The Factors For Upper Airway Collapsibility In Obese Adolescents With Obstructive Sleep Apnea Syndrome

The obstructive sleep apnea syndrome (OSAS) refers to a breathing disordercharacterized by recurrent cessations in breathing rhythm or momentary or sustainedreductions in the breath amplitude, sufficient to cause significant arterial hypoxemia andhypercapnia. These apneas are sleep specific, and commonly associated with sleepfragmentation and intermittent hypoxemia.The prevalence of OSAS in children has been increasing since it was first described inthe1970s as a clinical entity in children, and is now recognized to be a common cause ofmorbidity in the pediatric population, resulting in cardiovascular, neurobehavioral, growthand inflammatory complications. Despite the high prevalence and significant morbidity ofpediatric OSAS, we are only now beginning to understand its pathophysiology. Four clinicalphenotypes associated with OSAS in children have been recognized since the original reportincluding adenotonsillar hypertrophy, craniofacial malformations and syndromic conditions,primary neuromuscular disorders and obesity. The prevalence of OSAS can be expected toincrease in association with the burgeoning pediatric obesity epidemic. Previous reports haveassociated obesity from ealy infancy to late childrenhood obesity with OSAS. Theprevalence of OSAS in obese children may increase the risk by more than fourfold.Currently, multiple studies about OSAS in adults and children have demonstrated thatanatomic factors restricting the upper airway and neuronal factors increasing thecollapsibility of the upper airway are important mechanistic contributors for OSAS. Innormal weight children, OSAS has associations with adenotonsillar hypertrophy. Suchhypertrophy was reported in obese OSAS children. The hormone change when body growthand local and systematic inflammatory reaction associated with obesity may induceadenotonsillar hypertrophy. It was reported that the soft tissue around upper airway constrictthe area of upper airway in obese adult OSAS, such as fat pad, soft palate, lateral pharyngealwall, tongue. However, little is known about the anatomical analysis for nasal pharynx andsoft tissue around upper airway in obese children with OSAS. However, not all obesechildren suffered from OSAS. There was no obstruction in upper airway during wakefulnessin obese OSAS children with adenotonsillar hypertrophy, because of higher neuromotor toneawake; In some obese OSAS patients, after removal of the anatomical factors by surgery, the symptoms persist or reoccur. This indicates that there must be some other anatomical orfunctional factors contributing the pathophysiological mechanism in obese children withOSAS. The functional factors increasing the collapsibility of upper airway includeneuromuscular tone, changes of tissue characters and increasing of resistance. The adultstudies found mild inspiratory negative pressure can lead the obstruction of upper airwaywithout activation of upper airway dilator muscles, so did the studies in children. Thecorrelation between obesity and the degree of upper airway collapsibility in obese adultswith OSAS indicated the proneness to OSAS in such patients. We can reasonablyhypothesize that there will be such functional deficient in obese children with OSAS. It isnot well understood for the role of ventilatory drive in adult and children. Some studiesshowed there was subtle abnormality between patients and controls. We thereforehypothesize that ventilatory drive abnormality will induce OSAS in obese children similar toadult OSAS.Adolescence, the transition from childhood to adulthood, is a period of developmentknown to have major sleep issues. It is reported that the symptom in children with OSASunderwent adenotonsillectomy reoccurred when they went into adolescence. In addition, Theprevalence of obesity during this adolescents age is higher that of prepuber stage. However,It remains virtually unstudied in relation to OSAS and the effects of pediatric obesity onupper airway collapsibility. Therefore the pathophysiology of obese adolescents with OSASneeds to be evaluated. Our overall hypothesis is that OSAS develops when a structural loadis acquired by an individual with an underlying impairment of upper airway neuromotorfunction.This is a matched case-dual control study with a complementary interventionalcomponent. The subjects, aged from12to16, were classified into obese OSAS group, obesecontrol group and lean control group. All subjects will be phenotyped by polysomnography,pressure-flow relationship measurement technology, muscle activity electrophysiology andmagnetic resonance imaging assessment of upper airway, hypercapnic ventilatory responsesand pulmonary function testing. The anatomical and neuromotor tone factors of upperairway will be evaluated in the three groups.The results showed the following:(1) In the activated state, the slope of pressure–flow relationship was higher in theobese OSAS compared to obese controls and lean controls (P <0.0005); In the hypotonicstate, the slope of pressure–flow relationship was higher in obese OSAS and obese controls compared to lean controls (P <0.0005, P <0.05respectively).(2) Pharyngeal closing pressure (Pcrit) was higher in obese OSAS compared to obesecontrols and lean controls (P <0.005, P <0.0005, respectively).(3) In the activated state, the slope of Genioglossus activity–nasal pressurerelationship (EMGgg–PN) was higher in obese controls compared to obese OSAS and leancontrols (P <0.005, P <0.0005, respectively). The activated slope of EMGgg–PN washigher than the hypotonic slope in obese controls and lean controls (P <0.0005, P <0.005,respectively).(4) The volumes of tonsils, adenoids and lateral pharyngeal wall were higher in obeseOSAS compared to obese controls and lean controls (P <0.05, P <0.0005, and P <0.02,respectively); the volume of tongue was higher in obese OSAS and obese controls comparedto lean controls (P <0.05).(5) The relationship between PFR and the volume of lateral pharyngeal wall waspositive in the lean control group both in the activated and hypotonic state (P <0.05); In theactivated state, the relationships were positive (P <0.02) in obese OSAS and negative inobese controls (P <0.05).(6) During wakefulness, the slopes of hypercapnic ventilatory responses (HCVR) werehigher in obese OSAS and obese controls compared to lean controls, however, no significantdifferences were found in the three groups after controlled for weight; During sleep, theventilatory responses to CO2was lower in the obese OSAS compared to the two controlgroups expressed as the following index: minute ventilation (VE, P <0.005), the inspiratoryfolw (Flow, P <0.01), tidal volume (VT, P <0.01), inspiratory time (TI, P <0.05) and VT/TI(P <0.005).From the above results, we can draw the following conclusions:1. The upper airway neuromotor tone was decreased in obese adolescents with OSAS,which increased the collapsibility of upper airway, thus OSAS.2. Obese adolescents without OSAS had an increased neuromotor tone of upperairway during sleep to compensate the anatomical abnormality.3. Obesity can increase the volume of the soft tissues around upper airway restrictingthe size of upper airway. The pharyngeal lateral wall may play an important role inthe anatomical fators in the obese adolescents with OSAS and can increase thecollapsibility of upper airway.4. The central ventilatory drive was blunted during sleep in obese adolescents with OSAS.