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Neonatal respiratory distress syndrome is a potentially life-threatening condition that is often treated with the delivery of exogenous surfactants through a process called surfactant replacement therapy. This therapy includes the administration of the liquid surfactant through an endotracheal tube and mechanical ventilation. Due to the difficulty of imaging neonate lungs during this therapy, the success of surfactant delivery is often determined by observational techniques and evaluation of blood oxygen levels. The limitation of imaging creates challenges in evaluating the distribution of surfactant in airways. To address this limitation, we designed a computational, eight-generation, asymmetric neonate lung model using morphometric data to mimic the geometric structure of the human airway tree and fabricated it using an additive manufacturing technique. We used our model to study two-aliquot delivery of a clinically rated liquid surfactant under two different orientations to evaluate its distribution in airways. Our study offers a complex lung airway tree design that mimics the native geometry of the human airway tree to enable studies of therapeutics transport in airways.
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Patients with obstructive sleep apnea have suppressed levels of soluble cytokine receptors involved in neurodegenerative disease, but normal levels with airways therapy
Abstract Purpose Obstructive sleep apnea (OSA) results in systemic intermittent hypoxia. By one model, hypoxic stress signaling in OSA patients alters the levels of inflammatory soluble cytokines TNF and IL6, damages the blood brain barrier, and activates microglial targeting of neuronal cell death to increase the risk of neurodegenerative disorders and other diseases. However, it is not yet clear if OSA significantly alters the levels of the soluble isoforms of TNF receptors TNFR1 and TNFR2 and IL6 receptor (IL6R) and co-receptor gp130, which have the potential to modulate TNF and IL6 signaling. Methods Picogram per milliliter levels of the soluble isoforms of these four cytokine receptors were estimated in OSA patients, in OSA patients receiving airways therapy, and in healthy control subjects. Triplicate samples were examined using Bio-Plex fluorescent bead microfluidic technology. The statistical significance of cytokine data was estimated using the nonparametric Wilcoxon rank-sum test. The clustering of these high-dimensional data was visualized using t -distributed stochastic neighbor embedding (t-SNE). Results OSA patients had significant twofold to sevenfold reductions in the soluble serum isoforms of all four cytokine receptors, gp130, IL6R, TNFR1, and TNFR2, as compared with control individuals ( p = 1.8 × 10 −13 to 4 × 10 −8 ). Relative to untreated OSA patients, airways therapy of OSA patients had significantly higher levels of gp130 ( p = 2.8 × 10 −13 ), IL6R ( p = 1.1 × 10 −9 ), TNFR1 ( p = 2.5 × 10 −10 ), and TNFR2 ( p = 5.7 × 10 −9 ), levels indistinguishable from controls ( p = 0.29 to 0.95). The data for most airway-treated patients clustered with healthy controls, but the data for a few airway-treated patients clustered with apneic patients. Conclusions Patients with OSA have aberrantly low levels of four soluble cytokine receptors associated with neurodegenerative disease, gp130, IL6R, TNFR1, and TNFR2. Most OSA patients receiving airways therapy have receptor levels indistinguishable from healthy controls, suggesting a chronic intermittent hypoxia may be one of the factors contributing to low receptor levels in untreated OSA patients.
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- PAR ID:
- 10276929
- Date Published:
- Journal Name:
- Sleep and Breathing
- ISSN:
- 1520-9512
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1007/s11325-020-02205-y
