Mechanisms and Management of Obstructive Sleep Apnea: A Translational Overview

Abstract

Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of upper airway obstruction during sleep, resulting in apnea and hypopnea. While anatomical factors, such as increased upper airway collapsibility, significantly contribute to OSA, emerging evidence highlights the importance of non-anatomical mechanisms, including impaired pharyngeal muscle responsiveness, low arousal threshold, and elevated ventilatory loop gain. The interplay of these factors leads to respiratory instability, fragmented sleep, and systemic complications. Additional pathophysiological influences such as obesity, aging, sex differences, and central nervous system dysfunction exacerbate cardiovascular and metabolic comorbidities. Advancements in diagnostic methods, including cephalometry and polysomnography, along with therapies such as continuous positive airway pressure, mandibular advancement devices, and hypoglossal nerve stimulation, underscore the necessity for personalized treatment approaches. Although surgical interventions targeting multi-level airway obstructions show potential for successful treatment, they remain limited by variability in long-term efficacy. A thorough understanding of the multifactorial mechanisms underlying OSA is crucial for improving diagnostic accuracy and tailoring patient-specific management strategies. This review summarizes recent findings, clarifying the complex pathophysiology of OSA and highlighting a multidimensional approach to optimize patient outcomes.

INTRODUCTION

Obstructive sleep apnea (OSA) is a widely recognized disorder characterized by recurrent respiratory events, such as apnea and hypopnea, resulting from upper airway (UA) obstruction during sleep [1]. Historically, patients with OSA have demonstrated specific anatomical features contributing to airway restriction, including an elongated uvula, a long and drooping soft palate, enlarged tonsils, redundant pharyngeal folds, flaccid and redundant posterior tonsillar pillars, and a hypertrophied tongue [2]. When airway obstruction is suspected, polysomnography, the gold-standard diagnostic method, is traditionally used to classify respiratory events into obstructive, central, and mixed types. Additionally, cephalometry, flexible laryngoscopy with the Müller maneuver, and rhinomanometry have been employed to identify anatomically compromised regions and guide treatment decisions [3,4]. Recent studies indicate that OSA is a heterogeneous disorder with complex, multifaceted pathophysiological mechanisms, diverse clinical manifestations, and variable respiratory events [5]. While anatomical collapsibility of the UA significantly contributes to apnea events, increasing evidence recognizes the critical roles played by non-anatomical factors such as arousal threshold and ventilatory loop gain in the development of OSA [6].

Repetitive UA obstruction in OSA can cause hypoxemia and hypercapnia, stimulating respiratory control mechanisms to increase respiratory drive and restore airway patency [7]. However, this corrective mechanism often triggers arousals, disrupting sleep continuity and resulting in marked sleep fragmentation. Additionally, associated sympathetic nervous system activation contributes to cardiovascular comorbidities, including systemic hypertension and increased cardiovascular strain [8].

Pathophysiological processes underlying OSA are closely linked with cardiovascular conditions such as hypertension, myocardial infarction, and stroke [9,10], as well as metabolic disorders including diabetes and metabolic syndrome [11]. Furthermore, recurrent hypoxemia and sleep disruptions significantly impact the central nervous system, potentially causing depression, impaired attention, and memory deficits, thereby substantially diminishing patients’ quality of life [12].

Therefore, OSA must be understood as a systemic condition extending beyond simple UA obstruction to involve complex and multifactorial pathophysiological mechanisms. These insights highlight the need for a multidimensional approach to diagnosing and managing OSA, customized to the individual characteristics of each patient. This review provides a comprehensive summary of recent developments regarding the pathophysiology of OSA. This article does not contain any studies with human participants or animals performed by any of the authors.

A SIMPLE MODEL FOR OSA: BALANCING DILATING AND COLLAPSING FORCES

When conceptualizing the UA as a cylindrical structure, its openness or collapsibility is determined by the balance between dilating and collapsing forces [13]. Collapsing forces include tissue pressure from the surrounding structures and the intraluminal negative pressure generated during diaphragmatic contraction (Fig. 1), influencing both upper and lower airway segments [13].

Fig. 1.

A simple model of obstructive sleep apnea.

According to Bernoulli’s principle, airflow velocity increases as it passes through narrowed airway segments, resulting in reduced intraluminal air pressure and an increased tendency for airway collapse. Anatomical abnormalities that constrict the UA further accelerate airflow velocity, intensify the reduction in intraluminal pressure, enhance airway collapsibility, and ultimately make the airway more susceptible to obstruction [14].

Enlarged tonsils and a low-lying palate are prominent anatomical contributors to airway obstruction in patients with OSA [15]. In these cases, the oropharyngeal airway commonly acts as a bottleneck, with airflow velocity increasing at narrowed sites and thus exacerbating collapsing forces as described by Bernoulli’s principle. Consequently, surgical interventions such as uvulopalatopharyngoplasty (UPPP) and septoplasty, which widen the UA, increase intraluminal pressure, reduce collapsing forces, and result in improved apnea-hypopnea index (AHI) and decreased snoring [16]. However, these improvements are not consistently sustained across all patients.

Mouth breathing also influences UA patency by shifting the mandible, tongue, and hyoid bone posteroinferiorly, thus narrowing the pharyngeal airway. Conversely, closing the mouth helps reopen the airway, particularly in the retroglossal region. Surgical procedures such as nasal surgery that promote nasal breathing over mouth breathing can reduce AHI and ameliorate OSA symptoms. Nevertheless, even with interventions targeting breathing mechanics, anatomical factors remain critically influential in patients with OSA.

While UPPP is effective at alleviating obstructive apnea in certain patients, its long-term success rate is approximately 44.4% [17]. Moreover, there are cases in which postoperative snoring improves but obstructive apnea persists. Such suboptimal outcomes may result from limitations in diagnostic accuracy, inappropriate surgical techniques, or anatomical changes occurring in regions not addressed by the surgery. For example, following treatment that resolves anatomical UA narrowing, persistent apnea should prompt precise reassessment to identify the actual bottleneck.

In OSA patients, the retroglossal area of the oropharynx often represents the primary bottleneck [18]. Inadequate widening of this region following UPPP may account for the limited effectiveness of single-level surgical approaches. This underscores the necessity of considering multi-level obstruction in treatment planning. Multi-level surgery has demonstrated superior outcomes compared to single-level UPPP in severe OSA, reducing AHI by up to 76%, compared to a 48% reduction with single-level UPPP [19]. Overall, multi-level surgery appears to be more effective than single-level procedures.

Currently, continuous positive airway pressure (CPAP) and maxillomandibular advancement are considered standard or rescue treatments for OSA [20]. These approaches address the entire airway, including the nasopharyngeal, retropalatal, retroglossal, and hypopharyngeal regions, making them among the most effective therapeutic strategies [18]. Nevertheless, single-level surgeries such as UPPP may possess specific advantages beyond simply widening the UA. Although UPPP is not a surgical procedure that resolves multilevel obstructions, it partially widens the UA, allowing the use of hypoglossal nerve stimulation (HGNS) in patients who are not candidates for HGNS surgery due to complete central palatal collapse. For example, complete circumferential constriction typically contraindicates HGNS. However, postoperative evaluations have shown that UPPP can decrease postoperative mean AHI and modify UA obstruction patterns, with 25% exhibiting no collapse, 58% displaying complete anteroposterior collapse, and 16.7% demonstrating partial anteroposterior collapse [21]. Additionally, palatopharyngoplasty can alter collapse patterns not only in the surgically targeted region but also in adjacent regions such as the tongue base [22]. Thus, single-level surgery might modify collapse patterns at specific sites and potentially influence collapsibility in other UA regions.

THE UA AS A MUSCULAR TUBE WITHOUT SKELETAL SUPPORT

Rather than functioning merely as a simple cylindrical structure, the UA is a complex muscular tube composed of multiple muscle groups without skeletal support [15]. Key muscle groups responsible for maintaining UA patency include the genioglossus, geniohyoid, levator veli palatini, tensor veli palatini, muscularis uvulae, and palatopharyngeus muscles, each with distinct directions of movement [15]. Notably, certain surgical procedures can alter the natural movement vectors of these muscles, increasing UA volume during wakefulness [23]. However, whether these structural modifications persist during the dynamic respiratory phases of sleep remains unclear.

Electromyographic (EMG) activity represents combined respiratory drive potentials and tonic membrane potentials of each muscle. EMG activity is recorded when neural activity surpasses a specific threshold, with each muscle demonstrating distinct respiratory patterns among individuals [24,25]. Some UA muscles exhibit phasic pre-activation, reaching peak EMG activity before inspiration begins. This pre-activation is a respiratory reflex that stabilizes the airway, mediated by tonic input and inspiratory drive stimulation of hypoglossal motoneurons. Additionally, the EMG activity of the genioglossus muscle consistently increases immediately before inspiration.

Airway patency is maintained through the interplay of tonic activity and phasic activity mediated by afferent reflexes, though these activities differ in characteristics [26]. Previous studies suggest phasic activation of the genioglossus muscle is strongly correlated with intra-pharyngeal negative pressure, highlighting its reflexive role in maintaining airway patency [26,27]. In contrast, the tensor veli palatini muscle primarily stabilizes the soft palate. These differences underscore the specialized roles of each muscle, with the genioglossus predominantly involved in dynamic airway dilation during inspiration, whereas the tensor veli palatini provides structural support [26,27].

For instance, when inspiratory drive decreases, trigeminal motoneuron activation can sustain EMG activity in the tensor veli palatini muscle, thus stabilizing the soft palate and supporting nasopharyngeal patency [27]. Conversely, the genioglossus muscle, primarily innervated by the hypoglossal nerve, is the principal UA dilator, responding reflexively to negative intra-luminal pressure during inspiration [27]. While both tensor veli palatini and genioglossus muscles contribute to UA patency, the genioglossus muscle has a more dominant role in preventing airway collapse, particularly during sleep.

Women and older adults exhibit distinct pathophysiological characteristics in OSA, influencing both disease severity and manifestation patterns. Women, particularly before menopause, typically have less collapsible UAs and lower critical closing pressures (Pcrit), alongside higher arousability. These features often result in shorter yet more frequent respiratory events and increased sleep fragmentation. In contrast, aging is associated with increased pharyngeal collapsibility, partly due to diminished tissue elasticity and neuromuscular responsiveness. Post-menopausal women also display greater collapsibility compared to younger women, likely due to hormonal changes. Furthermore, aging is linked to elevated loop gain and decreased UA neuromuscular compensation. These physiological differences necessitate sex- and age-specific treatment strategies for OSA, such as titrating CPAP pressure, tailoring surgical interventions, or employing adjunctive pharmacological therapy [6,28].

THE STARLING RESISTOR MODEL FOR OSA

The classical Starling resistor model offers a simplified explanation of OSA, primarily focusing on the balance of collapsing and dilating forces within the oropharynx and hypopharynx [29]. However, this model simplifies the roles of the nasal cavity and lungs, treating them as non-collapsible and functionally passive segments. During inspiration, air initially passes through the non-collapsible nasal cavity before entering collapsible segments such as the nasopharynx, oropharynx, and hypopharynx [30]. Subsequently, it flows through non-collapsible structures such as the trachea, eventually reaching the lungs. The collapsible segments are prone to collapse due to surrounding tissue volume and pressure, while the nasal cavity and lungs are characterized by non-collapsible, relatively static structures (Fig. 2) [29].

Fig. 2.

The Starling resistor model of obstructive sleep apnea.

Nonetheless, the nasal cavity is not merely a passive conduit. It functions dynamically, adjusting patency in response to factors such as temperature, humidity, and sleep state. Variations in nasal resistance, airflow, and pressure activate nasal mechanoreceptors, influencing UA muscle tone, collapsibility, and minute ventilation [26]. Importantly, the nasal cavity contributes approximately 50% of total airway resistance, highlighting its crucial role in respiratory mechanics and its potential impact on OSA pathophysiology. Consequently, nasal resistance, airflow, pressure, and mechanoreceptor activity are closely intertwined with OSA [31].

Pathological nasal conditions such as septal deviation, chronic hypertrophic rhinitis, and nasal polyps can exacerbate OSA symptoms by increasing nasal resistance. Notably, interventions addressing these conditions have been associated with improvements in OSA severity. Specifically, septoplasty, inferior turbinoplasty, and functional endoscopic sinus surgery have demonstrated potential benefits in enhancing airway patency and reducing respiratory events [29].

However, the degree of OSA improvement following nasal surgery remains inconsistent, as demonstrated by comparative studies between sham septoplasty and conventional septoplasty [32]. These studies revealed variability in outcomes, indicating that nasal interventions alone might not universally resolve OSA symptoms. Nasal surgery is most effective when combined with other therapeutic approaches, such as primary treatments, and when tailored to improve subjective sleep satisfaction among OSA patients.

The classical Starling resistor model also neglects the roles of the trachea and lungs and does not accurately predict lung airflow [29]. Lung expansion during diaphragmatic contraction pulls the trachea downward, elongating and stabilizing the UA, thereby resisting collapse [33]. This mechanism can be impaired in individuals with conditions such as muscular dystrophy, morbid obesity, or chest deformities.

Therefore, while the Starling resistor model provides valuable insights into OSA pathophysiological mechanisms, it should be considered a foundational framework useful for conceptualizing OSA-related dynamics. A more integrated model accounting for complex interactions among various airway segments and structures is necessary to fully understand the pathophysiology of OSA.

AN INTEGRATED MODEL FOR OSA

Given that the UA operates as a collapsible muscular tube lacking skeletal support, interpreting OSA requires a more comprehensive and integrated model compared to traditional frameworks, such as the Starling resistor or simplistic cylindrical models [23] (Fig. 3). OSA arises from a complex interplay of anatomical, neuromuscular, and physiological factors, with four primary mechanisms underlying its pathophysiology: UA anatomy, pharyngeal muscle responsiveness, ventilatory loop gain, and arousal threshold [34]. Persistent obstructive apnea following UA surgery may result from these multifactorial mechanisms, each contributing to OSA’s intricate pathophysiology [34]. This complexity underscores the importance of a multidisciplinary approach for diagnosis and management [35].

Fig. 3.

An integrated model of obstructive sleep apnea. NP, nasopharynx; OP, oropharynx; HP, hypopharynx; ULC, upper lateral cartilage; LLC, lower lateral cartilage.

ANATOMICAL COLLAPSIBILITY

Anatomical collapsibility of the UA is a primary pathophysiological mechanism in OSA, influenced by several factors. Obesity-induced hypertrophy of pharyngeal soft tissues and increased fat deposition in the tongue can reduce airway diameter [35]. Excessive soft tissue surrounding the airway or skeletal framework narrowing, such as from a small maxilla or mandible, can elevate extraluminal tissue pressure, further narrowing the airway [36].

Central fat deposition linked to obesity can decrease lung volumes, elevate the diaphragm, and reduce longitudinal traction, exacerbating pharyngeal collapsibility [1,26]. Obesity correlates strongly with increased AHI; a 10% weight gain is associated with a 32% increase in AHI, underscoring the significance of weight management [37].

Pcrit, a critical parameter for assessing airway collapsibility and mechanical stability, is defined as the intraluminal pressure at which airway collapse occurs, stopping airflow [38]. It serves as a reference point for evaluating UA structural integrity. Patients with OSA exhibit higher Pcrit values than healthy individuals, indicating increased airway collapsibility and vulnerability [38]. Men typically have higher Pcrit values than women, possibly due to differences in airway length, thickness, and tissue distribution [39]. Post-menopausal women also show increased airway collapsibility, likely related to hormonal shifts and fat redistribution [40]. Age-related increases in airway collapsibility correlate with longer airways and reduced tissue elasticity around the airway [40]. However, about 20% of OSA patients have Pcrit values similar to healthy individuals, indicating that other mechanisms beyond anatomical collapsibility contribute to OSA [6].

Therapeutic approaches reducing airway collapsibility include mandibular advancement devices (MADs), CPAP, weight loss, positional therapy, and airway-enlarging surgeries. CPAP effectively reduces Pcrit, and weight loss enhances airway stability, alleviating OSA symptoms [40]. MADs advances the mandible anteriorly, increasing airway diameter and reducing Pcrit in a dose-dependent manner [41]. HGNS can also improve UA muscle responsiveness, offering potential benefits [42].

In addition to conventional therapies, emerging interventions targeting non-anatomical mechanisms have garnered increasing interest. Pharmacologic modulation of loop gain with agents such as acetazolamide or supplemental oxygen has demonstrated the ability to stabilize ventilatory control and reduce apnea frequency in selected patients [43]. These treatments function by reducing chemoreflex sensitivity and ventilatory overshoot, making them particularly effective for patients with high loop gain [44].

Moreover, drug-induced sleep endoscopy has become an essential tool for personalizing surgical strategies [45]. By directly visualizing the pattern and location of UA collapse during sedation-induced sleep, drug-induced sleep endoscopy allows clinicians to customize multi-level surgery according to individual anatomical vulnerabilities. This tailored approach may yield better outcomes than traditional surgery-selection methods, particularly in complex or refractory OSA cases [45,46].

LOW UA MUSCLE RESPONSIVENESS

In addition to anatomical collapsibility, non-anatomical factors significantly contribute to OSA development [6]. The pharyngeal dilator muscles, notably the genioglossus, play critical roles in maintaining UA patency. Approximately 30% of OSA patients exhibit reduced pharyngeal muscle responsiveness to negative-pressure stimuli, substantially contributing to UA obstruction during sleep [6,34].

During sleep, particularly rapid eye movement (REM) sleep, diminished negative-pressure reflexes result in reduced genioglossus muscle activation, elevating the risk of airway collapse [47]. Pharyngeal muscle neural stimulation is more suppressed during REM sleep than during non-REM sleep, further increasing susceptibility to UA obstruction [48]. Men tend to be more susceptible to UA collapse due to lower compensatory capabilities and lower baseline muscle activity compared to women [40].

Age-related declines in pharyngeal dilator muscle function may result from chronic hypoxia and mechanical damage to the UA, leading to UA neuropathy [49]. These declines exacerbate airway obstruction and worsen OSA symptoms. HGNS, which increases genioglossus muscle activity, has been proposed as an effective strategy for improving airway stability [42].

LOW AROUSAL THRESHOLD

Arousal threshold refers to the level of negative intrathoracic pressure required to trigger cortical arousal during apnea events [50]. Patients with a low arousal threshold frequently experience arousals, disrupting sleep continuity and exacerbating OSA by diminishing overall sleep quality. Repeated arousals interfere with deep sleep, increasing respiratory instability during sleep [5].

Women generally exhibit lower arousal thresholds than men, resulting in shorter respiratory events [48]. Although this lower threshold helps maintain airway stability through earlier arousals, it also heightens susceptibility to respiratory instability [39]. Age-related changes in arousal threshold are not notably pronounced, though younger men generally possess higher thresholds, gradually decreasing with age. These changes may reflect age-related shifts in sleep architecture [40]. Conversely, no significant age-related differences in arousal thresholds have been observed among women [49].

Despite its clinical importance, low arousal threshold remains underrecognized in treatment paradigms. Pharmacological strategies designed to increase arousal thresholds can enhance sleep stability and improve tolerance to treatments such as CPAP. Eszopiclone, a non-benzodiazepine sedative, has demonstrated efficacy in raising arousal thresholds and significantly improving nightly CPAP adherence in patients with this phenotype. In a randomized controlled trial, patients treated with eszopiclone achieved adherence comparable to those naturally possessing higher arousal thresholds [51]. These findings support the selective use of sedative medications in patients prone to frequent respiratory arousals, especially when behavioral or interface-based adherence strategies have been unsuccessful [51,52].

HIGH LOOP GAIN

Instability in ventilatory control significantly contributes to OSA pathogenesis, with loop gain being a crucial factor. Loop gain quantifies the ratio of ventilatory response to respiratory disturbances. Patients with high loop gain exhibit excessive ventilatory responses to minimal CO₂ fluctuations [35]. This hyper-responsiveness can lead to hypocapnia, decreased respiratory drive, and worsened apnea [6].

High loop gain predominantly occurs during non-REM sleep and is especially pronounced in patients with moderate to severe OSA [53]. Loop gain typically increases with aging, observed in both men and women [39]. In men, elevated loop gain is linked to increased frequency of central apnea and respiratory instability [40]. Women also demonstrate a gradual increase in loop gain with age, although its interaction with other endotypic traits appears relatively limited [40].

Elevated loop gain contributes to periodic respiratory instability, reflecting vulnerability in ventilatory control systems of OSA patients. Therapeutic strategies aiming to reduce loop gain include pharmacological agents such as acetazolamide, which decreases ventilatory chemoreflex sensitivity [42]. CPAP also effectively mitigates respiratory instability and reduces loop gain. HGNS may further modulate loop gain, stabilizing respiratory control [42].

Beyond laboratory-based assessments, simplified in-lab and at-home methods have been developed to estimate physiological traits, including arousal threshold and loop gain [44]. For example, CPAP dial-up and dial-down protocols can measure ventilatory responses to controlled airflow and pressure disturbances. These methods are non-invasive, reproducible, and suitable for broader clinical application without requiring invasive instrumentation or specialized research equipment [54,55]. Integrating such phenotyping methods into routine practice may facilitate tailored treatments—such as sedative medications for low arousal threshold or acetazolamide for high loop gain—based on individual patient profiles [44].

COMPREHENSIVE STRATEGY FOR TREATING OSA

As previously described, four phenotypic traits of OSA can be measured and illustrated, including UA anatomy with collapsibility, UA muscle responsiveness, respiratory arousal threshold, and loop gain (Fig. 4) [6]. In Fig. 5A, the stable breathing point (intersection between the 1/loop gain and UAG lines) lies above the arousal threshold, indicating the patient has OSA. In Fig. 5B, medical or surgical interventions that enlarge UA caliber or volume without enhancing muscle activity increase passive ventilation (V_passive), shifting the UAG line upward (*UAG). This adjustment places the stable breathing point below the arousal threshold, potentially resolving or improving OSA.

Fig. 4.

Pathophysiological causes of repetitive upper airway obstruction during sleep.

Fig. 5.

Comprehensive strategy for treating obstructive sleep apnea. (A) Baseline condition in which the stable breathing point lies above the arousal threshold, indicating obstructive sleep apnea. (B) Enlargement of the upper airway increases passive ventilation (from V_passive to *V_passive) and shifts the upper airway gain (UAG) line upward (*UAG), placing the stable breathing point below the arousal threshold. (C) A rise in loop gain (making new *1/loop gain) causes respiratory instability, returning the stable breathing point above the threshold and leading to obstructive sleep apnea recurrence. (D) Enlargement of the upper airway combined with enhanced muscle responsiveness further increases V_passive (*V_passive) and steepens the UAG slope (**UAG), relocating the stable breathing point below the threshold. (E) Pharmacologic adjustment of the arousal threshold shifts the threshold line (from a to b) and can reposition the stable breathing point depending on the patient’s baseline physiology. The graph in Fig. 5 is not based on actual measurement data; it is for illustrative purposes. V_eupnea, eupneic ventilation; V_passive, passive ventilation.

In Fig. 5C, the patient’s baseline condition mirrors Fig. 5B, but loop gain increases significantly, causing respiratory instability. Consequently, the stable breathing point returns above the arousal threshold line, causing OSA recurrence. In Fig. 5D, under conditions similar to Fig. 5C, an intervention such as HGNS enlarges UA volume and increases muscle responsiveness. This treatment elevates V_passive (as in Fig. 5B) and steepens the slope of the UAG line further (**UAG), relocating the stable breathing point below the arousal threshold line and potentially curing or significantly improving OSA. Changes in arousal threshold can also shift the stable breathing point position.

In Fig. 5E, the patient’s baseline condition matches Fig. 5C. Adjusting the arousal threshold through pharmacological treatments can reposition the stable breathing point either above or below the threshold. In patients with a low arousal threshold (line a), arousal occurs before stable breathing is achieved below the threshold line. However, a medication that shifts the arousal threshold from line a to line b allows the stable breathing point to fall below the newly adjusted threshold (line b).

Modifying only the arousal threshold without understanding the patient’s other physiological conditions—such as loop gain and UA responsiveness—can be risky. It may result in more frequent respiratory events, longer event durations, or more severe oxygen desaturation episodes.

CONCLUSION

This review highlights the diverse pathophysiological mechanisms underlying OSA, emphasizing its multifactorial nature. OSA cannot be attributed solely to anatomical UA collapsibility; it also involves critical non-anatomical contributors such as pharyngeal muscle dysfunction, low arousal threshold, and high loop gain (Fig. 4). Understanding these multifaceted mechanisms is crucial for developing effective therapeutic strategies tailored to individual patient profiles. Personalized treatments based on a comprehensive evaluation of these mechanisms are essential for improving patient outcomes and advancing OSA management. Developing simpler methods for accurately determining the OSA endotype will be a pivotal next step.

HIGHLIGHTS

▪ Key mechanisms of obstructive sleep apnea include upper airway collapsibility, low pharyngeal muscle activity, low arousal threshold, and high loop gain, contributing to respiratory instability.

▪ Personalized approaches including continuous positive airway pressure, mandibular advancement devices, surgery, and hypoglossal nerve stimulation can improve outcomes by targeting specific pathophysiological traits.

▪ Single- and multi-level operations can modify airway collapsibility, with their long-term success depending on precisely identifying obstruction sites.

▪ Integrating anatomical, neuromuscular, and ventilatory factors is essential for optimizing treatment efficacy and addressing individual patient needs