Dataset Information

Obstructive sleep apnea and rhonchopathy are associated with downregulation of trefoil factor family peptide 3 (TFF3)-Implications of changes in oral mucus composition.

ABSTRACT: Trefoil factor family (TFF) peptides belong to the family of mucin-associated peptides and are expressed in most mucosal surfaces. TFF peptides carry out functions such as proliferation and migration enhancement, anti-apoptosis, and wound healing. Moreover, TFFs are associated with mucins and interact with them as "linker peptides", thereby influencing mucus viscosity. To test the hypothesis that in rhonchopathy and obstructive sleep apnea (OSA) changes occur in the expression of TFF3 and -2 that could contribute to changes in mucus viscosity, leading to an increase in upper airway resistance during breathing.RT-PCR, Western-blot, immunohistochemistry and ELISA were performed to detect and quantify TFF3 and -2 in uvula samples. In addition, 99 saliva samples from patients with mild, moderate or severe OSA, as well as samples from rhonchopathy patients and from healthy volunteers, were analyzed by ELISA.TFF3 was detected in all uvula samples. Immunohistochemistry revealed a subjectively decreasing antibody reactivity of the uvula epithelia with increasing disease severity. ELISA demonstrated significantly higher TFF3 saliva protein concentrations in the healthy control group compared to cases with rhonchopathy and OSA. Predisposing factors of OSA such as BMI or age showed no correlation with TFF3. No significant changes were observed with regard to TFF2.The results suggest the involvement of TFF3 in the pathogenesis of rhonchopathy and OSA and lead to the hypothesis that reduction of TFF3 production by the epithelium and subepithelial mucous glands of the uvula contribute to an increase in breathing resistance due to a change in mucus organization.

SUBMITTER: Siber-Hoogeboom R

PROVIDER: S-EPMC5640215 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Obstructive sleep apnea and rhonchopathy are associated with downregulation of trefoil factor family peptide 3 (TFF3)-Implications of changes in oral mucus composition.

Siber-Hoogeboom Regina R Schicht Martin M Hoogeboom Sebastian S Paulsen Friedrich F Traxdorf Maximilian M

PloS one 20171013 10

<h4>Study objectives</h4>Trefoil factor family (TFF) peptides belong to the family of mucin-associated peptides and are expressed in most mucosal surfaces. TFF peptides carry out functions such as proliferation and migration enhancement, anti-apoptosis, and wound healing. Moreover, TFFs are associated with mucins and interact with them as "linker peptides", thereby influencing mucus viscosity. To test the hypothesis that in rhonchopathy and obstructive sleep apnea (OSA) changes occur in the expr ...[more]

PMID: 29028798

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Project description:Rationale: Oral appliance therapy is efficacious in many patients with obstructive sleep apnea (OSA), but prediction of treatment outcome is challenging. Small, detailed physiological studies have identified key OSA endotypic traits (pharyngeal collapsibility and loop gain) as determinants of greater oral appliance efficacy.Objectives: We used a clinically applicable method to estimate OSA traits from routine polysomnography and identify an endotype-based subgroup of patients expected to show superior efficacy.Methods: In 93 patients (baseline apnea-hypopnea index [AHI], ≥20 events/h), we examined whether polysomnography-estimated OSA traits (pharyngeal: collapsibility and muscle compensation; nonpharyngeal: loop gain, arousal threshold, and ventilatory response to arousal) were associated with oral appliance efficacy (percentage reduction in AHI from baseline) and could predict responses to treatment. Multivariable regression (with interactions) defined endotype-based subgroups of "predicted" responders and nonresponders (based on 50% reduction in AHI). Treatment efficacy was compared between the predicted subgroups (with cross-validation).Results: Greater oral appliance efficacy was associated with favorable nonpharyngeal traits (lower loop gain, higher arousal threshold, and lower response to arousal), moderate (nonmild, nonsevere) pharyngeal collapsibility, and weaker muscle compensation (overall R2 = 0.30; adjusted R2 = 0.19; P = 0.003). Predicted responders (n = 54), compared with predicted nonresponders (n = 39), exhibited a greater reduction in AHI from baseline (mean [95% confidence interval], 73% [66-79] vs. 51% [38-61]; P < 0.0001) and a lower treatment AHI (8 [6-11] vs. 16 [12-20] events/h; P = 0.002). Differences persisted after adjusting for clinical covariates (including baseline AHI, body mass index, and neck circumference).Conclusions: Quantifying OSA traits using clinical polysomnography can identify an endotype-based subgroup of patients that is highly responsive to oral appliance therapy. Prospective validation is warranted.

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Dataset Information

Obstructive sleep apnea and rhonchopathy are associated with downregulation of trefoil factor family peptide 3 (TFF3)-Implications of changes in oral mucus composition.

Publications

Obstructive sleep apnea and rhonchopathy are associated with downregulation of trefoil factor family peptide 3 (TFF3)-Implications of changes in oral mucus composition.

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