Chest
Volume 134, Issue 5, November 2008, Pages 911-918
Journal home page for Chest

Original Research
Sleep Medicine
Tumor Necrosis Factor-α Expression in Uvular Tissues Differs Between Snorers and Apneic Patients

https://doi.org/10.1378/chest.08-0886Get rights and content

Background

Inflammatory changes such as subepithelial edema and excessive inflammatory cell infiltration have been observed in uvular tissues of obstructive sleep apnea (OSA) subjects. The levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin-6 are elevated in the serum of apneic patients and have been proposed as mediators of muscle weakness. TNF-α has been shown to affect diaphragm contractility in mice and rabbit in vivo.

Objectives

To assess total and compartmental TNF-α expression in uvular tissues of apneic and nonapneic patients.

Methods

Uvular tissues were collected from 14 snorers without sleep disorders breathing, 14 subjects with OSA (OSA 1 group) whose body mass index (BMI) was similar to that of snorers, and 12 additional obese OSA subjects (OSA 2 group) who underwent an uvulopalatopharyngoplasty. Sections were examined using immunohistochemistry and Western blot analysis. TNF-α expression was evaluated in the musculus uvulae (MU), epithelial layer, and perimuscular tissues from proximal uvular sections.

Results

TNF-α was more highly expressed in whole uvular protein extracts of apneic groups than in snorers ([mean ± SEM] snorers, 100.5 ± 3.0%; OSA 1 group, 127.1 ± 6.9%; OSA 2 group, 140.7 ± 11.0%; p = 0.01). In the muscular area, TNF-α levels were higher in the more obese OSA subjects than in the other two groups (snorers, 100.3 ± 3%; OSA 1 group, 107.4 ± 0.7%; OSA 2 group, 124.1 ± 4.2%; p = 0.007). In the muscular area, TNF-α was correlated with BMI, but no relationship was found with the apnea-hypopnea index.

Conclusions

We conclude that MU is the major TNF-α source in uvular tissue and that TNF-α is more highly expressed in the heaviest OSA patients compared to less obese OSA patients and nonapneic snorers.

Section snippets

Subjects

Forty consecutive subjects who underwent UPPP for the treatment of OSA or nonapneic snoring were included in the study over a 4-year period. None of the subjects had been previously treated for OSA or snoring at the time of surgery. No subject was receiving therapy with neuroleptics, antidepressants, thyroid hormone, or any medication that affects breathing during sleep. No subjects with diabetes mellitus were included. Reported alcohol consumption went from absent (3 nonapneic subjects, 7

Subject Characteristics

Anthropometric and polysomnographic data of participating subjects are summarized in Table 1. There was a similar number of smokers in each group (three smokers among 14 nonapneic snorers; three smokers among 14 subjects in the OSA 1 group; and three smokers among 12 subjects in the OSA 2 group). The other subjects were nonsmokers or had stopped smoking for > 1 year. According to the selection criteria, patients in OSA 2 group had a significantly higher BMI than subjects in the two other groups

Discussion

We found that TNF-α is more highly expressed in the MU of obese patients and in the perimuscular area of nonapneic snorers. This suggests that in snoring patients with or without sleep apnea, obesity plays a more important role than sleep apnea status in the expression of inflammatory markers in uvula muscular tissue. However, the compartmental expression of TNF-α may also be influenced by sleep apnea status.

For a decade, systemic and UA inflammation has been linked to OSA, and it has been

Acknowledgment

The authors thank Doris Cantin, of the “Banque de tissus de l'Hôpital Laval,” for technical assistance, and Serge Simard for statistical analysis. We also thank the patients for their acceptance to participate in the study, and Dr. Sylvain Saint-Pierre for his collaboration during surgical procedures.

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    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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