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Sleep measures and morning plasma TNF-alpha levels in children with sleep-disordered breathing
David Gozal1, Laura D Serpero, Leila Kheirandish-Gozal
1Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA. dgozal@peds.bsd.uchicago.edu
Insights
Tumor necrosis factor-alpha (TNF-alpha) levels are elevated in children with obstructive sleep apnea, correlating with sleep fragmentation and daytime sleepiness. Treatment for sleep apnea reduces TNF-alpha and improves sleep latency.
Area of Science:
- Pediatric Sleep Medicine
- Immunology
- Respiratory Medicine
Background:
- Sleep disordered breathing in children is linked to increased daytime sleepiness.
- Tumor necrosis factor-alpha (TNF-alpha), an inflammatory cytokine, is implicated in excessive daytime sleepiness (EDS).
- Variability in EDS suggests other biologic correlates, like morning TNF-alpha levels, may exist.
Purpose of the Study:
- To investigate morning TNF-alpha plasma levels as a potential biologic correlate of EDS in children with sleep disordered breathing.
- To examine the relationship between TNF-alpha, obstructive sleep apnea severity, sleep fragmentation, and daytime sleepiness.
Main Methods:
- Assayed TNF-alpha plasma concentrations using ELISA in children undergoing evaluation for sleep disordered breathing.
- Conducted whole blood cultures and Multiple Sleep Latency Tests (MSLT) in a subset of children.
- Measured TNF-alpha levels, polysomnography, and MSLT before and after adenotonsillectomy in children with obstructive sleep apnea.
Main Results:
- Morning TNF-alpha levels were elevated in obstructive sleep apnea, particularly in severe cases, correlating with apnea-hypopnea index and sleep pressure score.
- Sleep pressure score and body mass index explained 36.2% of the variance in TNF-alpha levels.
- MSLT results correlated with whole blood culture-derived TNF-alpha, and levels decreased post-adenotonsillectomy.
Conclusions:
- TNF-alpha levels are elevated in pediatric obstructive sleep apnea, driven by sleep fragmentation and BMI.
- TNF-alpha levels are closely associated with the degree of sleepiness, as measured by MSLT.
- Adenotonsillectomy significantly reduces TNF-alpha levels and improves sleep latency.
Background:
Sleep disordered breathing in children is associated with severity-dependent increases in excessive daytime sleepiness (EDS). TNF-alpha is an inflammatory cytokine that has been implicated in EDS. Since, at any given level of apnea-hypopnea index, there is significant variability in EDS, we hypothesized that morning tumor necrosis factor (TNF)-alpha plasma levels may provide a biologic correlate of EDS.
Methods:
Children being evaluated for sleep disordered breathing underwent a blood draw after nocturnal polysomnography, and TNF-alpha plasma concentrations were assayed using ELISA. In a subset of 15 children with sleep disordered breathing and in 15 matched control subjects, whole blood cultures in the presence of lipopolysaccharide and Multiple Sleep Latency Test were conducted. Furthermore, 22 children with obstructive sleep apnea had TNF-alpha levels assayed and underwent nocturnal polysomnography and Multiple Sleep Latency Test before and after adenotonsillectomy.
Results:
In 298 children, morning TNF-alpha levels were globally increased in the presence of obstructive sleep apnea, particularly in more severe cases, and correlated with obstructive apnea-hypopnea index and sleep pressure score, a measure of respiratory-induced sleep fragmentation, but not with nadir Sa02. A stepwise logistic regression analysis revealed that sleep pressure score and body mass index accounted for 36.2% of the adjusted variance in TNF-alpha levels (P < 0.0001). Furthermore, multiple sleep latencies were correlated with whole blood culture-derived TNF-alpha levels (n = 15), and morning TNF-alpha levels decreased after adenotonsillectomy in 22 children.
Conclusions:
TNF-alpha levels are increased in pediatric obstructive sleep apnea, are primarily driven by sleep fragmentation and body mass index, and are closely associated with the degree of sleepiness, as measured by Multiple Sleep Latency Test. Furthermore, surgical treatment of obstructive sleep apnea results in significant reductions in TNF-alpha levels with reciprocal prolongations in sleep latency.
