Iron Deficiency Anemia Associated with High Risk of Asthma

Genetically predicted iron deficiency anemia (IDA) may be causally linked to an increased risk of asthma, according to new findings from Mendelian randomization (MR) analysis.¹

Data from observational studies have previously reported an increased risk of anemia from asthma. However, an investigative team from the Army Medical University in China postulates this causal relationship as more reliable, as MR analysis is less susceptible to confounding or reverse causation.

“Elucidating the underlying mechanisms by which IDA contributes to asthma susceptibility is critical to guide the prevention and treatment of asthma, and further research should identify the molecular and pathways through which IDA can initiate asthma,” wrote investigators, led by Wanwei Li, department of pediatrics, Daping Hospital, Army Medical University.

Asthma is a major global chronic disease, characterized by complex airflow obstruction, leading to dyspnea and wheezing.² Disease management includes assessing asthma control, related risk factors, and an appropriately adjusted medication cycle. The etiology of asthma is not well understood, but the interaction between genetic backgrounds and environmental factors is believed to play a critical role in its development.²

Previously reported data have reported a correlation between higher blood eosinophil levels and acute asthma exacerbations and disease severity.³ Other data show the probability of anemia is notably increased in patients with asthma.⁴

Thus, Li and colleagues conducted a two-sample MR analysis to evaluate the causal link between genetically determined IDA and the development of asthma.

The MR study was based on a large-scale genome-wide association study (GWAS). The primary analysis was based on IDA from the IEU consortium on asthma (n = 156,078), with the primary genetic tool for IDA including 72,261 individuals of European ancestry.

Anemia statistics included 12,434 anemia cases and 59,827 controls of European ancestry from the FinnGen Consortium. Asthma statistics included 20,629 cases and 135,449 controls.

Inverse variance weighted (IVW) served as the primary analysis method, with weighted medians and MR-Egger regression methods used to benefit robust estimates. Overall data correlating genetic variation with IDA and asthma were included to evaluate the effect of IDA on asthma.

Li and colleagues extracted 5 corresponding IDA-associated single nucleotide polymorphisms (SNPs) from the asthma GWAS data set. Upon analysis, genetically determined IDA was significantly associated with an increased risk of asthma (odds ratio [OR], 1.37 [95% CI, 1.09 - 1.72]; P = .007).

Similar risk estimates were identified using the weighted median models (OR, 1.23 [95% CI, 1.08 - 1.40]; P = .002). Overall, Li and colleagues indicated the consistency between the three MR models benefited the reliability of IDA as a proxy for the risk of asthma.

Analysis revealed no significant directional level of pleiotropy on the MR-egger test (P = .3972). Heterogeneity was suggested across both the MR-Egger (P <.001) and IVW (P <.001) regression tests.

Although various epidemiological studies have explored the potential impact of IDA on the development of asthma, Li and colleagues noted this is the first MR analysis to provide strong evidence of a causal relationship between IDA and asthma.

“This may mean that active iron supplementation in children with IDA may reduce the occurrence of asthma, and improving anemia may be effective for asthma patients in clinical practice,” they wrote.

References

1. _{Li M, Chen Z, Yang X, Li W. Causal relationship between iron deficiency anemia and asthma: a Mendelian randomization study. Front Pediatr. 2024;12:1362156. Published 2024 May 23. doi:10.3389/fped.2024.1362156}
2. _{Porsbjerg C, Melén E, Lehtimäki L, Shaw D. Asthma. Lancet. 2023;401(10379):858-873. doi:10.1016/S0140-6736(22)02125-0}
3. _{Tran TN, Khatry DB, Ke X, Ward CK, Gossage D. High blood eosinophil count is associated with more frequent asthma attacks in asthma patients. Ann Allergy Asthma Immunol. 2014;113(1):19-24. doi:10.1016/j.anai.2014.04.011}
4. _{Rhew K, Choi J, Kim K, Choi KH, Lee SH, Park HW. Increased Risk of Anemia in Patients with Asthma. Clin Epidemiol. 2023;15:31-38. Published 2023 Jan 5. doi:10.2147/CLEP.S394717}