Obstructive sleep apnea (OSA) is a common respiratory disorder, primarily characterized by two pathological features: chronic intermittent hypoxia (CIH) and sleep deprivation (SD). OSA has been identified as a risk factor for numerous diseases, and the inflammatory response related to programmed cell necrosis is believed to play a significant role in the occurrence and progression of multisystem damage induced by OSA, with increasing attention being paid to pyroptosis. Recent studies have indicated that OSA can elevate oxidative stress levels in the body, activating the process of pyroptosis within different tissues, ultimately accelerating organ dysfunction. However, the molecular mechanisms of pyroptosis in the multisystem damage induced by OSA remain unclear. Therefore, this review focuses on four major systems that have received concentrated attention in existing research in order to explore the role of pyroptosis in promoting renal diseases, cardiovascular diseases, neurocognitive diseases, and skin diseases in OSA patients. Furthermore, we provide a comprehensive overview of methods for inhibiting pyroptosis at different molecular levels, with the goal of identifying viable targets and therapeutic strategies for addressing OSA-related complications.

Background/Objectives: Current approaches to monitoring obstructive sleep apnea (OSA) risk primarily focus on structural or functional abnormalities, often neglecting systemic metabolic and physiological factors. Resource-intensive methods, such as polysomnography (PSG), limit their routine applicability. This study aimed to evaluate composite nutritional-inflammatory indices derived from routine blood markers to identify feasible indices for OSA management and explore their association with OSA risk. Methods: Data from 9622 adults in the NHANES (2015–2020) and GWAS datasets were analyzed using logistic regression, restricted cubic splines, machine learning, and Mendelian randomization (MR). These techniques were employed to identify nutritional-inflammatory indices associated with OSA risk. Random forest modeling identified body mass index (BMI) and albumin (ALB) as key components of the advanced lung cancer inflammation index (ALI). Causal relationships between ALI components and OSA were validated using MR. Results: ALI was significantly associated with OSA, with individuals in the highest ALI tertile exhibiting a 59% higher likelihood of OSA (OR = 1.59, 95% CI: 1.38–1.84; p < 0.001). BMI and ALB were identified as key contributors to ALI and confirmed as causal risk factors for OSA (BMI: OR = 1.91, 95% CI: 1.80–2.02; ALB: OR = 1.11, 95% CI: 1.04–1.19). Age, gender, and the neutrophil-to-lymphocyte ratio (NLR) were also significant predictors. Conclusions: This study identifies ALI as a potential composite index for assessing OSA risk. Integrating statistical modeling, machine learning, and causal inference techniques highlights the utility of nutritional-inflammatory indices in improving OSA monitoring and management in clinical practice.

Chronic intermittent hypoxia (CIH), the cardinal pathophysiological feature of obstructive sleep apnea, is increasingly recognized as an important modifier of metabolic dysfunction-associated steatotic liver disease (MASLD), but the underlying mechanisms remain incompletely understood. In this study, male C57BL/6 mice were fed a standard diet or a high-fat diet (HFD) and exposed to normoxia or CIH for 8 weeks. Histological, ultrastructural, biochemical, transcriptomic, proteomic, and metabolomic analyses were integrated to characterize hepatic alterations induced by CIH under metabolic stress. CIH markedly aggravated HFD-induced liver injury, as evidenced by increased body fat, hepatomegaly, serum transaminases, steatosis, mitochondrial ultrastructural alterations, and inflammatory infiltration. Mechanistically, CIH promoted hepatic lipid metabolic reprogramming by suppressing the PPARα/CPT1A fatty acid β-oxidation axis while enhancing the SREBP-1c/FASN/PLIN2 lipogenic pathway, impaired the Nrf2/HO-1/SLC7A11/GPX4 antioxidant defense system, increased lipid peroxidation and iron accumulation, and activated NF-κB/NLRP3 signaling. These findings support a multifactorial model in which CIH functions as an additional hypoxic stressor that exacerbates HFD-induced MASLD-like liver injury through coordinated metabolic, oxidative, and inflammatory dysregulation.