- Email: [email protected]
Pulmonary function abnormalities in young adults with thalassemia major
Pathophysiology 4 (1997) 131 – 134
Pulmonary function abnormalities in young adults with thalassemia major K.I. Gourgoullanis a,*, A. Gouslou b, G. Papaioannou b, C. Halkias b, N. Stathakis a, P.A. Molyvdas a a
Lung Function Laboratory of Physiology Department, Medical School Uni6ersity of Thessaly, 22, Papakyriazi, 412 22 Larissa, Greece b Thalassemia Department General Hospital of Larissa, Tsakalof 1 Larissa, Greece Received 13 September 1996; accepted 18 February 1997
Abstract Thalassemia seems to be the most common genetic disorder. The pathophysiologic mechanisms for lung impairment is not clear. Lung function tests in children showed small airway obstruction and restrictive lung changes. Forty-two patients, 22 females and 20 males, aged from 17 to 36 years old, with homozygous b-thalassemia were examined in a lung function laboratory. All patients received chelation therapy and none of them had history of respiratory disease. Lung function tests included spirometry, static lung volumes measured by a closed circuit helium rebreathing technique and diffusion capacity measured by the method of single breath diffusion of carbon monoxide. All patients, before these tests, had haematologic examinations (Hb, serum ferritin), electrocardiogram and echocardiogram. Only five out of 42 patients had completely normal pulmonary function. Four had only diffusion impairment, 18 restrictive and 15 combined (restrictive and obstructive) pattern of lung disease. Vital capacity (in 27 patients), total lung capacity (in 21 patients) and forced expiratory volume in the first second (in 30 patients) were abnormally reduced. The ratio of residual volume (RV) to total lung capacity (TLC) was increased in 19 patients. Patients with only diffusion impairment had statistically significant more increased serum ferritin value (4415 ng/ml) than other patterns of lung function. Patients with combined or restrictive pattern of lung function, had heart failure and osteoporosis more often than other patients. Heart failure and the aberrant growth process that limits the volume of peripheral airspace are perhaps the possible mechanisms for the restrictive lung disease, small airways obstruction and hyperinflation. © 1997 Elsevier Science B.V. Keywords: b-thalassemia major; Lung function
1. Introduction Thalassemia is considered the most common genetic disorder. About 3% of the world population carry b-thalassemia genes. In Greece, the prevalence varies, ranging from 5 to 15% in central areas [1]. The prognosis of b-thalassemia major depends on progressive cachexia and recurrent infections. Transfusion therapy permits the development in childhood but damages the organs progressively. The chronic administration of * Corresponding author. 0928-4680/97/$17.00 © 1997 Elsevier Science B.V. All rights reserved. PII S 0 9 8 - 4 6 8 0 ( 9 7 ) 0 0 1 7 1 - 5
large amounts of blood along with an inappropriate increase in iron absorbtion from the gastrointestinal tract inevitably leads to clinically significant hemosiderosis. The terminal event in transfused patients is most commonly refractory heart failure in adolescense or early adult life [2]. The pathophysiologic basis for lung impairment is not clear. The results of previous studies were contradictory. Pulmorary function tests, especially in children, showed small airway obstruction or restrictive lung changes [3,4]. The purpose of this study was the evaluation of lung volumes, flow rates and diffusion capacity only in early adults homozygous b-thalassemia patients.
132
K.I. Gourgoullanis et al. / Pathophysiology 4 (1997) 131–134 Table 2 Pulmonary function tests of 42 patients
2. Patients and methods Forty-two early adult patients (22 females and 20 males) with b-thalassemia major were studied. All patients attended the Thalassemia Department of the General Hospital of Larissa for routine evaluation of b-thalassemia. Their age ranged from 17 to 36 years (mean age, 21.9 years). All patients received chelation therapy with continuous subcutaneous injection of desferioxamine in a private dose ranged from 3 to 18 years (mean duration, 11.8 years). Five patients were smokers (for less than 5 years and smoked fewer than 20 cigarettes daily). None of them had a history of asthma or other chronic respiratory diseases. During the pulmonary function tests, all patients were in stable condition. Pulmonary function studies were carried out on a computerized laboratory instrument (Master Screen Diffusion, Jaeger). Vital Capacity and its subdivisions, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow rate (PEF) were obtained from spirometry. Total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV) were measured by a closed circuit helium rebreathing technique. Single breath diffusion of carbon monoxide gave the diffusion capacity (Dco). The value of Dco was corrected for hemoglobin concentration. Normal values for volumes, flows and diffusion capacity obtained from the equations of Morris and Burrows [5,6]. Cardiac function was evaluated by electrocardiogram and echocardiography. Parasternal long-axis and shortaxis and apical 4 and 2 chamber views were obtained [7]. Osteoporosis was evaluated by the designation of the density of bone by the method of dual-photon absorbtiometry. Serum ferritin was measured in an analyzer (ABOTT) with microparticle enzyme immunoassay. For statistical analysis the x 2 method was used. Relationships were considered significant if the P-value was lower than 0.05.
Table 1 Patient characteractics
Age (years) Transfusion onset (years) Total blood transfusions units Chelation therapy (years)
Mean
Range
21.9 2.2 6.22 11.8
17–36 0.16–23 –980 3–18
No. of patients 60 – 80%
\100%a
2 0 4 9 1
25 21 11 14 0
1 3 11 4 19
4 0 23
26 3 11
1 26 2
8 0
24 4
0 0
B60% Lung volumes VC TLC RV FRC RV/TLC Flow rates FEV1 FEV1/FVC MMEF Diffusion study Dco Dco/VA
a Percent of predicted values. All the other patients are between 80 and 100% of predicted values.
3. Results Table 1 shows that the age of the patients ranged from 17 to 36 years (Mean age 21.9 years). The total blood transfusions units per patient ranged from 140 to 980 units and the mean duration of chelation therapy was 11.8 years. Vital Capacity (VC) was reduced in 27 of 42 patients. TLC was reduced in 21 patients but the Residual Volume (RV) was reduced in only 15 and increased in 11 of 42 patients. Forced expiratory volume in the first second (FEV1) was reduced in 30 patients and the Mild Expiratory Fiow Rate (MMEF) in 34 patients. The diffusion capacity (Dco) was reduced in 32 patients. Only four of them had reduced the ratio Dco/VA (Diffusion Capacity/Alveolar Ventilation) (Table 2). Table 3 shows, that only five patients had normal lung function. The most common pattern of pulmonary function was the restrictive (18 patients). Patients with only diffusion impairment had statistically significant more serum ferritin values (4415 ng/ml) than other patterns of lung function. Table 4 shows, that none of the patients with normal lung function was over 21 years old. Nine of the 15 patients with combined pattern (restrictive and obstructive) and ten out of 18 with restrictive pattern aged over 21 years. Patients with combined pattern had statistically significant more often heart failure or osteoporosis than other lung function groups of patients.
4. Discussion Our study showed that almost all patients with bthalassemia major had abnormal lung function in early
K.I. Gourgoullanis et al. / Pathophysiology 4 (1997) 131–134
133
Table 3 Haematologlc data Lung function
Normal Only diffusion impairment Restrictive pattern Combined pattern
Mean value (range) Patients
Hb-pretranfusional (g)
Hb during diffusion test
Serum ferritin (ng/ml)
5 4 18 15
10.2 10.2 10.1 10.3
12.1 12.2 11.8 11.7
2440 4415 2840 3708
NS
NS
P
adult life. The most common types of respiratory disorders was the restrictive pattern and the combined pattern (obstructive and restrictive). The patients with only diffusion impairment had the highest serum ferritin levels. The lung function, as shown by the tests, deteriorates with age. TLC was reduced in half of the patients. RV was reduced in 25% and increased in another 25% of the patients. The ratio RV/TLC was increased in 19 and the MMEF was decreased in 34 out of 42 patients. It seems that these results do not agree with other previous studies. Keens et al. found normal TLC values in 12 thalassemia patients on a hypertransfusion programme [8]. On the contrary, Cooper et al., presented reduced TLC in seven out of 17 children with thalassemia major. The constant rate of carbon monoxide diffusion (Kco) was above the predicted mean value in 14 of 15 children [9]. Other studies reported reduced RV in 16 and reduced MMEF in 15 of 19 b-thalassemia major, ranging in age from 10 to 29 years [10]. Grisaru et al. showed that half of the b-thalassemia major aged from 8 to 33 years, had reduced lung volumes or diffusion [11]. The reasons for these discrepancies are the small number of patients and the great range of their age. Each of the previous studies evaluated fewer than thirty patients, including children and adults. The equations of predicted values for volumes and flow rates are completely different in children and adults [12]. Despite the various findings of pulmonary function tests, there seem to be only four types of pulmonary
B0.05
function in b-thalassemia major; normal function, only diffusion impairment, restrictive pattern and combined (restrictive and obstructive) pattern. The process from normal lung function to combined pattern, which is related to aging is statistically significant. Congestive heart failure, iron overload and pulmonary hypertension may contribute to these age related abnormalities [13,14]. Carbon monoxide diffusion capacity measures the transfer of a diffusion-limited gas across the alveolocapillary membrane [15]. Postmorten examinations of patients with thalassemia major who had received transfusions over long periods have revealed pulmonary iron deposition. Serum ferritin values have been directly correlated to iron deposits in the liver and presumably to iron deposition in the lung [10]. In our patients who had only diffusion impairment without disturbance of lung mechanics, the highest values of serum ferritin were described. The Kco (Dco/VA) in almost all patients was normal. High cardiac output is an important factor in the correction of Kco in thalassemia patients with pulmonary hypertension and heart failure. A pattern of restrictive pulmonary disease could develop in patients with thalassemia major from pulmonary fibrosis due to iron load and from an aberrant growth process that limits the volumes of peripheral airspaces. Even in children optimally transfused, the adolescent growth spurt is delayed. Bone biopsies from thalassemic patients showed osteopenia, decreased mineralization and a decreased number of bone forming sites. Our results showed that the majority of patients
Table 4 Patients’ data Lung function
Patients
Normal Only diffusion impairment Restrictive pattern Combined pattern
5 4 18 15
P
Age \21 years 0 1 10 9 B0.05
Heart failure 0 0 6 7 B0.05
Osteoporosis 1 2 12 13 B0.05
Splenectomy 1 0 6 5 NS
K.I. Gourgoullanis et al. / Pathophysiology 4 (1997) 131–134
134
with restrictive lung disease had findings of osteoporosis. Another reason for restrictive pattern could be the elevation of the diaphragm resulting from liver and spleen enlargement [8]. Many thalassemic patients develop obstructive lung disease additionally to the restrictive pattern. The increased RV/TLC ratio and the reduced MMEF are indexes of small airways disfunction. Possible explanations include recurrent pulmonary infections and a narrowing of the airways because of iron or reduced elastic fiber recoil. Heart failure with pulmonary vascular engorgement and interstitial oedema leads to a fall in lung compliance. The patients with combined pattern, obstructive and restrictive, have more often heart failure. The development of airways obstruction seems to be a terminal event in the process of the b-thalassemia major. Consequently, the iron overload, the discrepancy between the growth of thoracic cage and lung in adolescence and the heart failure may be the reasons for the abnormalities in lung volumes, flow rates and diffusion, which usually take place in b-thalassemia major.
References [1] J.N. Lukens, The thalassemias and related disorders: Quantitative disorders of hemoglobin synthesis, in: Wintrobe’s Clinical Hematology, Ninth Edition. Lea and Febiger, Philadelphia, 1993. [2] D.T. Kremastinos, P.K. Toutouzas, G.P. Vyssoulis, C.A. Vinitis, H.F. Vretan, D.G. Avgoustakis, Global and segmental left ventricular function in b-thalassemia, Cardiology 72 (1985) 129 – 139.
.
[3] A. Cohen, J. Mizanin, E. Shwartz, Treatment of iron overload in Cooley’s anemia, Ann. NY. Acad. Sci. 445 (1985) 274. [4] F. Santamaria, M.P. Villa, B. Werner, R. Cutrera, M. Barreto, R. Ronchetti, The effect of transfussion on pulmonary function in patients with thalassemia major, Pediatr. Pulmonol. 18 (1994) 139 – 142. [5] B. Burrows, K.E. Kasik, N.H. Niden, W. Barclay, Clinical usefulness of the single-breath-pulmonary diffusion capacity test, Am. Rev. Respir. Dis. 84 (1961) 789 – 806. [6] J.F. Morris, Spirometry in the evaluation of pulmonary function medical progress, West J. Med. 125 (1976) 110 – 118. [7] H. Feigenbaum, Echocardiography. Lee and Febiger Co, Philadelphia, 1986. [8] T.G. Keens, M.H. O’Neal, J.A. Ortega, C.B. Hyman, A.C.G. Platzker, Pulmonary function abnormalities in thalassemia patients on a hypertransfusion program, Pediatrics 65 (1980) 1013– 1017. [9] D.M. Cooper, A.L. Mansell, M.A. Weiner, W.E. Berdon, A. Chetty-Baktaviziam, L. Reid, R.B. Mellins, Low lung capacity and hypoxemia in children with thalassemia major, Am. Rev. Respir. Dis. 121 (1980) 639 – 646. [10] R.V. Hoyt, N. Scarpa, R.W. Wilmott, A. Cohen, E. Schwartz, Pulmonary function abnormalities in homozygous b-thalassemia, J. Pediatr. 109 (1986) 452 – 455. [11] D. Grisaru, A.W. Goldfard, M.S. Gotsman, E.A. Rachmilewitz, Y. Hasin, Deferoxamine improves left venticular function in b-thalassemia, Arch. Intern. Med. 146 (1986) 2344 – 2349. [12] G.E. Ruppel, Manual of pulmonary function testing. MosbyYear book, St Louis, 1994. [13] M. Fosburg, D. Nathan, Treatment of Cooley’s anemia, Blood 76 (1990) 435 – 444. [14] D. Grisaru, E.A. Rachmilewitz, M. Mosseri, M. Gotsman, J.S. Lafair, E. Okon, A. Goldfard, Y. Hasin, Cardiopulmonary assesment in Beta-thalassemia major, Chest 98 (1990) –1142. [15] J.B. West, Pulmonary Pathophysiology: the Essentials. Williams and Wilkins, Baltimore, 1992.
Pulmonary function abnormalities in young adults with thalassemia major K.I. Gourgoullanis a,*, A. Gouslou b, G. Papaioannou b, C. Halkias b, N. Stathakis a, P.A. Molyvdas a a
Lung Function Laboratory of Physiology Department, Medical School Uni6ersity of Thessaly, 22, Papakyriazi, 412 22 Larissa, Greece b Thalassemia Department General Hospital of Larissa, Tsakalof 1 Larissa, Greece Received 13 September 1996; accepted 18 February 1997
Abstract Thalassemia seems to be the most common genetic disorder. The pathophysiologic mechanisms for lung impairment is not clear. Lung function tests in children showed small airway obstruction and restrictive lung changes. Forty-two patients, 22 females and 20 males, aged from 17 to 36 years old, with homozygous b-thalassemia were examined in a lung function laboratory. All patients received chelation therapy and none of them had history of respiratory disease. Lung function tests included spirometry, static lung volumes measured by a closed circuit helium rebreathing technique and diffusion capacity measured by the method of single breath diffusion of carbon monoxide. All patients, before these tests, had haematologic examinations (Hb, serum ferritin), electrocardiogram and echocardiogram. Only five out of 42 patients had completely normal pulmonary function. Four had only diffusion impairment, 18 restrictive and 15 combined (restrictive and obstructive) pattern of lung disease. Vital capacity (in 27 patients), total lung capacity (in 21 patients) and forced expiratory volume in the first second (in 30 patients) were abnormally reduced. The ratio of residual volume (RV) to total lung capacity (TLC) was increased in 19 patients. Patients with only diffusion impairment had statistically significant more increased serum ferritin value (4415 ng/ml) than other patterns of lung function. Patients with combined or restrictive pattern of lung function, had heart failure and osteoporosis more often than other patients. Heart failure and the aberrant growth process that limits the volume of peripheral airspace are perhaps the possible mechanisms for the restrictive lung disease, small airways obstruction and hyperinflation. © 1997 Elsevier Science B.V. Keywords: b-thalassemia major; Lung function
1. Introduction Thalassemia is considered the most common genetic disorder. About 3% of the world population carry b-thalassemia genes. In Greece, the prevalence varies, ranging from 5 to 15% in central areas [1]. The prognosis of b-thalassemia major depends on progressive cachexia and recurrent infections. Transfusion therapy permits the development in childhood but damages the organs progressively. The chronic administration of * Corresponding author. 0928-4680/97/$17.00 © 1997 Elsevier Science B.V. All rights reserved. PII S 0 9 8 - 4 6 8 0 ( 9 7 ) 0 0 1 7 1 - 5
large amounts of blood along with an inappropriate increase in iron absorbtion from the gastrointestinal tract inevitably leads to clinically significant hemosiderosis. The terminal event in transfused patients is most commonly refractory heart failure in adolescense or early adult life [2]. The pathophysiologic basis for lung impairment is not clear. The results of previous studies were contradictory. Pulmorary function tests, especially in children, showed small airway obstruction or restrictive lung changes [3,4]. The purpose of this study was the evaluation of lung volumes, flow rates and diffusion capacity only in early adults homozygous b-thalassemia patients.
132
K.I. Gourgoullanis et al. / Pathophysiology 4 (1997) 131–134 Table 2 Pulmonary function tests of 42 patients
2. Patients and methods Forty-two early adult patients (22 females and 20 males) with b-thalassemia major were studied. All patients attended the Thalassemia Department of the General Hospital of Larissa for routine evaluation of b-thalassemia. Their age ranged from 17 to 36 years (mean age, 21.9 years). All patients received chelation therapy with continuous subcutaneous injection of desferioxamine in a private dose ranged from 3 to 18 years (mean duration, 11.8 years). Five patients were smokers (for less than 5 years and smoked fewer than 20 cigarettes daily). None of them had a history of asthma or other chronic respiratory diseases. During the pulmonary function tests, all patients were in stable condition. Pulmonary function studies were carried out on a computerized laboratory instrument (Master Screen Diffusion, Jaeger). Vital Capacity and its subdivisions, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow rate (PEF) were obtained from spirometry. Total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV) were measured by a closed circuit helium rebreathing technique. Single breath diffusion of carbon monoxide gave the diffusion capacity (Dco). The value of Dco was corrected for hemoglobin concentration. Normal values for volumes, flows and diffusion capacity obtained from the equations of Morris and Burrows [5,6]. Cardiac function was evaluated by electrocardiogram and echocardiography. Parasternal long-axis and shortaxis and apical 4 and 2 chamber views were obtained [7]. Osteoporosis was evaluated by the designation of the density of bone by the method of dual-photon absorbtiometry. Serum ferritin was measured in an analyzer (ABOTT) with microparticle enzyme immunoassay. For statistical analysis the x 2 method was used. Relationships were considered significant if the P-value was lower than 0.05.
Table 1 Patient characteractics
Age (years) Transfusion onset (years) Total blood transfusions units Chelation therapy (years)
Mean
Range
21.9 2.2 6.22 11.8
17–36 0.16–23 –980 3–18
No. of patients 60 – 80%
\100%a
2 0 4 9 1
25 21 11 14 0
1 3 11 4 19
4 0 23
26 3 11
1 26 2
8 0
24 4
0 0
B60% Lung volumes VC TLC RV FRC RV/TLC Flow rates FEV1 FEV1/FVC MMEF Diffusion study Dco Dco/VA
a Percent of predicted values. All the other patients are between 80 and 100% of predicted values.
3. Results Table 1 shows that the age of the patients ranged from 17 to 36 years (Mean age 21.9 years). The total blood transfusions units per patient ranged from 140 to 980 units and the mean duration of chelation therapy was 11.8 years. Vital Capacity (VC) was reduced in 27 of 42 patients. TLC was reduced in 21 patients but the Residual Volume (RV) was reduced in only 15 and increased in 11 of 42 patients. Forced expiratory volume in the first second (FEV1) was reduced in 30 patients and the Mild Expiratory Fiow Rate (MMEF) in 34 patients. The diffusion capacity (Dco) was reduced in 32 patients. Only four of them had reduced the ratio Dco/VA (Diffusion Capacity/Alveolar Ventilation) (Table 2). Table 3 shows, that only five patients had normal lung function. The most common pattern of pulmonary function was the restrictive (18 patients). Patients with only diffusion impairment had statistically significant more serum ferritin values (4415 ng/ml) than other patterns of lung function. Table 4 shows, that none of the patients with normal lung function was over 21 years old. Nine of the 15 patients with combined pattern (restrictive and obstructive) and ten out of 18 with restrictive pattern aged over 21 years. Patients with combined pattern had statistically significant more often heart failure or osteoporosis than other lung function groups of patients.
4. Discussion Our study showed that almost all patients with bthalassemia major had abnormal lung function in early
K.I. Gourgoullanis et al. / Pathophysiology 4 (1997) 131–134
133
Table 3 Haematologlc data Lung function
Normal Only diffusion impairment Restrictive pattern Combined pattern
Mean value (range) Patients
Hb-pretranfusional (g)
Hb during diffusion test
Serum ferritin (ng/ml)
5 4 18 15
10.2 10.2 10.1 10.3
12.1 12.2 11.8 11.7
2440 4415 2840 3708
NS
NS
P
adult life. The most common types of respiratory disorders was the restrictive pattern and the combined pattern (obstructive and restrictive). The patients with only diffusion impairment had the highest serum ferritin levels. The lung function, as shown by the tests, deteriorates with age. TLC was reduced in half of the patients. RV was reduced in 25% and increased in another 25% of the patients. The ratio RV/TLC was increased in 19 and the MMEF was decreased in 34 out of 42 patients. It seems that these results do not agree with other previous studies. Keens et al. found normal TLC values in 12 thalassemia patients on a hypertransfusion programme [8]. On the contrary, Cooper et al., presented reduced TLC in seven out of 17 children with thalassemia major. The constant rate of carbon monoxide diffusion (Kco) was above the predicted mean value in 14 of 15 children [9]. Other studies reported reduced RV in 16 and reduced MMEF in 15 of 19 b-thalassemia major, ranging in age from 10 to 29 years [10]. Grisaru et al. showed that half of the b-thalassemia major aged from 8 to 33 years, had reduced lung volumes or diffusion [11]. The reasons for these discrepancies are the small number of patients and the great range of their age. Each of the previous studies evaluated fewer than thirty patients, including children and adults. The equations of predicted values for volumes and flow rates are completely different in children and adults [12]. Despite the various findings of pulmonary function tests, there seem to be only four types of pulmonary
B0.05
function in b-thalassemia major; normal function, only diffusion impairment, restrictive pattern and combined (restrictive and obstructive) pattern. The process from normal lung function to combined pattern, which is related to aging is statistically significant. Congestive heart failure, iron overload and pulmonary hypertension may contribute to these age related abnormalities [13,14]. Carbon monoxide diffusion capacity measures the transfer of a diffusion-limited gas across the alveolocapillary membrane [15]. Postmorten examinations of patients with thalassemia major who had received transfusions over long periods have revealed pulmonary iron deposition. Serum ferritin values have been directly correlated to iron deposits in the liver and presumably to iron deposition in the lung [10]. In our patients who had only diffusion impairment without disturbance of lung mechanics, the highest values of serum ferritin were described. The Kco (Dco/VA) in almost all patients was normal. High cardiac output is an important factor in the correction of Kco in thalassemia patients with pulmonary hypertension and heart failure. A pattern of restrictive pulmonary disease could develop in patients with thalassemia major from pulmonary fibrosis due to iron load and from an aberrant growth process that limits the volumes of peripheral airspaces. Even in children optimally transfused, the adolescent growth spurt is delayed. Bone biopsies from thalassemic patients showed osteopenia, decreased mineralization and a decreased number of bone forming sites. Our results showed that the majority of patients
Table 4 Patients’ data Lung function
Patients
Normal Only diffusion impairment Restrictive pattern Combined pattern
5 4 18 15
P
Age \21 years 0 1 10 9 B0.05
Heart failure 0 0 6 7 B0.05
Osteoporosis 1 2 12 13 B0.05
Splenectomy 1 0 6 5 NS
K.I. Gourgoullanis et al. / Pathophysiology 4 (1997) 131–134
134
with restrictive lung disease had findings of osteoporosis. Another reason for restrictive pattern could be the elevation of the diaphragm resulting from liver and spleen enlargement [8]. Many thalassemic patients develop obstructive lung disease additionally to the restrictive pattern. The increased RV/TLC ratio and the reduced MMEF are indexes of small airways disfunction. Possible explanations include recurrent pulmonary infections and a narrowing of the airways because of iron or reduced elastic fiber recoil. Heart failure with pulmonary vascular engorgement and interstitial oedema leads to a fall in lung compliance. The patients with combined pattern, obstructive and restrictive, have more often heart failure. The development of airways obstruction seems to be a terminal event in the process of the b-thalassemia major. Consequently, the iron overload, the discrepancy between the growth of thoracic cage and lung in adolescence and the heart failure may be the reasons for the abnormalities in lung volumes, flow rates and diffusion, which usually take place in b-thalassemia major.
References [1] J.N. Lukens, The thalassemias and related disorders: Quantitative disorders of hemoglobin synthesis, in: Wintrobe’s Clinical Hematology, Ninth Edition. Lea and Febiger, Philadelphia, 1993. [2] D.T. Kremastinos, P.K. Toutouzas, G.P. Vyssoulis, C.A. Vinitis, H.F. Vretan, D.G. Avgoustakis, Global and segmental left ventricular function in b-thalassemia, Cardiology 72 (1985) 129 – 139.
.
[3] A. Cohen, J. Mizanin, E. Shwartz, Treatment of iron overload in Cooley’s anemia, Ann. NY. Acad. Sci. 445 (1985) 274. [4] F. Santamaria, M.P. Villa, B. Werner, R. Cutrera, M. Barreto, R. Ronchetti, The effect of transfussion on pulmonary function in patients with thalassemia major, Pediatr. Pulmonol. 18 (1994) 139 – 142. [5] B. Burrows, K.E. Kasik, N.H. Niden, W. Barclay, Clinical usefulness of the single-breath-pulmonary diffusion capacity test, Am. Rev. Respir. Dis. 84 (1961) 789 – 806. [6] J.F. Morris, Spirometry in the evaluation of pulmonary function medical progress, West J. Med. 125 (1976) 110 – 118. [7] H. Feigenbaum, Echocardiography. Lee and Febiger Co, Philadelphia, 1986. [8] T.G. Keens, M.H. O’Neal, J.A. Ortega, C.B. Hyman, A.C.G. Platzker, Pulmonary function abnormalities in thalassemia patients on a hypertransfusion program, Pediatrics 65 (1980) 1013– 1017. [9] D.M. Cooper, A.L. Mansell, M.A. Weiner, W.E. Berdon, A. Chetty-Baktaviziam, L. Reid, R.B. Mellins, Low lung capacity and hypoxemia in children with thalassemia major, Am. Rev. Respir. Dis. 121 (1980) 639 – 646. [10] R.V. Hoyt, N. Scarpa, R.W. Wilmott, A. Cohen, E. Schwartz, Pulmonary function abnormalities in homozygous b-thalassemia, J. Pediatr. 109 (1986) 452 – 455. [11] D. Grisaru, A.W. Goldfard, M.S. Gotsman, E.A. Rachmilewitz, Y. Hasin, Deferoxamine improves left venticular function in b-thalassemia, Arch. Intern. Med. 146 (1986) 2344 – 2349. [12] G.E. Ruppel, Manual of pulmonary function testing. MosbyYear book, St Louis, 1994. [13] M. Fosburg, D. Nathan, Treatment of Cooley’s anemia, Blood 76 (1990) 435 – 444. [14] D. Grisaru, E.A. Rachmilewitz, M. Mosseri, M. Gotsman, J.S. Lafair, E. Okon, A. Goldfard, Y. Hasin, Cardiopulmonary assesment in Beta-thalassemia major, Chest 98 (1990) –1142. [15] J.B. West, Pulmonary Pathophysiology: the Essentials. Williams and Wilkins, Baltimore, 1992.