Elsevier

Sleep Medicine

Volume 14, Issue 2, February 2013, Pages 172-176
Sleep Medicine

Original Article
Effect of adenotonsillectomy on c-reactive protein levels in children with obstructive sleep apnea: A meta-analysis

https://doi.org/10.1016/j.sleep.2012.11.011Get rights and content

Abstract

Objective

Children with obstructive sleep apnea syndrome (OSAS) have increased systemic inflammation, as assessed by c-reactive protein (CRP), and are at risk for substantial end-organ damage. Previous studies assessing the effect of adenotonsillectomy (T&A) on CRP in children with OSAS have yielded conflicting results. Therefore, the purpose of the current investigation was to perform a meta-analysis of the effect of T&A on CRP in children with OSAS and explore possible moderating factors.

Methods

Multiple databases (PubMed, CINAHL, and Cochrane) were searched for relevant studies. Effective size was calculated with standardized mean differences (SMD) and analyzed with random-effects model. Moderators were examined with mixed-effects models.

Results

Overall, T&A significantly reduced CRP (SMD = −0.79, 95% CI −1.33 to −0.25). We found significant between-study heterogeneity (Cochran’s Q = 54.6, df = 7, p < 0.001; I2 = 90.7%, 95% CI 77.5–98.2%; and H2 = 10.7, 95% CI 4.5–55.7). We did not find evidence of publication bias or significant effects of tested moderators (study year, study size, age, gender, obesity, apnea–hypopnea index, oxygen nadir, pre-surgical CRP, follow-up duration).

Conclusions

The results of the current study indicate that T&A significantly reduces CRP levels in children with OSAS. Despite the presence of significant between-study heterogeneity, we did not identify any significant moderating factors.

Introduction

Obstructive sleep apnea syndrome (OSAS) in children involves recurrent of partial or complete upper airway obstruction during sleep which interrupts normal gas exchange and causes sleep fragmentation [1]. Children with OSAS are thought of as being on the extreme end of the spectrum of sleep-disordered breathing with primary snoring at the lower end of the spectrum, and children with OSAS are at increased risk for substantial morbidity in multiple organ systems [1]. While the consequences of OSAS continue to be elucidated, its incidence continues to increase, especially in obese children [1].

Recently, systemic inflammation has emerged as a possible mechanism underlying the cardiovascular and neurocognitive morbidity associated with OSAS [2]. Investigations of systemic inflammation in OSAS have focused largely on the use of c-reactive protein (CRP) as a biomarker of inflammation. Most [3], [4], [5], [6], [7], [8], but not all [9], studies have demonstrated elevated CRP levels in children with OSAS. Furthermore, CRP was shown to be related to OSAS-mediated cognitive morbidity [10]. Because of the putative relationship between OSAS and systemic inflammation as measured by CRP, investigators have begun to examine the effect of adenotonsillectomy (T&A) on CRP levels in children with OSAS. To date, results across several studies have been quite variable, with some [5], [7], [11] showing a statistically significant beneficial effect of T&A on CRP levels while others [12], [13], [14] failed to replicate these findings. Furthermore, one study found significant moderating effects of obesity and post-surgical residual OSAS [5].

The question of whether or not T&A affects CRP in children with OSAS remains unresolved, despite previous investigation. There are several possible explanations for the lack of consistency in the results. One possibility is that the negative studies may have been under-powered, and this possibility is collaborated by the fact that all of the negative studies still showed a decrease in CRP despite it not reaching significance [12], [13], [14]. Another possible explanation of variable results across studies is that there are moderating factors such as, the presence of obesity or residual post operative OSAS, affecting the change in CRP. Therefore, the purpose of the current study is to perform a meta-analysis of the effect of T&A on CRP levels in children with OSAS and explore possible moderating factors affecting this relationship.

Section snippets

Methods

Using PubMed, CINAHL, and Cochrane databases, we searched the literature for relevant studies published before 10 July 2012, evaluating the effect of T&A on CRP in children with OSAS. In order to identify these studies, all searches were performed by combining terms relating the disease area (sleep), age group (pediatric or children), CRP (CRP or c-reactive protein), and intervention (adenotonsillectomy). Additional studies were identified by examining the reference lists of articles found

Results

The original search produced eight, one, and one articles from PubMed, CINAHL, and Cochrane databases, respectively. Each of these articles was selected and reviewed in detail. One study, [18] was excluded because it was a review article with no original data, one study, [19] was excluded because the treatment group was a combination of T&A/CPAP/nasal steroids and the corresponding author did not reply to a data request for the subgroup of interest, and another, [20] was excluded because the

Discussion

The current study utilized meta-analytic methods to investigate the effect of T&A and putative moderating factors on CRP levels in children with OSAS. Our results indicate that T&A exerts a statistically significant decrease in CRP levels. Furthermore, although we found evidence for significant between-study heterogeneity, none of the examined study-level factors significantly modified the main effect. We did not find evidence of publication bias, and no one study was vital for either the main

Limitations

Despite these important findings, our study was not without limitations. First, the number and size of studies included in the analysis was relatively small and larger and more numerous studies would allow for more precise effect size estimation as well as, more sophisticated moderator analysis. Second, meta-analysis only allows for analysis of moderating factors at the study-level rather than individual level. Third, some studies could not be included in all [19] or part [7], [12], [13] of the

Conclusion

In conclusion, the current meta-analysis demonstrated a significant reduction in CRP with T&A in children with OSAS. We did not identify any significant moderating factors despite the presence of significant between-study heterogeneity. These results have important clinical implications for the use of CRP as a biomarker in OSAS. Future studies ought to explore additional potential moderating factors such as, environmental or genetic interactions.

Conflict of Interest

The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2012.11.011.

. ICMJE Form for Disclosure of Potential Conflicts of Interest form.

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