Asthma is a chronic inflammatory disorder of the airways characterized by reversible airflow obstruction, bronchial hyperresponsiveness, and recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. It affects more than 260 million individuals worldwide and remains a major contributor to morbidity, healthcare utilization, and reduced quality of life across all age groups. Despite advances in pharmacological management, asthma continues to impose a substantial public health burden, particularly in low- and middle-income countries where delayed diagnosis and inadequate disease control are common [1]. The pathogenesis of asthma is complex and involves interactions between genetic susceptibility, environmental exposures, immune dysregulation, and nutritional factors [2].

Iron deficiency anemia (IDA) is the most prevalent nutritional deficiency globally, affecting nearly one-third of the world's population. It is particularly common among children, women of reproductive age, pregnant women, and individuals with chronic inflammatory conditions. Iron is an essential micronutrient required for oxygen transport, cellular metabolism, DNA synthesis, and normal immune function. Deficiency of iron can impair both innate and adaptive immune responses, alter cytokine production, and reduce antioxidant capacity, thereby potentially influencing the development and progression of inflammatory diseases, including asthma [3,4].

Recent evidence suggests that iron metabolism may play a significant role in respiratory health. Iron deficiency has been associated with impaired pulmonary function, increased susceptibility to respiratory infections, altered airway epithelial integrity, and exaggerated inflammatory responses. Experimental studies indicate that inadequate iron availability may enhance oxidative stress and promote T-helper 2 (Th2)-mediated immune responses, both of which are central mechanisms in allergic asthma. Conversely, excessive iron accumulation may also contribute to oxidative tissue injury, highlighting the importance of maintaining optimal iron homeostasis [5,6].

Several observational studies have investigated the relationship between iron deficiency anemia and asthma; however, the findings remain inconsistent. Some epidemiological studies have reported that individuals with iron deficiency anemia are at a higher risk of developing asthma and experience poorer disease control, more frequent exacerbations, and increased hospitalizations. In contrast, other studies have failed to demonstrate a significant association after adjustment for potential confounding factors such as age, sex, socioeconomic status, nutritional status, obesity, and comorbid allergic diseases [7,8]. These discrepancies may be attributable to variations in study design, population characteristics, diagnostic criteria for iron deficiency, and outcome assessment.

The biological plausibility of an association between iron deficiency anemia and asthma is supported by emerging evidence demonstrating that iron status influences multiple immune pathways involved in airway inflammation. Iron deficiency has been shown to affect macrophage function, T-cell proliferation, mast cell activation, and eosinophilic inflammation, all of which are implicated in asthma pathogenesis. Furthermore, recent genetic and Mendelian randomization studies have suggested a potential causal relationship between iron deficiency anemia and an increased risk of asthma, strengthening the hypothesis that iron metabolism may influence disease susceptibility rather than merely reflecting chronic inflammation [9].

Although several narrative reviews and observational studies have explored this topic, the available evidence has not been consistently synthesized with respect to study quality, patient characteristics, and clinical outcomes. A comprehensive systematic review is therefore warranted to critically evaluate the existing literature, summarize the strength of the evidence, identify knowledge gaps, and determine whether iron deficiency anemia is associated with the occurrence, severity, and clinical outcomes of asthma. The findings may have important implications for early identification of high-risk individuals, optimization of nutritional assessment, and future interventional research investigating iron supplementation as an adjunctive strategy in asthma management [10].

Study Design This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The review aimed to comprehensively evaluate the available evidence regarding the association between iron deficiency anemia (IDA) and asthma across pediatric and adult populations. The review protocol was developed prior to commencement of the study, and the methodology was predefined to minimize selection and reporting bias. Eligibility Criteria Studies were considered eligible if they met the following inclusion criteria: (1) observational studies, including cohort, case-control, and cross-sectional studies, as well as randomized controlled trials evaluating the association between iron deficiency anemia and asthma; (2) studies involving children or adults diagnosed with asthma according to recognized clinical or international guidelines; (3) studies assessing iron deficiency anemia using laboratory parameters such as hemoglobin, serum ferritin, serum iron, transferrin saturation, or total iron-binding capacity; and (4) studies reporting at least one clinically relevant outcome related to asthma, including prevalence, incidence, disease severity, asthma control, pulmonary function, frequency of exacerbations, emergency department visits, or hospitalization. Studies were excluded if they were case reports, case series involving fewer than ten participants, review articles, editorials, conference abstracts without full-text availability, animal or in vitro studies, duplicate publications, or studies lacking sufficient quantitative data for extraction. Information Sources and Literature Search A comprehensive electronic literature search was performed in PubMed/MEDLINE, Scopus, Embase, Web of Science, and the Cochrane Library from database inception until June 2026. Additionally, Google Scholar was searched to identify potentially relevant articles and grey literature. The reference lists of all eligible studies and relevant review articles were manually screened to identify additional studies not retrieved through the electronic search. The search strategy incorporated controlled vocabulary (Medical Subject Headings [MeSH]) and free-text keywords related to asthma and iron deficiency anemia. The primary search terms included "Asthma," "Bronchial Asthma," "Iron Deficiency Anemia," "Iron Deficiency," "Ferritin," "Hemoglobin," "Serum Iron," and "Iron Status," combined using Boolean operators (AND/OR). The search strategy was adapted appropriately for each electronic database. Study Selection All retrieved citations were imported into a reference management software, and duplicate records were removed. Two independent reviewers initially screened titles and abstracts to identify potentially eligible studies. Full texts of relevant articles were subsequently assessed for eligibility according to the predefined inclusion and exclusion criteria. Disagreements between reviewers were resolved through discussion, and when consensus could not be achieved, a third reviewer made the final decision. The study selection process was documented using the PRISMA 2020 flow diagram. Figure 1 Data Extraction A standardized data extraction form was developed before commencement of the review. The following variables were extracted independently by two reviewers: first author, publication year, country, study design, sample size, participant demographics, diagnostic criteria for asthma, definition of iron deficiency anemia, laboratory parameters used for diagnosis, duration of follow-up (where applicable), primary and secondary outcomes, effect estimates, and major study conclusions. Any discrepancies in extracted data were verified against the original publication and resolved by consensus. Quality Assessment The methodological quality of observational studies was evaluated using the Newcastle–Ottawa Scale (NOS), while randomized controlled trials were assessed using the Cochrane Risk of Bias (RoB 2) Tool. Each study was independently assessed by two reviewers, and disagreements were resolved through discussion. Data Synthesis Extracted data were summarized descriptively using tables and narrative synthesis. Studies were grouped according to study design, participant characteristics, and reported outcomes. Where sufficient homogeneity existed in study populations, exposure definitions, and outcome measures, quantitative findings were compared across studies to evaluate the consistency of the association between iron deficiency anemia and asthma. The overall strength of evidence was interpreted after considering study quality, consistency of findings, and potential sources of heterogeneity. Figure 1: PRISMA flowchart of the selected studies

Study Selection

The literature search identified 1,074 records from six electronic databases, including PubMed/MEDLINE, Embase, Scopus, Web of Science, the Cochrane Library, and Google Scholar. After removing 434 duplicate and ineligible records, 640 studies underwent title and abstract screening. Of these, 590 records were excluded because they were unrelated to the review question, were reviews, animal studies, conference abstracts, or did not investigate iron deficiency anemia in relation to asthma.

Full-text assessment was performed for 42 articles, of which 34 were excluded due to inappropriate study design, inadequate outcome reporting, absence of iron deficiency measurements, or insufficient data for extraction. Finally, 8 studies met the predefined eligibility criteria and were included in the qualitative synthesis. The study selection process is illustrated in the PRISMA 2020 flow diagram (Figure 1).

Table 1. Characteristics of Included Studies

Among the included studies, three were cross-sectional investigations, two were case-control studies, two were cohort studies, and one was a Mendelian randomization analysis. The studies represented diverse geographical regions, including North America, Asia, and Europe. Both pediatric and adult populations were included, with sample sizes ranging from fewer than 100 participants to nationwide databases comprising several hundred thousand individuals.

Table 2. Iron Parameters Evaluated Across Included Studies

Hemoglobin concentration and serum ferritin were the most frequently reported biomarkers of iron status. Serum ferritin was evaluated in four studies and consistently demonstrated lower levels among participants with asthma. Three studies additionally reported serum iron concentrations, while transferrin saturation and total iron-binding capacity were assessed less frequently. Overall, reduced iron stores appeared to be associated with poorer asthma-related outcomes.

Table 3. Summary of Asthma Outcomes Reported

The most frequently evaluated outcome was asthma prevalence, followed by disease severity and pulmonary function. Several studies reported that lower iron stores were associated with poorer asthma control, more frequent exacerbations, and increased healthcare utilization. Studies assessing lung function consistently observed reduced pulmonary function among individuals with lower iron status, although the parameters evaluated differed across studies.

Table 4. Overall Direction of Evidence

Overall, seven of the eight included studies supported a significant association between iron deficiency or iron deficiency anemia and asthma-related outcomes. Evidence from observational studies consistently suggested that reduced iron status was associated with increased asthma prevalence, poorer disease control, and greater clinical severity. One Mendelian randomization study further supported a potential causal relationship between genetically predicted iron deficiency anemia and asthma susceptibility. Although one observational study did not identify a statistically significant association after adjustment for confounding variables, the overall body of evidence favored an inverse relationship between iron status and asthma outcomes.

The present systematic review synthesized the available evidence regarding the association between iron deficiency anemia (IDA) and asthma. Overall, the included studies consistently suggested that reduced iron status, reflected by lower hemoglobin and serum ferritin concentrations, is associated with a greater likelihood of asthma, poorer pulmonary function, and increased disease severity. Although the available evidence remains limited and heterogeneous, the overall findings indicate that iron deficiency may represent an important yet underrecognized factor influencing asthma susceptibility and clinical outcomes. One of the principal findings of this review is that the majority of observational studies demonstrated significantly lower serum ferritin and hemoglobin concentrations among patients with asthma compared with healthy controls. Similarly, studies evaluating asthma severity observed that reduced iron stores were associated with more frequent exacerbations, poorer symptom control, and increased healthcare utilization. These observations are biologically plausible because iron plays an essential role in oxygen transport, mitochondrial function, antioxidant defense, and immune regulation. Iron deficiency has been shown to impair both innate and adaptive immune responses while promoting oxidative stress, thereby creating a pro-inflammatory environment that may aggravate airway inflammation and bronchial hyperresponsiveness [11,12]. The findings of this review are consistent with previous mechanistic studies demonstrating that disturbances in iron homeostasis contribute to airway inflammation. Iron regulates several immune pathways involved in allergic asthma, including macrophage activation, mast cell function, eosinophil survival, and T-helper type 2 (Th2) immune responses. Experimental studies have shown that reduced extracellular iron availability enhances allergic airway inflammation and promotes cytokine production, whereas restoration of normal iron homeostasis attenuates inflammatory responses. These mechanisms provide a biologically plausible explanation for the observed association between iron deficiency and asthma in clinical studies [13,14]. Our review also identified evidence suggesting that reduced iron stores are associated with impaired pulmonary function. Lower serum ferritin concentrations have been linked to reduced forced expiratory volume in one second (FEV₁), lower FEV₁/FVC ratios, and greater airflow limitation. Since iron is essential for oxygen transport and mitochondrial energy metabolism, chronic deficiency may impair respiratory muscle function and reduce exercise tolerance, thereby worsening respiratory symptoms. Moreover, iron deficiency may increase oxidative injury within airway epithelial cells, further contributing to airway remodeling and persistent inflammation [15,16]. An important contribution to the current evidence base is the emergence of genetic epidemiological studies. The recent Mendelian randomization study by Li and colleagues demonstrated that genetically predicted iron deficiency anemia was significantly associated with an increased risk of asthma, suggesting that the relationship may be causal rather than merely a consequence of chronic inflammation. In contrast, an earlier Mendelian randomization study evaluating circulating iron biomarkers did not identify a significant causal association between systemic iron status and asthma risk. These apparently conflicting findings may reflect differences in study populations, genetic instruments, exposure definitions, and outcome measures, highlighting the complexity of iron metabolism and its interaction with respiratory disease [17,18]. Nevertheless, together with observational evidence, these studies strengthen the hypothesis that iron metabolism may influence asthma pathogenesis. Despite these promising findings, several limitations within the available literature should be acknowledged. Most included studies were observational in nature, limiting the ability to establish temporal relationships and causality. Considerable heterogeneity was observed regarding diagnostic criteria for iron deficiency anemia, laboratory biomarkers used to assess iron status, asthma severity classification, and adjustment for confounding variables such as nutritional status, obesity, smoking, socioeconomic status, and chronic inflammatory disorders. Furthermore, relatively few studies evaluated pediatric populations separately, despite childhood being the period during which both asthma and iron deficiency are highly prevalent. The limited number of prospective cohort studies and randomized clinical trials further restricts the strength of current evidence [19]. Another important limitation is that iron deficiency and anemia frequently coexist with chronic inflammatory conditions, making it difficult to distinguish whether altered iron metabolism represents a causal factor or simply reflects systemic inflammation associated with asthma. Future studies should therefore incorporate standardized diagnostic criteria for iron deficiency, evaluate inflammatory biomarkers such as hepcidin and interleukin-6, and investigate whether correction of iron deficiency improves asthma control, lung function, and quality of life. Well-designed multicenter prospective cohorts and randomized controlled trials examining iron supplementation in iron-deficient asthmatic patients are particularly warranted [20-22]. Overall, the available evidence suggests that iron deficiency anemia is associated with an increased burden of asthma and adverse clinical outcomes. Although current data do not conclusively establish causality, the consistent association observed across multiple study designs, together with emerging genetic and mechanistic evidence, supports further investigation into iron metabolism as a potentially modifiable factor in asthma prevention and management. Routine assessment of iron status, particularly among patients with poorly controlled asthma or recurrent exacerbations, may facilitate earlier identification of nutritional deficiencies and provide opportunities for targeted therapeutic interventions.

This systematic review demonstrates that the current body of evidence supports a significant association between iron deficiency anemia and asthma, with most included studies reporting lower hemoglobin and serum ferritin levels among individuals with asthma compared to healthy controls. Reduced iron status was also associated with poorer asthma control, greater disease severity, impaired pulmonary function, and an increased risk of exacerbations in several studies. Emerging genetic evidence further suggests that iron deficiency anemia may contribute to asthma susceptibility, although the causal relationship requires further confirmation. Nevertheless, the available literature remains limited by methodological heterogeneity, predominantly observational study designs, and variations in the diagnostic criteria used for both asthma and iron deficiency. Future large-scale prospective studies and randomized controlled trials are needed to determine whether early identification and treatment of iron deficiency can improve asthma outcomes. Routine assessment of iron status may represent a valuable adjunct in the comprehensive management of patients with asthma.

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