Obstructive sleep apnea syndrome (OSAS) afflicts about 5% of adults in Western countries and is thought to play an important role in the pathogenesis of cardiovascular disorders and diabetes mellitus. Although the etiology of OSAS is uncertain, intense local and systemic inflammation are present in these patients. In the upper airway, this process may promote oropharyngeal inspiratory muscle dysfunction and amplify upper airway narrowing and collapsibility thereby worsening the frequency and duration of apneas during sleep. The presence of systemic inflammation, characterized by elevated levels of certain potent pro-inflammatory mediators, such as C-reactive protein, leptin, TNF-α, IL-1β, IL-6, reactive oxygen species and adhesion molecules, may predispose to the development of cardiovascular complications observed in patients with OSAS. Treatment with nasal CPAP abrogates, in part, local and systemic inflammation in these patients. Whether therapeutic interventions aimed at abating inflammation could be a useful adjunct in the treatment of OSAS merits further investigation.

1.
Young T, Peppard PE, Gottlieb DJ: Epidemiology of obstructive sleep apnea. Am J Resp Crit Care Med 2002;165:1217–1239.
2.
Hudgel DW: Mechanisms of obstructive sleep apnea. Chest 1992;101:541–549.
3.
Chaban R, Cole P, Hoffstein V: Site of upper airway obstruction in patients with idiopathic obstructive sleep apnea. Laryngoscope 1988;98:641–647.
4.
Schwab RJ, Gupta KB, Gefter WB, et al: Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Am J Respir Crit Care Med 1995;152:1673–1689.
5.
Woodson BT, Garancis JC, Toohill RJ: Histopathologic changes in snoring and obstructive sleep apnea syndrome. Laryngoscope 1991;101:1318–1322.
6.
Saul S, Kimmelman CP, Brooks JS, et al: Histopathology of sleep apnea. Trans Am Laryngol Assoc 1988;109:222–225.
7.
Sekosan M, Zakkar M, Wenig B, et al: Inflammation in the uvula mucosa of patients with obstructive sleep apnea. Laryngoscope 1996;106:1018–1020.
8.
Paulsen FP, Steven P, Tsokos M, et al: Upper airway epithelial structural changes in obstructive sleep disordered breathing. Am J Respir Crit Care Med 2002;166:501–509.
9.
Rubinstein I: Nasal inflammation in patients with obstructive sleep apnea. Laryngoscope 1995;105:175–177.
10.
Müns G, Rubinstein I, Singer P: Phagocytosis and oxidative burst of granulocytes in the upper respiratory tract in chronic and acute inflammation. J Otolaryngol 1995;24:105–110.
11.
Alwani A, Rubinstein I: The nose and OSA. Curr Opin Pulm Med 1998;4:361–362.
12.
Zakkar M, Sekosan M, Wenig B, et al: Decrease in immunoreactive neutral endopeptidase in uvula epithelium of patients with obstructive sleep apnea. Ann Otol Rhinol Laryngol 1997;106:474–477.
13.
Wasicko MJ, Hutt DA, Parisi RA, et al: The role of vascular tone in the control the upper airway collapsibility. Am Rev Respir Dis 1990;141:1569–1577.
14.
McNicholas WT, Coffey M, McDonnell T, et al: Abnormal respiration during sleep in normal subjects following selective topical oropharyngeal and nasal anesthesia. Am Rev Respir Dis 1987;135:1316–1319.
15.
Berry RB, Kouchi KG, Bower JL, et al: Effect of upper airway anesthesia on obstructive sleep apnea. Am J Respir Crit Care Med 1995;151:1857–1861.
16.
Friberg D, Gazelius B, Hökfelt T, et al: Abnormal afferent nerve endings in the soft palatal mucosa of sleep apneic and habitual snorers. Regul Peptides 1997;71:29–36.
17.
Lembeck F, Holzer P: Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Arch Pharmacol 1979;310:175–183.
18.
Kimoff RJ, Sforza E, Champagne V, et al: Upper airway sensation in snoring and obstructive sleep apnea. Am J Respir Crit Care Med 2001;164:250–255.
19.
Larsson H, Carlson-Nordlander B, Lindblad LE, et al: Temperature thresholds in the oropharynx of patients with obstructive sleep apnea syndrome. Am Rev Respir Dis 1992;146:1246–1249.
20.
Cohn M, Hesla PE, Kiel M, et al: Vibration frequency of snoring in obstructive sleep apnea syndrome. Chest 1986;89:529 S.
21.
Moldofsky H, Lue FA, Eisen J, et al: The relationship of interleukin-1 and immune functions to sleep in humans. Psychosom Med 1986;48:309–318.
22.
Opp MR, Krueger JM: An interleukin-1 receptor antagonist blocks interleukin-1 induced sleep and fever. Am J Physiol 1991;260:R453–R457.
23.
Krueger JM and Obal F Jr: Sleep Factors; in Saunders NA, Sullivan CE (eds): Sleep and Breathing. New York, Marcel Dekker, 1994, pp 79–112.
24.
Darko DF, Miller JC, Gallen C, et al: Sleep electroencephalogram delta frequency amplitude, night plasma levels of tumor necrosis factor-α and human immunodeficiency virus infection. Proc Natl Acad Sci USA 1995;92:12080–12086.
25.
Takahashi S, Tooley D, Kapás L, et al: Inhibition of tumor necrosis factor suppresses sleep in rabbits. Pflügers Arch. 1995;431:155–160.
26.
Vgontzas AN, Papanicolaou DA, Bixler EO: Elevation of plasma cytokines in disorders of excessive daytime sleepiness: Role of sleep disturbance and obesity. J Clin Endocrinol Metab 1997;82:1313–1316.
27.
Vgontzas AN, Papanicolaou DA, Bixler EO: Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 2000;85:1151–1158.
28.
Entzian P, Linnemann K, Schlaak M, et al: Obstructive sleep apnea and circadian rhythms of hormones and cytokines. Am J Respir Crit Care Med 1996;153:1080–1086.
29.
Patarca R, Klimas NG, Lutendorf S, et al: Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression. Clin Infect Dis 1994;18:S147–S153.
30.
Vreugdenhil G, Lowenberg B, Van Eijk HG et al: Tumor necrosis factor alpha is associated with the disease activity and the degree of anemia in patients with rheumatoid arthritis. Eur J Clin Invest 1992;22:488–493.
31.
Wilcox P, Milliken C, Bressler B: High dose tumor necrosis factor alpha produces an impairment of hamster diaphragm contractility. Am J Respir Crit Care Med 1996;153:1611–1615.
32.
Reid MB, Lannergen J, Westerblad H: Respiratory and limb muscle weakness induced by tumor necrosis factor alpha. Am J Respir Crit Care Med 2002;166:479–484.
33.
Li X, Moody MR, Engel D, et al: Cardiac specific overexpression of tumor necrosis factor alpha causes oxidative stress of contractile dysfunction in mouse diaphragm. Circulation 2000;102:1690–1696.
34.
McCord MJ: Oxygen derived free radicals in postischemic tissue injury. N Engl J Med 1985;312:159–163.
35.
Mutlu GM, Rubinstein I: Obstructive sleep apnea syndrome-associated nocturnal myocardial ischemia. Chest 2000;117:1534–1535.
36.
Olopade CO, Christon JA, Zakkar M, et al: Exhaled pentane and nitric oxide levels in patients with obstructive sleep apnea. Chest 1997;111:1500–1504.
37.
Sahebjani H: Changes in urinary uric acid excretion in obstructive sleep apnea before and after therapy with nasal continuous positive airway pressure. Chest 1998;113:1604–1608.
38.
Schulz R, Mahmoudi S, Hattar K, et al: Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Am J Respir Crit Care Med 2000;162:566–570.
39.
Dyugovskaya L, Lavie P, Lavie L: Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med 2002;165:934–939.
40.
Vassilakopoulos T, Katsaounou P, Karatza M-H, et al: Strenuous resistive breathing induces plasma cytokines. Am J Respir Crit Care Med 2002;166:1572–1578.
41.
Visser M, Bouter LM, McQuillan GM et al: Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999;282:2131–2135.
42.
Shamsuzzaman AS, Winnicki M, Lanfranchi P, et al: Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 2002;105:2462–2464.
43.
Yokoe T, Minoguchi K, Matsuo H, et al: Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 2003;107:1129–1134.
44.
Heinrich PC, Castell JV, Andus T: Interleukin-6 and the acute phase response. Biochem J 1990;265:621–636.
45.
Ip MSM, Lam KSL, Ho C, et al: Serum leptin and vascular risk factors in obstructive sleep apnea. Chest 2000;118:580–586.
46.
Finck BN, Johnson RW: Tumor necrosis factor alpha regulates secretion of the adipocyte-derived cytokine, leptin. Microsc Res Tech 2000;50:209–215.
47.
Alberti KGM, Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications: WHO Consultation. In Geneva, Switzerland: World Health Organization, 1999, pp 31–33.
48.
Chin K, Shimizu K, Nakamura T, et al: Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy. Circulation 1999;100:706–712.
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