Exploring the Interplay between Asthma and Hemoglobinopathies: A Comprehensive Review

Abstract

Asthma, a prevalent chronic respiratory condition characterized by inflammation of the airways and bronchoconstriction, has demonstrated a potential association with hemoglobinopathies such as thalassemia and sickle cell disease (SCD). Numerous studies have highlighted a higher prevalence of asthma among thalassemia patients compared to the general population, with rates ranging around 30%. Similarly, asthma frequently coexists with SCD, affecting approximately 20-48% of patients. Children with SCD often experience heightened lower airway obstruction and airway hyper-reactivity. Notably, the presence of asthma in SCD exacerbates respiratory symptoms and increases the risk of severe complications like acute chest syndrome, stroke, vaso-occlusive episodes, and early mortality. Several studies have noted a decrease in various cytokines such as IFN-γ and IL-10, along with higher levels of both IL-6 and IL-8, suggesting an overactivation of pro-inflammatory mechanisms in patients with hemoglobinopathies, which could trigger inflammatory conditions such as asthma. The exact mechanisms driving this association are better elucidated but may involve factors such as chronic inflammation, oxidative stress, and immune dysregulation associated with thalassemia-related complications like chronic hemolytic anemia and iron overload. This review aims to comprehensively analyze the relationship between asthma and hemoglobinopathies, with a focus on thalassemia and SCD. It emphasizes the importance of interdisciplinary collaboration among pulmonologists, hematologists, and other healthcare professionals to effectively manage this complex interplay. Understanding this link is crucial for improving care and outcomes in affected individuals.

Keywords: asthma; asthma management; asthma screening; children; cytokines; hemoglobinopathies; pediatrics; sickle cell disease; spirometry; thalassemia.

Figure 1

Stress and immune dynamics in pulmonary epithelium. Physical stress and bacterial and viral infections are sources of stress for the pulmonary epithelium, which responds by secreting TSLP and IL33. These stimulate dendritic cells and ILC2 cells to produce IL4 and IL13. On the other hand, the excess of heme in thalassemic patients causes an increase in the activity of heme oxygenase-1, leading to a decrease in the production of IL-10 and IFN-Y. These factors favor the transition from T0 to Th2 with the creation of a proallergenic phenotype.

Figure 2

Novel paradigm of hemolysis-associated AHR and an “asthma-like” condition in SCD. The image presents a biochemical pathway illustrating the impact of dysregulated arginine metabolism on pulmonary health. We show how hemolysis leads to an increase in arginase activity, shifting the metabolism of arginine away from the production of nitric oxide (NO). This metabolic shift increases ornithine, which contributes to lung structure changes associated with conditions like pulmonary hypertension, asthma, and pulmonary fibrosis, which are prevalent in SCD patients. The image highlights the conversion of arginine to ornithine, which is linked to pulmonary hypertension and possible fibrosis and how its increment may promote cell growth and vascular remodeling. Additionally, it outlines the role of inflammation in enhancing arginase activity during asthma attacks, which can result in acute arginine and NO deficiency.