Effects of continuous positive airway pressure therapy on systemic inflammation in obstructive sleep apnea: A meta-analysis

doi:10.1016/j.sleep.2013.07.006

Sleep Medicine

Volume 14, Issue 11, November 2013, Pages 1139-1150

https://doi.org/10.1016/j.sleep.2013.07.006 Get rights and content

Highlights

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Continuous positive airway pressure (CPAP) therapy could suppress systemic inflammation in obstructive sleep apnea (OSA) patients.
•
The differences in efficacy were present among the various inflammatory markers.
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More benefits were from therapy duration of ⩾3 months and adequate compliance.
•
Heightened systemic inflammatory levels in OSA may independent of obesity.

Abstract

Objectives

Our meta-analysis was performed to estimate the effect of continuous positive airway pressure (CPAP) therapy on systemic inflammation in patients with obstructive sleep apnea (OSA).

Methods

A comprehensive literature search of PubMed and EMBASE was performed for literature published up to January 2013. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy.

Results

A total of 35 studies involving 1985 OSA patients were included in the meta-analysis. Each study investigated one or more inflammatory markers: 24 studies on C-reactive protein (CRP), 16 studies on IL-6, 3 studies on IL-8, and 12 studies on tumor necrosis factor α (TNF-α). The results showed that the SMD (95% confidence interval [CI]) for CRP, IL-6, IL-8, and TNF-α were 0.452 (95% CI, 0.252–0.651), 0.299 (95% CI, 0.001–0.596), 0.645 (95% CI, 0.362–0.929), and 0.478 (95% CI, 0.219–0.736) in pre- and post-CPAP therapy, respectively. The subgroup analyses seemed to support better benefits with therapy duration of ⩾3 months and more adequate compliance (⩾4 h/night).

Conclusions

CPAP therapy could partially suppress systemic inflammation in OSA patients, and substantial differences were present among the various inflammatory markers.

Introduction

Obstructive sleep apnea (OSA) is the most common sleep disorder in clinical practice. Its growing worldwide prevalence may be due to the rising incidence of obesity in the public. OSA has been increasingly recognized as a major public health issue, as it has a significant influence on the incidence and prognosis of cardiovascular diseases [1]. The underlying pathophysiologic mechanisms on the influence of OSA to the development of cardiovascular disease have not been completely understood and may be multifactorial in origin. Increasing evidence suggests that inflammatory processes play a pivotal role in the pathogenesis of cardiovascular disease in OSA [2], [3]. Inflammatory markers, such as C-reactive protein (CRP), IL-6, IL-8, and tumor necrosis factor α (TNF-α), which have been proposed to be linked to the pathogenesis of systemic inflammation in cardiovascular disease, have been reported to be elevated in OSA patients [4].

Continuous positive airway pressure (CPAP) therapy is remarkably beneficial to the pathologic condition and prognosis of cardiovascular diseases in OSA but is inconsistent to systemic inflammation. Previous meta-analyses based on small sample size and studies indicated a significant decrease of CRP levels in OSA patients under CPAP therapy with adequate compliance (⩾4 h/night) [5], [6]. However, the effects of CPAP therapy on the decrease of other inflammatory factors and on those with poor compliance (<4 h/night) has not been answered. To better address this issue, a meta-analysis was performed to evaluate the effects of CPAP therapy on the inflammatory markers CRP, IL-6, IL-8, and TNF-α in OSA patients.

Section snippets

Literature search and selection

We comprehensively searched PubMed and EMBASE databases for literature published up to January 2013. The search was limited to human adults (aged ⩾ 18 years) with no language restrictions. The following search terms were used to query the databases, with combined free-text and subject-based parameters: C-reactive protein, CRP, tumor necrosis factor alpha, tumor necrosis factor α, TNF-alpha, TNF-α, interleukin-6, IL-6, interleukin-8, IL-8, positive airway pressure, CPAP, apnoea, and apnea. The

Characteristics of included studies

The selection process for studies included in the meta-analysis is outlined in Fig. 1. A total of 35 studies were found eligible for inclusion based on the set criteria for meta-analysis [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43]; these studies involved 1985 patients (men, 75.45%). Each study investigated one or more inflammatory

Discussion

Our meta-analysis assessed the effects of CPAP therapy in OSA patients on several inflammatory markers namely, CRP, IL-6, IL-8, and TNF-α. We chose these inflammatory markers because they have been widely studied and may closely link OSA with cardiovascular diseases; genetic variants of CRP, TNF-α, and IL-6 have been associated with OSA [44], [45], [46], [47]. The pooled results indicated that CPAP therapy could significantly decrease the levels of CRP, IL-6, IL-8, and TNF-α in OSA patients.

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.2013.07.006.

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

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¹: These authors equally contributed to this work.

View full text

Original ArticleEffects of continuous positive airway pressure therapy on systemic inflammation in obstructive sleep apnea: A meta-analysis

Highlights

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Literature search and selection

Characteristics of included studies

Discussion

Conflict of interest

Obstructive sleep apnea and cardiovascular disease

Cardiol Rev

Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome?

Postgrad Med J

Early and mid-term effects of obstructive apneas in myocardial injury and inflammation

Sleep Med

Biomarkers of sleep apnea

Chest

Effect of continuous positive airway pressure on C-reactive protein levels in sleep apnea: a meta-analysis

Otolaryngol Head Neck Surg

Impact of continuous positive airway pressure on C-reactive protein in patients with obstructive sleep apnea: a meta-analysis

Sleep Breath

The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions

J Epidemiol Community Health

Estimating the mean and variance from the median, range, and the size of a sample

BMC Med Res Methodol

Effects of nasal continuous positive airway pressure on soluble cell adhesion molecules in patients with obstructive sleep apnea syndrome

Am J Med

Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1

J Appl Physiol

Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure

Circulation

Effects of obesity on C-reactive protein level and metabolic disturbances in male patients with obstructive sleep apnea

Am J Med

Resistin levels in patients with obstructive sleep apnoea syndrome – the link to subclinical inflammation?

Med Sci Monit

Elevated production of tumor necrosis factor-alpha by monocytes in patients with obstructive sleep apnea syndrome

Chest

Effect of continuous positive airway pressure on soluble CD40 ligand in patients with obstructive sleep apnea syndrome

Chest

Association between lipid peroxidation and inflammation in obstructive sleep apnoea

Eur Respir J

Predictors of elevated nuclear factor-kappaB-dependent genes in obstructive sleep apnea syndrome

Am J Respir Crit Care Med

Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea

Am J Respir Crit Care Med

Decreased lipoprotein lipase in obstructive sleep apnea syndrome

Circ J

Fixed and autoadjusting continuous positive airway pressure treatments are not similar in reducing cardiovascular risk factors in patients with obstructive sleep apnea

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Original Article
Effects of continuous positive airway pressure therapy on systemic inflammation in obstructive sleep apnea: A meta-analysis