Asthma as a manifestation of Iron Deficiency Anemia - A Short Review

Gelbard A

Published on: 2023-09-29

Abstract

Iron plays a role in oxygen transport through the blood. It's likely that this mechanism is responsible for a well-established connection and correlation between lack of Iron in humans and the odds of developing Asthma, with its severity and poor outcome also strongly correlated to lack of Iron in the body.

This short review will bring forward several studies, usually described in their author's own words that highlight this above mentioned connection and explain it.

This of course will lead to the conclusion that further studies to examine iron supplementation to Asthma patients is strongly advocated. So far, only two studies could be found. Both in vivo, but both showing surprisingly positive results and I'll bring them also to conclude the results part of this review.

Keywords

Asthma; Anemia; Iron; Hemoglobin; Ferritin

Background

Asthma is a chronic lung disease affecting people of all ages. It is caused by inflammation and muscle tightening around the airways, which makes it harder to breathe. Symptoms can include coughing, wheezing, shortness of breath and chest tightness. These symptoms can be mild or severe and can come and go over time [1].

Iron is a chemical element with the symbol Fe (from Latin ferrum 'iron') and atomic number 26. It is, by mass, the most common element on Earth, just ahead of oxygen (32.1% and 30.1%, respectively), forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust. [2] The body of an adult human contains about 4 grams (0.005% body weight) of iron, mostly in hemoglobin and myoglobin. These two proteins play essential roles in vertebrate metabolism, respectively oxygen transport by blood and oxygen storage in muscles. To maintain the necessary levels, human iron metabolism requires a minimum of iron in the diet [2].

In this short review I'll show that Iron levels in the patients' bodies correlate negatively with the occurrence of Asthma, its severity and poor outcome. I'll therefore raise the hypothesis that Iron should be included in Asthma treatment, both as a protective agent and possibly as a therapeutic, depending on more studies.

Experimental Project Hypothesis

Iron in Asthma Patients

Lower levels of Iron and Hemoglobin in Asthma have been identified by numerous studies, we'll review them here:

Ahmad Eissa and co. examined "Iron deficiency anemia as a risk factor in childhood asthma". They divided the children into groups:

"Group I: 50 children with iron deficiency anemia, subdivided into group Ia: asthmatic children and group Ib: non asthmatic children. Group II: 50 children without iron deficiency anemia, subdivided into group IIa: asthmatic children and group IIb: non-asthmatic children.

There was a significant difference between the two groups regarding the number of asthmatics as they were more in group I. There was a significant positive correlation between hemoglobin level and pulmonary function parameters (FEV1, FVC, FEV1/FVC, PEF) in (group Ia). There was a significant positive correlation between serum ferritin level and pulmonary function parameters (FEV1, FVC, FEV1/FVC, PEF)" [3].

Another study, by Alkhateeb and co. also divided the patients into groups: " group I: 100 children with IDA (Iron deficiency Anemia)-who was subdivided into group Ia: Asthmatic children and group Ib: Non asthmatic children. Group II: 100 children without IDA, subdivided into group IIa: asthmatic children and group II b: non-asthmatic children.

The anemic group with asthma constitutes 66% of group I, while in group II the asthmatic children constituted 24% of included children." They've also found that "Anemic asthmatic children had significant difference regarding Pulmonary Function Tests (PFT) (FEV1, FVC, FVC/FEV1) in comparison to non-anemic asthmatics" [4].

Another study, by ElSayed and Eman Essa found that "Iron deficiency anemia was significantly more frequent in asthma cases compared to healthy controls. Serum iron and serum ferritin were significantly lower in asthmatic cases compared to controls. Non anemic asthmatics showed significantly lower hemoglobin, serum ferritin compared with non-anemic healthy controls. Moderate cases of asthma showed significant lower hemoglobin, red cell counts, serum ferritin compared with mild cases…All three groups "mild, moderate and severe" showed significant differences in these parameters" [5].

Another study, by Bener and co. examined "The impact of anemia and hemoglobin level as a risk factor for asthma and allergic diseases". They've found that "Anemia was more prevalent in asthmatics than controls. Lower Hb (Hemoglobin) levels were associated with more allergic disease and elevated serum IgE. The study revealed that Hb level, iron and ferritin deficiencies were considerably higher in asthmatic children compared to healthy children. There was a significant difference found in the mean values of Hb levels between asthmatic (10.58 ± 3.05 g/dL) and control children (11.75 ± 3.10) (P = 0.006). Besides, mean IgE was statistically significantly higher in asthmatic compared to control children (P < 0.001). There was a significant correlation between Hb level and total IgE in asthmatic compared to controls (r = 0.295 vs. r = 0.268, P = 0.001)" [6].

Ali HA and co. examined "The Role of Iron Status in Pediatric Asthma Severity", their findings are as follows:

"The study found that IDA was presented among 34% of the studied asthmatic patients compared to 20% in the control group (P<0.001). Moreover, the asthmatic attacks were significantly more frequent and severe in asthmatics with IDA (88.3%, 64.7%) than those without IDA (51.5%, 45.5%) (P<0.001) with frequent emergency room visits and hospital admissions among asthmatics with IDA (70.6%, 41.1%) (P=0.037, 0.041)" [7].

Another study, by Rhew and co. found "Increased Risk of Anemia in Patients with Asthma". Their results, in their own words: "This study included 3085 patients. During 5-y follow-up, anemia occurred in 203 (15.0%) patients with asthma and 79 (4.6%) healthy adults. Compared with healthy adults, the HR for anemia after adjusting for age, sex, and obesity was 4.06 (95% CI: 2.70– 6.09) in patients with asthma. In patients aged 18– 64.9 y, the adjusted HR of anemia was 3.27 (95% CI: 2.12– 5.04) in patients with asthma, compared to healthy patients. In patients > 65 y, this adjusted HR was 5.56 (95% CI: 1.31– 23.67)" [8].

Rashid and co. shared their findings regarding "Iron Deficiency and Iron Deficiency Anemia in Women with Bronchial Asthma":

"We found asthma cases had lower hemoglobin than control (mean±SD 10.92±1.34 vs. 12.30±0.73, p value 0.013), serum iron and serum ferritin were significantly lower (p value 0.016 and 0.000 respectively) and TIBC was higher (p value 0.000) in asthmatic cases as compared to controls. Non anemic asthmatics showed significant lower serum ferritin compared with non-anemic healthy controls (p value 0.005)" [9].

Brigham and co. found "Iron Status is Associated with Asthma and Lung Function in US Women". They report their results:

"Approximately 16% reported a lifetime history of asthma, 9% reported current asthma, and 5% reported a recent asthma episode/attack (n = 2906). Increased ferritin (iron stores) was associated with decreased odds of lifetime asthma, current asthma, and asthma attacks/episodes in the range of ferritin linearly correlated with iron stores (20-300ng/ml). The highest quintile of ferritin (>76 ng/ml) was also associated with a decreased odds of asthma" [10].

Just two studies, both in vivo, were conducted regarding the effect of Iron injection or supplementation on Asthma in mice [11,12].

Maazi and co. hypothesized the opposite of what is reported here in this review: that iron supplementation is actually a risk factor for asthma, but they're findings revealed the opposite. Here, in their own words:

"The prevalence of allergic diseases has increased dramatically during the last four decades and is paralleled by a striking increase in iron intake by infants in affluent societies. Several studies have suggested a link between increased iron intake and the marked increase in prevalence of allergic diseases. We hypothesized that the increased iron intake by infants offers an explanation for the increased prevalence of allergic disease in industrialized societies during the past four decades. A well-established mouse model of ovalbumin (OVA)-driven allergic asthma was used to test the effects of differences in iron intake and systemic iron levels on the manifestations of allergic asthma. Surprisingly, iron supplementation resulted in a significant decrease in airway eosinophilia, while systemic iron injections led to a significant suppression of both allergen-induced airway eosinophilia and hyper reactivity compared to placebo" [11].

Another study, by Hale and co. showed similar results:

"Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyper reactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an un-supplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation" [12].

To conclude, it's essential to further examine Iron levels and Iron deficiency in Asthma patients. The results brought here give a clear picture of why Iron deficiency could in fact be the cause of Asthma, and therefore Iron supplementation should be examined as a possible cure. Unfortunately, I could find only two studies examining Iron supplementation to Asthma, both of them in vivo. Studying of Iron supplementation for human Asthma patients to explore its effect, is therefore urgently needed.

Journal of Pulmonary Diseases and Respiratory Medicine

Asthma as a manifestation of Iron Deficiency Anemia - A Short Review

Abstract

Keywords

Background

Experimental Project Hypothesis

References