Talasemilerde Solunum Sistemi Bozuklukları

Talasemi majör, tüm dünyada önemli bir sağlık sorunu olup, yüksek maliyetli tedavi gerektiren bir hastalıktır. Hastaların çoğu ikinci dekatta tedaviye bağlı komplikasyonlar nedeniyle kaybedilmektedir. Son yıllarda kullanıma giren yeni tedavi rejimleri ve tedaviye bağlı komplikasyonların dikkatli bir şekilde izlenmesiyle hastaların beklenen yaşam süreleri artmaktadır. Düzenli kan transfüzyonları nedeniyle kalp, karaciğer ve akciğer gibi hayati organlarda ilerleyici demir birikimi görülmektedir. Akciğer de demir birikiminin yaşandığı organlardan birisidir. Akciğerlerdeki demir birikimi akciğer dinamiklerinde değişikliklere yol açmakta ve bu durum hastaların yaşam kalitesini olumsuz etkilemektedir. Bu hastalarda akciğerlerde demir birikiminin olduğu uzun süreden beri bilinen bir gerçek ise de, bu birikimin akciğerler üzerine nasıl etkide bulunduğu konusu hala tartışma konusudur

Respiratory System Disorders in Thalasemia

Thalassemia major is a worldwide healthcare problem requiring high cost medical treatment. Patients usually die of treatment associated complications in the second decade. However, improvements in treatment and meticulous follow-up strategies for treatment associated complications have led to an increase in expected life span of the patients. Regular transfusions cause progressive iron deposition in critical organs such as heart, liver and lungs. Iron deposition in the lungs results in respiratory dysfunction and impairment in quality of life of patients with thallassemia. Although iron deposition in respiratory system has been a known reality for many years in thallassemia, the effect of this deposition on respiratory functions has been an ongoing debate

PDF

___

1. Cunningham M. The thalassemias. In Nathan and Oski's Hematology of Infancy and Childhood, 7th edition (Eds SH Orkin, DG Nathan, D Ginsburg, AT Look, DE Fisher, SE Lux):1015-106. Philadephia, Saunders Elsevier, 2009.
2. Keser I. Hemoglobinopatilerde moleküler çalışmalar. Türkiye Klinikleri J Pediatr Sci.2007;3:9.
3. Martin A, Thompson A. Thalassemias. Pediatr Clin North Am. 2013;60:1383-91.
4. Whetherall DJ. Pathophsiology of thalassemia. Bailliere’s Clinical Hematology.1998;11:127-46.
5. Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med. 2005;353:1135-46.
6. Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood.2011;118:3479-88.
7. Ware HM, Kwiatkowski JL. Evaluation and treatment of transfusional iron overload in children. Pediatr Clin North Am. 2013;60:1393-406.
8. Lands LC, Woods S, Katsardis CH, Desmond K, Coates AL.The effects of diuresis and transfusion on pulmonary function in children with thalassemia Major. Pediatr Pulmonol. 1991;11:340-4.
9. Zheng G, Schaefer M, Karplus M. Hemoglobin Bohr effects: atomic origin of the histidine residue contributions. Biochemistry. 2013;52:8539-55.
10. Cappellini MD, Cohen A, Eleftheriou A, Piga A, Porter J, Taher A. Guidelines for the Clinical Management of Thalassaemia, 2nd edition. Nicosia (CY), Thalassaemia International Federation, 2008.
11. Salomon-Andonie J, Miasnikova G, Sergueeva A, Polyakova LA, Niu X, Nekhai S et al. Effect of congenital upregulation of hypoxia inducible factors on percentage of fetal hemoglobin in the blood. Blood.2013;122:3088-9.
12. Hoffman R. Thalassemia syndromes. In Hematology Basic Principles andPractice, 3rd edition (Eds R Hoffman, EJ Benz, SJ Shattil):485-509. Philadelphia, Churchill Livingstone, 2000.
13. Andrews NC, Ullrich CK, Fleming MD. Disorders of iron metabolism and sideroblastic anemia. Nathan and Oski's Hematology of Infancy and Childhood, 7th edition (Eds SH Orkin, DG Nathan, D Ginsburg, AT Look, DE Fisher, SE Lux):1054-74. Philadephia, Saunders Elsevier, 2009.
14. Başak N. Βeta Talasemide moleküler tanı ve yöntemleri. In Talasemi ve Hemoglobinopatiler Tanı ve Tedavi (Eds D Canatan, Y Aydınok):49-60. Antalya, Talasemi Federasyonu, 2007.
15. Higgs DR, Thein SL, Wood WG. Human haemoglobin. In The Thalassaemia Syndromes, 4th edition (Eds DJ Weatherall, JB Clegg):65-120. Oxford, Blackwell Science, 2001..
16. Çürük MA, Genç A, Huseynova P, Zeren F, Aksoy K. Çukurova’da alfa talasemigenotipleri ve Hb H hastalığı. Türkiye Klinikleri J Pediatr Sci.2007;3:17-23.
17. Vichinsky E. Complexity of alpha thalassemia: growing health problem with new approaches to screening, diagnosis, and therapy. Ann N Y Acad Sci.2010;1202:180-7.
18. Higgs DR. Alpha thalassemia: an overview. Current Views on Thalassemia.1992;31-40.
19. Musallam KM, Rivella S, Vichinsky E, Rachmilewitz EA. Non-transfusion-dependent thalassemias. Haematologica.2013;98:833-44.
20. Gümrük F. Hemoglobinopatilerin Tanı ve Tedavisinde Yenilikler. Ankara, Türk Hematoloji Dernegi, , 2006.
21. Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ.2008;86:480-7.
22. Kocak R, Alparslan ZN, Agridag G, Başlamisli F, Aksungur PD, Koltaş S.The frequency of anaemia, iron deficiency, hemoglobin S and beta thalassemia in the south of Turkey. Eur J Epidemiol. 1995;11:181-4.
23. Canatan D. Türkiye'de hemoglobinopatilerin epidemiyolojisi. Hematolog.2014;4-1:11-21.
24. Musallam KM, Taher AT, Rachmilewitz EA. Beta-thalassemia intermedia: a clinical perspective. Cold Spring Harb Perspect Med. 2012;2:a013482.
25. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;21:5-11.
26. Musallam KM, Cappellini MD, Taher AT. Iron overload in beta-thalassemia intermedia: an emerging concern. Curr Opin Hematol.2013;20:187-92.
27. Weatherall DJ. The definition and epidemiology of non-transfusion-dependent thalassemia. Blood Rev.2012;26:3-6.
28. Taher AT, Musallam KM, Karimi M, Cappellini MD. Contemporary approaches to treatment of beta-thalassemia intermedia. Blood Rev. 2012;26:24-7.
29. Rivella S. The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia. Blood Rev.2012;26:12-5.
30. Akar N. ThalassemiaSendromları. Ankara, Ankara Üniversitesi Tıp Fakültesi,1997.
31. Lanskowsky P. Manual of Pediatric Hematology and Oncology, 5th edition. Oxford, Academic Press, 2011. 200-7.
32. Izadyar S, Fazeli M, Izadyar M, Salamati P, Gholamrezanezhad A. Bone mineral density in adult patients with major thalassaemia: our experience and a brief review of the literature. Endokrynol Pol. 2012;63:264-9.
33. Chatterjee R, Shah FT, Davis BA, Byers M, Sooranna D, Bajoria R et al. Prospective study of histomorphometry, biochemical bone markers and bone densitometric response to pamidronate in beta-thalassaemia presenting with osteopenia-osteoporosis syndrome. Br J Haematol. 2012;159:462-71.
34. Gibbons R, Higgs DR, Olivieri NF, Wood WG. The β thalassaemias. In The Thalassaemia Syndromes, 4th edition (Eds DJ Weatherall, JB Clegg):287-356. Oxford, Blackwell Science, 2001.
35. Taher A, Isma'eel H, Cappellini MD. Thalassemia intermedia: revisited. Blood Cells Mol Dis. 2006;37:12-20.
36. Angelucci E, Brittenham GM, McLaren CE, Ripalti M, Baronciani D, Giardini C et al. Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med.2000;343:327-31.
37. St Pierre TG, Clark PR, Chua-Anusorn W. Measurement and mapping of liver iron concentrations using magnetic resonance imaging. Ann N Y Acad Sci.2005;1054:379-85.
38. Kremastinos DT, Farmakis D, Aessopos A, Hahalis G, Hamodraka E, Tsiapras D et al. Betathalassemia cardiomyopathy: history, present considerations, and future perspectives. Circ Heart Fail.2010;3:451-8.
39. Yang G, Liu R, Peng P, Long L, Zhang X, Yang W et al. How early can myocardial iron overload occur in beta thalassemia major? PLoS One.2014;9:e85379.
40. Cogliandro T, Derchi G, Mancuso L, Mayer MC, Pannone B, Pepe A et al. Guideline recommendations for heart complications in thalassemia major. J Cardiovasc Med (Hagerstown). 2008;9:515-25.
41. Aessopos A, Berdoukas V, Tsironi M. The heart in transfusion dependent homozygous thalassaemia today--prediction, prevention and management. Eur J Haematol.2008;80:93-106.
42. Berdoukas V, Chouliaras G, Moraitis P, Zannikos K, Berdoussi E, Ladis V. The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study. J Cardiovasc Magn Reson.2009;11:20.
43. Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med.1994;331:574-8.
44. Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J. 2001;22:2171-9.
45. Borgna-Pignatti C, Meloni A, Guerrini G, Gulino L, Filosa A, Ruffo GB et al. Myocardial iron overload in thalassaemia major. How early to check? Br J Haematol.2014;164:579-85.
46. Pepe A, Meloni A, Rossi G, Caruso V, Cuccia L, Spasiano A et al.Cardiac complications and diabetes in thalassaemia major: a large historical multicentre study. Br J Haematol.2013;163:520-7.
47. Li D, Dhawale P, Rubin PJ, Haacke EM, Gropler RJ. Myocardial signal response to dipyridamole and dobutamine: demonstration of the BOLD effect using a double-echo gradient-echo sequence. Magn Reson Med.1996;36:16-20.
48. Origa R, Danjou F, Cossa S, Matta G, Bina P, Dessì C et al. Impact of heart magnetic resonance imaging on chelation choices, compliance with treatment and risk of heart disease in patients with thalassaemia major. Br J Haematol.2013;163:400-3.
49. Kremastinos DT, Tsetsos GA, Tsiapras DP, Karavolias GK, Ladis VA, Kattamis CA. Heart failure in beta thalassemia: a 5-year follow-up study. Am J Med.2001;111:349-54.
50. Zervas A, Katopodi A, Protonotariou A, Livadas S, Karagiorga M, Politis C et al. Assessment of thyroid function in two hundred patients with beta-thalassemia major. Thyroid.2002;12:151-4.
51. Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica.2004;89:1187-93.
52. Vogiatzi MG, Macklin EA, Trachtenberg FL, Fung EB, Cheung AM, Vichinsky E et al. Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. Br J Haematol. 2009;146:546-56.
53. Multicentre study on prevalence of endocrine complications in thalassaemia major. Italian Working Group on Endocrine Complications in Non-endocrine Diseases. Clin Endocrinol (Oxf). 1995;42:581-6.
54. Jaruratanasirikul S, Chareonmuang R, Wongcharnchailert M, Laosombat V, Sangsupavanich P, Leetanaporn K. Prevalence of impaired glucose metabolism in beta-thalassemic children receiving hypertransfusions with a suboptimal dosage of iron-chelating therapy. Eur J Pediatr. 2008;167:873-6.
55. Chern JP, Lin KH, Lu MY, Lin DT, Lin KS, Chen JD etal. Abnormal glucose tolerance in transfusiondependent beta-thalassemic patients. Diabetes Care.2001;24:850-4.
56. Cavallo-Perin P, Pacini G, Cerutti F et al. Insulin resistance and hyperinsulinemia in homozygous beta-thalassemia. Metabolism.1995;44:281-6.
57. Sougleri M, Labropoulou-Karatza C, Paraskevopoulou P,Fragopanagou H, Alexandrides T.Chronic hepatitis C virus infection without cirrhosis induces insulin resistance in patients with alphathalassaemia major. Eur J Gastroenterol Hepatol.2001;13:1195-9.
58. Au WY, Lam WM, Chu WC, Tam S, Wong WK, Pennell DJ et al. A magnetic resonance imaging study of iron overload in hemopoietic stem cell transplant recipients with increased ferritin levels. Transplant Proc.2007;39:3369-74.
59. Papakonstantinou O, Ladis V, Kostaridou S, Maris T, Berdousi H, Kattamis Cet al. The pancreas in beta-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbances. Eur Radiol.2007;17:1535-43.
60. Noetzli LJ, Mittelman SD, Watanabe RM, Coates TD, Wood JC. Pancreatic iron and glucose dysregulation in thalassemia major. Am J Hematol.2012;87:155-60.
61. Farmaki K, Tzoumari I, Pappa C, Chouliaras G, Berdoukas V. Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major. Br J Haematol.2010;148:466-75.
62. Orvieto R, Leichter I, Rachmilewitz EA, Margulies JY. Bone density, mineral content, and cortical index in patients with thalassemia major and the correlation to their bone fractures, blood transfusions, and treatment with desferrioxamine. Calcif Tissue Int.1992;50:397-9.
63. Tyler PA, Madani G, Chaudhuri R, Wilson LF, Dick EA. The radiological appearances of thalassaemia. Clin Radiol.2006;61:40-52.
64. Lukens JN. The thalassemias and related disorders: quantitative disorders of hemoglobin synthesis. In Wintrobe' s Clinical Hematology 10th edition (Eds GR Lee, J Foerster, J Lukens, F Paraskevas, JP Greer, GM Rodgers):1405-48.Philadelphia, Williams&Wilkins,1999.
65. Gilfillan CP, Strauss BJ, Rodda CP, Bowden DK, Kean AM, Obaid M et al. A randomized, doubleblind, placebo-controlled trial of intravenous zoledronic acid in the treatment of thalassemiaassociated osteopenia. Calcif Tissue Int.2006;79:138-44.
66. Brill PW, Winchester P, Giardina PJ, Cunningham-Rundles S. Deferoxamine-induced bone dysplasia in patients with thalassemia major. AJR Am J Roentgenol.1991;156:561-5.
67. Chan YL, Li CK, Pang LM, Chik KW. Desferrioxamine-induced long bone changes in thalassaemic patients - radiographic features,prevalence and relations with growth. Clin Radiol.2000;55:610- 4.
68. Kellenberger CJ, Schmugge M, Saurenmann T, Di Gennaro L, Eber SW, Willi UV et al. Radiographic and MRI features of deferiprone-related arthropathy of the knees in patients with betathalassemia. AJR Am J Roentgenol.2004;183:989-94.
69. Canatan D, Akar N, Arcasoy A. Effects of calcitonin therapy on osteoporosis in patients with thalassemia. Acta Haematol.1995;93:20-4.
70. Bucher U, Reid L. Development of the intrasegmental bronchial tree: the pattern of branching and development of cartilage at various stages of intra-uterine life. Thorax.1961;16:207-18.
71. Cooper DM, Mansell AL, Weiner MA, Berdon WE, Chetty-Baktaviziam A, Reid L et al. Low lung capacity and hypoxemia in children with thalassemia major. Am Rev Respir Dis. 1980;121:639- 46.
72. Carnelli V, D'Angelo E, Pecchiari M, Ligorio M, D'Angelo E.Pulmonary dysfunction in transfusiondependent patients with thalassemia major. Am J Respir Crit Care Med.2003;168:180-4.
73. Landing BH, Nadorra R, Hyman CB, Ortega JA. Pulmonary lesions of thalassemia major. Perspect Pediatr Pathol.1987;11:82-96.
74. Grisaru D, Rachmilewitz EA, Mosseri M, Gotsman M, Lafair JS, Okon E et al. Cardiopulmonary assessment in beta-thalassemia major. Chest.1990;98:1138-42.
75. Factor JM, Pottipati SR, Rappoport I, Rosner IK, Lesser ML, Giardina PJ. Pulmonary function abnormalities in thalassemia major and the role of iron overload. Am J Respir Crit Care Med. 1994;149:1570-4.
76. Arora M, Chandra J, Suri JC, Narayan S, Dutta AK. Pulmonary function tests in beta thalassemia. Indian J Pediatr.2001;68:239-42.
77. Fung KP, Chow OK, So SY, Yuen PM. Pulmonary function in thalassemia major. J Pediatr. 1987;111:534-7.
78. Keens TG, O'Neal MH, Ortega JA, Hyman CB, Platzker AC. Pulmonary function abnormalities in thalassemia patients on a hypertransfusion program. Pediatrics.1980;65:1013-7.
79. Santamaria F, Villa MP, Werner B, Cutrera R, Barreto M, Ronchetti R. The effect of transfusion on pulmonary function in patients with thalassemia major. Pediatr Pulmonol.1994;18:139-43.
80. Li AM, Chan D, Li CK, Wong E, Chan YL, Fok TF. Respiratory function in patients with thalassaemia major: relation with iron overload. Arch Dis Child.2002;87:328-30.
81. Abu-Ekteish FM, Al-Rimawi HS, Al-Ali MK, Shehabi IM.Pulmonary function tests in children with beta-thalassemia major. Chron Respir Dis.2007;4:19-22.
82. Bourli E, Dimitriadou M, Economou M, Vlachaki E, Christoforidis A, Maratou E et al. Restrictive pulmonary dysfunction and its predictors in young patients with beta-thalassaemia major. Pediatr Pulmonol.2012;47:801-7.
83. Piatti G, Allegra L, Ambrosetti U, Cappellini MD, Turati F, Fiorelli G. Beta-thalassemia and pulmonary function. Haematologica.1999;84:804-8.
84. Jamal R, Baizura J, Hamidah A, Idris N, Jeffrey AH, Roslan H. Abnormalities in lung function among multiply-transfused thalassemia patients: results from a thalassemia center in Malaysia. Southeast Asian J Trop Med Public Health.2005;36:265-9.
85. Dimopoulou I, Kremastinos DT, Maris TG, Mavrogeni S, Tzelepis GE. Respiratory function in patients with thalassaemia and iron overload. Eur Respir J.1999;13:602-5.
86. Canatan D, Koc N. The effect of transfusion on pulmonary function tests in patients with thalassemia. Turk J Haematol.2004;21:137-9.
87. Khong PL, Chan GC, Lee SL, Au WY, Fong DY, Tsang KW et al. Beta-thalassemia major: thinsection CT features and correlation with pulmonary function and iron overload. Radiology. 2003;229:507-12.
88. King GG, Brown NJ, Diba C, Thorpe CW, Muñoz P, Marks GB et al. The effects of body weight on airway calibre. Eur Respir J.2005;25:896-901.
89. Witzleben CL, Wyatt JP. The effect of long survival on the pathology of thalassaemia major. J Pathol Bacteriol.1961;82:1-12.
90. Hoyt RW, Scarpa N, Wilmott RW, Cohen A, Schwartz E. Pulmonary function abnormalities in homozygous beta-thalassemia. J Pediatr.1986;109:452-5.
91. Sohn EY, Noetzli LJ, Gera A, Kato R, Coates TD, Harmatz P et al. Pulmonary function in thalassaemia major and its correlation with body iron stores. Br J Haematol.2011;155:102-5.
92. Priftis KN, Anthracopoulos MB, Tsakanika C, Tapaki G, Ladis V, Bush A et al. Quantification of siderophages in bronchoalveolar fluid in transfusional and primary pulmonary hemosiderosis. Pediatr Pulmonol.2006;41:972-7.
93. Freedman MH, Grisaru D, Olivieri N, MacLusky I, Thorner PS. Pulmonary syndrome in patients with thalassemia major receiving intravenous deferoxamine infusions. Am J Dis Child. 1990;144:565-9.
94. Borgna-Pignatti C, Galanello R. Thalassemias and related disorders: quantitative disorders of hemoglobin synthesis. In Wintrobe's Clinical Hematology. 12th ed. (Eds JP Greer, J Foerster, GM Rodgers, F Parakevas, B Glader, RT Means):1082-131. Philadelphia, Lippincott Williams and Wilkins; 2009.
95. Hazirolan T, Eldem G, Unal S, Akpinar B, Gümrük F, Alibek S et al. Dual-echo TFE MRI for the assessment of myocardial iron overload in beta-thalassemia major patients. Diagn Interv Radiol. 2010;16:59-62.
96. Sritippayawan S, Lekhanont P, Harnruthakorn C, Samransamruajkit R, Deerojanawong J, Seksarn P et al. Restrictive lung disease and serum TGF-beta1 in thalassemia major children. Asian Pac J Allergy Immunol.2005;23:121-6.
97. Guidotti F, Piatti G, Marcon A, Cassinerio E, Giuditta M, Roghi A et al. Pulmonary dysfunction in thalassaemia major: is there any relationship with body iron stores? Br J Haematol. 2017;176:309-314.

ISSN: 1300-3755
Yayın Aralığı: Yılda 4 Sayı
Başlangıç: 1992
Yayıncı: Çukurova Üniversitesi Tıp Fakültesi

Arşiv