Hemodynamic and Inflammatory Biomarkers of Obstructive Sleep Apnea (OSA): Effect of Maxillomandibular Advancement (MMA)

It has been shown that CRP, IL-6, and TNF alpha levels are increased in OSA patients; however, the literature is inconsistent in showing that OSA patients treated by CPAP can decrease CRP, IL-6 and TNF alpha levels. Mansour et al showed improvement in CRP, TNF alpha and IL6 after regular therapy by CPAP(1), and Yokoe et al also showed improvement in IL6 and CRP with CPAP(2). Serkan and Kohler didn’t find change in TNF alpha after 3-6 weeks of CPAP therapy (3). This may be due to poor patient compliance with the use of CPAP. Surgical correction is the definitive treatment for OSA and is independent of patient compliance. OSA patients have chronic intermittent hypoxia (CIH) and sleep fragmentation. The two conditions cause inflammation, oxidative stress and sympathetic activity. The consequences of OSA including hypertension, arrhythmias, heart failure, and stroke are caused by these factors (4). The purpose of this study is to determine if biomarkers (CRP, IL-6, TNF alpha) are affected by MMA when posterior airway space (PSA) improves, and apnea hypopnea index (AHI) is normalized. We hypothesize that biomarkers will decrease after MMA.

A prospective pilot study was undertaken with 8 patients undergoing MMA for OSA from 2013-2014. Inclusion criteria were patients who could not tolerate CPAP and an Apnea Hypopnea Index (AHI)>15 on polysomnography (PSG).  Two patients recruited were excluded. One was excluded because he was unable to have post-operative labs drawn and the other because he did not have a pre or post operative PSG. Blood and urine samples were taken pre-operatively and sent for analysis of TNF alpha, 8-Isoprostane, IL-6, and high sensitivity CRP. Postoperatively, blood and urine samples were taken at 3-6 months after surgery to evaluate the same set of biomarkers.

The AHI was improved overall. The average AHI pre-operatively was 54.05, and the average AHI postoperatively was 13.7 with one pending post operative PSG that is not included in the this data. There was no overall change in pre and post-operative IL-6, TNF alpha, 8-isoprostane, and high sensitivity CRP levels. Average pre-op IL-6 was <5 pg/mL, post-op was <5 pg/mL and pre-op TNF alpha was <5 pg/mL, post-op was <5 pg/mL. Average pre-op CRP was 2.8 mg/L and average post-op CRP was 2.3 mg/L. The average pre-op 8-isoprostane was 0.28 ng/mg, and the average post op value was 0.3 ng/mg.

MMA is effective in treating OSA by surgically advancing the jaws to increase the posterior airway. Our data showed successful treatment of OSA with MMA with a significantly reduced AHI in most patients involved in the study. However, could not demonstrate a significant decrease in CRP, IL-6, TNF alpha, and 8-isoprostane.

 1- Mansour, H. A. K.A., A. Fathy, and H. Aref. 2011. Effect of nasal continuous positive airway pressure on inflammatory mediators in patients with overlap syndrome. Egyptian Journal of Ear, Nose, Throat and Allied Sciences 12: 99–104

2- Yokoe, T., K. Minoguchi, H. Matsuo, H. Minoguchi, G. Yoshino, T. Hirano, and M. Adachi. 2003. 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 107: 1129 –1134.

3-Serkan Nural, Ersin Günay, Bilal Halici, Sefa Celik, and Mehmet Ünlü, Inflammatory Processes and Effects of Continuous Positive Airway Pressure (CPAP) in Overlap Syndrome 2012.

4- Erna S. Arnardottir, MS; Miroslaw Mackiewicz, PhD; Thorarinn Gislason, MD, PhD; Karen L. Teff, PhD; Allan I. Pack, MBChB, PhD.” Molecular Signatures of Obstructive Sleep Apnea in Adults: A Review and Perspective”, 2008.