Pulmonary Dysfunction in Patients with Transfusion-Dependent Thalassemia

Introduction Transfusion-dependent thalassemia (TDT) is a prevalent monogenic disorder characterized by an imbalance in hemoglobin peptide chain synthesis, leading to clinical manifestations such as anemia, hemolysis, and ineffective erythropoiesis. Iron overload, a consequence of repeated blood transfusions and increased intestinal iron absorption, is known to cause complications including heart failure, hepatic fibrosis, hypothyroidism, and hypopituitarism .etc. However, the impact of iron overload on pulmonary function has been relatively under-investigated. This study aimed to investigate the prevalence of pulmonary dysfunction in TDT patients and its association with iron overload.

Method A retrospective analysis was conducted on patients selected from the hematopoietic stem cell transplantation candidates between January 2019 and December 2023. The inclusion criteria were: 1) a confirmed diagnosis of TDT based on genetic testing and clinical presentation; 2) absence of pneumonia within two weeks before pulmonary function testing and no recent symptoms indicative of respiratory infection; 3) availability of complete clinical data, including routine blood tests within one week of pulmonary function testing, and serum ferritin levels, liver iron MRI, and cardiac iron MRI within six months. The exclusion criteria included: 1) a history of asthma, pulmonary hypertension, or heart disease; 2) pulmonary function tests conducted post-transplantation.Pulmonary function tests were performed by experienced physicians using body plethysmography and spirography (Jaeger Master Scree, Germany).

We performed statistical analyses using SPSS version 26.0. Independent t-test, non-parametric test, and chi-square test were used for comparison of normally distributed quantitative variables, non-normally distributed quantitative variables, and qualitative variables, respectively. Binary logistic regression was used for multivariate analysis. P<0.05 was considered statistically significant.

Results A total of 140 TDT patients were included in the study. The mean age of the patients was 8.7 ± 3.2 years, with a median serum ferritin (SF) level of 3791.4 ng/ml (interquartile range: 2424.1-5733.3 ng/ml). Pulmonary function abnormalities were detected in 46.43% (65 out of 140) of the patients, predominantly as diffusion dysfunction (26.43%), followed by ventilatory dysfunction (5.0%), and mixed pulmonary dysfunction (15.0%). An elevated serum ferritin level above 2500 ng/ml was significantly correlated with the occurrence of these abnormalities (odds ratio [OR] = 3.187, 95% confidence interval [CI]: 1.312-7.741, P = 0.010), whereas higher hemoglobin concentrations were associated with a protective effect (OR = 0.966, 95% CI: 0.943-0.989, P = 0.004).

Conclusion Our research has pinpointed SF levels exceeding 2500 ng/ml as a critical risk factor for impaired lung function in patients with TDT. In contrast, high hemoglobin levels serve as a protective factor. These findings emphasize the necessity of rigorous monitoring of iron levels and maintaining adequate hemoglobin concentrations to effectively manage TDT, ultimately enhancing patient care and survival.