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.

Alterations in Serum Adropin, Adiponectin, and Proinflammatory Cytokine Levels in OSAS

“…As a result, they determined that inflammation indicators increase in OSAS independent of BMI [24]. In a meta-analysis, Li et al reported that circulating TNF-alpha levels were significantly higher in OSAS patients than that of the controls, and this difference became more pronounced with an increased severity of OSAS [25]. It has been determined in another study by Popko et al examining the relationship between OSAS severity and inflammation indicators that plasma IL-1 beta levels increase with apnea intensity measured by AHI [26].…”

Biomarkers of dementia in obstructive sleep apnea

“…In a first meta-analysis of 15 studies, it was reported that blood hsCRP levels are higher in OSA patients compared to controls and that these levels are modulated by obesity and OSA severity [78]. The second meta-analysis of 47 articles found that blood TNF-α levels are also elevated in OSA subjects [79]. Finally, the third metaanalysis of 51 studies showed that blood levels of CRP, TNF-α, IL-6, IL-8 and adhesion molecules (ICAM-1, Selectins and VCAM-1) are increased in OSA subjects [80].…”

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

“…It has been recently demonstrated that IHR accelerated growth and vulnerability of atherosclerotic plaque, which probably acted by triggering the activation of TLR4/NF-κB signaling [4][5][6][7]. Acting as both up-stream and down-stream mediators of TLR signaling, tumor necrosis factor (TNF)-α has been shown to be upregulated in OSA patients, and this increase became more pronounced with the more severe grades of OSAS, indicating that TNF-α might be a promising circulating biomarker for the development of OSA [8]. In vitro experiments have shown that hypoxia enhance the response of endothelial and epithelial cells to oxidative stress through potentiating monocyte-derived dendritic cell and macrophage for release of TNF-α via MAP3K8 and ERK pathways [9][10][11][12].…”