Gut microbiota dysbiosis in autism spectrum disorder: 10 years of progress on compositional alterations, metabolic/immune mechanisms, and therapeutic strategies.

Obstructive sleep apnea (OSA) is a chronic respiratory disorder characterized by repeated episodes of upper-airway collapse during sleep, which fragment rest and cause repeated oxygen desaturations. Its effects go beyond daytime sleepiness, as it is associated with arterial hypertension and with cardiovascular and cerebrovascular disease, and it multiplies the risk of traffic accidents, making it a public-health problem with an impact on the healthcare system []. The accident risk in untreated patients is estimated at 2.4 times that of the general population, reaching 3 to 7 times in severe cases [,]. In Spain, OSA is estimated to affect several million people, although the exact burden depends on the diagnostic definition and severity threshold used []. Previous Spanish estimates reported that approximately 1.2–2.15 million people may have OSA, with only 5–9% being diagnosed []. Underdiagnosis remains particularly relevant, especially among women, with population-based data suggesting that up to 93% of women with moderate-to-severe sleep apnea may remain clinically undiagnosed []. This hidden burden is clinically relevant, since OSA is strongly associated with cardiometabolic and neurocognitive comorbidity. Metabolic syndrome is highly prevalent among adults with polysomnography-confirmed OSA, with recent meta-analytic evidence estimating a pooled prevalence of 55.4% []. Hypertension is one of the most closely related cardiovascular conditions, affecting approximately 50% of patients with OSA, while OSA may be present in up to 80% of patients with resistant hypertension []. Severe untreated OSA has also been associated with increased mortality and cardiovascular risk, including ischemic heart disease, heart failure, arrhythmias and stroke [,,,,]. In addition, sleep-disordered breathing has been linked to a 26% higher risk of developing cognitive impairment []. Among the main risk factors, obesity plays a central role, together with age and male sex []. OSA also entails an economic and healthcare burden. The direct healthcare costs associated with the untreated disease in Spain have been estimated at more than EUR 5 billion per year, and sleep units manage a high and growing volume of patients on CPAP treatment. When there is clinical suspicion, diagnosis requires a sleep study: although polysomnography is the reference test, home respiratory polygraphy is the usual technique in routine care. OSA is confirmed when the apnea-hypopnea index (AHI) is ≥15 events/hour, or ≥5 accompanied by related clinical symptoms []. The reference treatment is continuous positive airway pressure (CPAP), which keeps the upper airway open, reduces respiratory events and improves oxygenation and daytime sleepiness []. However, its benefit depends on adherence; a patient is considered adherent when they use the device at least 4 h per night on ≥70% of nights [], a threshold that between 46% and 83% of patients do not reach []. The underlying problem is the difficulty of anticipating which patients will maintain adequate adherence, since this is confirmed only after prolonged follow-up and depends on multiple factors—e.g., OSA severity, tolerance, perceived benefit, comorbidities and initial use—that are rarely integrated into an individualized estimate of the risk of treatment discontinuation or low use.