Evidence of Lymphocyte Alveolitis by Bronchoalveolar Lavage in Thalassemic Patients with Pulmonary Dysfunction

Abstract

Pulmonary dysfunction represents one of the least studied complications in thalassemic patients. Probably, it is due to the absence of pulmonary symptoms. There are few works in the literature, and contradictory results have been published. The aim of this study was to define the spirometric pattern and the possible causes of lung impairment by testing bronchoalveolar lavage (BAL) with pathological pulmonary function tests (PFTs). Furthermore, diffusion capacity tests for carbon monoxide corrected for hemoglobin value (Dco*) were performed. We studied 48 thalassemic patients (27 F and 21 M), with an age range from 8 to 23 years, divided into two groups on the basis of PFTs results. Thus, group A was formed by 16 patients with restrictive spirometric patterns of whom 14 had also reduced Dco* values and group B consisted of 32 patients with normal PFTs and Dco* values. Patients of group A underwent chest high-resolution computing tomography (CHRCT) and BAL whose fluid was analyzed by microbiologic and cytological assays. A pathological CHRCT picture was present in 8 patients. Nine out of 16 patients who accepted to undergo BAL had a chronological age greater than 17 years with a mean bone age of 13.9 years. BAL results showed lymphocyte alveolitis in 6 patients and a normal cytogram in 3, while alveolar iron-laden macrophages were present in 4 out of 6 patients with alveolitis and 2 out of 3 patients with normal cytogram. Moreover, all examined BAL fluids showed a normal CD4/CD8 ratio, while only 2 patients showed an altered serum CD4/CD8 ratio. We demonstrated the presence of (1) lung-restrictive syndrome in 16 of the oldest thalassemic patients; (2) lymphocyte alveolitis in 6 patients, and (3) a picture of interstitial fibrosis by CHRCT in 8 of them. All these data are suggestive of a diagnosis of interstitial lung disease secondary to thalassemia. BAL helped to identify the presence of alveolar iron-laden macrophages that represented a local defense mechanism against free iron. This latter finding therefore might be the primary cause of the lung impairment promoting an oxidative damage. Further studies are needed to investigate this hypothesis and therapeutical potentials.

Pulmonary Iron Overload in Thalassemia major Presenting as Small Airway Disease

“…Both restrictive and obstructive defects including impairment of carbon monoxide diffusion capacity (DL CO ) are found in thalassemia major patients [1, 2, 3, 4, 5, 6, 7, 8, 11]. Our patient’s raised diffusion coefficient is therefore not typical, although we cannot find an explanation for this discrepancy in the previously published literature.…”

“…The mechanism of airway obstruction in thalassemia major has been attributed to oxidative damage as a result of free iron deposition within the airway epithelium [6, 7, 11]. The role of macrophages in sequestering free iron to reduce the oxidative effect is highlighted by the presence of iron-laden macrophages within the bronchial mucosa in our case [11].…”

“…Pulmonary dysfunction has been attributed partially or fully to iron overload in some studies [2, 6, 7]. The lack of consensus on this issue is further compounded by a lack of antemortem histopathological and radiological evidence of pulmonary iron overload [5, 9, 10, 11, 12]. …”

“…Our patient’s raised diffusion coefficient is therefore not typical, although we cannot find an explanation for this discrepancy in the previously published literature. Small airway obstruction with air trapping (elevated RV and RV/TLC) has been reported as the main functional abnormality [6, 7], while other studies have reported predominantly restrictive lung defects with some airway obstruction [1, 2, 3, 4, 11]. Although a formal methacholine challenge test has not been performed, it is very unlikely that our patient’s airway disease is the result of occult asthma as there were no symptoms typical of asthma or reversibility.…”

Evidence of a Restrictive Spirometric Pattern in Older Thalassemic Patients

“…Our data showed a correlation between serum ferritin levels and the entity of pulmonary dysfunction, even though further studies are necessary for careful determination of the iron overload. Only in this way, will it be possible to confirm this crucial correlation, even though iron deposition was also observed on autopsy in the lungs of thalassemic patients [26]. We have recently published a study on bronchoalveolar lavage in thalassemic patients the results of which highlighted a lymphocyte alveolitis with the presence of alveolar iron-laden macrophages and a picture of interstitial fibrosis by chest high-resolution computed tomography [27].…”