Evaluation of clinical and genetic factors in obstructive sleep apnoea.

Purpose: To evaluate the correlation between several presumed candidate genes for obstructive sleep apnoea (OSA) and clinical OSA phenotypes and propose a predictive comprehensive model for diagnosis of OSA. Methods: This case-control study compared polysomnographic patterns, clinical data, morbidities, dental factors and genetic data for polymorphisms in PER3, BDNF, NRXN3, APOE, HCRTR2, MC4R between confirmed OSA cases and ethnically matched clinically unaffected controls. A logistic regression model was developed to predict OSA using the combined data. Results: The cohort consisted of 161 OSA cases and 81 controls. Mean age of cases was 53.5 ± 14.0 years, mostly males (57%) and mean body mass index (BMI) of 27.5 ± 4.3 kg/m2. None of the genotyped markers showed a statistically significant association with OSA after adjusting for age and BMI. A predictive algorithm included the variables gender, age, snoring, hypertension, mouth breathing and number of T alleles of PER3 (rs228729) presenting 76.5% specificity and 71.6% sensitivity. Conclusions: No genetic variant tested showed a statistically significant association with OSA phenotype. Logistic regression analysis resulted in a predictive model for diagnosing OSA that, if validated by larger prospective studies, could be applied clinically to allow risk stratification for OSA.

A mandibular advancement device associated with lingual control: a new treatment option for obstructive sleep apnea?

PURPOSE: Oral appliances (OA) have become the main alternative to positive pressure airway devices (PAP) for the control of obstructive sleep apnea (OSA). Despite literature support, controversies about the mode of action and the effectiveness of these devices persist. The aim of this study was to evaluate the efficacy of modified mandibular advancement devices (MAD) in patients with OSA who failed treatment with MAD and to evaluate the role of the tongue as a factor in patients who failed treatment with MAD. MATERIALS AND METHODS: Patients unable to control the apnea-hypopnea index (AHI) using a MAD were subsequently treated with a modified version that included a tongue trimming accessory. The objective was to stabilize the tongue by preventing it from sliding with the consequent collapse of the upper airway (UA). New polysomnography (PSG) was performed with the modified MAD in place. RESULTS: A total of 20 patients who failed MAD therapy were studied including 15 men (75%) with mean age (± standard deviation) of 58.5 ± 13.1 years and BMI 29.6 ± 5.0 Kg/m2. After installing the tongue trimmer, the number of patients who achieved complete success with the new MAD (AHI < 5) went from 0 to 30% and those who achieved partial success (5 < AHI < 10) went from 0 to 20%. The number of patient responders (AHI reduced by at least 50%) went from 20 to 75%. CONCLUSION: The results suggest that the tongue, even in the presence of a MAD, may be one of the contributing factors for the collapse of the UA and consequent device ineffectiveness. By stabilizing the tongue through the insertion of a tongue trimmer, the MAD became more effective in many cases.

Whole-exome identifies germline variants in families with obstructive sleep apnea syndrome.

Background: Obstructive sleep apnea syndrome (OSAS) (OMIM #107650) is characterized by complete or partial obstruction of the upper airways, resulting in periods of sleep associated apnea. OSAS increases morbidity and mortality risk from cardiovascular and cerebrovascular diseases. While heritability of OSAS is estimated at ∼40%, the precise underlying genes remain elusive. Brazilian families with OSAS that follows as seemingly autosomal dominant inheritance pattern were recruited. Methods: The study included nine individuals from two Brazilian families displaying a seemingly autosomal dominant inheritance pattern of OSAS. Whole exome sequencing of germline DNA were analyzed using Mendel, MD software. Variants selected were analyzed using Varstation® with subsequent analyses that included validation by Sanger sequencing, pathogenic score assessment by ACMG criteria, co-segregation analyses (when possible) allele frequency, tissue expression patterns, pathway analyses, effect on protein folding modeling using Swiss-Model and RaptorX. Results: Two families (six affected patients and three unaffected controls) were analyzed. A comprehensive multistep analysis yielded variants in COX20 (rs946982087) (family A), PTPDC1 (rs61743388) and TMOD4 (rs141507115) (family B) that seemed to be strong candidate genes for being OSAS associated genes in these families. Conclusion: Sequence variants in COX20, PTPDC1 and TMOD4 seemingly are associated with OSAS phenotype in these families. Further studies in more, ethnically diverse families and non-familial OSAS cases are needed to better define the role of these variants as contributors to OSAS phenotype.

Severe obstructive sleep apnea treatment with oral appliance: the impact on obstructive, central and mixed events.

PURPOSE: The aim of this study is to evaluate the effectiveness of two types of oral appliance (OA) in the treatment of severe obstructive sleep apnea syndrome (OSAS) and their impact on the reduction of obstructive, central and mixed apneas. METHODS: Forty-eight patients suffering from severe OSAS with a history of non-adherence to positive airway pressure therapy were treated with OA (lingual orthosis and combined orthosis). Polysomnography exams were performed before and after treatment. Computed tomography and cephalometric radiography were requested for all patients to evaluate the titrated position of the OA and the airspace obtained. Statistical tests used the Minitab, version 17, program. The level of statistical significance was 5%. RESULTS: Before treatment, the mean AHI was 56.3 ± 19.1 events/h. It decreased to 8.1 ± 5.2 after the OA titration (p ≤ 0.001). There was a significant reduction in obstructive events from 43.0 ± 20.2 to 7.1 ± 4.6 events/h (p ≤ 0.001). The reduction in central events after OA treatment was also significant (from 5.1 ± 9.3 to 0.8 ± 1.9 events/h; p ≤ 0.001), whereas that in mixed events decreased from 6.4 ± 9.5 to 0.1 ± 0.3 events/h (p ≤ 0.001). The minimum oxygen saturation also showed significant improvement after treatment (p ≤ 0.001). There was no statistically significant difference between both OA with respect to central events (p = 0.22) or mixed events (p = 0.98). CONCLUSION: The treatment was effective in reducing obstructive events which were evaluated through the AHI and minimum oxygen saturation. The oral appliances also normalized central and mixed events among patients with severe OSAS.