Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction caused by a loss of upper airway dilator muscle tone during sleep and an inadequate compensatory response by these muscles in the context of an anatomically compromised airway. The genioglossus (GG) is the main upper airway dilator muscle. Currently, continuous positive airway pressure is the first-line treatment for OSA. Nevertheless, problems related to poor adherence have been described in some groups of patients. In recent years, new OSA treatment strategies have been developed to improve GG function. (A) Hypoglossal nerve electrical stimulation leads to significant improvements in objective (apnea-hypopnea index, or AHI) and subjective measurements of OSA severity, but its invasive nature limits its application. (B) A recently introduced combination of drugs administered orally before bedtime reduces AHI and improves the responsiveness of the GG. (C) Finally, myofunctional therapy also decreases AHI, and it might be considered in combination with other treatments. Our objective is to review these therapies in order to advance current understanding of the prospects for alternative OSA treatments.

Background/Objectives: Obstructive sleep apnea (OSA) is marked by repetitive occurrences of upper airway (UA) obstruction during sleep. Morbidities impacting the metabolic, cardiovascular (CV) and neurological systems are correlated with OSA. Only a few studies have described the existence of different characteristics depending on sex and, to date, the girl phenotype in OSA pediatrics is not well known. The objective of this systematic review is to identify the specific phenotype of OSA in pediatric and adolescent females compared to males. Methods: A systematic review was performed. The terms “pediatric sleep apnea” and “sex differences” were used to look for publications using PubMed, the Cochrane Library and Web of Science. Inclusion criteria: (1) peer-reviewed journal articles written in English; (2) investigations conducted on individuals diagnosed with OSA; and (3) investigations providing information about sex differences. Exclusion criteria: (1) studies carried out with individuals aged 18 years and older; (2) studies involving a sample size of fewer than 10 patients; and (3) editorials, letters and case reports. Results: Fifteen studies were included and classified in sections related to sex-based differences. Conclusions: Limited information related to sex-based OSA differences in the pediatric population exists. These differences are conditioned by hormonal status, and are minimal in the premenarcheal period. Moreover, adolescent women present a lower prevalence of obesity and craniofacial alterations, lower OSA severity related to higher UA area and earlier tonsil regression. Hyperactivity is more frequent in boys. Some studies pointed to a higher risk of high diastolic blood pressure in girls than in boys.

Obstructive sleep apnea (OSA) has been identified as a cardiovascular (CV) risk factor. The potential of OSA promoting the synthesis of CV biomarkers in acute coronary syndrome (ACS) is unknown. Ischemia-modified albumin (IMA) has been identified as a specific CV biomarker. The aim of this study was to evaluate the role of IMA as a potential biomarker for determining the impact of OSA in ACS patients. A total of 925 patients (15.5% women, age: 59 years, body mass index: 28.8 kg/m²) from the ISAACC study (NCT01335087) were included. During hospitalization for ACS, a sleep study for OSA diagnosis was performed and blood samples extraction for IMA determination were obtained. IMA values were significantly higher in severe OSA (median (IQR), 33.7 (17.2–60.3) U/L) and moderate (32.8 (16.9–58.8) U/L) than in mild/no OSA (27.7 (11.8–48.6) U/L) (p = 0.002). IMA levels were very weakly related to apnea–hypopnea index (AHI) as well as hospital and intensive care unit stay, although they only maintained a significant relationship with days of hospital stay after adjusting for sex, age and BMI (ß = 0.410, p = 0.013). The results of the present study would suggest a potentially weaker role of OSA in the synthesis of the CV risk biomarker IMA in patients with ACS than in primary prevention.

Current data support an increase in the prevalence of high blood pressure (HBP) in pediatric patients with sleep-disordered breathing (SDB). Adeno-tonsillectomy has been shown to be an effective treatment for most patients. Our objective was to determine the prevalence of HBP in pediatric patients with SDB and the impact of adeno-tonsillectomy with a multicenter, longitudinal, and prospective study that included 286 children referred for suspected SDB. The diagnosis of SDB was established by polysomnography (PSG) and the diagnosis of HBP by 24-h ambulatory blood pressure monitoring (ABPM). In patients without SDB and SDB without treatment indication, these tests were repeated six months after the baseline visit. For patients with medical treatment for SDB, the tests were repeated six months after the treatment initiation. Finally, in patients with surgery indication, ABPM was performed just before surgical treatment and ABPM and PSG six months after the intervention. The study contributes to elucidating the association between SDB and HBP in pediatric patients. Moreover, it contributes to determining if intervention with adeno-tonsillectomy is associated with BP reduction. The results have direct implications for the management of SDB, providing essential information on treatment indications for existing clinical guidelines. NCT03696654.

In the context of the prevailing interest in biomarkers that can assess cardiovascular (CV) risk in obstructive sleep apnea (OSA), ischemia-modified albumin (IMA) is proposed as a potential risk predictor. To evaluate whether IMA levels predict recurrent CV events in patients with acute coronary syndrome (ACS) and OSA, and whether continuous positive airway pressure (CPAP) treatment modifies this risk. This post hoc analysis is based on data from the ISAACC study, including 1.011 non-sleepy patients with an ACS. During hospitalization for ACS, a sleep study was conducted and blood samples for IMA determination were obtained. Patients were categorized by their apnea-hypopnea index (AHI) in non-OSA (AHI 34.1 U/L, respectively). The OSA group was randomized to either CPAP or usual care. The recurrence of CV events was evaluated over a 36-months follow-up. Adjusted cox regression models showed that the OSA group with high IMA level had a significantly reduced risk for CV event recurrence compared with the non-OSA group (HR [95 % CI] 0.59 [0.38-0.93], p = 0.024). In the OSA group with high IMA level, CPAP treatment did not significantly reduce CV recurrence. OSA was associated with higher IMA levels in patients with ACS. Interestingly, patients with both OSA and high IMA experienced fewer CVEs during follow-up. CPAP treatment demonstrated a non-significant risk reduction in patients with low IMA, whereas no effect was noted in those with high IMA.

Cardiovascular (CV) disease, such as heart disease, stroke and CV death, are well-established complications of Obstructive Sleep Apnea (OSA). However, it has not been demonstrated the effect of continuous positive airway pressure (CPAP) on the prevention of CV events. It is imperative to identify useful biomarkers to determine patients that could benefit from such treatment. The value of ischemia-modified albumin (IMA) was analyzed and its relationship with CV risk in OSA patients. 1181 (82% males, median age: 58 years, Body Mass Index: 29.2 kg/m2) patients from the ISAACC (NCT01335087; n: 1008) and bioSAOS (n: 173) cohorts were included. All patients underwent a sleep study for OSA diagnosis and blood samples analysis for IMA determination. IMA values were significantly higher in moderate and severe OSA [mean (IQR) 33.7 (19.8-59.9) (U/l); 35 (19.3-59.8) (U/l), p: 0.004 respectively] than in patients without or with mild OSA [28.3 (13.2-52.4)(U/l)]. The IMA levels were positively correlated with the AHI and were related to high blood pressure and a procoagulation status in these patients. In conclusion, for patients with high CV morbidity, IMA was related to OSA severity. This biomarker could be useful to determine the CV risk added by OSA in these types of patients.