Tumor necrosis factor alpha is a promising circulating biomarker for the development of obstructive sleep apnea syndrome: a meta-analysis

Abstract

Obstructive sleep apnea syndrome (OSAS) is a chronic inflammatory disorder. The relationship between tumor necrosis factor alpha (TNF-alpha) and OSAS has been widely evaluated, but the results thus far remain inconclusive. We thereby decided to quantify the changes of TNF-alpha between OSAS patients and controls by a meta-analysis. This study complies with the MOOSE guidelines. Two reviewers independently searched articles and abstracted relevant data. In total, 47 articles (59 studies) were analyzed, including 2857 OSAS patients and 2115 controls. Overall, OSAS patients had a significantly higher level of circulating TNF-alpha than controls (weighted mean difference [WMD]: 9.66 pg/mL, 95% confidence interval [CI]: 8.66 to 11.24, P<0.001), but with significant heterogeneity (I2: 99.7%). After adjusting for potential missing studies, the overall estimate was weakened but still significant (filled WMD: 2.63 pg/mL, 95% CI: 2.56 to 2.70, P<0.001). When studies were stratified by OSAS severity, the changes in circulating TNF-alpha between patients and controls increased gradually with the more severe grades of OSAS. In patients with mild, mild-to-moderate, moderate, moderate-to-severe and severe OSAS, circulating TNF-alpha was higher than respective controls by 0.99, 1.48. 7.79, 10.08 and 8.85 pg/mL, with significant heterogeneity (I2: 91.2%, 74.5%, 97.6%, 99.0% and 98.1%). In conclusion, our findings demonstrated that circulating TNF-alpha was significantly higher in OSAS patients than in controls, and this difference became more pronounced with the more severe grades of OSAS, indicating that TNF-alpha might be a promising circulating biomarker for the development of OSAS.

Keywords: mean difference; meta-analysis; obstructive sleep apnea syndrome; tumor necrosis factor alpha.

Figure 1. The forest plot for circulating TNF-alpha changes between OSAS patients and controls

Abbreviations: WMD, weighted mean difference; 95% CI, 95% confidence interval; I-squared, inconsistency index. The x-axis represents the changes of circulating TNF-alpha between patients and controls in pg/mL.

Figure 2. The Begg's (the upper) and filled (the lower) funnel plots for circulating TNF-alpha changes between OSAS patients and controls

In the upper plot, the “md_tnf” in the y-axis is the mean difference of circulating TNF-alpha in pg/mL, and the “s.e. of: md_tnf” in the x-axis is the standard error of mean difference in circulating TNF-alpha. In the lower plot, the “theta” is the mean difference of circulating TNF-alpha in pg/mL, and the “s.e. of: theta” is the standard error of mean difference in circulating TNF-alpha.