Study Finds Link Between Thalassemia, Risk of Asthma

The study showed children with thalassemia had a greater risk of both atopic and non-atopic asthma.

Children with genetic hemoglobinopathies appear to be at a higher risk of developing asthma, according to a new study of more than 800 children.

Writing in the journal PLoS One, corresponding author Yao-Hsu Yang, MD, MPH, of Chang Gung University College of Medicine in Taiwan, and colleagues, explained that previous research into children with hemoglobinopathies have suggested that those children have higher rates of pulmonary complications. Hemoglobinopathies are a category of disorder in which patients have either dysfunctional hemoglobin molecules or lower-than-normal amounts of the molecules.

However, little research has been conducted investigating links between the disorders and asthma specifically. Yang and colleagues decided to focus on thalassemia, the second-most common hemoglobinopathy after sickle cell disease. About 5% of people globally have thalassemia, an autosomal recessive disorder in which subjects have a decrease or absence of certain hemoglobin units. The disorder has 2 subtypes, alpha and beta. Patients with intermediate or major beta thalassemia have higher rates of restrictive pulmonary function and pulmonary hypertension, the investigators noted.

Yang and colleagues used a cohort of patients from Taiwan’s health insurance research database. Eight hundred children with thalassemia were identified, and each was matched with 4 control children who had similar demographics, including birth year and sex.

The investigators found that, among the group with thalassemia, asthma rates were 41.81 cases per 1000 person-years. Among the control group, the rate was just 25.7 per 1000 person-years. Those data translated into an adjusted hazard ratio of 1.37 (95% confidence interval [CI], 1.19–1.58).

“This is a nationwide population-based cohort study based on an extremely large database adjusted for risk factors for asthma,” Yang and colleagues wrote. “The results suggested that thalassemic children had a higher risk of developing asthma than children without thalassemia at a younger age.”

The risk was especially high for boys, the analysis showed. Those in the thalassemia cohort had an adjusted incidence hazard ratio of 1.45 (95% CI = 1.02–1.73) compared to boys in the non-thalassemia cohort. That tracks generally with higher rates of asthma among boys compared with girls in the population as a whole, Yang and colleagues said.

“The frequency of asthma starts to change from being higher in males to higher in females around puberty,” they said. “In our study, thalassemic boys had a higher rate of asthma than control cohorts which is consistent with previous reports.”

The children in the study were born between 1997 and 2010, though the children were diagnosed with asthma at around age 3, on average.

The investigators also found that children with thalassemia had higher rates of both atopic and non-atopic asthma, compared with children without thalassemia.

In terms of the reason for the apparent connection between thalassemia and asthma, authors noted that an earlier study suggested thalassemia led to greater rigidity of red blood cells in the capillary bed, which in turn could cause bronchial hyperactivity. However, Yang and colleagues said that mechanism has not yet been proven. The authors also posited another theory.

“Recently, we found that thalassemic patients had a higher incidence of low respiratory tract infection, which may be linked to a higher incidence of asthma or asthma exacerbation,” they said.

The authors concluded more research is needed to better understand the connections. They also said more attention should be paid to early diagnosis and prevention of asthma among this patient group.

Hsieh H, Huang L, Yu H, et al. Pediatric thalassemic patients have higher incidence of asthma: A nationwide population-based retrospective cohort study. PLoS One. Published online November 4, 2021. doi:10.1371/journal.pone.0258727

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