Oxidative Stress and Inflammation after Continuous Positive Airway Pressure Therapy in Patients with Severe Obstructive Sleep Apnea
Khanaphaphon Wuttiumporn, Wilaiwan Khrisanapant, Watchara Boonsawat, Orapin Pasurivong, Benjamas Intarapoka, Justin Thomas Reese
Sleep and Hypnosis: A Journal of Clinical Neuroscience and Psychopathology 2018;20(4):275-282
Background: It has been demonstrated that moderate to severe obstructive sleep apnea (OSA) leads to generation of reactive oxygen species and inflammation. We evaluated whether continuous positive airway pressure (CPAP) treatment progressively improves oxidative stress and inflammation, and whether an association exists in severe OSA patients between severity of OSA and biomarkers of oxidative stress and inflammation.
Methods:Forty patients with severe OSA (apnea hypopnea index, AHI: 37.8 ± 5.8 /h) that were newly diagnosed using polysomnography were recruited. Patients received CPAP treatment for six months. Patients were assigned to CPAP and non-CPAP treatment groups in equal numbers. The levels of malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high sensitivity C-reactive protein (hs-CRP), neutrophils to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) were measured prior to and after three and six months of therapy.
Results: AHI was positively correlated with MDA (r = 0.4728, p < 0.01), ALT (r = 0.6081, p < 0.001), AST (r = 0.6299, p < 0.001), NLR (r = 0.3943, p < 0.05), PLR (r = 0.3319, p < 0.05), and hs-CRP (r = 0.5728, p < 0.001). In the CPAP but not in non-CPAP treatment group, MDA, AST, NLR, PLR, and hs-CRP levels (p < 0.001), and ALT (p < 0.05) levels were improved after three and six months of treatment. After six months, MDA levels decreased further compared to MDA levels at three months, and this decrease was significant (p < 0.001).
Conclusion: Our study demonstrates that CPAP therapy in severe OSA patients produces clinical benefits by improving oxidative stress and inflammation progressively, and that severity of OSA is correlated with oxidative stress and inflammation.
REFERENCES
Aron-Wisnewsky, J., Clement, K., & Pépin, J.-L. (2016). Nonalcoholic fatty liver disease and obstructive sleep apnea. Metabolism, 65(8), 1124-1135. doi: 10.1016/j.metabol.2016.05.004
Asker, S., Asker, M., Sarikaya, E., Sunnetcioglu, A., Aslan, M., & Demir, H. (2015). Oxidative stress parameters and their correlation with clinical, metabolic and polysomnographic parameters in severe obstructive sleep apnea syndrome. International Journal of Clinical and Experimental Medicine, 8(7), 11449-11455.
Cakmak, E., Duksal, F., Altinkaya, E., Acibucu, F., Dogan, O. T., Yonem, O., & Yilmaz, A. (2015). Association Between the Severity of Nocturnal Hypoxia in Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Damage. Hepatitis Monthly, 15(11), e32655. doi: 10.5812/hepatmon.32655
Calvin, A. D., Albuquerque, F. N., Lopez-Jimenez, F., & Somers, V. K. (2009). Obstructive Sleep Apnea, Inflammation, and the Metabolic Syndrome. Metabolic Syndrome and Related Disorders, 7(4), 271-277. doi: 10.1089/met.2008.0093
Carpagnano, G. E., Lacedonia, D., & Foschino-Barbaro, M. P. (2011). Non-invasive study of airways inflammation in sleep apnea patients. Sleep Medicine Reviews, 15(5), 317-326. doi: 10.1016/j.smrv.2010.12.005
Celec, P., Hodosy, J., Behuliak, M., Palffy, R., Gardlik, R., Halcak, L., & Mucska, I. (2012). Oxidative and carbonyl stress in patients with obstructive sleep apnea treated with continuous positive airway pressure. Sleep Breath, 16(2), 393-398. doi: 10.1007/s11325-011-0510-4
Chin, K., Nakamura, T., Takahashi, K., Sumi, K., Ogawa, Y., Masuzaki, H., Nakamura, T. (2003). Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients. The American Journal of Medicine, 114(5), 370-376. doi: 10.1016/S0002-9343(02)01570-X
Daltro, C., Cotrim, H. P., Alves, E., de Freitas, L. A., Araujo, L., Boente, L., Portugal, T. (2010). Nonalcoholic fatty liver disease associated with obstructive sleep apnea: just a coincidence? Obes Surg, 20(11), 1536-1543. doi: 10.1007/s11695-010-0212-1
Epstein, L. J., Kristo, D., Strollo, P. J., Jr., Friedman, N., Malhotra, A., Patil, S. P., Weinstein, M. D. (2009). Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. Journal of Clinical Sleep Medicine, 5(3), 263-276.
Gowda, S., Desai, P. B., Hull, V. V., Math, A. A. K., Vernekar, S. N., & Kulkarni, S. S. (2009). A review on laboratory liver function tests. The Pan African Medical Journal, 3, 17.
Heinrich, J., Spiesshofer, J., Bitter, T., Horstkotte, D., & Oldenburg, O. (2015). Implications of revised AASM rules on scoring apneic and hypopneic respiratory events in patients with heart failure with nocturnal Cheyne-Stokes respiration. Sleep Breath, 19(2), 489-494. doi: 10.1007/s11325-014-1014-9
Hernandez, C., Abreu, J., Abreu, P., Colino, R., & Jimenez, A. (2006). Effects of nasal positive airway pressure treatment on oxidative stress in patients with sleep apnea-hypopnea syndrome. Archivos de Bronconeumologia, 42(3), 125-129.
Jouët, P., Sabaté, J.-M., Maillard, D., Msika, S., Mechler, C., Ledoux, S.,Coffin, B. (2007). Relationship between Obstructive Sleep Apnea and Liver Abnormalities in Morbidly Obese Patients: A Prospective Study. Obesity Surgery, 17(4), 478. doi: 10.1007/s11695-007-9085-3
Kallwitz, E. R., Herdegen, J., Madura, J., Jakate, S., & Cotler, S. J. (2007). Liver enzymes and histology in obese patients with obstructive sleep apnea. Journal of Clinical Gastroenterology, 41(10), 918-921. doi: 10.1097/01.mcg.0000225692.62121.55
Kim, J., Lee, S. J., Choi, K.-M., Lee, S. K., Yoon, D. W., Lee, S. G., & Shin, C. (2016). Obstructive Sleep Apnea Is Associated with Elevated High Sensitivity C-Reactive Protein Levels Independent of Obesity: Korean Genome and Epidemiology Study. PLOS ONE, 11(9), e0163017. doi: 10.1371/journal.pone.0163017
Kivanc, T., & Kulaksizoglu, S. (2017). Importance of laboratory parameters in patients with obstructive sleep apnea and their relationship with cardiovascular diseases. Journal of Clinical Laboratory Analysis, doi: 10.1002/jcla.22199
Kohler, M., Stoewhas, A. C., Ayers, L., Senn, O., Bloch, K. E., Russi, E. W., & Stradling, J. R. (2011). Effects of continuous positive airway pressure therapy withdrawal in patients with obstructive sleep apnea: a randomized controlled trial. American Journal of Respiratory and Critical Care Medicine, 184(10), 1192-1199. doi: 10.1164/rccm.201106-0964OC
Koseoglu, H. I., Altunkas, F., Kanbay, A., Doruk, S., Etikan, I., & Demir, O. (2015). Platelet-lymphocyte ratio is an independent predictor for cardiovascular disease in obstructive sleep apnea syndrome. Journal of Thrombosis and Thrombolysis, 39(2), 179-185. doi: 10.1007/s11239-014-1103-4
Kritikou, I., Basta, M., Vgontzas, A. N., Pejovic, S., Liao, D., Tsaoussoglou, M., Chrousos, G. P. (2014). Sleep apnoea, sleepiness, inflammation and insulin resistance in middle-aged males and females. European Respiratory Journal, 43(1), 145-155. doi: 10.1183/09031936.00126712
Luangaram, S., Kukongviriyapan, U., Pakdeechote, P., Kukongviriyapan, V., & Pannangpetch, P. (2007). Protective effects of quercetin against phenylhydrazine-induced vascular dysfunction and oxidative stress in rats. Food and Chemical Toxicology, 45(3), 448-455. doi: 10.1016/j.fct.2006.09.008
McDaid, C., Duree, K. H., Griffin, S. C., Weatherly, H. L., Stradling, J. R., Davies, R. J., Westwood, M. E. (2009). A systematic review of continuous positive airway pressure for obstructive sleep apnoea-hypopnoea syndrome. Sleep Medicine Review, 13(6), 427-436. doi: 10.1016/j.smrv.2009.02.004
NI, A. (2016). Reference Values of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio and Mean Platelet Volume in Healthy Adults in North Central Nigeria. Journal of Blood and Lymph, 6(1). doi: 10.4172/2165-7831.1000143
Ryan, S., Taylor, C. T., & McNicholas, W. T. (2009). Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome? Thorax, 64(7), 631-636. doi: 10.1136/thx.2008.105577
Shamsuzzaman, A. S. M., Winnicki, M., Lanfranchi, P., Wolk, R., Kara, T., Accurso, V., & Somers, V. K. (2002). Elevated C-Reactive Protein in Patients With Obstructive Sleep Apnea. Circulation, 105(21), 2462-2464. doi: 10.1161/01.cir.0000018948.95175.03
Shpirer, I., Copel, L., Broide, E., & Elizur, A. (2010). Continuous positive airway pressure improves sleep apnea associated fatty liver. Lung, 188(4), 301-307. doi: 10.1007/s00408-009-9219-6
Stradling, J. R., Schwarz, E. I., Schlatzer, C., Manuel, A. R., Lee, R., Antoniades, C., & Kohler, M. (2015). Biomarkers of oxidative stress following continuous positive airway pressure withdrawal: data from two randomised trials. European Respiratory Journal, 46(4), 1065-1071. doi: 10.1183/09031936.00023215
Tichanon, P., Wilaiwan, K., Sopida, S., Orapin, P., Watchara, B., & Banjamas, I. (2016). Effect of Continuous Positive Airway Pressure on Airway Inflammation and Oxidative Stress in Patients with Obstructive Sleep Apnea. Canadian Respiratory Journal, 2016, 3107324. doi: 10.1155/2016/3107324
Toyama, Y., Murase, K., Azuma, M., Hamada, S., Tachikawa, R., Kubo, T., Chin, K. (2014). Impacts of long-term CPAP therapy on fatty liver in male OSA patients with abdominal obesity. European Respiratory Journal, 44(Suppl 58).
Wang, L., Li, J., Xie, Y., & Zhang, X. G. (2010). Association between serum homocysteine and oxidative stress in elderly patients with obstructive sleep apnea/hypopnea syndrome. Biomedical Environmental Sciences, 23(1), 42-47. doi: 10.1016/s0895-3988(10)60030-x
Yamauchi, M., Nakano, H., Maekawa, J., Okamoto, Y., Ohnishi, Y., Suzuki, T., & Kimura, H. (2005). Oxidative stress in obstructive sleep apnea. Chest, 127(5), 1674-1679. doi: 10.1378/chest.127.5.1674