Pathophysiology of pediatric obstructive sleep apnea

Abstract

Sleep-disordered breathing is a common and serious cause of metabolic, cardiovascular, and neurocognitive morbidity in children. The spectrum of obstructive sleep-disordered breathing ranges from habitual snoring to partial or complete airway obstruction, termed obstructive sleep apnea (OSA). Breathing patterns due to airway narrowing are highly variable, including obstructive cycling, increased respiratory effort, flow limitation, tachypnea, and/or gas exchange abnormalities. As a consequence, sleep homeostasis may be disturbed. Increased upper airway resistance is an essential component of OSA, including any combination of narrowing/retropositioning of the maxilla/mandible and/or adenotonsillar hypertrophy. However, in addition to anatomic factors, the stability of the upper airway is predicated on neuromuscular activation, ventilatory control, and arousal threshold. During sleep, most children with OSA intermittently attain a stable breathing pattern, indicating successful neuromuscular activation. At sleep onset, airway muscle activity is reduced, ventilatory variability increases, and an apneic threshold slightly below eupneic levels is observed in non-REM sleep. Airway collapse is offset by pharyngeal dilator activity in response to hypercapnia and negative lumenal pressure. Ventilatory overshoot results in sudden reduction in airway muscle activation, contributing to obstruction during non-REM sleep. Arousal from sleep exacerbates ventilatory instability and, thus, obstructive cycling. Paroxysmal reductions in pharyngeal dilator activity related to central REM sleep processes likely account for the disproportionate severity of OSA observed during REM sleep. Understanding the pathophysiology of pediatric OSA may permit more precise clinical phenotyping, and therefore improve or target therapies related to anatomy, neuromuscular compensation, ventilatory control, and/or arousal threshold.

Figure 1.

Top: Three-year-old normal control male subject. Sagittal images from various points in the respiratory cycle show no significant change in airway diameter at the level of the hypopharynx (arrows in image 1) or nasopharynx (arrowheads in image 2). Bottom: Eleven-year-old male patient with obstructive sleep apnea (OSA). Sagittal images from various points of the respiratory cycle demonstrate airway collapse at the level of the hypopharynx (arrows in images 1 and 2). The palatine tonsils (P in image 2) are enlarged and are seen to move inferiorly and medially during the respiratory cycle to obstruct the airway (image 2). The adenoids are enlarged (A in images 1 and 2). Modified by permission from Reference .

Figure 2.

Static airway cross-sectional area versus pressure curves at the level of the soft palate for a series of children with obstructive sleep apnea (OSA) (right) and control subjects (left). The closing pressure defined as zero area is higher in OSA. Modified by permission from Reference .

Figure 3.

Left: Normal control child. Nasal pressure (P_N) versus maximal inspiratory flow (V̇i_max) is plotted subsequent to a series of negative pressure challenges, using the active (solid circles) and relatively passive (open circles) techniques. The relatively passive technique minimizes neuromuscular activation of the upper airway and results in a critical closing pressure of −22 cm H₂O. The active technique facilitates pharyngeal dilator activity and resulted in a less collapsible upper airway. Right: Patient with obstructive sleep apnea (OSA). There is no change in airway collapsibility between the active and relatively passive techniques. Modified by permission from Reference .

Figure 4.

Raw data from three normal children during stage 4 sleep, demonstrating the range of genioglossus EMG (EMGgg) responsiveness and nasal airflow (Flow) during six negative pressure challenges. Each tracing represents approximately 4 minutes. (A) No increase in the EMGgg or flow is evident during the negative pressure challenges. (B) A small increase in the EMGgg occurs during challenges 2–6. An increase in inspiratory flow is evident on breaths 4 and 5 during challenges 2–4. (C) A brisk EMGgg response accompanies challenges 2–6 and is associated with flow at or above baseline without arousal. Reproduced by permission from Reference .

Figure 5.

A series of apneic–hypopneic events associated with reductions in the tonic and phasic genioglossal electromyogram (EMGgg). GG = genioglossus; MTA = moving time average. Reproduced by permission from Reference .