Pathophysiology of OSAS in Children
Obstructive sleep apnea occurs when the upper airway patency is restricted or collapses during inspiration. Such collapse is a dynamic process that involves interactions between sleep state, upper airway mechanics, and respiratory drive. Both functional and anatomic factors may tilt the balance toward airway collapse.
Transition to the sleep state will normally result in elevations of upper airway resistance, primarily linked to reductions in airway diameter resulting from reduced tone of the pharyngeal dilator and constrictor muscles, the latter being responsible for conferring a degree of rigidity to the airway wall. The most significant anatomic risk factor for OSAS in nonobese healthy children is adenotonsillar hypertrophy. The adenoids and tonsils grow progressively during childhood and reach their peak in the prepubertal years, coinciding with the peak incidence of childhood OSAS. In normal children, the airway size grows proportionately with the soft tissues surrounding it. However, it remains unclear how the airway grows in proportion to the surrounding tissues in children with OSAS. Volumetric measurements of the upper airway using MRI have shown that the volume of the upper airway was smaller in children with OSAS compared with controls, and that the combined size of the adenoids and tonsils correlates with the severity of OSAS. Using upper airway endoscopy under anesthesia, the anatomic region of maximal narrowing has identified at the level of the adenoids and soft palate. These findings were supported by two MRI studies showing that the maximal narrowing of the upper airway occurs in the retropalatal region, where the soft palate, adenoids and tonsils overlap in the three-dimensional space. Disproportionate proliferation of the adenoids and tonsils occurs in children with allergic rhinitis, asthma, and children exposed to cigarette smoking or upper airway respiratory infections, particularly viruses. Such disproportionate growth undoubtedly predisposes these children to develop OSAS. Alternatively, the possibility exists that viral infections during early life, particularly respiratory viruses such as respiratory syncitial virus, may trigger, in susceptible individuals, a neuroimmunomodulatory response within the lymphoid tissues of the upper airway, favoring the onset of rapid lymphoid tissue proliferation, particularly when exposure to environmental conditions such as allergens, pollution, or subsequent viruses occur. Preliminary evidence for such assumptions has been reported and indeed points to the higher degree of basal proliferation of upper airway lymphoid tissues in vitro, the presence of a respiratory syncitial virus gene expression signature, and the corroboration of both these findings in a retrospective assessment of OSAS frequency among children having required hospital admission for respiratory syncitial virus bronchiolitis.
In addition to the increased volume of the adenoids and tonsils, increase in the volume of the soft palate has been shown in children with OSAS compared with controls. No difference in the overall volume of the tongue was found in children with OSAS.
Another potential factor playing a role in the pathophysiology of OSAS is the length of the collapsible segment of the upper airway. It has recently been shown that during puberty, the upper airways become longer in boys than girls (partially due to laryngeal descent), which may partially explain the similar prevalence of OSAS in prepubertal boys and girls but substantially higher prevalence in post-pubertal boys and adult men. Although childhood OSAS is associated with adenotonsillar hypertrophy, it is not exclusively due to large tonsils and adenoids alone. Indeed, patients with OSAS do not obstruct their upper airway during wakefulness, indicating that structural factors alone cannot be fully responsible for this condition. In addition, studies have failed to show a definitive correlation between adenotonsillar size and OSAS. Furthermore, a measurable percentage of children with adenotonsillar hypertrophy, are not cured by surgical removal of tonsils and adenoids in the absence of other known risk factors for OSAS, and temporary resolution of OSAS after surgery with recurrence during adolescence has also been reported. Thus, the current understanding is that childhood OSAS is a dynamic process in which increased upper airway collapsibility is present, and results from a combination of structural and neuromotor abnormalities, rather than from structural abnormalities alone.
The stability of the upper airway is predicted on neuromuscular activation, arousal threshold and ventilatory control. In contrast to adults, the overall ventilatory drive in response to hypoxia and hypercapnia during wakefulness is normal in otherwise healthy children with OSAS. However, the central ventilatory drive plays a role in augmenting upper airway neuromotor reflexes and tone. Normal children have brisker upper airway reflexes during sleep than adults, perhaps due to their greater central ventilatory drive. These reflexes appear to be blunted in children with OSAS. Both children and adults with OSAS have blunted respiratory perception of upper airway occlusion during sleep. Arousal, an important defense mechanism in response to upper airway obstruction, appears to be mediated via mechanoreceptor stimulation and the degree of respiratory effort. Children with OSAS have abnormal responses to inspiratory resistive loading during sleep. Indeed, it has been shown that children with OSAS will arouse at a significantly higher inspiratory resistive load than controls, particularly during REM sleep, which is when most obstructive events in children occur. This blunted arousal response and the relatively lessened collapsibility of the upper airway in children may collectively contribute to the presence of reduced frequency of obstructive apneic events and prolonged obstructive hypoventilation in children with OSAS while asleep.
Increased risk for pediatric OSAS occur in children with allergy, a family history of OSAS, children born prematurely, in African–American children and in children with chronic upper and lower respiratory tract diseases. Studies of family cohorts suggest that genetic factors also play a role in the pathophysiology of OSAS. It is possible that genetic factors affect anatomic features, ventilatory drive or both.
Several medical conditions are known to be associated with OSAS in children. These conditions include upper airway narrowing due to craniofacial anomalies, children with neuromuscular abnormalities or hypotonia, children with Down syndrome, Prader Willi syndrome, mucopolysaccharide storage disease, allergic rhinitis, laryngomalacia, choanal atresia/stenosis, micrognatia, cleft palate after surgical repair, turbinate hypertrophy, deviated septum and maxillary constriction, and hypothyroidism.
Recent studies indicate that localized inflammation in the nasopharyngeal area is also involved in the pathophysiology of OSAS in children. Indeed, assessment of adenotonsillar tissues from children with OSAS has revealed robust increases in inflammatory cell proliferation (particularly T-cell lymphocytes), and increased expression of proinflammatory cytokines and other inflammatory mediators, such as TNF-α, IL-6 and IL-1α, when compared with adenotonsillar tissues removed in the context of treatment of children with recurrent tonsillitis. It is postulated that among the conglomerate of potential factors accounting for the unique inflammatory profile of adenotonsillar tissues in OSAS, respiratory viruses (see earlier) and recurrent vibration of the upper airway will promote localized inflammation with subsequent mucosal swelling and overexpression of inflammatory cytokines. Further studies examining exhaled breath condensate and induced sputum in children with OSAS have similarly revealed the upregulation of localized inflammatory processes in upper airway tissues. Taken together, the increased collapsibility of the upper airway that is universally present in children with OSAS is the conglomerate result of a cluster of multifactorial interactions between local inflammatory processes in the airway that promote lymphadenoid proliferation and reduced protective reflexes, structural and anatomic factors, and altered neural and muscular elements both in the periphery and centrally.