European Journal of Cardiovascular Medicine

Thalassemia is a hereditary hemoglobin disorder characterized by defective synthesis of globin chains, leading to chronic anemia and a lifelong dependence on blood transfusion. The term thalassemia originates from the Greek words thalassa (sea) and haima (blood), reflecting its early recognition among populations residing around the Mediterranean region. The disorder was first clinically described by Cooley and Lee in 1925, and later formally named by Whipple and Bradford in 1932. Thalassemia is inherited in an autosomal recessive manner and represents one of the most common monogenic disorders worldwide. Although it has a high prevalence in Mediterranean countries, the Middle East, and Southeast Asia, global migration has contributed to its widespread distribution across continents.¹

India bears a substantial burden of thalassemia, with nearly 10% of the world’s thalassemic births occurring annually in the country.² The prevalence of β-thalassemia trait in India ranges from 1% to 17%, with a carrier frequency of approximately 3–4%, varying across different regions and ethnic groups.² This high disease burden poses significant challenges to the healthcare system, particularly in pediatric populations requiring long-term management.

Advances in medical care over the past three decades—especially regular blood transfusion protocols and effective iron chelation therapy—have markedly improved survival and quality of life in children with β-thalassemia major. As a result, thalassemia has transitioned from a rapidly fatal condition to a chronic disease compatible with prolonged survival. However, repeated blood transfusions inevitably result in progressive iron overload, with deposition in vital organs such as the liver, heart, pancreas, and endocrine glands. Pulmonary involvement has also been reported in patients with thalassemia, though it has received relatively limited clinical attention.

Pulmonary dysfunction in thalassemia is often subclinical and may not present with overt respiratory symptoms, leading to under-recognition. Several studies have reported restrictive ventilatory defects as the most common abnormality, while others have identified obstructive or mixed patterns of lung dysfunction.³˒⁴ The exact pathophysiological mechanisms underlying pulmonary impairment in thalassemia remain unclear and are likely multifactorial, involving iron deposition, chronic anemia, repeated infections, and transfusion-related complications.

Attempts to correlate serum ferritin levels with pulmonary function abnormalities have yielded inconsistent and conflicting results.⁵˒⁶ Furthermore, there is a paucity of data from India—particularly from certain regions—regarding systematic evaluation of pulmonary function in children with β-thalassemia major. In view of these gaps, the present study was undertaken to assess pulmonary function abnormalities in children with β-thalassemia major and to explore their association with iron overload.

A hospital-based cross-sectional study was conducted. The study was carried out in the Department of Pediatrics of a tertiary care teaching hospital. Children aged 5–15 years with a confirmed diagnosis of β-thalassemia major, admitted for periodic blood transfusion in the pediatric ward, were included in the study. Inclusion Criteria • Children aged 5 to 15 years • Confirmed diagnosis of β-thalassemia major • Receiving regular blood transfusions Exclusion Criteria • Children with previously diagnosed pulmonary diseases such as asthma, bronchiectasis, or other chronic lung disorders • Children with congenital heart disease or rheumatic heart disease Written informed consent was obtained from the parents or legal guardians of all participating children. Confidentiality of patient information was strictly maintained. Children fulfilling the inclusion and exclusion criteria were enrolled consecutively. A detailed clinical history was obtained for each participant, including: • Age at first blood transfusion • Total number of blood transfusions received • Duration of iron chelation therapy A thorough general physical examination was performed, and findings were recorded using a pre-designed proforma. Prior to blood transfusion, venous blood samples were collected for: • Serum ferritin level • Pre-transfusion hemoglobin concentration Serum ferritin levels were measured using the electrochemiluminescence method on a Cobas 6000 analyzer. Pulmonary function tests (PFTs) were performed using a spirometer (RMS Helios) in accordance with standard guidelines. Testing was conducted within 24 hours of blood transfusion. Parameters assessed included forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and FEV₁/FVC ratio. Pulmonary function patterns were categorized as normal, restrictive, obstructive, or mixed (Annexure 1).

A total of 70 children with β-thalassemia major, aged 5–15 years, were included in the study. All children underwent pulmonary function testing and serum ferritin estimation as per the study protocol. Out of the 70 children evaluated, 54 (77.1%) demonstrated abnormal pulmonary function test (PFT) results, while 16 (22.9%) had normal pulmonary function.

Among children with abnormal PFTs, the restrictive pattern was the most commonly observed abnormality, seen in 48 children (88.9%), followed by obstructive pattern in 3 children (5.6%) and a combined restrictive–obstructive pattern in 3 children (5.6%). The mean age of children with abnormal pulmonary function was 8.3 ± 2.5 years. Among these, 31 were males and 23 were females, with a male-to-female ratio of 1.35:1.

Table 1: Pattern of Pulmonary Function Test Results (N = 70)

The mean values of pulmonary function parameters are summarized in Table 2. Reduced FVC% was the most common abnormality observed, followed by reductions in FEV₁, PEFR, and FEF25–75%. Most children had a normal FEV₁/FVC ratio, consistent with a predominantly restrictive pattern of lung involvement.

Table 2: Pulmonary Function Test Parameters (N = 70)

Pearson correlation analysis demonstrated a significant negative correlation between age and selected pulmonary function parameters. Increasing age was associated with declining FVC%, FEV₁%, and PEFR, indicating progressive pulmonary involvement with advancing age.

Table 3: Correlation Between Age and Pulmonary Function Parameters (N = 70)

* Significant
** Highly significant

The mean serum ferritin levels were higher among children with restrictive pulmonary dysfunction compared to those with normal or other abnormal PFT patterns. However, no statistically significant difference was observed in mean serum ferritin levels across different pulmonary function categories.

Table 4: Comparison of Serum Ferritin Levels with Pulmonary Function Pattern (N = 70)

† ANOVA test

Pulmonary involvement is a recognized but often under-evaluated complication in children with β-thalassemia major. The pattern of lung dysfunction reported in thalassemia varies widely and may present as restrictive, obstructive, or mixed ventilatory defects. Previous studies have documented the prevalence of pulmonary dysfunction in thalassemia to range from 29% to 86%, reflecting heterogeneity in study populations, disease severity, and assessment methods. In the present study, 77.1% of children demonstrated abnormal pulmonary function, indicating a high burden of subclinical respiratory involvement.

The restrictive pattern was the predominant abnormality observed, accounting for nearly 89% of children with abnormal pulmonary function. This finding is consistent with several earlier studies that have reported restrictive ventilatory defects as the most common pulmonary abnormality in thalassemia major. Despite consistent observations across studies, the precise etiopathogenesis of restrictive lung dysfunction remains unclear. Proposed mechanisms include chronic anemia, recurrent hypoxia, repeated blood transfusions, iron deposition in lung tissue, adverse effects of chelation therapy, and altered lung growth during childhood.

In the present study, age showed a significant negative correlation with FVC%, FEV₁%, and PEFR, indicating progressive decline in pulmonary function with increasing age. These findings are in agreement with reports by Abu-Ekteish et al., who demonstrated worsening restrictive abnormalities with advancing age in thalassemic children. Similar trends have been noted in other studies, suggesting that cumulative disease burden and prolonged exposure to pathogenic factors contribute to progressive pulmonary impairment.

Although restrictive lung disease was predominant, a small proportion of children exhibited obstructive and combined ventilatory patterns. Obstructive dysfunction has been attributed to early bronchial involvement, air trapping, and bronchial wall changes, as reported in some studies where obstructive patterns were more prevalent. However, such findings were relatively uncommon in the present study. The combined pattern, observed in a minority of children, may represent overlapping mechanisms or limitations in early detection, as suggested in previous literature.

Analysis of individual pulmonary function parameters revealed that reduced FVC was the most frequent abnormality, followed by reductions in FEV₁, PEFR, and FEF25–75%, while the FEV₁/FVC ratio remained normal in most children. This pattern further supports the predominance of restrictive lung involvement. Although more than half of the children showed reduced FEF25–75%, isolated small airway disease was not inferred, as reductions were also noted in other spirometric indices.

The role of iron overload in the development of pulmonary dysfunction remains controversial. While elevated serum ferritin levels have been associated with lung injury and increased mortality risk in some studies, the present study did not demonstrate a statistically significant association between serum ferritin levels and pulmonary function patterns. Although children with higher ferritin levels (>2500 ng/mL) showed lower mean spirometric values, these differences were not statistically significant. This lack of association may be explained by the fact that serum ferritin is an indirect marker of total body iron stores and may fluctuate with chelation therapy, inflammation, and recent transfusions.

Overall, the findings suggest that pulmonary dysfunction in β-thalassemia major is likely multifactorial, with contributions from chronic anemia, altered lung development, iron overload, and long-term transfusion-related effects rather than a single causative factor.

Pulmonary function abnormalities were observed in 54 (77.1%) children with β-thalassemia major. The restrictive pattern was the most common abnormality (88.9%), followed by obstructive and combined patterns. A significant proportion of children demonstrated reduced FVC, FEV₁, PEFR, and FEF25–75%, while the FEV₁/FVC ratio remained normal in most cases. Pulmonary function declined with increasing age, indicating progressive respiratory involvement.Serum ferritin levels did not show a significant correlation with pulmonary dysfunction, suggesting that factors beyond iron overload contribute to lung impairment. Clinical Implication Regular pulmonary function testing should be incorporated into the routine evaluation of children with β-thalassemia major, even in the absence of respiratory symptoms, to allow early detection and monitoring of pulmonary involvement.

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