Prevalence of pulmonary dysfunction in patients with beta thalassemia major: a systematic review and meta-analysis

  • Amar Taksande Department of Paediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Sawangi Meghe, Wardha, Maharashtra State
  • Yash Dalal Department of Paediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Sawangi Meghe, Wardha, Maharashtra State
  • Himanshi Jindal Department of Paediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Sawangi Meghe, Wardha, Maharashtra State
  • Taksande Bharati Department of Paediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Sawangi Meghe, Wardha, Maharashtra State
Keywords: thalassemia; pulmonary dysfunction; restrictive; obstructive; iron overload; serum ferritin


Background Many studies have been conducted on heart, liver, and endocrine abnormalities in thalassemia; however, studies on pulmonary dysfunction (PD) have been limited. Previous studies on the prevalence of restrictive lung disease (RLD) and obstructive lung disease (OLD) in β-thalassemia major patients have lacked agreement.

Objective To assess the prevalence of PD in β-thalassemia major patients by systematic review of the literature and meta-analysis.

Methods We searched Cochrane library, PubMed, Web of Science, MEDLINE, Scopus, and Embase for relevant articles. Articles were selected according to the inclusion criteria and data were extracted. The primary outcome was prevalence of pulmonary dysfunction in β-thalassemia major with 95% confidence interval (95%CI). Subgroup analyses were applied to explore the prevalence in different age groups, regions, and serum ferritin levels. Sensitivity analysis and publication bias assessment were also conducted.

Results A total of 37 studies comprising 1,467 cases were included in this analysis. Pulmonary dysfunction was present in 64.7% (95%CI 57.6 to 71.1) of cases. The pooled prevalence of RLD (44.9%) was higher than that of OLD (7.6%) and diffusion impairment (DI) (35.6%). Subgroup analysis revealed that the region with the highest pooled prevalence of PD was the Americas (75.2%). The highest prevalence of RLD and DI was found in Asia (48.2% and 44.6%, respectively) and that of OLD in Europe (9.7%). Sensitivity analysis showed that the pooled results were robust.

Conclusion A high prevalence of pulmonary dysfunction, mainly RLD rather than OLD, was detected in β-thalassemia major patients.


1. Survival and Complications in Thalassemia - BORGNA?PIGNATTI - 2005 - Annals of the New York Academy of Sciences - Wiley Online Library [Internet]. [cited 2020 Sep 12]. Available from:
2. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;5:11. DOI: 10.1186/1750-1172-5-11.
3. Kountouris P, Lederer CW, Fanis P, Feleki X, Old J, Kleanthous M. IthaGenes: an interactive database for haemoglobin variations and epidemiology. PloS One. 2014;9:e103020. DOI: 10.1371/journal.pone.0103020.
4. Ladis V, Karagiorga-Lagana M, Tsatra I, Chouliaras G. Thirty-year experience in preventing haemoglobinopathies in Greece: achievements and potentials for optimisation. Eur J Haematol. 2013;90:313–22. DOI: 10.1111/ejh.12076.
5. Shah FT, Sayani F, Trompeter S, Drasar E, Piga A. Challenges of blood transfusions in ?-thalassemia. Blood Rev. 2019;37:100588. DOI: 10.1016/j.blre.2019.100588.
6. Fung EB, Harmatz PR, Lee PDK, Milet M, Bellevue R, Jeng MR, et al. Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease. Br J Haematol. 2006;135:574–82. DOI: 10.1111/j.1365-2141.2006.06332.x.
7. Lobo C, ?ngulo IL, Aparicio LR, Drelichman GI, Zanichelli MA, Cancado R, et al. Retrospective epidemiological study of Latin American patients with transfusional hemosiderosis: the first Latin American epidemiological study in iron overload – the RELATH study. Hematology. 2011;16:265–73. DOI: 10.1179/102453311X13085644680302.
8. Carnelli V, D’Angelo E, Pecchiari M, Ligorio M, D’Angelo E. Pulmonary dysfunction in transfusion-dependent patients with thalassemia major. Am J Respir Crit Care Med. 2003;168:180–4. DOI: 10.1164/rccm.200211-1292OC.
9. 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. DOI: 10.1136/adc.87.4.328.
10. Azarkeivan A, Mehrvar A, SohrabPour H, Mehrvar N, Vosough P. Pulmonary function test in transfusion-dependent ?-thalassemia patients. Pediatr Hematol Oncol. 2008;25:598–606. DOI: 10.1080/08880010802237294.
11. Filosa A, Esposito V, Meoli I, Baron I, Romano L. Evidence of lymphocyte alveolitis by bronchoalveolar lavage in thalassemic patients with pulmonary dysfunction. Acta Haematol. 2000;103:90–5. DOI: 10.1159/000041026.
12. Kanj N, Shamseddine A, Gharzeddine W, Kanj M, Nasr TA, Koussa S, et al. Relation of ferritin levels to pulmonary function in patients with thalassemia major and the acute effects of transfusion. Eur J Haematol. 2000;64:396–400. DOI: 10.1034/j.1600-0609.2000.90106.x.
13. 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. DOI: 10.1164/ajrccm.149.6.8004315.
14. Tai DY, Wang YT, Lou J, Wang WY, Mak KH, Cheng HK. Lungs in thalassaemia major patients receiving regular transfusion. Eur Respir J. 1996;9:1389–94. DOI: 10.1183/09031936.96.09071389.
15. Fung KP, Chow OK, So SY, Yuen PM. Pulmonary function in thalassemia major. J Pediatr. 1987;111:534–7. DOI: 10.1016/s0022-3476(87)80113-0.
16. 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. DOI: 10.1164/arrd.1980.121.4.639.
17. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12. DOI: 10.1001/jama.283.15.2008.
18. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. DOI: 10.1136/bmj.b2535.
19. Viera A, Garrett J. Understanding interobserver agreement: the kappa statistic. Fam Med. 2005;37:360-3. PMID: 15883903.
20. Hoy D, Brooks P, Woolf A, Blyth F, March L, Bain C, et al. Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. J Clin Epidemiol. 2012;65:934–9. DOI: 10.1016/j.jclinepi.2011.11.014.
21. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Int J Surg. 2014;12:1500–24. DOI: 10.1016/j.ijsu.2014.07.014.
22. Higgins J, Green S. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011] [cited YEAR MONTH DATE]. The Cochrane Collaboration, 2011. Available from:
23. Borenstein M, Hedges L, Higgins J, Rothstein H. Meta-regression. In: Introduction to meta-analysis. Chichester: John Wiley and Sons; 2009. p. 187–203.
24. Borenstein M, Rothstein H. Comprehensive meta-analysis: a computer program for research synthesis computer program. Englewood Cliffs: Biostat, Inc; 1999.
25. 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. PMID: 7367114.
26. Hoyt RW, Scarpa N, Wilmott RW, Cohen A, Schwartz E. Pulmonary function abnormalities in homozygous beta-thalassemia. J Pediatr. 1986;109:452–5. DOI: 10.1016/s0022-3476(86)80116-0.
27. 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. DOI: 10.1378/chest.98.5.1138.
28. Cracowski C, Wuyam B, Klein V, Lévy P. Lung function and exercise capacity in thalassaemia major. Eur Respir J. 1998;12:1130–6. DOI: 10.1183/09031936.98.12051130.
29. Kivity S, Gazy C, Heno N, Greif Z, Topilsky M. Effect of the Leukostop filter on pulmonary function following blood transfusion in patients with thalassemia major. Pediatr Pulmonol. 1999;28:277–81. DOI: 10.1002/(sici)1099-0496(199910)28:4<277::aid-ppul7>;2-3.
30. 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. DOI: 10.1183/09031936.99.13360299.
31. Filosa A, Esposito V, Meoli I, Stefanelli F, Cassandro R. Evidence of a restrictive spirometric pattern in older thalassemic patients. Respiration. 2001;68:273–8. DOI: 10.1159/000050510.
32. Arora M, Chandra J, Suri JC, Narayan S, Dutta AK. Pulmonary function tests in beta thalassemia. Indian J Pediatr. 2001;68:239–42. DOI: 10.1007/BF02723198.
33. Khong PL, Chan GC, Lee SL, Au WY, Fong DY, Tsang KW, et al. ?-Thalassemia major: thin-section CT features and correlation with pulmonary function and iron overload. Radiology. 2003;229:507–12. DOI: 10.1148/radiol.2292021805.
34. 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. PMID: 15906681.
35. Sritippayawan S, Lekhanont P, Harnruthakorn C, Samransamruajkit R, Deerojanawong J, Seksarn P, et al. Restrictive lung disease and serum TGF-[beta] 1 in thalassemia major children. Asian Pac J Allergy Immunol. 2005;23:121. PMID: 16252842.
36. Said M, Sastroasmoro S, Gatot D, Supriyatno B, Ananta Y. Comparison of pulmonary functions of thalassemic and of healthy children. Paediatr Indones. 2016;45:1–6. DOI: 10.14238/pi45.1.2005.1-6.
37. Piatti G, Allegra L, Fasano V, Gambardella C, Bisaccia M, Cappellini MD. Lung function in ?-thalassemia patients: a longitudinal study. Acta Haematol. 2006;116:25–9. DOI: 10.1159/000092344.
38. Parakh A, Dubey AP, Chowdhury V, Sethi GR, Jain S, Hira HS. Study of pulmonary function tests in thalassemic children. J Pediatr Hematol Oncol. 2007;29:151–5. DOI: 10.1097/MPH.0b013e318033a73d.
39. 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. DOI: 10.1177/1479972306070376.
40. Rahim F, Keikhaei B, Ebadi A. Clinical manifestation of pulmonary dysfunction in B—thalassemia major. J Med Sci. 2008;8:484–90. DOI: 10.3923/jms.2008.484.490.
41. Eidani I, Keikhaei B, Rahim F, Bagheri A. Evaluation of pulmonary function in beta-thalassemia major patients. Pak J Med Sci. 2009;25:749–54.
42. 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. DOI: 10.1111/j.1365-2141.2011.08808.x.
43. Alyasin S, Moghtaderi M, Amin R, Kashef S, Karimi M. Pulmonary function test in transfusion-dependent ?-thalassemia major patients: a pilot study. Pediatr Hematol Oncol. 2011;28:329–33. DOI: 10.3109/08880018.2010.543449.
44. Bourli E, Dimitriadou M, Economou M, Vlachaki E, Christoforidis A, Maratou E, et al. Restrictive pulmonary dysfunction and its predictors in young patients with ?-thalassaemia major. Pediatr Pulmonol. 2012;47:801–7. DOI: 10.1002/ppul.22506.
45. Noori NM, Keshavarz K, Shahriar M. Cardiac and pulmonary dysfunction in asymptomatic beta-thalassanemia major. Asian Cardiovasc Thorac Ann. 2012;20:555–9. DOI: 10.1177/0218492312439706.
46. Hamed AelS, Ragab IA, Kamel TB, Abd-El-Gawad AO. Effect of using bedside leukocyte filter on pulmonary functions in patients with thalassemia major. Pediatr Hematol Oncol. 2013;30:761–7. DOI: 10.3109/08880018.2013.838724.
47. Gülhan B, Yalç?n E, Ünal ?, O?uz B, Özçelik U, Ersöz DD, et al. Effects of blood transfusion on cytokine profile and pulmonary function in patients with thalassemia major. Clin Respir J. 2016;10:153–62. DOI: 10.1111/crj.12193.
48. Ozyoruk D, Misirlioglu ED. Pulmonary functions in children with thalassemia major. J Pediatr Hematol Oncol. 2015;37:605–10. DOI: 10.1097/MPH.0000000000000425.
49. Boddu A, Kumble A, Mahalingam S, Baliga BS, Achappa B. Pulmonary dysfunction in children with beta thalassemia major in relation with iron overload-a cross sectional hospital based study. Asian J Med Sci. 2015;6:47–50. DOI: 10.3126/AJMS.V615.11782.
50. 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;176:309–14. DOI: 10.1111/bjh.14396.
51. Nandurkar P, Goel M, Sharma S. A study on cardiopulmonary function tests in thalassemia major patients (6-14 years) and its correlation to serum ferritin. J Pulm Respir Med. 2018;8:450. DOI:10.4172/2161-105X.1000450.
52. Gadiparthi M, Bhaskaranand N, Kini PG, Hebbar SA, Mundkur SC. Pulmonary function tests in ? thalassemia major and its correlation with serum ferritin levels. Int J Contemp Pediatr. 2019;6:306–9. DOI: 10.18203/2349-3291.ijcp20190450.

53. Abd El Hakeem AA, Mousa SMO, AbdelFattah MT, AbdelAziz AO, Abd El Azeim SS. Pulmonary functions in Egyptian children with transfusion-dependent ?-thalassemia. Transfus Med. 2019;29:55–60. DOI: 10.1111/tme.12539.
54. Elsehaimy LA, Zineldin MF, Khalil WA. Evaluation of pulmonary functions in pediatric patients with beta-thalassemia major. Al-Azhar Assiut Med J. 2019;17:264-7 DOI: 10.4103/AZMJ.AZMJ_46_19.
55. Kazgan T, Yagci-Küpeli? B, Özhan AK. Asymptomatic respiratory dysfunction in patients with thalassemia major. Cukurova Med J. 2019;44:1317–22. DOI: 10.17826/cumj.525791.
56. Harsoor J, Ratageri VH, Shilpa C, Illalu S, Wari P. Pulmonary function tests in children with beta-thalassemia major. Karnataka Pediatr J. 2020;35:52-6. DOI:10.25259/KPJ_2_2020.
57. Witzleben CL, Wyatt JP. The effect of long survival on the pathology of thalassæmia major. J Pathol Bacteriol. 1961;82:1-12. PMID: 13786138
58. 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. DOI: 10.1002/ppul.1950180304.
How to Cite
Taksande A, Dalal Y, Jindal H, Bharati T. Prevalence of pulmonary dysfunction in patients with beta thalassemia major: a systematic review and meta-analysis. PI [Internet]. 20Jan.2022 [cited 31Mar.2023];62(1):7-6. Available from:
Pediatric Respirology
Received 2020-11-07
Accepted 2022-01-20
Published 2022-01-20