The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells

Obstructive sleep apnea syndrome (OSAS) patients suffer from cardiovascular morbidity, which is the leading cause of death in this disease. Based on our previous work with transformed cell lines and primary rat cardiomyocytes, we determined that upon incubation with sera from pediatric OSAS patients, the cell’s morphology changes, NF-κB pathway is activated, and their beating rate and viability decreases. These results suggest an important link between OSAS, systemic inflammatory signals and end-organ cardiovascular diseases. In this work, we confirmed and expanded these observations on a new in vitro system of beating human cardiomyocytes (CM) differentiated from human embryonic stem cells (hES). Our results show that incubation with pediatric OSAS sera, in contrast to sera from healthy children, induces over-expression of NF-κB p50 and p65 subunits, marked reduction in CMs beating rate, contraction amplitude and a strong reduction in intracellular calcium signal. The use of human CM cells derived from embryonic stem cells has not been previously reported in OSAS research. The results further support the hypothesis that NF-κB dependent inflammatory pathways play an important role in the evolution of cardiovascular morbidity in OSAS. This study uncovers a new model to investigate molecular and functional aspects of cardiovascular pathology in OSAS.

556 Lost to Follow-Up: Post-Operative Polysomnography in High-Risk, Pediatric OSAs

Introduction Post-operative polysomnography (PSG) is recommended in certain pediatric populations at risk for residual sleep disordered breathing: moderate to severe obstructive sleep apnea syndrome (OSAS), obesity, craniofacial abnormalities, and neurologic disorders. In light of multiple stakeholders involved in follow-up management, variability in completion of a post-operative PSG may exist. We hypothesize that patients with isolated severe OSAS or severe plus a co-morbidity will have greater incidence of a post-operative PSG. Methods A chart review of 373 pediatric patients revealed 67 patients who met inclusion criteria for our high-risk cohort. Chart review included the presence of an ENT, Primary Care, or Sleep Medicine encounter, time to follow-up, the presence of a post-operative PSG, time to post-operative PSG, and the presence of an annual follow-up with any provider. Results Although 83% of our cohort followed-up with any provider, only 31% completed a post-operative PSG. Patients consistently followed-up with ENT 6–8 weeks postoperatively (76%) and haphazardly followed-up with primary care (38%). All patients with a Sleep Medicine follow-up (19%, n=13) completed a post-operative PSG, with 11 of the 13 occurring within 1 year from surgery. There was no significant difference across isolated moderate, isolated severe, or moderate/severe with a comorbidity for incidence of follow-up by specialty, annual follow-up, or post-operative PSG completion. However, patients with isolated severe (AHI >10) completed a PSG on average 13.5 weeks post-operatively which was significantly sooner than 36.2 weeks for isolated moderate OSA (p=0.04). Conclusion Although Sleep Medicine providers may consistently follow AASM practice parameters, variability exists for which patients return to complete a post-operative PSG. Severity of OSAS or presence of a concerning co-morbidity does not seem to correlate with acquiring a postoperative PSG. An inconsistent standard across disciplines may contribute to this discrepancy. These findings will inform future quality improvement discussions with key stakeholders. In light of this baseline assessment, we plan to recommend a standardized, multi-disciplinary care pathway for the management of high-risk, pediatric OSAS. Support (if any) None

Adenoid Hypertrophy, Craniofacial Growth and Obstructive Sleep Apnea: A Crucial Triad in Children

: Age-related (physiological) AH is an important problem in pediatric otorhinolaryngology. Since the beginning of the 70s, there has been an increase in the proportion of children with pharyngeal tonsil hypertrophy. Functional disorders of the oropharynx in children occupy the second place based on their incidence (after disorders of the musculoskeletal system). In the previous years there have been an increase in the incidence and prevalence of obstructive sleep apnea syndrome (OSAS) among children. In most cases of pediatric OSAS, upper airway obstruction occurs from the nasopharynx to the oropharynx, caused by upper airway stenosis. Consequences of untreated OSAS in children can be inattention and behavioral problems, daytime sleepiness, and in more severe cases are associated with a variety of comorbidities. The current review discussed the links between hypertrophied adenoids, craniofacial development and OSAS in children taking into account physiological and pathophysiological aspects as well as clinical evaluation of the problem.