The roles of TNF-alpha and the soluble TNF receptor I on sleep architecture in OSA.
OBJECTIVE
Patients with obstructive sleep apnea (OSA) have been described to have increased levels of inflammatory cytokines (particularly TNF-alpha) and have severely disturbed sleep architecture. Serum inflammatory markers, even in normal individuals, have been associated with abnormal sleep architecture. Not much is known about the role the TNF receptor plays in the inflammation of OSA nor if it is associated with changes in sleep architecture or arousals during the night. We hypothesized that the TNF receptor might play an important role in the inflammation as well as sleep architecture changes in patients with OSA.


METHODS
Thirty-six patients with diagnosed (AHI > 15) but untreated OSA were enrolled in this study. Baseline polysomnograms as well as TNF-alpha and soluble TNF receptor I (sTNF-RI) serum levels were obtained on all patients. We evaluated the association between serum levels of TNF-alpha and sTNF-RI with various polysomongraphic characteristics, including sleep stages and EEG arousals.


RESULTS
sTNF-RI levels were significantly correlated with snore arousals (r value 0.449, p value 0.009), spontaneous movement arousals (r value 0.378, p value 0.025), and periodic limb movement arousals (r value 0.460, p value 0.008). No statistically significant correlations were observed with TNF-alpha to any polysomnographic variables. To control for statistical significance with multiple comparisons, a MANOVA was performed with TNF-alpha and sTNF-RI as dependent variables and sleep architecture measures and arousals as independent variables. The model for sTNF-RI was statistically significant (F value 2.604, p value 0.03), whereas the model for TNF-alpha was not, suggesting sleep quality significantly affects sTNF-RI. Hierarchal linear regression analysis demonstrated that sTNF-RI was independently associated with spontaneous movement arousal index scores after controlling for age, body mass index, and sleep apnea severity.


CONCLUSIONS
These findings suggest that sTNF-RI is associated with arousals during sleep, but not with other measures in patients with OSA.
Yue
Herbert J
HJ
Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA. hyue@ucsd.edu
Mills
Paul J
PJ
Ancoli-Israel
Sonia
S
Loredo
José S
JS
Ziegler
Michael G
MG
Dimsdale
Joel E
JE
D015992:Body Mass Index; D045422:Continuous Positive Airway Pressure / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010108:Oxyhemoglobins / Q000378:metabolism; D017286:Polysomnography / Q000379:methods; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D012894:Sleep Stages / Q000502:physiology; D047990:TNF Receptor-Associated Factor 1 / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D010108:Oxyhemoglobins; D047990:TNF Receptor-Associated Factor 1; D014409:Tumor Necrosis Factor-alpha