阻塞性睡眠呼吸暂停与咽喉反流

doi:10.6040/j.issn.1673-3770.0.2024.056

摘要/Abstract

摘要： 因咽喉反流(laryngopharyngeal reflux, LPR)就诊于耳鼻咽喉头颈外科门诊患者可达10%,而全球人口中有近10亿30~69岁之间的成年人可能患有阻塞性睡眠呼吸暂停(obstructive sleep apnea, OSA),从以上数据可知两种疾病对众多患者的生活质量造成了不良影响,加重他们医疗负担。OSA和LPR拥有诸多共同发病基础,如肥胖、年龄、饮酒等,临床实践发现二者存在高共患率,OSA患者较普通人群中LPR的发生率高达数倍(5.0%~30.0% vs. 45.2%)。通过深入剖析与研究大量学者对两种疾病内在联系的科研文献,对二者之间关系、治疗现状、相关机制有了较为深刻的认识。现针对上述三点加以综述,旨在为研究OSA和LPR的内在联系提供研究方向,并为临床诊治策略提供依据。

关键词: 阻塞性睡眠呼吸暂停, 咽喉反流, 机制, 治疗, 诊断

Abstract: Up to 10% of patients may present to the otolaryngology, head and neck surgery clinic with laryngopharyngeal reflux(LPR), and nearly 1 billion adults around the world aged 30-69 years may suffer from obstructive sleep apnea(OSA), indicating that both diseases have affected the quality of life of many patients and increased their medical burden. OSA and LPR share many common factors such as obesity, age, alcohol consumption, etc. Clinical practice has shown that there is a high co-morbidity between the two, and the prevalence of LPR in OSA patients is several times higher than in the general population(5.0%-30.0% vs. 45.2%). Through in-depth analysis and study of a large body of scientific literature on the relationship between the two conditions, we have gained a deeper understanding of the relationship between the two conditions, the current status of treatment, and the mechanisms involved. We review the above three points with the aim of providing research directions for the study of the intrinsic relationship between OSA and LPR, and the basis for clinical diagnosis and treatment strategies.

Key words: Obstructive sleep apnea, Laryngopharyngeal reflux, Mechanism, Treatment, Diagnosis

中图分类号:

R766

刘莲莲,李进让. 阻塞性睡眠呼吸暂停与咽喉反流[J]. 山东大学耳鼻喉眼学报, 2024, 38(6): 15-22.

LIU Lianlian, LI Jinrang. Obstructive sleep apnea and laryngopharyngeal reflux[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 15-22.

参考文献

[1] Obstructive sleep apnea in adults: epidemiology, clinical presentation, and treatment options[J]. Adv Cardiol, 2011, 46: 1-42. doi:10.1159/000327660
[2] Benjafield AV, Ayas NT, Eastwood PR, et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis[J]. Lancet Respir Med, 2019, 7(8): 687-698. doi:10.1016/S2213-2600(19)30198-5
[3] 苏小凤, 刘霖, 仲琳, 等. 中国阻塞性睡眠呼吸暂停综合征患病率的Meta分析[J]. 中国循证医学杂志, 2021, 21(10): 1187-1194. doi:10.7507/1672-2531.202106103 SU Xiaofeng, LIU Lin, ZHONG Lin, et al. Prevalence of obstructive sleep apnea syndrome in China: a meta-analysis[J]. Chinese Journal of Evidence-Based Medicine, 2021, 21(10): 1187-1194. doi:10.7507/1672-2531.202106103
[4] Senaratna CV, Perret JL, Lodge CJ, et al. Prevalence of obstructive sleep apnea in the general population: a systematic review[J]. Sleep Med Rev, 2017, 34: 70-81. doi:10.1016/j.smrv.2016.07.002
[5] Lechien JR, Akst LM, Hamdan AL, et al. Evaluation and management of laryngopharyngeal reflux disease: state of the art review[J]. Otolaryngol Head Neck Surg, 2019, 160(5): 762-782. doi:10.1177/0194599819827488
[6] Xiao SF, Li JR, Zheng HL, et al. An epidemiological survey of laryngopharyngeal reflux disease at the otorhinolaryngology-head and neck surgery clinics in China[J]. Eur Arch Otorhinolaryngol, 2020, 277(10): 2829-2838. doi:10.1007/s00405-020-06045-0
[7] Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease(GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury[J]. Laryngoscope, 1991, 101(4 Pt 2 Suppl 53): 1-78. doi:10.1002/lary.1991.101.s53.1
[8] Stabenau K, Johnston N. How I approach laryngopharyngoesophageal reflux(LPR)[J]. Curr Gastroenterol Rep, 2021, 23(12): 27. doi:10.1007/s11894-021-00823-4
[9] Magliulo G, Iannella G, Polimeni A, et al. Laryngopharyngeal reflux in obstructive sleep apnoea patients: literature review and meta-analysis[J]. Am J Otolaryngol, 2018, 39(6): 776-780. doi:10.1016/j.amjoto.2018.09.006
[10] Gouveia CJ, Yalamanchili A, Ghadersohi S, et al. Are chronic cough and laryngopharyngeal reflux more common in obstructive sleep apnea patients?[J]. Laryngoscope, 2019, 129(5): 1244-1249. doi:10.1002/lary.27557
[11] Teklu M, Gouveia CJ, Yalamanchili A, et al. Predicting obstructive sleep apnea status with the reflux symptom index in a sleep study population[J]. Laryngoscope, 2020, 130(12): E952-E957. doi:10.1002/lary.28592
[12] Campanholo MAT, Caparroz FA, Vidigal TA, et al. Assessment of laryngopharyngeal reflux and obstructive sleep apnea: a population-based study[J]. Laryngoscope, 2022, 132(9): 1877-1882. doi:10.1002/lary.30061
[13] Tamin S, Siregar D, Hutauruk SM, et al. Association between laryngopharyngeal reflux and obstructive sleep apnea in adults[J]. Peer J, 2022, 10: e13303. doi:10.7717/peerj.13303
[14] Wang Z, Li SH, Zuo CC, et al. Correlation between rapid eye movement sleep duration and laryngopharyngeal reflux in patients with obstructive sleep apnea[J]. Ear Nose Throat J, 2023: 1455613231214653. doi:10.1177/01455613231214653
[15] Ji PP, Shi L, Xing DX, et al. The effect of laryngopharyngeal reflux on arousal in patients with obstructive sleep apnea[J]. Acta Otolaryngol, 2022, 142(5): 438-442. doi:10.1080/00016489.2022.2075033
[16] Tang X, Tang Q, Li S, et al. Changes in laryngopharyngeal reflux after uvulopalatopharyngoplasty for obstructive sleep apnea: An observational study[J]. Laryngoscope Investig Otolaryngol, 2021, 7(1): 266-273. Published 2021 Dec 25. doi:10.1002/lio2.718
[17] Lechien JR, Schindler A, Hamdan AL, et al. The development of new clinical instruments in laryngopharyngeal reflux disease: the international project of young otolaryngologists of the International Federation of Oto-rhino-laryngological Societies[J]. Eur Ann Otorhinolaryngol Head Neck Dis, 2018, 135(5S): S85-S91. doi:10.1016/j.anorl.2018.05.013
[18] Elhennawi DM, Ahmed MR, Abou-Halawa AS. Correlation of obstructive sleep apnoea and laryngopharyngeal reflux: phmetry study[J]. Clin Otolaryngol, 2016, 41(6): 758-761. doi:10.1111/coa.12640
[19] 王晓晔, 韩德民, 叶京英. 阻塞性睡眠呼吸暂停低通气综合征与夜间咽喉反流的相关性研究[J]. 中华耳鼻咽喉头颈外科杂志, 2008, 43(3): 163-168. doi:10.3321/j.issn: 1673-0860.2008.03.002 WANG Xiaoye, HAN Demin, YE Jingying. Research on the relationship between obstructive sleep apnea hypopnea syndrome and nocturnal laryngopharyngeal reflux[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2008, 43(3): 163-168. doi:10.3321/j.issn: 1673-0860.2008.03.002
[20] Wang L, Han HL, Wang G, et al. Relationship between reflux diseases and obstructive sleep apnea together with continuous positive airway pressure treatment efficiency analysis[J]. Sleep Med, 2020, 75: 151-155. doi:10.1016/j.sleep.2020.07.024
[21] Wang CC, Lien HC, De Virgilio A, et al. Airway pH monitoring in patients with suspected obstructive sleep apnoea using the Dx-pH oropharyngeal probe: preliminary report of a prospective cohort study[J]. Clin Otolaryngol, 2014, 39(6): 352-358. doi:10.1111/coa.12297
[22] Liu L, Wang X, Zhang J, et al. Relationship Between Laryngopharyngeal Reflux and Obstructive Sleep Apnea in Adult Males[J]. J Voice,2023,12:S0892-1997(23)00294-1. doi: 10.1016/j.jvoice.2023.09.018
[23] 王磊, 李保卫, 王刚, 等. 阻塞性睡眠呼吸暂停低通气综合征患者夜间碱反流初步研究[J]. 山东大学耳鼻喉眼学报, 2023, 37(6): 75-79, 92. doi:10.6040/j.issn.1673-3770.0.2022.138 WANG Lei, LI Baowei, WANG Gang, et al. A preliminary study on nocturnal alkali reflux in OSAHS patients[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(6): 75-79, 92. doi:10.6040/j.issn.1673-3770.0.2022.138
[24] Xiao YL, Liu FQ, Li J, et al. Gastroesophageal and laryngopharyngeal reflux profiles in patients with obstructive sleep apnea/hypopnea syndrome as determined by combined multichannel intraluminal impedance-pH monitoring[J]. Neurogastroenterol Motil, 2012, 24(6): e258-e265. doi:10.1111/j.1365-2982.2012.01920.x
[25] Xavier SD, Eckley CA, Duprat AC, et al. Temporal association between respiratory events and reflux in patients with obstructive sleep apnea and laryngopharyngeal reflux[J]. J Clin Sleep Med, 2019, 15(10): 1397-1402. doi:10.5664/jcsm.7960
[26] Wang L, Liu X, Liu YL, et al. Correlation of pepsin-measured laryngopharyngeal reflux disease with symptoms and signs[J]. Otolaryngol Head Neck Surg, 2010, 143(6): 765-771. doi:10.1016/j.otohns.2010.08.018
[27] 孙红村, 江文博, 邱小雯, 等. 阻塞性睡眠呼吸暂停低通气综合征患者唾液中胃蛋白酶含量测定的研究[J]. 中国耳鼻咽喉头颈外科, 2020, 27(1): 37-39. doi:10.16066/j.1672-7002.2020.01.010 SUN Hongcun, JIANG Wenbo, QIU Xiaowen, et al. Salivary pepsin measurement in patients with obstructive sleep apnea hypopnea syndrome[J]. Chinese Archives of Otolaryngology-Head and Neck Surgery, 2020, 27(1): 37-39. doi:10.16066/j.1672-7002.2020.01.010
[28] Bobin F, Lechien JR. Association between oropharyngeal ph-monitoring, pepsin saliva concentration and degree of apnea-hypopnea index of obstructive sleep apnea[J]. J Otolaryngol Head Neck Surg, 2023, 52(1): 68. doi:10.1186/s40463-023-00675-0
[29] Iannella G, Vicini C, Polimeni A, et al. Laryngopharyngeal Reflux Diagnosis in Obstructive Sleep Apnea Patients Using the Pepsin Salivary Test[J]. Int J Environ Res Public Health, 2019, 16(11): 2056. Published 2019 Jun 10. doi:10.3390/ijerph16112056
[30] Wang JS, Li JR, Nie Q, et al. Are multiple tests necessary for salivary pepsin detection in the diagnosis of laryngopharyngeal reflux?[J]. Otolaryngol Head Neck Surg, 2022, 166(3): 477-481. doi:10.1177/01945998211026837
[31] Zhang J, Li J, Zhang Y, et al. Multitime point pepsin testing can double the rate of the diagnosis of laryngopharyngeal reflux[J]. Laryngoscope Investig Otolaryngol,2021,6(6):1389-1394. doi:10.1002/lio2.700
[32] Johnston N, Wells CW, Blumin JH, et al. Receptor-mediated uptake of pepsin by laryngeal epithelial cells[J]. Ann Otol Rhinol Laryngol, 2007, 116(12): 934-938. doi:10.1177/000348940711601211
[33] Yue RY, Xing DX, Qin J, et al. The effect of obstructive sleep apnea surgery on laryngopharyngeal reflux with obstructive sleep apnea[J]. Acta Otolaryngol, 2020, 140(8): 697-701. doi:10.1080/00016489.2020.1755448
[34] Song B, Jung YG, Hong SD, et al. Therapeutic effect of multilevel surgery on laryngopharyngeal reflux in obstructive sleep apnea patients: impact on the reflux symptom index and reflux finding score[J]. Clin Exp Otorhinolaryngol, 2022, 15(4): 346-353. doi:10.21053/ceo.2022.00563
[35] 齐智伟, 张淑君, 张宇丽, 等. 手术治疗OSA合并咽喉反流患者的疗效分析[J]. 临床耳鼻咽喉头颈外科杂志, 2019, 33(10): 923-925, 931. doi:10.13201/j.issn.1001-1781.2019.10.006 QI Zhiwei, ZHANG Shujun, ZHANG Yuli, et al. The surgical effect on obstructive sleep apnea with laryngopharyngeal reflux[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2019, 33(10): 923-925, 931. doi:10.13201/j.issn.1001-1781.2019.10.006
[36] Kim SJ, Kim HY, Jeong JI, et al. Changes in the reflux symptom index after multilevel surgery for obstructive sleep apnea[J]. Clin Exp Otorhinolaryngol, 2017, 10(3): 259-264. doi:10.21053/ceo.2017.00052
[37] Eryılmaz A, Eri?瘙塂en L, Demir UL, et al. Management of patients with coexisting obstructive sleep apnea and laryngopharyngeal reflux disease[J]. Eur Arch Otorhinolaryngol, 2012, 269(12): 2575-2580. doi:10.1007/s00405-012-2062-z
[38] Choi JH, Lee E, Hong SD,et al. Potential Therapeutic Effect of Continuous Positive Airway Pressure on Laryngopharyngeal Reflux in Obstructive Sleep Apnea Patients[J]. J Clin Med,2021,10(13):2861. doi:10.3390/jcm10132861
[39] Tawaranurak K, Werathammo M. Effect of positive airway pressure compliance on laryngopharyngeal reflux in obstructive sleep apnea patients[J]. BMC Res Notes,2023,16(1):124. doi:10.1186/s13104-023-06390-3
[40] Tamanna S, Campbell D, Warren R, Ullah MI. Effect of CPAP Therapy on Symptoms of Nocturnal Gastroesophageal Reflux among Patients with Obstructive Sleep Apnea[J]. J Clin Sleep Med,2016,12(9):1257-1261. doi:10.5664/jcsm.6126
[41] Steward DL. Pantoprazole for sleepiness associated with acid reflux and obstructive sleep disordered breathing[J]. Laryngoscope, 2004, 114(9): 1525-1528. doi:10.1097/00005537-200409000-00003
[42] Suurna MV, Welge J, Surdulescu V, et al. Randomized placebo-controlled trial of pantoprazole for daytime sleepiness in GERD and obstructive sleep disordered breathing[J]. Otolaryngol Head Neck Surg, 2008, 139(2): 286-290. doi:10.1016/j.otohns.2008.03.012
[43] 柴小花, 张宁, 许艳芳, 等. 质子泵抑制剂在阻塞性睡眠呼吸暂停低通气综合征伴咽喉反流者中的应用[J]. 中国耳鼻咽喉颅底外科杂志, 2012, 18(3): 179-182 CHAI Xiaohua, ZHANG Ning, XU Yanfang, et al. Application of proton pump inhibitor to patients with obstructive sleep apnea hypopnea syndrome accompanied by laryngopharyngeal reflux[J]. Chinese Journal of Otorhinolaryngology-Skull Base Surgery, 2012, 18(3): 179-182
[44] 陈姗, 李兰. 并发咽喉反流的睡眠呼吸暂停低通气综合征儿童临床治疗初步观察[J]. 中华耳鼻咽喉头颈外科杂志, 2014, 49(5): 379-383. doi:10.3760/cma.j.issn.1673-0860.2014.05.006 CHEN Shan, LI Lan. Observation the clinical curative effect of children's laryngopharyngeal reflux and sleep apnea hypopnea syndrome[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2014, 49(5): 379-383. doi:10.3760/cma.j.issn.1673-0860.2014.05.006
[45] 王军, 高刚, 秦阳, 等. 奥美拉唑联合莫沙必利预先给药对咽喉反流合并OSAHS患者行悬雍垂腭咽成形术的影响[J]. 海军医学杂志, 2022, 43(10): 1136-1140. doi:10.3969/j.issn.1009-0754.2022.10.028 WANG Jun, GAO Gang, QIN Yang, et al. Effects of pre? administration of omeprazole combined with mosapride on laryngopharyngeal reflux and uvulopalatopharyngoplasty in the patients with obstructive sleep apnea hypopnea syndrome[J]. Journal of Navy Medicine, 2022, 43(10): 1136-1140. doi:10.3969/j.issn.1009-0754.2022.10.028
[46] 杨利波. 老年阻塞性睡眠呼吸暂停低通气综合征并发咽喉反流疾病的抗反流疗效及其影响因素探讨[J]. 临床耳鼻咽喉头颈外科杂志, 2016, 30(8): 645-648. doi:10.13201/j.issn.1001-1781.2016.08.016 YANG Libo. The curative effect of anti-reflux treatment in the elderly patients with laryngopharyngeal reflux and obstructive sleep apnea hypopnea syndrome and its influencing factors[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2016, 30(8): 645-648. doi:10.13201/j.issn.1001-1781.2016.08.016
[47] Eskiizmir G, Kezirian E. Is there a vicious cycle between obstructive sleep apnea and laryngopharyngeal reflux disease?[J]. Med Hypotheses, 2009, 73(5): 706-708. doi:10.1016/j.mehy.2009.04.042
[48] 邓月琴, 王路, 陈怀宏, 等. 胃蛋白酶在舌扁桃体组织中的表达及临床意义[J]. 中华耳鼻咽喉头颈外科杂志, 2017, 52(7): 525-530. doi:10.3760/cma.j.issn.1673-0860.2017.07.009 DENG Yueqin, WANG Lu, CHEN Huaihong, et al. Expression and significance of pepsin in lingual tonsil hypertrophy[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2017, 52(7): 525-530. doi:10.3760/cma.j.issn.1673-0860.2017.07.009
[49] Suzuki M, Saigusa H, Kurogi R, et al. Arousals in obstructive sleep apnea patients with laryngopharyngeal and gastroesophageal reflux[J]. Sleep Med, 2010, 11(4): 356-360. doi:10.1016/j.sleep.2009.09.008
[50] Stein MR. Possible mechanisms of influence of esophageal acid on airway hyperresponsiveness[J]. Am J Med, 2003, 115(3): 55-59. doi:10.1016/s0002-9343(03)00194-3
[51] Boyle JT, Tuchman DN, Altschuler SM, et al. Mechanisms for the association of gastroesophageal reflux and bronchospasm[J]. Am Rev Respir Dis, 1985, 131(5): S16-S20. doi:10.1164/arrd.1985.131.S5.S16
[52] Kuribayashi S, Massey BT, Hafeezullah M, et al. Upper esophageal sphincter and gastroesophageal junction pressure changes act to prevent gastroesophageal and esophagopharyngeal reflux during apneic episodes in patients with obstructive sleep apnea[J]. Chest, 2010, 137(4): 769-776. doi:10.1378/chest.09-0913
[53] Qu Y, Ye JY, Han DM, et al. Esophageal functional changes in obstructive sleep apnea/hypopnea syndrome and their impact on laryngopharyngeal reflux disease[J]. Chin Med J, 2015, 128(16): 2162-2167. doi:10.4103/0366-6999.162506
[54] Lang IM, Medda BK, Shaker R. Mechanisms of reflexes induced by esophageal distension[J]. Am J Physiol Gastrointest Liver Physiol, 2001, 281(5): 1246-1263. doi:10.1152/ajpgi.2001.281.5.G1246
[55] Gilani S, Quan SF, Pynnonen MA, et al. Obstructive sleep apnea and gastroesophageal reflux: a multivariate population-level analysis[J]. Otolaryngol Head Neck Surg, 2016, 154(2): 390-395. doi:10.1177/0194599815621557
[56] Lim KG, Morgenthaler TI, Katzka DA. Sleep and nocturnal gastroesophageal reflux: an update[J]. Chest, 2018, 154(4): 963-971. doi:10.1016/j.chest.2018.05.030
[57] Souza RF, Bayeh L, Spechler SJ, et al. A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2α: a potential role for targeting HIF-2α to prevent and treat reflux esophagitis[J]. Curr Opin Pharmacol, 2017, 37: 93-99. doi:10.1016/j.coph.2017.10.004
[58] Huo XF, Agoston AT, Dunbar KB, et al. Hypoxia-inducible factor-2α plays a role in mediating oesophagitis in GORD[J]. Gut, 2017, 66(9): 1542-1554. doi:10.1136/gutjnl-2016-312595
[59] Oh SM, Choi SH, Kim HJ, et al. The association between obstructive sleep apnea during REM sleep and autonomic dysfunction as measured by heart rate variability[J]. Sleep Breath, 2019, 23(3): 865-871. doi:10.1007/s11325-018-01779-y
[60] Wang AM, Wang G, Huang N, et al. Association between laryngopharyngeal reflux disease and autonomic nerve dysfunction[J]. Eur Arch Otorhinolaryngol, 2019, 276(8): 2283-2287. doi:10.1007/s00405-019-05482-w

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