1932

Abstract

Obstructive sleep apnea (OSA) is a worldwide disease whose prevalence is increasing as obesity rates increase. The link between obesity and OSA is likely to be the deposition of fat in the tongue, compromising upper airway size. The role of obesity varies in different ethnic groups, with Chinese being particularly sensitive to increases in weight. OSA lends itself to a personalized approach to diagnosis and therapy. For example, different clinical OSA subtypes likely benefit from therapy in different ways. Hypoglossal nerve stimulation is a useful second-line therapy in patients who cannot tolerate continous positive airway pressure (CPAP) machines or intraoral devices. Technological advances allow patients to participate in their own care, and doing so improves CPAP compliance. We are entering a future where we can focus efforts to predict and prevent OSA on an individual level.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-042915-102623
2017-01-14
2024-12-08
Loading full text...

Full text loading...

/deliver/fulltext/med/68/1/annurev-med-042915-102623.html?itemId=/content/journals/10.1146/annurev-med-042915-102623&mimeType=html&fmt=ahah

Literature Cited

  1. Peppard PE, Young T, Barnet JH. 1.  et al. 2013. Increased prevalence of sleep-disordered breathing in adults. Am. J. Epidemiol. 177:1006–14US OSA prevalence has increased in both genders and all age groups following increased obesity. [Google Scholar]
  2. Jenkinson C, Davies RJ, Mullins R. 2.  et al. 1999. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial. Lancet 353:2100–5 [Google Scholar]
  3. Weaver TE, Laizner AM, Evans LK. 3.  et al. 1997. An instrument to measure functional status outcomes for disorders of excessive sleepiness. Sleep 20:835–43 [Google Scholar]
  4. Sassani A, Findley LJ, Kryger M. 4.  et al. 2004. Reducing motor-vehicle collisions, costs, and fatalities by treating obstructive sleep apnea syndrome. Sleep 27:453–58 [Google Scholar]
  5. Lavie L. 5.  2009. Oxidative stress—a unifying paradigm in obstructive sleep apnea and comorbidities. Prog. Cardiovasc. Dis. 51:303–12 [Google Scholar]
  6. Reinke C, Bevans-Fonti S, Drager LF. 6.  et al. 2011. Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes. J. Appl. Physiol. 1985 111:881–90 [Google Scholar]
  7. Duran-Cantolla J, Aizpuru F, Martinez-Null C. 7.  et al. 2009. Obstructive sleep apnea/hypopnea and systemic hypertension. Sleep Med. Rev 13:323–31 [Google Scholar]
  8. Pack AI, Gislason T. 8.  2009. Obstructive sleep apnea and cardiovascular disease: a perspective and future directions. Prog. Cardiovasc. Dis. 51:434–51 [Google Scholar]
  9. Marin JM, Carrizo SJ, Vicente E. 9.  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 365:1046–53 [Google Scholar]
  10. Aronson D, Nakhleh M, Zeidan-Shwiri T. 10.  et al. 2014. Clinical implications of sleep disordered breathing in acute myocardial infarction. PLOS ONE 9:e88878 [Google Scholar]
  11. Li M, Hou WS, Zhang XW. 11.  et al. 2014. Obstructive sleep apnea and risk of stroke: a meta-analysis of prospective studies. Int. J. Cardiol. 172:466–69 [Google Scholar]
  12. Yaggi HK, Concato J, Kernan WN. 12.  et al. 2005. Obstructive sleep apnea as a risk factor for stroke and death. N. Engl. J. Med. 353:2034–41 [Google Scholar]
  13. Mehra R, Benjamin EJ, Shahar E. 13.  et al. 2006. Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study. Am. J. Respir. Crit. Care Med. 173:910–16 [Google Scholar]
  14. Harsch IA, Schahin SP, Radespiel-Tröger M. 14.  et al. 2004. Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am. J. Respir. Crit. Care Med. 169:156–62 [Google Scholar]
  15. Schahin SP, Nechanitzky T, Dittel C. 15.  et al. 2008. Long-term improvement of insulin sensitivity during CPAP therapy in the obstructive sleep apnoea syndrome. Med. Sci. Monit 14:CR117–21 [Google Scholar]
  16. Punjabi NM, Sorkin JD, Katzel LI. 16.  et al. 2002. Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am. J. Respir. Crit. Care Med. 165:677–82 [Google Scholar]
  17. Ip MS, Lam B, Ng MM. 17.  et al. 2002. Obstructive sleep apnea is independently associated with insulin resistance. Am. J. Respir. Crit. Care Med. 165:670–76 [Google Scholar]
  18. Campos-Rodriguez F, Martinez-Garcia MA, Martinez M. 18.  et al. 2013. Association between obstructive sleep apnea and cancer incidence in a large multicenter Spanish cohort. Am. J. Respir. Crit. Care Med. 187:99–105Multicenter cohort study from Spain indicates that OSA patients have an increased incidence of cancer. [Google Scholar]
  19. Nieto FJ, Peppard PE, Young T. 19.  et al. 2012. Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study. Am. J. Respir. Crit. Care Med. 186:190–94Untreated OSA affects mortality of all cancers in a negative way. [Google Scholar]
  20. Yaffe K, Laffan AM, Harrison SL. 20.  et al. 2011. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA 306:613–19There is increased mild cognitive impairment or dementia with moderate OSA in older women. [Google Scholar]
  21. Colten HR, Altevogt BM. 21.  2006. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem Washington, DC: Natl. Acad. Press [Google Scholar]
  22. Yamagishi K, Ohira T, Nakano H. 22.  et al. 2010. Cross-cultural comparison of the sleep-disordered breathing prevalence among Americans and Japanese. Eur. Respir. J. 36:379–84 [Google Scholar]
  23. Lee SD, Kang SH, Ju G. 23.  et al. 2014. The prevalence of and risk factors for sleep-disordered breathing in an elderly Korean population. Respiration 87:372–78 [Google Scholar]
  24. Tan A, Cheung YY, Yin J. 24.  et al. 2016. Prevalence of sleep-disordered breathing in a multiethnic Asian population in Singapore: a community-based study. Respirology 5:943–50 [Google Scholar]
  25. Lee RW, Vasudavan S, Hui DS. 25.  et al. 2010. Differences in craniofacial structures and obesity in Caucasian and Chinese patients with obstructive sleep apnea. Sleep 33:1075–80 [Google Scholar]
  26. Chen X, Wang R, Zee P. 26.  et al. 2015. Racial/ethnic differences in sleep disturbances: the Multi-Ethnic Study of Atherosclerosis (MESA). Sleep 38:877–88 [Google Scholar]
  27. Bouscoulet LT, Vazquez-Garcia JC, Muino A. 27.  et al. 2008. Prevalence of sleep related symptoms in four Latin American cities. J. Clin. Sleep Med. 4:579–85 [Google Scholar]
  28. Tufik S, Santos-Silva R, Taddei JA. 28.  et al. 2010. Obstructive sleep apnea syndrome in the Sao Paulo Epidemiologic Sleep Study. Sleep Med 11:441–46 [Google Scholar]
  29. Shafazand S, Wallace DM, Vargas SS. 29.  et al. 2012. Sleep disordered breathing, insomnia symptoms, and sleep quality in a clinical cohort of US Hispanics in South Florida. J. Clin. Sleep Med. 8:507–14 [Google Scholar]
  30. Baldwin CM, Ervin AM, Mays MZ. 30.  et al. 2010. Sleep disturbances, quality of life, and ethnicity: the Sleep Heart Health Study. J. Clin. Sleep Med. 6:176–83 [Google Scholar]
  31. Hrubos-Strøm H, Randby A, Namtvedt SK. 31.  et al. 2011. A Norwegian population-based study on the risk and prevalence of obstructive sleep apnea. The Akershus Sleep Apnea Project (ASAP). J. Sleep Res. 20:162–70 [Google Scholar]
  32. Sforza E, Chouchou F, Collet P. 32.  et al. 2011. Sex differences in obstructive sleep apnoea in an elderly French population. Eur. Respir. J. 37:1137–43 [Google Scholar]
  33. Heinzer R, Vat S, Marques-Vidal P. 33.  et al. 2015. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir. Med. 3:310–18 [Google Scholar]
  34. Li M, Hou WS, Zhang XW. 34.  et al. 2014. Obstructive sleep apnea and risk of stroke: a meta-analysis of prospective studies. Int. J. Cardiol. 172:466–69 [Google Scholar]
  35. Morgenstern M, Wang J, Beatty N. 35.  et al. 2014. Obstructive sleep apnea: an unexpected cause of insulin resistance and diabetes. Endocrinol. Metab. Clin. North Am. 43:187–204 [Google Scholar]
  36. Arisoy A, Sertogullarindan B, Ekin S. 36.  et al. 2016. Sleep apnea and fatty liver are coupled via energy metabolism. Med. Sci. Monit 22:908–13 [Google Scholar]
  37. Spira AP, Blackwell T, Stone KL. 37.  et al. 2008. Sleep-disordered breathing and cognition in older women. J. Am. Geriatr. Soc. 56:45–50 [Google Scholar]
  38. Osorio RS, Gumb T, Pirraglia E. 38.  et al. 2015. Sleep-disordered breathing advances cognitive decline in the elderly. Neurology 84:1964–71 [Google Scholar]
  39. Kim SJ, Lee JH, Lee DY. 39.  et al. 2011. Neurocognitive dysfunction associated with sleep quality and sleep apnea in patients with mild cognitive impairment. Am. J. Geriatr. Psychiatry 19:374–81 [Google Scholar]
  40. Guarnieri B, Adorni F, Musicco M. 40.  et al. 2012. Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients. Dement. Geriatr. Cogn. Disord. 33:50–58 [Google Scholar]
  41. Kang Y, Greaves B, Perry RR. 41.  1996. Effect of acute and chronic intermittent hypoxia on DNA topoisomerase II alpha expression and mitomycin C-induced DNA damage and cytotoxicity in human colon cancer cells. Biochem. Pharmacol. 52:669–76 [Google Scholar]
  42. Marshall NS, Wong KK, Cullen SR. 42.  et al. 2014. Sleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer incidence and mortality in the Busselton Health Study cohort. J. Clin. Sleep Med. 10:355–62 [Google Scholar]
  43. Lim DC, Brady DC, Soans R. 43.  et al. 2016. Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature. J. Appl. Physiol. 121:78–88 [Google Scholar]
  44. Chang WP, Liu ME, Chang WC. 44.  et al. 2014. Sleep apnea and the subsequent risk of breast cancer in women: a nationwide population-based cohort study. Sleep Med 15:1016–20 [Google Scholar]
  45. Chen JC, Hwang JH. 45.  2014. Sleep apnea increased incidence of primary central nervous system cancers: a nationwide cohort study. Sleep Med 15:749–54 [Google Scholar]
  46. Fang HF, Miao NF, Chen CD. 46.  et al. 2015. Risk of cancer in patients with insomnia, parasomnia, and obstructive sleep apnea: a nationwide nested case-control study. J. Cancer 6:1140–47 [Google Scholar]
  47. Martinez-Garcia MA, Campos-Rodriguez F, Duran-Cantolla J. 47.  et al. 2014. Obstructive sleep apnea is associated with cancer mortality in younger patients. Sleep Med 15:742–48 [Google Scholar]
  48. Kendzerska T, Leung RS, Hawker G. 48.  et al. 2014. Obstructive sleep apnea and the prevalence and incidence of cancer. Can. Med. Assoc. J. 186:985–92 [Google Scholar]
  49. Shantha GPS, Kumar AA, Cheskin LJ. 49.  et al. 2015. Association between sleep-disordered breathing, obstructive sleep apnea, and cancer incidence: a systematic review and meta-analysis. Sleep Med 16:1289–94 [Google Scholar]
  50. Zhang XB, Peng LH, Lyu Z. 50.  et al. 2015. Obstructive sleep apnoea and the incidence and mortality of cancer: a meta-analysis. Eur. J. Cancer Care In press. doi: 10.1111/ecc.12427 [Google Scholar]
  51. Almendros I, Montserrat JM, Ramirez J. 51.  et al. 2012. Intermittent hypoxia enhances cancer progression in a mouse model of sleep apnoea. Eur. Respir. J. 39:215–17 [Google Scholar]
  52. Gaustad JV, Simonsen TG, Roa AMA. 52.  et al. 2013. Tumors exposed to acute cyclic hypoxia show increased vessel density and delayed blood supply. Microvasc. Res. 85:10–15 [Google Scholar]
  53. Almendros I, Montserrat JM, Torres M. 53.  et al. 2012. Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep apnea. Sleep Med 13:1254–60 [Google Scholar]
  54. Almendros I, Montserrat JM, Torres M. 54.  et al. 2013. Intermittent hypoxia increases melanoma metastasis to the lung in a mouse model of sleep apnea. Respir. Physiol. Neurobiol. 186:303–7 [Google Scholar]
  55. Almendros I, Wang Y, Becker L. 55.  et al. 2014. Intermittent hypoxia-induced changes in tumor-associated macrophages and tumor malignancy in a mouse model of sleep apnea. Am. J. Respir. Crit. Care Med. 189:593–601 [Google Scholar]
  56. Cortese R, Almendros I, Wang Y. 56.  et al. 2015. Tumor circulating DNA profiling in xenografted mice exposed to intermittent hypoxia. Oncotarget 6:556–69 [Google Scholar]
  57. Perini S, Martinez D, Montanari CC. 57.  et al. 2016. Enhanced expression of melanoma progression markers in mouse model of sleep apnea. Rev. Port Pneumol. 22:209–13 [Google Scholar]
  58. Hakim F, Wang Y, Zhang SXL. 58.  et al. 2014. Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. Cancer Res 74:1329–37 [Google Scholar]
  59. Hood L. 59.  2013. Systems biology and P4 medicine: past, present, and future. Rambam Maimonides Med. J 4:e0012 [Google Scholar]
  60. Flores M, Glusman G, Brogaard K. 60.  et al. 2013. P4 medicine: how systems medicine will transform the healthcare sector and society. Pers. Med. 10:565–76 [Google Scholar]
  61. Gharib SA, Khalyfa A, Abdelkarim A. 61.  et al. 2012. Integrative miRNA-mRNA profiling of adipose tissue unravels transcriptional circuits induced by sleep fragmentation. PLOS ONE 7:e37669 [Google Scholar]
  62. Gozal D, Jortani S, Snow AB. 62.  et al. 2009. Two-dimensional differential in-gel electrophoresis proteomic approaches reveal urine candidate biomarkers in pediatric obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 180:1253–61 [Google Scholar]
  63. Khalyfa A, Kheirandish-Gozal L, Bhattacharjee R. 63.  et al. 2016. Circulating microRNAs as potential biomarkers of endothelial dysfunction in obese children. Chest 149:786–800 [Google Scholar]
  64. Mullington JM, Abbott SM, Carroll JE. 64.  et al. 2016. Developing biomarker arrays predicting sleep and circadian-coupled risks to health. Sleep 39:727–36 [Google Scholar]
  65. Isetta V, Leon C, Torres M. 65.  et al. 2014. Telemedicine-based approach for obstructive sleep apnea management: building evidence. Interact. J. Med. Res 3:e6 [Google Scholar]
  66. Isetta V, Negrin MA, Monasterio C. 66.  et al. 2015. A Bayesian cost-effectiveness analysis of a telemedicine-based strategy for the management of sleep apnoea: a multicentre randomised controlled trial. Thorax 70:1054–61 [Google Scholar]
  67. Kuna ST, Shuttleworth D, Chi LQ. 67.  et al. 2015. Web-based access to positive airway pressure usage with or without an initial financial incentive improves treatment use in patients with obstructive sleep apnea. Sleep 38:1229–36Using a website for patients to check CPAP usage improves CPAP compliance. [Google Scholar]
  68. Parthasarathy S, Wendel C, Haynes PL. 68.  et al. 2013. A pilot study of CPAP adherence promotion by peer buddies with sleep apnea. J. Clin. Sleep Med. 9:543–50 [Google Scholar]
  69. Chi L, Comyn FL, Mitra N. 69.  et al. 2011. Identification of craniofacial risk factors for obstructive sleep apnoea using three-dimensional MRI. Eur. Respir. J. 38:348–58 [Google Scholar]
  70. Schwab RJ, Pasirstein M, Pierson R. 70.  et al. 2003. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am. J. Respir. Crit. Care Med. 168:522–30 [Google Scholar]
  71. Chi L, Comyn FL, Keenan BT. 71.  et al. 2014. Heritability of craniofacial structures in normal subjects and patients with sleep apnea. Sleep 37:1689–98 [Google Scholar]
  72. Schwab RJ, Pasirstein M, Kaplan L. 72.  et al. 2006. Family aggregation of upper airway soft tissue structures in normal subjects and patients with sleep apnea. Am. J. Respir. Crit. Care Med. 173:453–63 [Google Scholar]
  73. Guilleminault C, Riley R, Powell N. 73.  1984. Obstructive sleep apnea and abnormal cephalometric measurements. Implications for treatment. Chest 86:793–94 [Google Scholar]
  74. Lowe AA, Santamaria JD, Fleetham JA. 74.  et al. 1986. Facial morphology and obstructive sleep apnea. Am. J. Orthod. Dentofacial Orthop. 90:484–91 [Google Scholar]
  75. Lyberg T, Krogstad O, Djupesland G. 75.  1989. Cephalometric analysis in patients with obstructive sleep apnoea syndrome. I. Skeletal morphology. J. Laryngol. Otol. 103:287–92 [Google Scholar]
  76. Miles PG, Vig PS, Weyant RJ. 76.  et al. 1996. Craniofacial structure and obstructive sleep apnea syndrome—a qualitative analysis and meta-analysis of the literature. Am. J. Orthod. Dentofacial Orthop. 109:163–72 [Google Scholar]
  77. Young T, Palta M, Dempsey J. 77.  et al. 1993. The occurrence of sleep-disordered breathing among middle-aged adults. N. Engl. J. Med. 328:1230–35 [Google Scholar]
  78. Nashi N, Kang S, Barkdull GC. 78.  et al. 2007. Lingual fat at autopsy. Laryngoscope 117:1467–73 [Google Scholar]
  79. Kim AM, Keenan BT, Jackson N. 79.  et al. 2014. Tongue fat and its relationship to obstructive sleep apnea. Sleep 37:1639–48Dixon imaging shows that obese subjects with OSA have more tongue fat than weight-matched controls. [Google Scholar]
  80. Brennick MJ, Delikatny J, Pack AI. 80.  et al. 2014. Tongue fat infiltration in obese versus lean Zucker rats. Sleep 37:1095–1102 [Google Scholar]
  81. Brennick MJ, Pack AI, Ko K. 81.  et al. 2009. Altered upper airway and soft tissue structures in the New Zealand Obese mouse. Am. J. Respir. Crit. Care Med. 179:158–69 [Google Scholar]
  82. Chirinos JA, Gurubhagavatula I, Teff K. 82.  et al. 2014. Continuous positive airway pressure, weight loss, or both for obstructive sleep apnea. N. Engl. J. Med. 370:2265–75Treating obesity and OSA has much larger effect on blood pressure than either treatment alone. [Google Scholar]
  83. Wellman A, Edwards BA, Sands SA. 83.  et al. 2013. A simplified method for determining phenotypic traits in patients with obstructive sleep apnea. J. Appl. Physiol. 1985 114:911–22 [Google Scholar]
  84. Eckert DJ, White DP, Jordan AS. 84.  et al. 2013. Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am. J. Respir. Crit. Care Med. 188:996–1004Identified an OSA subgroup with minimal airway collapsibility but high loop gain (unstable ventilatory control) [Google Scholar]
  85. Sands SA, Eckert DJ, Jordan AS. 85.  et al. 2014. Enhanced upper-airway muscle responsiveness is a distinct feature of overweight/obese individuals without sleep apnea. Am. J. Respir. Crit. Care Med. 190:930–37 [Google Scholar]
  86. Ye LC, Plan GW, Ratcliffe SJ. 86.  et al. 2014. The different clinical faces of obstructive sleep apnoea: a cluster analysis. Eur. Respir. J. 44:1600–7Three subgroups identified within OSA: disturbed sleep (insomnia), minimally symptomatic, and excessive sleepiness. [Google Scholar]
  87. Vavougios GD, Natsios G, Pastaka C. 87.  et al. 2016. Phenotypes of comorbidity in OSAS patients: combining categorical principal component analysis with cluster analysis. J. Sleep Res. 25:31–38 [Google Scholar]
  88. Gagnadoux F, Le Vaillant M, Paris A. 88.  et al. 2016. Relationship between OSA clinical phenotypes and CPAP treatment outcomes. Chest 149:288–90 [Google Scholar]
  89. Strollo PJ Jr., Soose RJ, Maurer JT. 89.  et al. 2014. Upper-airway stimulation for obstructive sleep apnea. N. Engl. J. Med. 370:139–49Hypoglossal nerve stimulation is effective in a subset of OSA patients who cannot tolerate CPAP. [Google Scholar]
  90. Strollo PJ, Gillespie MB, Soose RJ. 90.  et al. 2015. Upper airway stimulation for obstructive sleep apnea: durability of the treatment effect at 18 months. Sleep 38:1593–98 [Google Scholar]
  91. Woodson BT, Soose RJ, Gillespie MB. 91.  et al. 2016. Three-year outcomes of cranial nerve stimulation for obstructive sleep apnea: the STAR trial. Otolaryngol. Head Neck Surg. 154:181–88 [Google Scholar]
  92. Pietzsch JB, Liu S, Garner AM. 92.  et al. 2015. Long-term cost-effectiveness of upper airway stimulation for the treatment of obstructive sleep apnea: a model-based projection based on the STAR trial. Sleep 38:735–44 [Google Scholar]
/content/journals/10.1146/annurev-med-042915-102623
Loading
/content/journals/10.1146/annurev-med-042915-102623
Loading

Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error