Annals of Hematology

, Volume 97, Issue 5, pp 755–762 | Cite as

Sleep-disordered breathing in patients with sickle cell disease

  • Vikram M. Raghunathan
  • Peter L. Whitesell
  • Seah H. Lim
Review Article


Sickle cell disease is one of the most common hereditary hemoglobinopathies worldwide, and its vaso-occlusive and hemolytic crises cause considerable patient morbidity. A growing body of evidence has shown that sleep-disordered breathing, and in particular, obstructive sleep apnea, occurs at high frequency in the sickle cell population, and that there is significant overlap in the underlying pathophysiology of these two conditions. Through a variety of mechanisms including nocturnal hypoxemia and increased oxidative stress, production of pro-inflammatory cytokines, and endothelial dysfunction, sickle cell anemia and sleep-disordered breathing potentiate each other’s clinical effects and end-organ complications. Here, we will review the shared pathophysiologic mechanisms of these conditions and discuss their clinical sequelae. We will also examine the results of studies that have been carried out with clinical intervention of nocturnal hypoxemia in patients with sickle cell disease in the attempts to overcome the complications of the disease. Finally, we will propose the areas of investigation that merit further investigations in future in patients with sickle cell disease and sleep-disordered breathing.


Sickle cell disease Sleep-disordered breathing Clinical characteristics Common pathophysiologic pathways 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Wetter DW, Young TB, Bidwell TR, Badr MS, Palta M (1994) Smoking as a risk factor for sleep-disordered breathing. Arch Intern Med 154(19):2219–2224. CrossRefPubMedGoogle Scholar
  2. 2.
    Redline S, Tishler PV, Schluchter M, Aylor J, Clark K, Graham G (1999) Risk factors for sleep-disordered breathing in children: association with race, obesity, and respiratory problems. Am J Respir Crit Care Med 159(5):1527–1532. CrossRefPubMedGoogle Scholar
  3. 3.
    Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM (2013) Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 177(9):1006–1014. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Redline S, Kump K, Tishler PV, Browner I, Ferrette V (1994) Gender differences in sleep-disordered breathing in a community-based sample. Am J Respir Crit Care Med 149(3):722–726. CrossRefPubMedGoogle Scholar
  5. 5.
    Seda G, Tsai S, Lee-Chiong T (2014) Medication effects on sleep and breathing. Clin Chest Med 35(3):557–569. CrossRefPubMedGoogle Scholar
  6. 6.
    Peppard PE, Austin D, Brown RL (2007) Association of alcohol consumption and sleep disordered breathing in men and women. J Clin Sleep Med 3(3):265–270PubMedPubMedCentralGoogle Scholar
  7. 7.
    Poirrier AL, Pire S, Raskin S, Limme M, Poirrier R (2012) Contribution of postero-anterior cephalometry in obstructive sleep apnea. Laryngoscope 122(10):2350–2354. CrossRefPubMedGoogle Scholar
  8. 8.
    Ho AW, Moul DE, Krishna J (2016) Neck circumference-height ratio as a predictor of sleep related breathing disorder in children and adults. J Clin Sleep Med 12(03):311–317. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Petrov ME, Lichstein KL (2016) Differences in sleep between black and white adults: an update and future directions. Sleep Med 18:74–81. CrossRefPubMedGoogle Scholar
  10. 10.
    Gileles-Hillel A, Kheirandish-Gozal L, Gozal D (2015) Hemoglobinopathies and sleep—the road less traveled. Sleep Med Rev 24:57–70. CrossRefPubMedGoogle Scholar
  11. 11.
    Downes M, de Haan M, Kirkham FJ, and Telfer PT (2017) Parent reported sleep problems in preschool children with sickle cell anemia and controls in East London. Pediatr Blood Cancer 64(6).
  12. 12.
    Rogers VE, Lewin DS, Winnie GB, Geiger-Brown J (2010) Polysomnographic characteristics of a referred sample of children with sickle cell disease. J Clin Sleep Med 6(4):374–381PubMedPubMedCentralGoogle Scholar
  13. 13.
    Narang I, Kadmon G, Lai D, Dhanju S, Kirby-Allen M, Odame I, Amin R, Lu Z, Al-Saleh S (2015) Higher nocturnal and awake oxygen saturations in children with sickle cell disease receiving hydroxyurea therapy. Ann Am Thorac Soc 12(7):1044–1049. CrossRefPubMedGoogle Scholar
  14. 14.
    Samuels MP, Stebbens VA, Davies SC, Picton-Jones E, Southall DP (1992) Sleep related upper airway obstruction and hypoxemia in sickle cell disease. Arch Dis Child 67(7):925–929. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Lehman GC, Bell TR, Fenella FJ et al (2012) Enuresis associated with sleep disordered breathing in children with sickle cell anemia. J Urol 188(4):1572–1577. CrossRefGoogle Scholar
  16. 16.
    Rosen CL, Debaun MR, Strunk RC, Redline S, Seicean S, Craven DI, Gavlak JCD, Wilkey O, Inusa B, Roberts I, Goodpaster RL, Malow B, Rodeghier M, Kirkham FJ (2014) Obstructive sleep apnea and sickle cell anemia. Pediatrics 134(2):273–281. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Mascarenhas MI, Loureiro HC, Ferreira T, Dias A (2015) Sleep pathology characterization in sickle cell disease: case-control study. Pediatr Pulmonol 50(4):396–401. CrossRefPubMedGoogle Scholar
  18. 18.
    Whitesell P, Owoyemi O, Oneal P et al (2016) Sleep-disordered breathing and nocturnal hypoxemia in young adults with sickle cell disease. Sleep Med 22:47–49. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Sharma S, Efird JT, Knupp C, Kadali R, Liles D, Shiue K, Boettger P, Quan SF (2015) Sleep disorders in adult sickle cell patients. J Clin Sleep Med 11(3):219–223. PubMedPubMedCentralGoogle Scholar
  20. 20.
    Al-Saqqaf R, Merdad R, Wali SO et al (2017) The prevalence of obstructive sleep apnea in adult patients with sickle cell disease. J Appl Hematol 8:16–22CrossRefGoogle Scholar
  21. 21.
    Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524–551. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Winterbourn CC (1985) Free-radical production and oxidative reactions of hemoglobin. Environ Health Perspect 64:321–330. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gutsaeva DR, Montero-Huerta P, Parkerson JB, Yerigenahally SD, Ikuta T, Head CA (2014) Molecular mechanisms underlying synergistic adhesion of sickle red blood cells by hypoxia and low nitric oxide bioavailability. Blood 123(12):1917–1926. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Morris CR, Kuypers FA, Larkin S, Vichinsky EP, Styles LA (2000) Patterns of arginine and nitric oxide in patients with sickle cell disease with vaso-occlusive crisis and acute chest syndrome. J Pediatr Hematol Oncol 22(6):515–520. CrossRefPubMedGoogle Scholar
  25. 25.
    Kaditis A, Alexopoulos E, Ntamagka G, Chaidas K, Karathanasi A, Gougoura S, Papathanasiou AA, Liakos P, Zintzaras E, Gourgoulianis K (2010) Serum nitrite and nitrate levels in children with obstructive sleep-disordered breathing. Sleep Med 11(3):258–262. CrossRefPubMedGoogle Scholar
  26. 26.
    Kheirandish-Gozal L, Khalyfa A, Gozal D, Bhattacharjee R, Wang Y (2013) Endothelial dysfunction in children with obstructive sleep apnea is associated with epigenetic changes in the eNOS gene. Chest 143(4):971–977. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Kheirandish-Gozal L, Wang Y, Duggan RC, Harshan Vardhan S, Tan HL, Molero Ramirez H, Khalyfa A, Bhattacharjee R, Bandla HPR, Gozal D (2014) Nitric oxide production by monocytes in children with OSA and endothelial dysfunction. Clin Sci 127(5):323–330. CrossRefPubMedGoogle Scholar
  28. 28.
    Conran N, Franco-Penteado CF, Costa FF (2009) Newer aspects of the pathophysiology of sickle cell disease vaso-occlusion. Hemoglobin 33(1):1–16. CrossRefPubMedGoogle Scholar
  29. 29.
    Krishnan S, Setty Y, Betal SG, Vijender V, Rao K, Dampier C, Stuart M (2010) Increased levels of the inflammatory biomarker C-reactive protein at baseline are associated with childhood sickle cell vasocclusive crises. Br J Haematol 148(5):797–804. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Lard LR, Mul FP, de Haas M, Roos D, Duits AJ (1999) Neutrophil activation in sickle cell disease. J Leukoc Biol 66(3):411–415CrossRefPubMedGoogle Scholar
  31. 31.
    Lum AF, Wun T, Staunton D, Simon SI (2004) Inflammatory potential of neutrophils detected in sickle cell disease. Am J Hematol 76(2):126–133. CrossRefPubMedGoogle Scholar
  32. 32.
    Krishnan S, Siegel J, Pullen G Jr, Hevelow M, Dampier C, Stuart M (2008) Increased von Willebrand factor antigen and high molecular weight multimers in sickle cell disease associated with nocturnal hypoxemia. Thromb Res 122(4):455–458. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Francis RB Jr (1989) Elevated fibrin D-dimer fragment in sickle cell anemia: evidence for activation of coagulation during the steady state as well as in painful crisis. Haemostasis 19(2):105–111PubMedGoogle Scholar
  34. 34.
    Stuart MJ, Setty BN (2001) Hemostatic alterations in sickle cell disease: relationships to disease pathophysiology. Pediatr Pathol Mol Med 20(1):27–46CrossRefPubMedGoogle Scholar
  35. 35.
    Noubouossie DF, Le PQ, Corazza F et al (2012) Thrombin generation reveals high procoagulant potential in the plasma of sickle cell disease children. Am J Hematol 87(2):145–149. CrossRefPubMedGoogle Scholar
  36. 36.
    Shah N, Thornburg C, Telen MJ, Ortel TL (2012) Characterization of the hypercoagulable state in patients with sickle cell disease. Thromb Res 130(5):e241–e245. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Gozal D, Crabtree VM, Sans Capdevila O, Witcher LA, Kheirandish-Gozal L (2007) C-reactive protein, obstructive sleep apnea, and cognitive dysfunction in school-aged children. Am J Respir Crit Care Med 176(2):188–193. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kaditis AG, Gozal D, Khalyfa A, Kheirandish-Gozal L, Capdevila OS, Gourgoulianis K, Alexopoulos EI, Chaidas K, Bhattacharjee R, Kim J, Rodopoulou P, Zintzaras E (2014) Variants in C-reactive protein and IL-6 genes and susceptibility to obstructive sleep apnea in children: a candidate-gene association study in European American and Southeast European populations. Sleep Med 15(2):228–235. CrossRefPubMedGoogle Scholar
  39. 39.
    Gozal D, Serpero LD, Kheirandish-Gozal L, Capdevila OS, Khalyfa A, Tauman R (2010) Sleep measures and morning plasma TNF-alpha levels in children with sleep-disordered breathing. Sleep 33(3):319–325. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Li AM, Hung E, Tsang T, Yin J, So HK, Wong E, Fok TF, Ng PC (2007) Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea. Thorax 62(1):75–79. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Altintas N, Çetinoğlu E, Yuceege M, Acet AN, Ursavas A, Firat H, Karadag M (2015) Neutrophil-to-lymphocyte ratio in obstructive sleep apnea; a multi center, retrospective study. Eur Rev Med Pharmacol Sci 19(17):3234–3240PubMedGoogle Scholar
  42. 42.
    Telen MJ (2007) Role of adhesion molecules and vascular endothelium in the pathogenesis of sickle cell disease. Hematol Educ Program Am Soc Hematol:84–90Google Scholar
  43. 43.
    Zennadi R, Hines PC, De Castro LM, Cartron JP, Parise LV, Telen MJ (2004) Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions. Blood 104(12):3774–3781. CrossRefPubMedGoogle Scholar
  44. 44.
    Turhan A, Weiss LA, Mohandas N, Coller BS, Frenette PS (2002) Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc Natl Acad Sci U S A 99(5):3047–3051. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Inwald DP, Kirkham FJ, Peters MJ, Lane R, Wade A, Evans JP, Klein NJ (2000) Platelet and leucocyte activation in childhood sickle cell disease: association with nocturnal hypoxaemia. Br J Haematol 111(2):474–481. CrossRefPubMedGoogle Scholar
  46. 46.
    Israel LP, Benharoch D, Gopas J, Goldbart AD (2013) A pro-inflammatory role for nuclear factor kappa B in childhood obstructive sleep apnea syndrome. Sleep 36(12):1947–1955. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Ai J, Epstein PN, Gozal D, Yang B, Wurster R, Cheng ZJ (2007) Morphology and topography of nucleus ambiguus projections to cardiac ganglia in rats and mice. Neuroscience 149(4):845–860. CrossRefPubMedGoogle Scholar
  48. 48.
    Lin M, Ai J, Li L, Huang C, Chapleau MW, Liu R, Gozal D, Wead WB, Wurster RD, Cheng ZJ (2008) Structural remodeling of nucleus ambiguus projections to cardiac ganglia following chronic intermittent hypoxia in C57BL/6J mice. J Comp Neurol 509(1):103–117. CrossRefPubMedGoogle Scholar
  49. 49.
    Mansukhani MP, Kara T, Caples SM, Somers VK (2014) Chemoreflexes, sleep apnea, and sympathetic dysregulation. Curr Hypertens Reports 16(9):476. CrossRefGoogle Scholar
  50. 50.
    Sangkatumvong S, Khoo MC, Kato R et al (2011) Peripheral vasoconstriction and abnormal parasympathetic response to sighs and transient hypoxia in sickle cell disease. Am J Respir Crit Care Med 184(4):474–481. CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Ataga KI, Sood N, De Gent G, Kelly E, Henderson AG, Jones S, Strayhorn D, Lail A, Lieff S, Orringer EP (2004) Pulmonary hypertension in sickle cell disease. Am J Med 117(9):665–669. CrossRefPubMedGoogle Scholar
  52. 52.
    Minic M, Granton JT, Ryan CM (2014) Sleep disordered breathing in group 1 pulmonary arterial hypertension. J Clin Sleep Med 10(3):277–283. PubMedPubMedCentralGoogle Scholar
  53. 53.
    Poludasu S, Ramkissoon K, Salciccioli L, Kamran H, Lazar JM (2013) Left ventricular systolic function in sickle cell anemia: a meta-analysis. J Cardiac Fail 19(5):333–341. CrossRefGoogle Scholar
  54. 54.
    Pack AI, Gislason T (2009) Obstructive sleep apnea and cardiovascular disease: a perspective and future directions. Prog Cardiovasc Dis 51(5):434–451. CrossRefPubMedGoogle Scholar
  55. 55.
    Chouchou F, Pichot V, Pepin JL et al (2013) Sympathetic overactivity due to sleep fragmentation is associated with elevated diurnal systolic blood pressure in healthy elderly subjects: the PROOF-SYNAPSE study. Eur Heart J 34(28):2122–2131. CrossRefPubMedGoogle Scholar
  56. 56.
    Loke YK, Brown JW, Kwok CS, Niruban A, Myint PK (2012) Association of obstructive sleep apnea with risk of serious cardiovascular events: a systematic review and meta-analysis. Circulation Cardiovasc Qual Outcomes 5(5):720–728. CrossRefGoogle Scholar
  57. 57.
    Querejeta Roca G, Redline S et al (2013) Sleep apnea is associated with subclinical myocardial injury in the community. The ARIC-SHHS study. Am J Respir Crit Care Med 188(12):1460–1465. CrossRefPubMedGoogle Scholar
  58. 58.
    Gladwin MT, Kato GJ (2005) Cardiopulmonary complications of sickle cell disease: role of nitric oxide and hemolytic anemia. Hematol Am Soc Hematol Educ Program 51–57Google Scholar
  59. 59.
    Garg UC, Hassid A (1990) Nitric oxide-generating vasodilators inhibit mitogenesis and proliferation of BALB/C 3T3 fibroblasts by a cyclic GMP-independent mechanism. Biochem Biophys Res Commun 171(1):474–479. CrossRefPubMedGoogle Scholar
  60. 60.
    Sarkar R, Webb RC, Stanley JC (1995) Nitric oxide inhibition of endothelial cell mitogenesis and proliferation. Surgery 118(2):274–279. CrossRefPubMedGoogle Scholar
  61. 61.
    Lau YT, Ma WC (1996) Nitric oxide inhibits migration of cultured endothelial cells. Biochem Biophys Res Commun 221(3):670–674. CrossRefPubMedGoogle Scholar
  62. 62.
    Fitch RM, Vergona R, Sullivan ME, Wang YX (2001) Nitric oxide synthase inhibition increases aortic stiffness measured by pulse wave velocity in rats. Cardiovasc Res 51(2):351–358. CrossRefPubMedGoogle Scholar
  63. 63.
    Aessopos A, Farmakis D, Tsironi M, Diamanti-Kandarakis E, Matzourani M, Fragodimiri C, Hatziliami A, Karagiorga M (2007) Endothelial function and arterial stiffness in sickle-thalassemia patients. Atherosclerosis 191(2):427–432. CrossRefPubMedGoogle Scholar
  64. 64.
    Kariya K, Kawahara Y, Araki S, Fukuzaki H, Takai Y (1989) Antiproliferative action of cyclic GMP-elevating vasodilators in cultured rabbit aortic smooth muscle. Atherosclerosis 80(2):143–147. CrossRefPubMedGoogle Scholar
  65. 65.
    Strunk RC, Brown MS, Boyd JH, Bates P, Field JJ, DeBaun MR (2008) Methacholine challenge in children with sickle cell disease: a case series. Pediatr Pulmonol 43(9):924–929. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Wedderburn CJ, Rees D, Height S, Dick M, Rafferty GF, Lunt A, Greenough A (2014) Airways obstruction and pulmonary capillary blood volume in children with sickle cell disease. Pediatr Pulmonol 49(7):716–722. CrossRefPubMedGoogle Scholar
  67. 67.
    Intzes S, Kalpatthi RV, Short R, Imran H (2013) Pulmonary function abnormalities and asthma are prevalent in children with sickle cell disease and are associated with acute chest syndrome. Pediatr Hematol Oncol 30(8):726–732. CrossRefPubMedGoogle Scholar
  68. 68.
    Glassberg JA, Chow A, Wisnivesky J, Hoffman R, Debaun MR, Richardson LD (2012) Wheezing and asthma are independent risk factors for increased sickle cell disease morbidity. Br J Haematol 159(4):472–479. CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Boyd JH, Macklin EA, Strunk RC, DeBaun MR (2007) Asthma is associated with increased mortality in individuals with sickle cell anemia. Haematologica 92(8):1115–1118. CrossRefPubMedGoogle Scholar
  70. 70.
    Brockmann PE, Bertrand P, Castro-Rodriguez JA (2014) Influence of asthma on sleep disordered breathing in children: a systematic review. Sleep Med Rev 18(5):393–397. CrossRefPubMedGoogle Scholar
  71. 71.
    Kheirandish-Gozal L, Dayyat EA, Eid NS, Morton RL, Gozal D (2011) Obstructive sleep apnea in poorly controlled asthmatic children: effect of adenotonsillectomy. Pediatr Pulmonol 46(9):913–918. CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Ohene-Frempong K, Weiner S, Sleeper L et al (1998) Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 91(1):288–294PubMedGoogle Scholar
  73. 73.
    Kirkham FJ, Hewes DKM, Prengler M, Wade A, Lane R, Evans JPM (2001) Nocturnal hypoxaemia and central-nervous-system events in sickle-cell disease. Lancet 357(9269):1656–1659. CrossRefPubMedGoogle Scholar
  74. 74.
    Arzt M, Young T, Finn L, Skatrud JB, Bradley TD (2005) Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med 172(11):1447–1451. CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Wang WC, Langston JW, Steen RG, Wynn LW, Mulhern RK, Wilimas JA, Kim FM, Figueroa RE (1998) Abnormalities of the central nervous system in very young children with sickle cell anemia. J Pediatr 132(6):994–998. CrossRefPubMedGoogle Scholar
  76. 76.
    Hollocks MJ, Kok TB, Kirkham FJ, Gavlak J, Inusa BP, DeBaun MR, de Haan M (2012) Nocturnal oxygen desaturation and disordered sleep as a potential factor in executive dysfunction in sickle cell anemia. J Int Neuropsychol Soc JINS 18(1):168–173. CrossRefPubMedGoogle Scholar
  77. 77.
    Hill CM, Hogan AM, Onugha N, Harrison D, Cooper S, McGrigor VJ, Datta A, Kirkham FJ (2006) Increased cerebral blood flow velocity in children with mild sleep disordered breathing: a possible association with abnormal neuropsychological function. Pediatr. 118(4):e1100–e1108. CrossRefGoogle Scholar
  78. 78.
    Biggs SN, Vlahandonis A, Anderson V, Bourke R, Nixon GM, Davey MJ, Horne RSC (2014) Long-term changes in neurocognition and behavior following treatment of sleep disordered breathing in school-aged children. Sleep 37(1):77–84. CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Donaldson JF, Rees RW, Steinbrecher HA (2014) Priapism in children: a comprehensive review and clinical guideline. J Pediatr Urol 10(1):11–24. CrossRefPubMedGoogle Scholar
  80. 80.
    Roizenblatt M, Figueiredo MS, Cancado RD et al (2012) Priapism is associated with sleep hypoxemia in sickle cell disease. J Urol 188(4):1245–1251. CrossRefPubMedGoogle Scholar
  81. 81.
    Ferré A, Vila J, Jurado MJ, Arcalis N, Camps J, Cambrodi R, Romero O (2012) Sleep-related painful erections associated with obstructive sleep apnea syndrome. Arch Sex Behav 41(4):1059–1063. CrossRefPubMedGoogle Scholar
  82. 82.
    Abouda M, Jomni T, Yangui F, Charfi MR, Arnulf I (2016) Sleep-related painful erections in a patient with obstructive sleep apnea syndrome. Arch Sex Behav 45(1):241–245. CrossRefPubMedGoogle Scholar
  83. 83.
    Wolf RB, Kassim AA, Goodpaster RL, DeBaun MR (2014) Nocturnal enuresis in sickle cell disease. Expert Rev Hematol 7(2):245–254. CrossRefPubMedGoogle Scholar
  84. 84.
    Sakellaropoulou AV, Hatzistilianou MN, Emporiadou MN, Aivazis VT, Goudakos J, Markou K, Athanasiadou-Piperopoulou F (2012) Association between primary nocturnal enuresis and habitual snoring in children with obstructive sleep apnoea hypopnea syndrome. Arch Med Sci AMS 8(3):521–527. CrossRefPubMedGoogle Scholar
  85. 85.
    Barone JG, Hanson C, DaJusta DG, Gioia K, England SJ, Schneider D (2009) Nocturnal enuresis and overweight are associated with obstructive sleep apnea. Pediatr 124(1):e53–e59. CrossRefGoogle Scholar
  86. 86.
    Alexopoulos EI, Kostadima E, Pagonari I, Zintzaras E, Gourgoulianis K, Kaditis AG (2006) Association between primary nocturnal enuresis and habitual snoring in children. Urol 68(2):406–409. CrossRefPubMedGoogle Scholar
  87. 87.
    Basha S, Bialowas C, Ende K, Szeremeta W (2005) Effectiveness of adenotonsillectomy in the resolution of nocturnal enuresis secondary to obstructive sleep apnea. Laryngoscope 115(6):1101–1103. CrossRefPubMedGoogle Scholar
  88. 88.
    Firoozi F, Batniji R, Aslan AR, Longhurst PA, Kogan BA (2006) Resolution of diurnal incontinence and nocturnal enuresis after adenotonsillectomy in children. J Urol 175(5):1885–1888. CrossRefPubMedGoogle Scholar
  89. 89.
    Adeyoju AB, Olujohungbe AB, Morris J et al (2002) Priapism in sickle-cell disease; incidence, risk factors and complications-an international multicentre study. BJU Int 90(9):898–902. CrossRefPubMedGoogle Scholar
  90. 90.
    Emond AM, Holman R, Hayes RJ, Serjeant GR (1980) Priapism and impotence in homozygous sickle cell disease. Arch Intern Med 140(11):1434–1437. CrossRefPubMedGoogle Scholar
  91. 91.
    Madu AJ, Ubesie A, Ocheni S, Chinawa J, Madu KA, Ibegbulam OG, Nonyelu C, Eze A (2014) Priapism in homozygous sickle cell patients: important clinical and laboratory associations. Med Princ Pract 23(3):259–263. CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Hirshkowitz M, Karacan I, Arcasoy MO, Acik G, Narter EM, Williams RL (2005) Erectile dysfunction, obstructive sleep apnea syndrome and nasal CPAP treatment. Sleep Med 6:333–339CrossRefGoogle Scholar
  93. 93.
    Soukhova-O’Hare GK, Shah ZA, Lei ZM, Nozdrachev AD, Rao CV, Gozal D (2008) Erectile dysfunction in a murine model of sleep apnea. Am J Respir Crit Care Med 178(6):644–650. CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Anele UA, Burnett AL (2015) Erectile dysfunction after sickle cell disease-associated recurrent ischemic priapism: profile and risk factors. J Sex Med 12(3):713–719. CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Hargrave DR, Wade A, Evans JP, Hewes DK, Kirkham FJ (2003) Nocturnal oxygen saturation and painful sickle cell crises in children. Blood 101(3):846–848. CrossRefPubMedGoogle Scholar
  96. 96.
    Marshall MJ, Bucks RS, Hogan AM, Hambleton IR, Height SE, Dick MC, Kirkham FJ, Rees DC (2009) Auto-adjusting positive airway pressure in children with sickle cell anemia: results of a phase I randomized controlled trial. Haematologica 94(7):1006–1010. CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Ip H, Kesse-Adu R, Howard J, Hart N (2013) Low flow nocturnal oxygen therapy does not suppress haemoglobin levels or increase painful crises in sickle cell disease. Br J Haematol 161(3):455–456. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Vikram M. Raghunathan
    • 1
  • Peter L. Whitesell
    • 2
  • Seah H. Lim
    • 1
    • 3
  1. 1.Department of MedicineBrown University Warren Alpert Medical SchoolProvidenceUSA
  2. 2.Department of MedicineHoward University College of MedicineWashingtonUSA
  3. 3.Rhode Island HospitalProvidenceUSA

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