[A PhD completed. Developments in diagnosis and treatment of obstructive sleep apnea]. / Serie: Hora est. Ontwikkelingen in de diagnostiek en behandeling van obstructieve slaapapneu.

Identification of phenotypes and endotypes contributes to a better understanding of the complex pathophysiology and heterogeneous clinical presentation of obstructive sleep apnea. The general goal of this dissertation was to determine the added value of the identification and use of potential predictors; risk factors associated with obstructive sleep apnea and factors influencing treatment outcome. By identifying predictors, the specificity and sensitivity of diagnostic tools can be increased. In addition, these predictors can provide guidance in choosing from the treatment options, which could subsequently lead to an increase in treatment success. The phenotypes studied in this dissertation are: snoring sound, dental parameters and positional dependency. The predictive value of specific manoeuvres and tools during sleep endoscopy for treatment success with a mandibular repositioning device was also studied. Finally, the innovative treatment for obstructive sleep apnea, hypoglossal nerve stimulation was investigated.

The association between biomarker angiopoietin-like protein five and obstructive sleep apnea in patients undergoing bariatric surgery.

PURPOSE: Obstructive sleep apnea (OSA) is prevalent in the bariatric population. OSA should be recognized in patients undergoing bariatric surgery preoperatively to prevent peri- and post-operative complications. Lipid metabolism-related biomarkers are associated with OSA. Triglyceride metabolism is, among others, regulated by angiopoietin-like protein five (ANGPTL5). We aimed to evaluate the level of ANGPTL5 in patients with OSA of different severity levels before and after bariatric surgery. METHODS: We performed a single-center prospective cohort study including a consecutive series of patients who underwent bariatric surgery. We collected the clinical data, polysomnography (PSG) or polygraphy (PG) parameters, and plasma derived via venipuncture before and 6 to 12 months after surgery. Lipid profile, glucose levels, and ANGPTL5 levels were assessed. ANGPTL5 levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The study included 88 patients for analysis. The patients were divided into two subgroups: no or mild OSA (apnea-hypopnea index (AHI) < 15 events/hour, n = 57) and moderate-to-severe OSA (AHI ≥ 15 events/hour, n = 31). The ANGPTL5 level was higher in the moderate-to-severe OSA group (20.5 [15.6, 26.5] ng/mL) compared to the no or mild OSA group (16.3 [12.5, 19.4] ng/mL) (p = 0.008). A significant positive correlation was observed between ANGPTL5 and AHI (ρ = 0.256, p = 0.017), apnea index (AI) (ρ = 0.318, p = 0.003), and triglyceride levels (ρ = 0.240, p = 0.025). ANGPTL5 levels were reduced significantly after bariatric surgery in both moderate-to-severe OSA (15.6 [10.3, 18.7] ng/mL) and no or mild OSA (13.4 [9.2, 15.8] ng/mL) groups, though to a lower level in the group without or mild OSA. Post-surgery, the significant positive correlation between ANGPTL5 and AHI (ρ = 0.210, p = 0.047), AI (ρ = 0.230, p = 0.034), and triglyceride (ρ = 0.397, p < 0.001) remained. CONCLUSION: The data showed increased levels of ANGPTL5 in patients with moderate-to-severe OSA. Both AHI and ANGPTL5 levels decreased significantly after bariatric surgery. We also report an association between ANGPTL5 levels and OSA severity.

Increased plasma ANGPTL7 levels with increased obstructive sleep apnea severity.

Background: Weight-loss surgery is one of the recommended methods for treating obstructive sleep apnea (OSA) in obese patients. While weight reduction is critical to relieve symptoms of OSA, the biochemical factors involved in post-surgery improvement are still unknown. We aimed to explore the link between ANGPTL7 and OSA in patients with different OSA severity. Furthermore, we examined the effect of treating OSA with bariatric surgery on ANGPTL7 level. Methods: We quantified levels of circulating ANGPTL7 in fasting plasma and adipose tissue samples of 88 participants before and after bariatric surgery. Confocal microscopy analyses were also performed to assess the ANGPTL7 expression in subcutaneous white adipose tissue biopsies obtained from people with moderate-to-severe OSA compared to those with none or mild OSA. The study involved 57 individuals with none or mild OSA and 31 patients with moderate-to-severe OSA. Results: Levels of circulating ANGPTL7 were significantly higher in people with moderate-to-severe OSA (1440 ± 1310 pg/ml) compared to the none or mild OSA group (734 ± 904 pg/ml, p = 0.01). The increase in ANGPTL7 correlated significantly and positively with the apnea-hypopnea index (AHI, r = .226, p = .037), and AHI-supine (r = .266, p = .019) in participants with moderate-to-severe OSA. Multivariate logistic regression analysis demonstrated an association between ANGPTL7 and OSA severity (log2 ANGPTL7; OR =1.24, p = 0.024). ANGPTL7 levels exhibited significant positive correlations with the levels of TG and oxLDL (p-value = 0.002 and 0.01 respectively). Bariatric surgery reduced the levels of both ANGPTL7 and AHI significantly. Conclusion: Here we report significantly increased levels of ANGPTL7 both in the circulation and in adipose tissue of patients with OSA, which concurred with increased inflammation and OSA severity. Levels of ANGPTL7 decreased significantly as OSA showed a significant improvement post-surgery supporting a potential role for ANGPTL7 in either OSA progression or a role in an OSA-related mechanism.

The predictive value of drug-induced sleep endoscopy for treatment success with a mandibular advancement device or positional therapy for patients with obstructive sleep apnea.

PURPOSE: As drug-induced sleep endoscopy (DISE) can provide additional diagnostic information on collapse patterns of the upper-airway, it is widely used in patients with obstructive sleep apnea (OSA). Although more controversial, DISE may also predict the success of treatment with a mandibular advancement device (MAD) and/or positional therapy (PT). In 2018, we proposed a prediction model to investigate the predictive value of passive maneuvers during DISE - such as jaw thrust and changes in body position - on upper-airway patency. Based on the outcomes of various studies, we then adjusted our DISE protocol to better mimic the effect of a MAD, PT, or a combination of both. The aim of this study was to verify whether or not our adjustments would increase the value of DISE as a selection tool. METHODS: This single-center retrospective cohort study involved a consecutive series of patients with OSA. Patients were included if a DISE had been performed in supine and non-supine sleeping position and with and without a boil-and-bite MAD in situ between December 2018 and February 2020. The VOTE scoring system was used to evaluate the obstruction at four levels of the upper-airway. RESULTS: Among 94 patients included. the median apnea-hypopnea index (AHI) was 16.2 (events/h). As a temporary MAD during DISE reduced obstruction by 54% and jaw thrust by 57%, both mimicked the effect of the custom-made MADs referred to in the literature, which reduces the AHI by 60%. Head-and-trunk rotation reduced obstruction by 55% and thus mimicked the effect of PT, which is known to reduce the AHI by 50%. CONCLUSION: A jaw thrust, a temporary MAD, and head-and-trunk rotation during DISE all seem to mimic the treatment effects of MAD and PT. These findings may be of added value when choosing OSA treatment. To prove the predictive value of these maneuvers during DISE, a prospective study should be performed.