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Sleep and Breathing
Published in: Sleep and Breathing 3/2007

01-09-2007 | Original Article

Inflammatory proteins in patients with obstructive sleep apnea with and without daytime sleepiness

Authors: Mónica de la Peña Bravo, Laura D. Serpero, Antonia Barceló, Ferran Barbé, Alvar Agustí, David Gozal

Published in: Sleep and Breathing | Issue 3/2007

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Abstract

Excessive daytime sleepiness (EDS) is one of the most frequent symptoms in patients with obstructive sleep apnea syndrome (OSAS). However, not all patients with OSAS manifest EDS. The aim of this study was to assess whether differential circulatory levels of inflammatory mediators would account for differences in somnolence among patients with OSAS. Patients were prospectively recruited from referral patient cohort to the university hospital sleep center. A total of 50 consecutive patients with OSAS undergoing overnight polysomnography with or without EDS and 20 controls were evaluated. EDS was assessed using the Epworth sleepiness scale (ESS) and the multiple sleep latency test after overnight polysomnography. EDS was defined when the ESS was >10 and the mean sleep latency <10 min. Fasting blood was drawn in the morning after polysomnography. Circulating levels of tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), intercellular adhesion molecule 1 (ICAM-1), 8-isoprostaglandin F2α (8-iso-PGF2α), and P-selectin were measured with commercially available high sensitivity kits. Although patients with OSAS have elevated levels of ICAM-1, IL-6, and TNFα, there were no statistically significant differences in any of the inflammatory mediators between patients with EDS and without EDS. Emergence of EDS in the context of OSA does not appear to result from the selective increase of any particular somnogenic substance, i.e., TNFα, IL-6, ICAM-1, 8-iso-PGF2α, and P-selectin in the context of sleep-disordered breathing.
Literature
1.
Douglas NJ, Polo O (1994) Pathogenesis of obstructive sleep apnoea/hypopnoea syndrome (Review) (34 refs). Lancet 344(8923):653–655PubMedCrossRef
2.
Young T, Palta M, Dempsey J et al (1993) The occurrence of sleep-disordered breathing among middle-aged adults (see comment). N Engl J Med 328(17):1230–1235PubMedCrossRef
3.
Carrera M, Barbe F, Sauleda J et al (1999) Patients with obstructive sleep apnea exhibit genioglossus dysfunction that is normalized after treatment with continuous positive airway pressure. Am J Respir Crit Care Med 159(6):1960–1966PubMed
4.
Young TB (2004) Epidemiology of daytime sleepiness: definitions, symptomatology, and prevalence. J Clin Psychiatry 65(Suppl 16):12–16PubMed
5.
Findley LJ, Barth JT, Powers DC et al (1986) Cognitive impairment in patients with obstructive sleep apnea and associated hypoxemia. Chest 90(5):686–690PubMed
6.
Aldrich MS (1989) Automobile accidents in patients with sleep disorders. Sleep 12(6):487–494PubMed
7.
Findley LJ (1990) Automobile driving in sleep apnea. Prog Clin Biol Res 345:337–343PubMed
8.
Beutler LE, Ware JC, Karacan I et al (1981) Differentiating psychological characteristics of patients with sleep apnea and narcolepsy. Sleep 4(1):39–47PubMed
9.
Vgontzas AN, Bixler EO, Chrousos GP (2003) Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance. J Intern Med 254(1):32–44PubMedCrossRef
10.
ICSD—Diagnostic Classification Committee, Thorpy MJ C, American sleep disorders Association (1990) International classification of sleep disorders: diagnostic and coding manual. Rochester, Minnesota
11.
Newman AB, Spiekerman CF, Enright P et al (2000) Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group. J Am Geriatr Soc 48(2):115–123PubMed
12.
Barbe F, Mayoralas LR, Duran J et al (2001) Treatment with continuous positive airway pressure is not effective in patients with sleep apnea but no daytime sleepiness. a randomized, controlled trial. Ann Intern Med 134(11):1015–1023PubMed
13.
Mastorakos G, Chrousos GP, Weber JS (1993) Recombinant interleukin-6 activates the hypothalamic–pituitary–adrenal axis in humans. J Clin Endocrinol Metab 77(6):1690–1694PubMedCrossRef
14.
Papanicolaou DA, Tsigos C, Oldfield EH et al (1996) Acute glucocorticoid deficiency is associated with plasma elevations of interleukin-6: does the latter participate in the symptomatology of the steroid withdrawal syndrome and adrenal insufficiency? J Clin Endocrinol Metab 81(6):2303–2306PubMedCrossRef
15.
Entzian P, Linnemann K, Schlaak M et al (1996) Obstructive sleep apnea syndrome and circadian rhythms of hormones and cytokines. Am J Respir Crit Care Med 153(3):1080–1086PubMed
16.
Vgontzas AN, Papanicolaou DA, Bixler EO et al (1997) Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 82(5):1313–1316PubMedCrossRef
17.
Vgontzas AN, Papanicolaou DA, Bixler EO et al (2000) Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 85(3):1151–1158PubMedCrossRef
18.
Vgontzas AN, Zoumakis E, Lin HM et al (2004) Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor necrosis factor-alpha antagonist. J Clin Endocrinol Metab 89(9):4409–4413PubMedCrossRef
19.
Yudkin JS, Kumari M, Humphries SE et al (2000) Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148(2):209–214PubMedCrossRef
20.
Marin JM, Carrizo SJ, Vicente E et al (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea–hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365(9464):1046–1053PubMed
21.
Nieto FJ, Young TB, Lind BK et al (2000) Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 283(14):1829–1836PubMedCrossRef
22.
Peker Y, Hedner J, Norum J et al (2002) Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up. Am J Respir Crit Care Med 166(2):159–165PubMedCrossRef
23.
Peppard PE, Young T, Palta M et al (2000) Prospective study of the association between sleep-disordered breathing and hypertension (see comment). N Engl J Med 342(19):1378–1384PubMedCrossRef
24.
Shahar E, Whitney CW, Redline S et al (2001) Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study (see comment). Am J Respir Crit Care Med 163(1):19–25PubMed
25.
Dean RT, Wilcox I (1993) Possible atherogenic effects of hypoxia during obstructive sleep apnea. Sleep 16(8 Suppl):S15–S21PubMed
26.
Hedner JA, WISCE (1994) Speculations on the interaction between vascular disease and obstructive sleep apnea. In: Dekker M (ed) Sleep and breathing. INC, New York
27.
Lavie L (2003) Obstructive sleep apnoea syndrome—an oxidative stress disorder (comment) (Review) (130 refs). Sleep Med Rev 7(1):35–51PubMedCrossRef
28.
Schulz R, Mahmoudi S, Hattar K et al (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 162(2 Pt 1):566–570PubMed
29.
Barcelo A, Miralles C, Barbe F et al (2000) Abnormal lipid peroxidation in patients with sleep apnoea. Eur Respir J 16(4):644–647PubMedCrossRef
30.
Awad JA, Morrow JD, Takahashi K et al (1993) Identification of non-cyclooxygenase-derived prostanoid (F2-isoprostane) metabolites in human urine and plasma. J Biol Chem 268(6):4161–4169PubMed
31.
Roberts LJ, Morrow JD (2000) Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med 28(4):505–513PubMedCrossRef
32.
Schwedhelm E, Maas R, Troost R et al (2003) Clinical pharmacokinetics of antioxidants and their impact on systemic oxidative stress. Clin Pharmacokinet 42(5):437–459PubMedCrossRef
33.
Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352(16):1685–1695PubMedCrossRef
34.
Simonini A, Moscucci M, Muller DW et al (2000) IL-8 is an angiogenic factor in human coronary atherectomy tissue. Circulation 101(13):1519–1526PubMed
35.
Haught WH, Mansour M, Rothlein R et al (1996) Alterations in circulating intercellular adhesion molecule-1 and L-selectin: further evidence for chronic inflammation in ischemic heart disease. Am Heart J 132(1 Pt 1):1–8PubMed
36.
Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362(6423):801–809PubMedCrossRef
37.
Pober JS, Bevilacqua MP, Mendrick DL et al (1986) Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol 136(5):1680–1687PubMed
38.
Chin K, Nakamura T, Shimizu K et al (2000) Effects of nasal continuous positive airway pressure on soluble cell adhesion molecules in patients with obstructive sleep apnea syndrome. Am J Med 109(7):562–567PubMedCrossRef
39.
El Solh AA, Mador MJ, Sikka P et al (2002) Adhesion molecules in patients with coronary artery disease and moderate-to-severe obstructive sleep apnea. Chest 121(5):1541–1547PubMedCrossRef
40.
Blankenberg S, Barbaux S, Tiret L (2003) Adhesion molecules and atherosclerosis. Atherosclerosis 170(2):191–203PubMedCrossRef
41.
Blann AD, McCollum CN (1998) Increased soluble P-selectin in peripheral artery disease: a new marker for the progression of atherosclerosis. Thromb Haemost 80(6):1031–1032PubMed
42.
Ridker PM, Buring JE, Rifai N (2001) Soluble P-selectin and the risk of future cardiovascular events. Circulation 103(4):491–495PubMed
43.
Carskadon MA, Dement WC, Mitler MM et al (1986) Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep 9(4):519–524PubMed
44.
Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14(6):540–545PubMed
45.
Benbadis SR, Mascha E, Perry MC et al (1999) Association between the Epworth sleepiness scale and the multiple sleep latency test in a clinical population. Ann Intern Med 130(4 Pt 1):289–292PubMed
46.
Ohga E, Nagase T, Tomita T et al (1999) Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome. J Appl Physiol 87(1):10–14PubMed
47.
Haddy N, Sass C, Droesch S et al (2003) IL-6, TNF-alpha and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort. Atherosclerosis 170(2):277–283PubMedCrossRef
48.
Rothlein R, Mainolfi EA, Czajkowski M et al (1991) A form of circulating ICAM-1 in human serum. J Immunol 147(11):3788–3793PubMed
49.
Morisaki N, Saito I, Tamura K et al (1997) New indices of ischemic heart disease and aging: studies on the serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1) in patients with hypercholesterolemia and ischemic heart disease. Atherosclerosis 131(1):43–48PubMedCrossRef
50.
Ridker PM, Hennekens CH, Roitman-Johnson B et al (1998) Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet 351(9096):88–92PubMedCrossRef
51.
Zund G, Uezono S, Stahl GL et al (1997) Hypoxia enhances induction of endothelial ICAM-1: role for metabolic acidosis and proteasomes. Am J Physiol 273(5 Pt 1):C1571–C1580PubMed
52.
Blann AD, Steele C, McCollum CN (1997) The influence of smoking on soluble adhesion molecules and endothelial cell markers. Thromb Res 85(5):433–438PubMedCrossRef
53.
Ponthieux A, Herbeth B, Droesch S et al (2004) Biological determinants of serum ICAM-1, E-selectin, P-selectin and L-selectin levels in healthy subjects: the Stanislas study. Atherosclerosis 172(2):299–308PubMedCrossRef
54.
Bokinsky G, Miller M, Ault K et al (1995) Spontaneous platelet activation and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure. A preliminary investigation. Chest 108(3):625–630PubMed
55.
Eisensehr I, Ehrenberg BL, Noachtar S et al (1998) Platelet activation, epinephrine, and blood pressure in obstructive sleep apnea syndrome. Neurology 51(1):188–195PubMed
56.
Geiser T, Buck F, Meyer BJ et al (2002) In vivo platelet activation is increased during sleep in patients with obstructive sleep apnea syndrome. Respiration 69(3):229–234PubMedCrossRef
57.
Hui DS, Ko FW, Fok JP et al (2004) The effects of nasal continuous positive airway pressure on platelet activation in obstructive sleep apnea syndrome. Chest 125(5):1768–1775PubMedCrossRef
58.
Sanner BM, Konermann M, Tepel M et al (2000) Platelet function in patients with obstructive sleep apnoea syndrome. Eur Respir J 16(4):648–652PubMedCrossRef
59.
von Kanel R, Dimsdale JE (2003) Hemostatic alterations in patients with obstructive sleep apnea and the implications for cardiovascular disease. Chest 124(5):1956–1967CrossRef
60.
Robinson GV, Pepperell JC, Segal HC et al (2004) Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax 59(9):777–782PubMedCrossRef
61.
Olson LJ, Olson EJ, Somers VK (2004) Obstructive sleep apnea and platelet activation: another potential link between sleep-disordered breathing and cardiovascular disease. Chest 126(2):339–341PubMedCrossRef
62.
Papanicolaou DA, Wilder RL, Manolagas SC et al (1998) The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 128(2):127–137PubMed
63.
Biasucci LM, Vitelli A, Liuzzo G et al (1996) Elevated levels of interleukin-6 in unstable angina. Circulation 94(5):874–877PubMed
64.
Carpagnano GE, Kharitonov SA, Resta O et al (2002) Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients. Chest 122(4):1162–1167PubMedCrossRef
65.
Yokoe T, Minoguchi K, Matsuo H et al (2003) 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 107(8):1129–1134PubMedCrossRef
66.
Inoue Ki, Takano H, Yoshikawa T et al (2003) Interleukin-6, Obstructive Sleep Apnea, and Obesity. Chest 124(4):1621–162a
67.
Teramoto S, Yamamoto H, Ouchi Y (2003) Increased C-reactive protein and increased plasma interleukin-6 may synergistically affect the progression of coronary atherosclerosis in obstructive sleep apnea syndrome. Circulation 107(5):E40PubMedCrossRef
68.
Tauman R, Ivanenko A, O’Brien LM et al (2004) Plasma C-reactive protein levels among children with sleep-disordered breathing. Pediatrics 113(6):e564–e569PubMedCrossRef
69.
Bauer J, Hohagen F, Ebert T et al (1994) Interleukin-6 serum levels in healthy persons correspond to the sleep-wake cycle. Clin Investig 72(4):315PubMedCrossRef
70.
De Simoni MG, De Luigi A, Gemma L et al (1993) Modulation of systemic interleukin-6 induction by central interleukin-1. Am J Physiol Regul Integr Comp Physiol 265(4):R739–R742
71.
Opp MR (2002) Cytokines and sleep promotion: a potential mechanism for disorders of excessive daytime sleepiness. In: Pack AI (ed) Sleep apnea: pathogenesis, diagnosis, and treatment. Dekker, New York, pp 327–352
72.
Vgontzas AN, Papanicolaou DA, Bixler EO et al (1999) Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab 84(8):2603–2607PubMedCrossRef
73.
Vgontzas AN, Zoumakis E, Bixler EO et al (2004) Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. J Clin Endocrinol Metab 89(5):2119–2126PubMedCrossRef
74.
Vgontzas AN, Papanicolaou DA, Bixler EO et al (1999) Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab 84(8):2603–2607PubMedCrossRef
75.
Fang J, Wang Y, Krueger JM (1997) Mice lacking the TNF 55 kDa receptor fail to sleep more after TNFalpha treatment. J Neurosci 17(15):5949–5955PubMed
76.
Takahashi S, Kapas L, Krueger JM (1996) A tumor necrosis factor (TNF) receptor fragment attenuates TNF-alpha- and muramyl dipeptide-induced sleep and fever in rabbits. J Sleep Res 5(2):106–114PubMedCrossRef
77.
Minoguchi K, Tazaki T, Yokoe T et al (2004) Elevated production of tumor necrosis factor-α by monocytes in patients with obstructive sleep apnea syndrome. Chest 126(5):1473–1479PubMedCrossRef
78.
Row BW, Liu R, Xu W et al (2003) Intermittent hypoxia is associated with oxidative stress and spatial learning deficits in the rat. Am J Respir Crit Care Med 167(11):1548–1553PubMedCrossRef
79.
Zhan G, Serrano F, Fenik P et al (2005) NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine model of sleep apnea. Am J Respir Crit Care Med 172(7):921–929PubMedCrossRef
80.
Yamauchi M, Nakano H, Maekawa J et al (2005) Oxidative stress in obstructive sleep apnea. Chest 127(5):1674–1679PubMedCrossRef
81.
Morrow JD, Hill KE, Burk RF et al (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A 87(23):9383–9387PubMedCrossRef
82.
Janssen LJ (2000) Isoprostanes: generation, pharmacology, and roles in free-radical-mediated effects in the lung. Pulm Pharmacol Ther 13(4):149–155PubMedCrossRef
83.
Dworski D, Jackson L, Roberts L et al (2001) Assessment of oxidant stress in allergic asthma by measurement of the major urinary metabolite of F2-isoprostane, 15-F2t-IsoP (8-iso-PGF2). Clin Exp Allergy 31(3):387PubMedCrossRef
84.
Pratico D, Basili S, Vieri M et al (1998) Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2alpha-III, an index of oxidant stress. Am J Respir Crit Care Med 158(6):1709–1714PubMed
85.
Montuschi P, Ciabattoni G, Paredi P et al (1998) 8-Isoprostane as a biomarker of oxidative stress in interstitial lung diseases. Am J Respir Crit Care Med 158(5 Pt 1):1524–1527PubMed
Metadata
Title
Inflammatory proteins in patients with obstructive sleep apnea with and without daytime sleepiness
Authors
Mónica de la Peña Bravo
Laura D. Serpero
Antonia Barceló
Ferran Barbé
Alvar Agustí
David Gozal
Publication date
01-09-2007
Publisher
Springer-Verlag
Published in
Sleep and Breathing / Issue 3/2007
Print ISSN: 1520-9512
Electronic ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-007-0100-7

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