5/h), 47 children had mild SDB, and 42 children were classified as control subjects (AHI < 1/h). All of the control children were recruited from the community

Discussion

This study conclusively demonstrates that children with SDB have elevated circulating levels of plasma P-selectin, a surface marker of platelet activation, and that P-selectin is correlated with components of SDB, namely the severity of oxyhemoglobin desaturation and the respiratory arousal index. Our current findings suggest that inflammatory processes associated with atherogenesis and leading to activation of P-selectin are elicited by SDB in children. Interestingly, although elevated ICAM-1

Acknowledgment

We are grateful to the parents and children who participated in this study and to the technical staff who performed the polysomnography.

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Obstructive sleep apnea syndrome (OSAS) may be central neurologic (<5%) or obstructive (>95%) in origin and is a relatively prevalent condition in children. It affects 1%-5% of children aged 2-8 years and is caused by a variety of different pathophysiologic abnormalities. Cardiovascular, metabolic, and neurocognitive comorbidities can occur in both children and adults when left untreated. It also can cause severe behavioral problems in children. The American Academy of Pediatrics recommends that all children be screened with an appropriate history and physical examination for symptoms and signs suggestive of OSAS. The diagnosis is primarily made clinically and confirmed by polysomnographic findings. Treatment depends on the child's age, underlying medical problems, polysomnography findings, and whether or not there is upper airway obstruction usually secondary to enlarged adenoids and/or tonsils, allergic and nonallergic rhinitis, acute and chronic sinusitis, and other upper airway pathology. If enlarged adenoid or tonsils or both conditions exist, an adenoidectomy, tonsillectomy, or adenotonsillectomy remains the treatment of choice. Pharmacotherapy of OSAS has shown some effect in children with mild symptoms. This paper reviews the prevalence, pathophysiology, clinical presentation, diagnosis, and treatment of OSAS.
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Citation Excerpt :
When the authors used AHI, the AHI ranged from AHI >1 to AHI >5/hrTST. Most of the studies assessed blood biomarkers [41–44,46,49–52,54–57,59–62,66–68,74], while seven studied urinary biomarkers [47,48,53,58,63,64,73], four explored for potential biomarkers in saliva [69–72], and three studies involved EBC [45,65,75]. A summary of the study descriptive characteristics can be found in Table 1.
The overall validity of biomarkers in the diagnosis of obstructive sleep apnea (OSA) remains unclear. We conducted a scoping review to provide assessments of biomarkers characteristics in the context of obstructive sleep apnea (OSA) and to identify gaps in the literature. A scoping review of studies in humans without age restriction that evaluated the potential diagnostic value of biological markers (blood, exhaled breath condensate, salivary, and urinary) in the OSA diagnosis was undertaken. Retained articles were those focused on the identification of biomarkers in subjects with OSA, the latter being confirmed with a full overnight or home-based polysomnography (PSG). Search strategies for six different databases were developed. The methodology of selected studies was classified using an adaptation of the evidence quality criteria from the American Academy of Pediatrics. Additionally the biomarkers were classified according to their potential clinical application. We identified 572 relevant studies, of which 117 met the inclusion criteria. Eighty-two studies were conducted in adults, 34 studies involved children, and one study had a sample composed of both adults and children. Most of the studies evaluated blood biomarkers. Potential diagnostic biomarkers were found in nine pediatric studies and in 58 adults studies. Only nine studies reported sensitivity and specificity, which varied substantially from 43% to 100%, and from 45% to 100%, respectively. Studies in adults have focused on the investigation of IL-6, TNF-α and hsCRP. There was no specific biomarker that was tested by a majority of authors in pediatric studies, and combinatorial urine biomarker approaches have shown preliminary promising results. In adults IL-6 and IL-10 seem to have a favorable potential to become a good biomarker to identify OSA.

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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

Dr. Tauman was supported by an Ohio Valley AHA Fellowship.

This study was supported by National Institutes of Health Grant HL-65270, Department of Education Grant H324E011001, Centers for Disease Control and Prevention Grant E11/CCE 422081–01, The Children's Foundation Endowment for Sleep Research, and the Commonwealth of Kentucky Research Challenge Trust Fund.

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Chest

Original ResearchPlasma Adhesion Molecules in Children With Sleep-Disordered Breathing

Study objectives

Design

Setting

Participants

Measurements and results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Acknowledgment

Am J Med

Chest

Am J Cardiol

Chest

Chest

Chest

Chest

Sleep Med Rev

Lancet

Atherosclerosis

Am J Med

Thromb Res

Lancet

Atherosclerosis

Population-based study of sleep-disordered breathing as a risk factor for hypertension

Arch Intern Med

Sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study

JAMA

Prospective study of the association between sleep-disordered breathing and hypertension

N Engl J Med

Sleep-disordered breathing and coronary artery disease: long-term prognosis

Am J Respir Crit Care Med

Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study

Am J Respir Crit Care Med

C reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women

N Engl J Med

High sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease

Circulation

Direct proinflammatory effect of C-reactive protein on human endothelial cells

Circulation

The pathogenesis of atherosclerosis: a perspective for the 1990s

Nature

Overlapping patterns of activation of human endothelial cells by interleukin-1, tumor necrosis factor, and immune interferon

J Immunol

Increased soluble P-selectin in peripheral artery disease: a new marker for the progression of atherosclerosis [letter]

Thromb Haemost

Soluble P-selectin and the risk of future cardiovascular events

Circulation

Heart rate variability in children with obstructive sleep apnea

Sleep

Autonomic cardiovascular control in children with obstructive sleep apnea

Clin Autonom Res

Autonomic dysfunction in children with sleep-disordered breathing

Sleep

Blood pressure in children with obstructive sleep apnea

Am J Respir Crit Care Med

Original Research
Plasma Adhesion Molecules in Children With Sleep-Disordered Breathing