Dynamics of Circulating CD14/CD16 Monocyte Subsets in Obstructive Sleep Apnea Syndrome Patients upon Hypoglossal Nerve Stimulation

Abstract

Background: Obstructive sleep apnea syndrome (OSAS) is a widespread respiratory disease that is associated with recurrent breathing intermissions at night. The corresponding oxidative stress triggers a low-grade systemic inflammation which leads to alterations of different immune cells in the peripheral blood. The current standard treatment for OSAS is continuous positive airway pressure (CPAP), whereas hypoglossal nerve stimulation (HNS) has been established as a second-line treatment option for CPAP failure. The aim of the study was to investigate the influence of HNS for OSAS patients on the distribution and differentiation of circulating monocyte subsets in connection with the clinical parameters. Materials and Methods: Therefore, a detailed analysis of the distribution of CD14/CD16 characterized monocyte subsets in the peripheral blood of OSAS patients before and after HNS therapy was performed by flow cytometry. Furthermore, values of BMI (body mass index), ODI (oxygen desaturation index), and ESS (Epworth Sleepiness Scale) were measured. Results: These OSAS patients significantly improved AHI and ESS scores under HNS. In addition, HNS revealed the potential to ensure normal distributions of blood monocyte subsets and even improved the monocyte dynamics in selected OSAS patients, but there were no significant correlations with AHI, ODI, HNS usage, and daytime sleepiness. Conclusions: We conclude that HNS-related positive effects on the oxygenation of the peripheral blood as well as affect the distribution of circulating monocyte subsets, but clinical OSAS correlations are missing. Far more individual clinical, cellular and molecular factors are involved in this sensitive and complex regulatory network and have to be elucidated in further studies.

Keywords: CPAP therapy; HNS therapy; monocyte subsets; obstructive sleep apnea syndrome.

Figure 1

Values of BMI (body mass index), AHI (apnea–hypopnea index), ODI (oxygen desaturation index), and Epworth Sleepiness Scale (ESS) before and after HNS therapy. *: p < 0.05; **: p < 0.01. Post hoc power calculation was performed for the significant differences and revealed values of 100% for both AHI and ODI.

Figure 2

Correlation analysis between HNS usage time (h/week) and BMI (body mass index), AHI (apnea–hypopnea index), ODI (oxygen desaturation index), and Epworth Sleepiness Scale (ESS) before and after HNS therapy, respectively. A multivariate progression with the Pearson correlation was performed. The correlation coefficient (r) and p-values are shown for each correlation. *: p < 0.05; **: p < 0.01.

Figure 3

Flow cytometric analysis of monocyte subsets. Monocyte measurements from whole blood samples revealed the percentages of classical monocytes (CM), CD16⁺ intermediate (IM), and non-classical monocytes (NCM) in OSAS patients prior to and after HNS treatment.

Figure 4

Flow cytometric analysis of classical monocytes before (pre) and after (post) HNS treatment. (A): Example flow cytometry gating scheme of peripheral monocyte subsets of patient O105 before and after 12-month HNS treatment. (B): Whole blood analysis revealed an improvement in five patients, a decrease in classical monocytes in two patients, and an unchanged level in one patient upon HNS treatment. Patients’ numbers are given in case of redistributed monocyte abundances.

Figure 5

Correlation analysis between different parameters (BMI, AHI, ODI, ESS) measured in OSAS patients. A multivariate progression with the Pearson correlation was carried out. The correlation coefficient (r) is given for each pair.