Epidemiology of lung diseses in thalassemia
Answers
The β-thalassemias constitute a group of inherited disorders of hemoglobin synthesis primarily existing in the low- or middle-income countries of the tropical belt stretching from sub-Saharan Africa, through the Mediterranean region and the Middle East, to South and Southeast Asia. Continued migration has also greatly expanded the reach of these diseases into large, multiethnic cities in Europe and North America, thus making such disorders a global public health concern.1 Distinction of the various forms of β-thalassemia relies on clinical grounds. Patients with β-thalassemia major present to medical attention in early childhood with severe anemia requiring life-long transfusion and iron chelation therapy for survival.2 Conversely, patients with β-thalassemia intermedia present later in childhood with milder anemia and remain largely transfusion-independent.3 Such variation in phenotype has been attributed to several environmental and genetic factors that alter the α/β-chain imbalance and subsequent ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process in β-thalassemia.4
Clinical Perspective on p 345
Among the sequelae associated with a diagnosis of β-thalassemia, pulmonary arterial hypertension (PAH) has received great attention in recent years.5 Prevalence rates exceeded 50% in some studies. Although the exact mechanisms implicated in the pathogenesis of PAH in β-thalassemia remain unclear, its association with several risk factors and with subsequent right-sided heart failure have been illustrated.5,6 The main concern is that most available studies that evaluated PAH in patients with β-thalassemia established the diagnosis solely based on echocardiographic criteria, without systematic confirmation on right heart catheterization, a procedure that is recommended in international guidelines as the standard of care.7–9 More importantly, recent evidence from patients with sickle cell disease (SCD) echoed earlier studies in other conditions which established that the use of echocardiography alone results in a considerable number of false positive diagnoses that are not confirmed on right heart catheterization.10 Hence, the true prevalence of PAH in patients with β-thalassemia remains unidentified. Such information not only has implications on health care use measures, but will also aid in proper interpretation of available studies highlighting risk factors and outcomes associated with PAH in this patient population. In this line, we aimed to evaluate the prevalence of PAH in a large group of patients with β-thalassemia using standard diagnostic criteria involving confirmatory right heart catheterization. The role of several risk factors was also evaluated.
Methods
Participants
This was a multicenter, cross-sectional study of β-thalassemia patients followed at 8 thalassemia comprehensive care centers taking part of the Italian Webthal project. Webthal is a computerized clinical record network for all thalassemia patients attending the participating centers and is commonly used for collaborative research studies. We included all adult (≥18 years) patients with a diagnosis of β-thalassemia major or intermedia defined as per standard criteria11 (n=1330), and excluded patients with chronic restrictive lung disease or a left ventricular ejection fraction of ≤50% on last echocardiography in whom pulmonary hypertension, if confirmed, would not be classified as PAH but would be attributed to left heart or lung disease (n=21). A total of 1309 patients were eligible for the study. The study was conducted over a 12-month period (January 20, 2012 through January 20, 2013). The institutional review boards at all participating centers approved the study protocol and all participants signed a written informed consent before inclusion (ClinicalTrials.gov Identifier: NCT01496963).
Answer:
To determine the predominant abnormality of pulmonary function in patients with thalassemia major (TM), we evaluated 29 patients with TM who were receiving hypertransfusion therapy and chelation with desferrioxamine (DFO), and who ranged in age from 6 to 40 yr (mean 19.8 +/- 8.5 yr). A reduction in the total lung capacity (TLC) was the most striking abnormality, found in 21 of 29 patients (79%). Fourteen of these patients (67%) had a moderate or severe reduction in TLC. Expiratory flow rates, FEV1, and FEF25-75 were decreased below predicted values in 48 and 17% of the patients, respectively, but no patients had pure obstructive disease. Significant hypoxemia (oxygen saturation of less than 95%) was observed in only one patient. There was a significant inverse correlation between TLC and patient age (p < 0.003), transfusional iron burden (p < 0.003) and DFO ratio (p < 0.024). Restrictive disease is the predominant abnormality of pulmonary function in TM, with a mixed restrictive-obstructive pattern in a small number of patients. The restrictive disease becomes more severe with increasing age, and the degree and duration of iron overload appear to be important in its pathogenesis. The role of DFO therapy in preventing the pulmonary complications associated with TM requires further study.