scholarly journals Detailed evaluation of the upper airway in the Dp(16)1Yey mouse model of Down syndrome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tatsunori Takahashi ◽  
Noriaki Sakai ◽  
Tomonori Iwasaki ◽  
Timothy C. Doyle ◽  
William C. Mobley ◽  
...  

AbstractA high prevalence of obstructive sleep apnea (OSA) has been reported in Down syndrome (DS) owing to the coexistence of multiple predisposing factors related to its genetic abnormality, posing a challenge for the management of OSA. We hypothesized that DS mice recapitulate craniofacial abnormalities and upper airway obstruction of human DS and can serve as an experimental platform for OSA research. This study, thus, aimed to quantitatively characterize the upper airway as well as craniofacial abnormalities in Dp(16)1Yey (Dp16) mice. Dp16 mice demonstrated craniofacial hypoplasia, especially in the ventral part of the skull and the mandible, and rostrally positioned hyoid. These changes were accompanied with a shorter length and smaller cross-sectional area of the upper airway, resulting in a significantly reduced upper airway volume in Dp16 mice. Our non-invasive approach, a combination of computational fluid dynamics and high-resolution micro-CT imaging, revealed a higher negative pressure inside the airway of Dp16 mice compared to wild-type littermates, showing the potential risk of upper airway collapse. Our study indicated that Dp16 mice can be a useful model to examine the pathophysiology of increased upper airway collapsibility of DS and to evaluate the efficacy of therapeutic interventions for breathing and sleep anomalies.

Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 1032
Author(s):  
Ashley L. Saint-Fleur ◽  
Alexa Christophides ◽  
Prabhavathi Gummalla ◽  
Catherine Kier

Obstructive Sleep Apnea (OSA) is a form of sleep-disordered breathing characterized by upper airway collapse during sleep resulting in recurring arousals and desaturations. However, many aspects of this syndrome in children remain unclear. Understanding underlying pathogenic mechanisms of OSA is critical for the development of therapeutic strategies. In this article, we review current concepts surrounding the mechanism, pathogenesis, and predisposing factors of pediatric OSA. Specifically, we discuss the biomechanical properties of the upper airway that contribute to its primary role in OSA pathogenesis and examine the anatomical and neuromuscular factors that predispose to upper airway narrowing and collapsibility.


1993 ◽  
Vol 74 (6) ◽  
pp. 2694-2703 ◽  
Author(s):  
M. J. Wasicko ◽  
J. S. Erlichman ◽  
J. C. Leiter

We sought to determine if the upper airway response to an added inspiratory resistive load (IRL) during wakefulness could be used to predict the site of upper airway collapse in patients with obstructive sleep apnea (OSA). In 10 awake patients with OSA, we investigated the relationship between resistance in three segments of the upper airway (nasal, nasopharyngeal, and oropharyngeal) and three muscles known to influence these segments (alae nasi, tensor veli palatini, and genioglossus) while the patient breathed with or without a small IRL (2 cmH2O.l–1.s). During IRL, patients with OSA exhibited increased nasopharyngeal resistance and no significant increase in either the genioglossus or tensor veli palatini activities. Neither nasal resistance nor alae nasi EMG activity was affected by IRL. We contrasted this to the response of five normal subjects, in whom we found no change in the resistance of either segment of the airway and no change in the genioglossus EMG but a significant activation of the tensor palatini. In six patients with OSA, we used the waking data to predict the site of upper airway collapse during sleep and we had limited success. The most successful index (correct in 4 of 6 patients) incorporated the greatest relative change in segmental resistance during IRL at the lowest electromyographic activity. We conclude, in patients with OSA, IRL narrows the more collapsible segment of the upper airway, in part due to inadequate activation of upper airway muscles. However, it is difficult to predict the site of upper airway collapse based on the waking measurements where upper airway muscle activity masks the passive airway characteristics.


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