Pulmonary dysfunction in thalassaemia major: is there any relationship with body iron stores?

Abstract

Although pulmonary function abnormalities in thalassaemia major (TM) were described in 1980, the pathogenetic mechanism is not clear and data are contradictory, probably because of study heterogeneity and the multifactorial nature of the pathogenesis. We retrospectively analysed 73 adult TM patients to evaluate the prevalence of pulmonary dysfunction in adult TM and investigate relationships with iron load. All patients underwent body plethysmography and carbon monoxide diffusion (DLCO) was assessed in 63, in addition to blood tests, echocardiogram and T2* myocardial and liver magnetic resonance imaging. Restrictive lung disease was present in 26 (35·6%) patients. Serum ferritin levels were higher in patients with restrictive pattern (1526 μg/l vs. 975 μg/l, P = 0·05). Restrictive lung disease did not correlate with cardiac or liver iron overload. However, considering only patients with serum ferritin >2500 μg/l, those with restrictive pattern also had heart (T2* 14·28 ± 9·99 ms vs. 31·59 ± 7·43 ms) and liver iron overload (LIC 16·02 ± 8·44 mg vs. 5·02 ± 2·69 mg Fe/g dry weight) compared to those without restrictive pattern. Twenty-five patients (39·7%) had decreased DLCO. No correlation was observed with iron parameters. In our data restrictive pattern was predominant; we observed a relationship with serum ferritin levels suggesting that iron, particularly its chronic effect, could play a role in the pathogenesis of pulmonary disease.

Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease

“…It is of note that restrictive lung disease is the predominant pulmonary dysfunction in patients with thalassemia major ( Carnelli et al, 2003 , Guidotti et al, 2016 , Kanj et al, 2000 ). Due to ineffective erythropoiesis and blood transfusion requirements, these patients present with increased systemic iron levels and parenchymal iron overload.…”

“…In patients with chronic obstructive pulmonary disease (COPD), iron deposits in alveolar macrophages (AM) and the percentage of iron loaded macrophages is associated with increased disease severity ( Philippot et al, 2014 ). On the other hand thalassemia major, a disease characterized by transfusional iron overload, has been associated with impaired lung function ( Carnelli et al, 2003 , Guidotti et al, 2016 , Kanj et al, 2000 ). However, whether pulmonary iron accumulation contributes to disease onset and progression is poorly understood.…”

Iron Homeostasis in the Lungs—A Balance between Health and Disease

“…Pulmonary dysfunction, in particular restrictive lung disease, is frequently observed in patients with thalassemia major (TM), a disease characterized by severe iron accumulation [186,187,188,189]. It has been speculated that abnormal lung function in those patients might be a consequence of chronic iron overload [189]. Supporting this hypothesis, a restrictive pattern was observed in a mouse model of iron overload, caused by a mutation in FPN that confers resistance to hepcidin binding [56].…”

Beta-Talasemia: Un mundo de complicaciones con nuevas alternativas de tratamiento.

“…Sin embargo, a pesar de la correcta aplicación de intervenciones diagnósticas y terapéuticas los pacientes talasémicos pueden experimentar enfermedades secundarias o complicaciones que han asumido un papel nuevo e importante en el curso de esta enfermedad en los últimos años [43,44]. La hipoxia, la eritropoyesis ineficaz y la sobrecarga de hierro contribuyen a producir las complicaciones en múltiples órganos; de los cuales el Universidad de Manizales -Facultad de Ciencias de la Salud hígado, el corazón y las glándulas endocrinas son los órganos afectados con mayor frecuencia y es en quienes finalmente se observan complicaciones cirrosis, insuficiencia cardíaca y defectos endocrinos (hipotiroidismo, hipopituitarismo, hipogonadismo, hipoparatiroidismo) [45]. A continuación se hablará de algunas de estas de manera más detallada.…”