Sleep and Breathing

, Volume 21, Issue 3, pp 697–701 | Cite as

Hydroxyurea treatment effect on children with sickle cell disease and obstructive sleep apnea

  • Anthony J. Grady
  • Jane S. Hankins
  • Brent Haberman
  • Robert Schoumacher
  • Rose Mary Stocks
Sleep Breathing Physiology and Disorders • Short Communication



While hydroxyurea is the mainstay of treatment for many of the comorbidities associated with sickle cell disease, its effect on obstructive sleep apnea has not been fully investigated. The purpose of this project is to help characterize the effects of hydroxyurea on obstructive sleep apnea in children with sickle cell disease and determine its therapeutic role in the condition.


Chart review was conducted on two pediatric patients with sickle cell disease who experienced resolution of obstructive sleep apnea following hydroxyurea administration.


After undergoing approximately 11 months of hydroxyurea therapy, sleep apnea symptoms improved and obstructive sleep apnea resolution was confirmed by repeat polysomnography in both cases. This resolution was largely secondary to a reduction in the obstructive component of the apnea hypopnea index, highlighting a previously unreported association.


As adenotonsillectomy is associated with significant risks in patients with sickle cell disease, it appears reasonable to consider a period of observation for improvement of obstructive sleep apnea following hydroxyurea administration rather than directly proceeding with surgery.


Obstructive sleep apnea Sickle cell disease Hydroxyurea Pediatric Adenotonsillectomy Polysomnography 


  1. 1.
    Hankins JS, Verevkina NI, Smeltzer MP, Wu S, Aygun B, Clarke DF (2014) Assessment of sleep-related disorders in children with sickle cell disease. Hemoglobin 38(4):244–251. doi:10.3109/03630269.2014.919941 CrossRefPubMedGoogle Scholar
  2. 2.
    Rosen CL, Debaun MR, Strunk RC, Redline S, Seicean S, Craven DI, Gavlak JC, 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. doi:10.1542/peds.2013-4223 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Strauss TBA, Sin SMS, Marcus CLMF, Mason TBAMDP, McDonough JMMS, Allen JLMD, Caboot JBMD, Bowdre CYP, Jawad AFP, Smith-Whitley KMD, Ohene-Frempong KMD, Pack AIMDP, Arens RMD (2012) Upper airway lymphoid tissue size in children with sickle cell disease. Chest 142(1):94–100CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Minter KR, Gladwin MT (2001) Pulmonary complications of sickle cell anemia. A need for increased recognition, treatment, and research. Am J Respir Crit Care Med 164(11):2016–2019. doi:10.1164/ajrccm.164.11.2104101 CrossRefPubMedGoogle Scholar
  5. 5.
    Needleman JP, Setty BN, Varlotta L, Dampier C, Allen JL (1999) Measurement of hemoglobin saturation by oxygen in children and adolescents with sickle cell disease. Pediatr Pulmonol 28(6):423–428CrossRefPubMedGoogle Scholar
  6. 6.
    Duke RL, Scott JP, Panepinto JA, Flanary VA (2006) Perioperative management of sickle cell disease children undergoing adenotonsillectomy. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 134(3):370–373. doi:10.1016/j.otohns.2005.11.001 CrossRefGoogle Scholar
  7. 7.
    Hankins JS, Ware RE, Rogers ZR, Wynn LW, Lane PA, Scott JP, Wang WC (2005) Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study. Blood 106(7):2269–2275. doi:10.1182/Blood-2004-12-4973 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ferster A, Vermylen C, Cornu G, Buyse M, Corazza F, Devalck C, Fondu P, Toppet M, Sariban E (1996) Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial. Blood 88(6):1960–1964PubMedGoogle Scholar
  9. 9.
    Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW (2011) Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet (London, England) 377(9778):1663–1672. doi:10.1016/s0140-6736(11)60355-3 CrossRefGoogle Scholar
  10. 10.
    Narang I, Dhanju S, Amin R, Al-Saleh S, Kadman G, Lai D (2014) Impact of hydroxyurea in sleep disordered breathing in children with sickle cell disease. Sleep 37:A336Google Scholar
  11. 11.
    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. Annals of the American Thoracic Society 12(7):1044–1049. doi:10.1513/AnnalsATS.201410-473OC CrossRefPubMedGoogle Scholar
  12. 12.
    Okoli K, Irani F, Horvath W (2009) Pathophysiologic considerations for the interactions between obstructive sleep apnea and sickle hemoglobinopathies. Med Hypotheses 72(5):578–580. doi:10.1016/j.mehy.2008.12.012 CrossRefPubMedGoogle Scholar
  13. 13.
    Salles C, Ramos RT, Daltro C, Nascimento VM, Matos MA (2009) Association between adenotonsillar hypertrophy, tonsillitis and painful crises in sickle cell disease. J Pediatr 85(3):249–253. doi:10.2223/JPED.1898 Google Scholar
  14. 14.
    Everett MT (1979) The cause of tonsillitis. The Practitioner 223(1334):253–259PubMedGoogle Scholar
  15. 15.
    Finch PMD, Stocks RMMDP, Smeltzer MPMS, Kimble AFNP, Schoumacher RMD, Hankins JSMDMS (2013) Effects of adenotonsillectomy on polysomnographic parameters in children with sickle cell disease. Pediatr Blood Cancer 60(7):E26–E28CrossRefPubMedGoogle Scholar
  16. 16.
    Ijaduola GT, Akinyanju OO (1987) Chronic tonsillitis, tonsillectomy and sickle cell crises. J Laryngol Otol 101(5):467–470CrossRefPubMedGoogle Scholar
  17. 17.
    Gozal D, Serpero LD, Sans Capdevila O, Kheirandish-Gozal L (2008) Systemic inflammation in non-obese children with obstructive sleep apnea. Sleep Med 9(3):254–259. doi:10.1016/j.sleep.2007.04.013 CrossRefPubMedGoogle Scholar
  18. 18.
    Lavie L (2003) Obstructive sleep apnoea syndrome—an oxidative stress disorder. Sleep Med Rev 7(1):35–51CrossRefPubMedGoogle Scholar
  19. 19.
    Dayyat E, Serpero LD, Kheirandish-Gozal L, Goldman JL, Snow A, Bhattacharjee R, Gozal D (2009) Leukotriene pathways and in vitro adenotonsillar cell proliferation in children with obstructive sleep apnea. Chest 135(5):1142–1149. doi:10.1378/chest.08-2102 CrossRefPubMedGoogle Scholar
  20. 20.
    Zhang D, Xu C, Manwani D, Frenette PS (2016) Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology. Blood 127(7):801–809. doi:10.1182/blood-2015-09-618538 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lemonne N, Charlot K, Waltz X, Ballas SK, Lamarre Y, Lee K, Hierso R, Connes C, Etienne-Julan M, Romana M, Connes P (2015) Hydroxyurea treatment does not increase blood viscosity and improves red blood cell rheology in sickle cell anemia. Haematologica 100(10):e383–e386. doi:10.3324/haematol.2015.130435 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Reiter CD, Wang X, Tanus-Santos JE, Hogg N, Cannon RO 3rd, Schechter AN, Gladwin MT (2002) Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 8(12):1383–1389. doi:10.1038/nm799 CrossRefPubMedGoogle Scholar
  23. 23.
    Niu X, Nouraie M, Campbell A, Rana S, Minniti CP, Sable C, Darbari D, Dham N, Reading NS, Prchal JT, Kato GJ, Gladwin MT, Castro OL, Gordeuk VR (2009) Angiogenic and inflammatory markers of cardiopulmonary changes in children and adolescents with sickle cell disease. PLoS One 4(11):e7956. doi:10.1371/journal.pone.0007956 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Rana S, Houston PE, Wang WC, Iyer RV, Goldsmith J, Casella JF, Reed CK, Rogers ZR, Waclawiw MA, Thompson B (2014) Hydroxyurea and growth in young children with sickle cell disease. Pediatrics 134(3):465–472. doi:10.1542/peds.2014-0917 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Saboisky JP, Butler JE, Gandevia SC, Eckert DJ (2012) Functional role of neural injury in obstructive sleep apnea. Front Neurol 3:95. doi:10.3389/fneur.2012.00095 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Loredo JS, Ancoli-Israel S, Kim EJ, Lim WJ, Dimsdale JE (2006) Effect of continuous positive airway pressure versus supplemental oxygen on sleep quality in obstructive sleep apnea: a placebo-CPAP-controlled study. Sleep 29(4):564–571CrossRefPubMedGoogle Scholar
  27. 27.
    Aljadeff G, Gozal D, Bailey-Wahl SL, Burrell B, Keens TG, Ward SL (1996) Effects of overnight supplemental oxygen in obstructive sleep apnea in children. Am J Respir Crit Care Med 153(1):51–55. doi:10.1164/ajrccm.153.1.8542162 CrossRefPubMedGoogle Scholar
  28. 28.
    Marcus CL, Moore RH, Rosen CL, Giordani B, Garetz SL, Taylor HG, Mitchell RB, Amin R, Katz ES, Arens R, Paruthi S, Muzumdar H, Gozal D, Thomas NH, Ware J, Beebe D, Snyder K, Elden L, Sprecher RC, Willging P, Jones D, Bent JP, Hoban T, Chervin RD, Ellenberg SS, Redline S (2013) A randomized trial of adenotonsillectomy for childhood sleep apnea. N Engl J Med 368(25):2366–2376. doi:10.1056/NEJMoa1215881 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Chervin RD, Ellenberg SS, Hou X, Marcus CL, Garetz SL, Katz ES, Hodges EK, Mitchell RB, Jones DT, Arens R, Amin R, Redline S, Rosen CL (2015) Prognosis for spontaneous resolution of OSA in children. Chest 148(5):1204–1213. doi:10.1378/chest.14-2873 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Li AM, Au CT, Ng SK, Abdullah VJ, Ho C, Fok TF, Ng PC, Wing YK (2010) Natural history and predictors for progression of mild childhood obstructive sleep apnoea. Thorax 65(1):27–31. doi:10.1136/thx.2009.120220 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Anthony J. Grady
    • 1
  • Jane S. Hankins
    • 2
  • Brent Haberman
    • 3
  • Robert Schoumacher
    • 3
  • Rose Mary Stocks
    • 1
  1. 1.Department of Otolaryngology, Head and Neck SurgeryUniversity of Tennessee Health Science CenterMemphisUSA
  2. 2.Department of HematologySt. Jude Children’s Research HospitalMemphisUSA
  3. 3.Department of Pediatric PulmonologyUniversity of Tennessee Health Science CenterMemphisUSA

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