Pulmonary Iron Overload in Thalassemia major Presenting as Small Airway Disease

Abstract

Lung function abnormalities that are associated with thalassemia major are variable with etiology that is yet undetermined. Some studies have suggested that pulmonary iron deposition is a probable cause for these lung defects although there has been no antemortem histopathological and radiological evidence for this. We report a case of thalassemia major with biopsy-proven pulmonary iron overload, in which thoracic high-resolution computed tomography revealed a morphological-functional correlation consistent with small airway disease.

Effects of Iron Chelators on Pulmonary Iron Overload and Oxidative Stress in β-Thalassemic Mice

“…mitochondria, lysosomes) and activation of fibroblasts [9,23] . Our study demonstrates that iron overload in BKO mice results in pulmonary iron deposition characterized by epithelial damage and increased numbers of iron-laden alveolar macrophages, similar to that observed in postmortem lung samples from thalassemia major patients [6,24,25] . Moreover, pulmonary fibrosis was observed in BKO mice.…”

“…This iron burden resulted in lung epithelial injuries, fibrosis and corresponded with increased lipid peroxidation and decreased tissue catalase activity. Treatment with DF or L1 resulted in a reduction of iron-laden alveolar macrophages and decreased oxidative thromboembolisms, pulmonary airway obstructions, hypertension, hypoxemia and abnormal pulmonary function; particularly in splenectomized thalassemia-major patients requiring routine blood transfusions [3][4][5][6] . Although there is no confirmed direct correlation with body iron stores, clinical data implicates excessive iron burden from thalassemia major in the etiology of small airway disease and restrictive lung disease that often accompany thalassemia major [4,7] .…”

β-Thalassemia Major: Thin-Section CT Features and Correlation with Pulmonary Function and Iron Overload

“…The proposed mechanisms of airway obstruction in ␤-thalassemia major include oxidative damage as a result of free iron deposition within the airway epithelium (10,11). This theory is supported by the identification of iron-laden macrophages and lymphocyte alveolitis within the bronchial mucosa and in bronchoalveolar lavage fluid, suggesting that free iron deposition is a toxic mechanism.…”

“…In two published series, thin-section CT was performed in selected patients with ␤-thalassemia major who underwent pulmonary function testing, but the findings were not described in detail (4,6). Recently, using thin-section CT, we found diffuse centrilobular nodules and air trapping in a patient with ␤-thalassemia major who was subsequently confirmed to have small-airway disease at histopathologic examination (11). Thus, the purpose of our study was to describe and quantify the thin-section CT imaging features of the lung in patients with ␤-thalassemia major and determine the correlation between thin-section CT findings, pulmonary function test results, and iron overload.…”

HFE gene variants and iron-induced oxygen radical generation in idiopathic pulmonary fibrosis

“…Increased levels of haemosiderin iron are also found in pulmonary veno-occlusive disease, where Prussian blue stained alveolar macrophages and type II pneumocytes are seen in the absence of frank fibrosis [31], and in diffuse alveolar damage, concomitant with moderate to severe alveolar haemorrhage [32]. Finally, in some transfusion-dependent thalassaemia patients, systemic iron overload has been associated with functional and histopathological abnormalities, including bronchial iron deposition and fibrosis [33][34][35].…”