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ORIGINAL ARTICLE
Year : 2015  |  Volume : 28  |  Issue : 2  |  Page : 477-482

Low magnesium concentration in erythrocytes of children with acute asthma


Department of Pediatrics, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt

Date of Submission05-Sep-2013
Date of Acceptance20-Oct-2013
Date of Web Publication31-Aug-2015

Correspondence Address:
Mohammed Saber Fahmy
Department of Pediatrics, Diarb Negm Hospital, ABO Eid Dirab Negm, Sharkia 44661
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.163905

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  Abstract 

Objectives
Magnesium (Mg) is thought to be an important element in the pathogenesis of acute asthma attacks. This study aimed at investigating plasma and erythrocyte Mg of acute asthmatic children and correlating them with asthma severity.
Background
Continuous efforts are still exerted to understand the natural history and pathogenesis of acute asthma to alleviate its burden on children and their families. Mg is an abundant intracellular cation. It is involved in numerous physiological functions, including protein folding, intracellular signaling, enzymatic reactions involving protein and nucleic acid metabolisms, and enzyme catalysis. Mg is involved in pathophysiological reactions related to asthma; it has been shown to relax bronchial smooth muscles in vitro and to dilate asthmatic airways in vivo. It has been shown that intravenous administration or inhalation of Mg could alleviate symptoms in acute asthma.
Patients and methods
This case-control study included 43 Egyptian outpatients with acute asthma. A total of 21 apparently matched healthy children were included as controls. All candidates had measurements of plasma and erythrocytic Mg levels during an acute asthma exacerbation.
Findings
No significant differences were detected in plasma Mg levels between cases and controls (0.71 ± 0.12 vs. 0.76 ± 0.1 mmol/l, respectively, P = 0.14). However, erythrocytic Mg levels were significantly reduced in cases when compared with controls (1.2 ± 0.08 vs. 2.01 ± 0.14 mmol/l, respectively, P < 0.001).
Conclusion
Erythrocytic Mg levels were significantly lower during acute asthma, and were negatively correlated with severity of exacerbation, whereas plasma Mg did not significantly change.

Keywords: acute, asthma, erythrocytes, magnesium


How to cite this article:
Hassane FM, Khatab AA, Saliem SS, Fahmy MS. Low magnesium concentration in erythrocytes of children with acute asthma. Menoufia Med J 2015;28:477-82

How to cite this URL:
Hassane FM, Khatab AA, Saliem SS, Fahmy MS. Low magnesium concentration in erythrocytes of children with acute asthma. Menoufia Med J [serial online] 2015 [cited 2020 Apr 6];28:477-82. Available from: http://www.mmj.eg.net/text.asp?2015/28/2/477/163905


  Introduction Top


Bronchial asthma is a clinical syndrome and a group of diseases with common symptoms, based on different etiological and pathogenic mechanisms [1] . Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. Asthmatic episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment [2] . According to the WHO, asthma is the most common chronic respiratory disorder among children. Magnesium (Mg) is the second most abundant intracellular cation, and it is a cofactor in more than 3000 enzymatic reactions involving energy metabolism, protein, and nucleifc acid synthesis. Serum Mg contributes less than 1% to total amount in the body, and its function as a marker for Mg deficiency is doubtful. Therefore, an increasing interest can be noted in the measurement of its intracellular concentration [3] . On the basis of the critical role of Mg in the regulation of bronchial smooth muscle cell contractility through its effects on calcium transport activation and phosphorylation/dephosphorylation of intracellular reactions, it has been proposed that the intracellular Mg content may determine the excitability of these cells [4] . Hence, determination of Mg concentration in erythrocytes may be used in the evaluation of asthma pathophysiology. There are recommendations for using intravenous magnesium sulfate in acute asthma [4] . The treatment of bronchial asthma aims at enabling the child to engage in normal everyday activities, more exactly to be involved in physical activities and sports without restrictions [5] . Magnesium sulfate has been considered as an adjunct therapy for severe and life-threatening asthma exacerbation.


  Patients and methods Top


A case-control study was conducted over a 1-year period from April 2012 to April 2013 in Menoufiya and Zagazig University Hospitals, Pediatric Department. The study was carried out on 64 Egyptian children including 37 boys and 27 girls. Children were selected and classified into two groups. Group I constituted 43 patients diagnosed with bronchial asthma, their age ranging from 2 to 11 years and having acute asthma attack. Those asthmatic patients were further subclassified into 21 (48.8%) with mild asthma, seven (16.3%) with moderate asthma, and 15 (34.9%) with severe asthma, according to the pediatrics asthma score. Group II constituted 21 apparently healthy children matched with group I in terms of age and sex and used as controls. The study was approved by the ethical committee and consent was taken from the patients

All children included in the study were subjected to complete history taking, physical examination, and investigations including complete blood count, intracorpuscular, and plasma Mg levels analyzed with atomic absorption spectrophotometry and chest radiography.


  Results Top


Our study showed increase in asthma occurrence among male patients, although there was no statistically significant difference between cases and control with regard to height and weight. In addition, there was an increase in asthma frequency among the urban areas compared with the rural areas; however, there was no statistically significant difference. The present study showed increase in asthma occurrence among children with a family history of atopy, with a statistically significant difference, and also increase in asthma occurrence among children with smoking family members, with no statistically significant difference. The present study also showed statistical significant higher BMI in asthmatic children when compared with the control group. This study showed significant difference in radiographic findings in acute severe asthma. Our study showed highly statistically significant higher eosinophilic count in asthmatic children compared with controls. This study showed highly significant lower intracorpuscular Mg level in asthmatic children regardless of the severity compared with the healthy ones, with no significant difference in plasma Mg level in both the groups. Our study showed that no statistically significant correlation was found between BMI and asthma severity. The present study showed highly significant positive correlation between asthma severity and eosinophilic count, with no statistically significant correlation between asthma severity and red blood cell (RBC) count and age. Our study showed highly significant negative correlation between asthma severity and RBCs' Mg level, with no statistically significant correlation between asthma severity and plasma Mg level. The present study showed no significant correlation between age and RBC count with regard to RBCs' Mg level in asthmatic children, but there is significant negative correlation between RBCs' Mg level and eosinophilic count. On the contrary, there was no significant correlation between age, RBC count, and eosinophilic count with regard to plasma Mg level in asthmatic children.


  Discussion Top


Asthma is the most common inflammatory chronic disease in childhood. It is characterized by hyper-responsiveness of lower airways of patients who are susceptible to several factors, including immunologic and environmental factors [6] . Mg is involved in pathophysiological reactions related to asthma; it has been shown to relax the bronchial smooth muscles in vitro and to dilate asthmatic airways in vivo [7] . Our study aimed at measuring Mg concentrations in the erythrocytes of children with acute asthma exacerbations, comparing them with matched healthy controls. In our study, asthma was reported to be more common in boys than in girls (62.8 and 37.2%, respectively). These results appear reasonable and in accordance with Shaaban et al. [8] who reported that asthma was more common in boys than in girls. This may be related to narrower airways and increased airway tone. In addition, Hassane et al. [9] , in their study, reported that asthma was more common in boys than in girls. In the current study, the majority of asthmatic children were with positive family history of atopy (76.7%). This result is in accordance with Magdy et al. [10] who stated that positive family history of asthma was a risk factor for asthma. Whereas family history of asthma is common, it is neither sufficient nor necessary for the development of asthma [11] . In the current study, most of the asthmatic children were living in urban areas (60.5%); this result is in accordance with Abdel Hai et al. [12] who stated that residence of urban areas accounted for more than 79% of the asthma cases, whereas those of rural residence accounted only for 20.7%. This result is not in accordance with Yawn [13] who reported that the rural environment has a rich mixture of allergens from seasonal crops, abundant wildflower and weed growth, dust and animal dander in barns and silos, air pollution (e.g. ozone, methane gas from manure), and noxious odors from landfills, which are frequently located in the rural areas. In our study, passive smoking was reported in 53.5% of the asthmatic children. This means that exposure to tobacco smoke is one of the most consistent risk factors in the development and exacerbation of asthma. This result is in accordance with Vargas et al. [14] who found that environmental tobacco smoke exposure has been associated with the increased use of the emergency department for acute asthma care. Anthropometric measures of weight and height showed a statistically nonsignificant difference between patients and control groups (P > 0.05), whereas BMI showed a statistically significant difference (P < 0.05). This result is in accordance with some studies that found a correlation between obesity and the risk of asthma, with both having increased in recent years [15] . Several factors may be at play including decreased respiratory function owing to a buildup of fat and the fact that adipose tissue leads to a proinflammatory state [16] . No statistically significant correlation was found between BMI and asthma severity (P > 0.05). This result is in accordance with Hom et al. [17] , who found that BMI was not associated with asthma severity in pediatric patients, and Behmanesh et al. [18] , who showed that in some groups of asthmatic patients (5-10 years) there is no association between the increased BMI and severity of asthma. Whereas Cassol et al. [19] showed that there is a positive association between obesity and asthma severity. Although this study does not agree with our results, it was conducted on adolescents, which might explain the different findings. In our study, there was a statistically highly significant difference in radiographic findings in acute severe asthma compared with control subjects (χ2 = 36.3 and P < 0.001). In children with severe asthma, chest radiograph shows bilaterally increased air volume, low diaphragms, wide diaphragmatic angles, and often a slender cardiac silhouette with a prominent pulmonic arch. However, such a radiograph is not diagnostic of asthma itself, but rather of its complications: pneumonitis, atelectasis, and, rarely, extra-alveolar air trapping. The differential diagnosis has to rule out 'pseudo asthma' because of cystic fibrosis, alveolitis, achalasia, and foreign body aspiration [20] . Eddy and Kelly [21] reported that the rate of chest x ray (CXR) ordering in acute asthma was high with a low yield of relevant positive findings in the mild and moderate groups. Therefore, they suggested that routine CXR may be warranted in patients with severe asthma. With regard to hematological parameters, the mean hemoglobin levels showed a statistically nonsignificant difference between patients and controls (P > 0.05), whereas eosinophilic count was markedly elevated in the patients' group (group I) than in controls, and showed a highly statistically significant higher eosinophilic count in asthmatic children compared with controls (P < 0.001). There is a very highly significant positive correlation between asthma severity and eosinophilic count (P < 0.001), with no statistically significant correlation between asthma severity and hemoglobin and age (P > 0.05). However, Bede [22] found that plasma Hb levels were significantly decreased to different extents in both the Mg-treated and the placebo-treated groups. In parallel, he observed significant increases in the whole blood Hb concentrations in both groups. Lee et al. [23] examined 268 asthmatic children and found that there is a positive correlation between total eosinophilic count and severity of bronchial asthma (P < 0.01), and this is especially marked in exercise-induced bronchoconstriction in children. They concluded that exercise-induced bronchoconstriction may reflect a state of eosinophilic inflammation in the airway of asthmatic children. Our study shows a statistically highly significant lower intracorpuscular Mg level in asthmatic children compared with healthy control (P < 0.001), with no significant difference in plasma Mg level among both groups (P > 0.05). This finding agrees with the results of previous similar works such as Amin et al. [24] , who found that plasma levels of Mg were not significantly different between acute asthmatic children and controls. Sedighi et al. [4] conducted a study that reported no significant differences in plasma Mg (P = 0.06). In contrast with plasma Mg, this study detected that erythrocytic Mg levels were significantly lower during acute asthmatic episodes in our studied children when compared with controls. These findings support the study's hypothesis. Similar results were recorded by Amin et al. [24] who investigated the intracellular and extracellular Mg concentrations of the same group of acute asthmatics before and after receiving rescue treatment (no Mg treatment was given). It was found that plasma Mg levels did not differ significantly. However, erythrocytic Mg concentration was found to increase significantly after receiving treatment for acute asthma. This reflects that Mg content of the body - measured intracellularly in erythrocytes - was deficient at the onset of acute asthma attack, that it started to increase after the attack, and that this change could not have been detected if we relied on plasma Mg measurement. Sedighi et al. [4] reported significantly reduced erythrocytic Mg in acute asthmatic children compared with controls. Zervas et al. [3] reported similar results in adults during acute asthma; they concluded that acute asthma was associated with lower erythrocyte Mg content, whereas plasma levels remained unchanged. Meanwhile, Jiang et al. [25] showed that the concentration of plasma and erythrocyte Mg declined significantly in the asthmatic group than in the control group. In another prospective study on 93 chronic stable asthmatic patients, the prevalence of hypomagnesaemia was 27% and it was associated with the severity of asthma [26] . With regard to the severity of asthma, the study shows a highly significant decrease in RBCs' Mg level in acute mild, moderate, and severe asthmatic children compared with controls (P < 0.001), with no statistically significance in plasma Mg level between patients and controls (P > 0.05), although there was a statistically significant lower RBCs' Mg level in severe asthma attack compared with mild and moderate attack (P < 0.001), with no significant difference in plasma Mg level (P > 0.05). Our study showed a highly significant negative correlation between asthma severity and RBCs' Mg level (P < 0.001) with no correlation between asthma severity and plasma Mg level (P > 0.05). Similarly, Amin et al. [24] stated that there was a significant negative correlation between erythrocytic Mg and severity of asthma attack. Bede [22] stated that a statistically significant decrease was found in serum-free Mg at the end of the Mg treatment period in mild asthmatics without clinical consequences. In moderate asthmatics, no significant change has been observed. There was no change in serum-free Mg at the end of the placebo treatment period either in mild or moderate asthmatic patients. There was no significant correlation between age and hemoglobin level with regard to RBCs' Mg level in asthmatic children (P > 0.05), but there is significant negative correlation between RBCs' Mg level and eosinophilic count (P < 0.001). There is no significant correlation between age, hemoglobin level, and eosinophilic count with regard to plasma Mg level in asthmatic children. Low erythrocytic Mg reflects relative Mg deficiency in other cell types pertinent to asthma, such as inflammatory cells, smooth and skeletal muscle cells [24] . This agrees with the findings of Hashimoto et al. [27] who reported that 40% of asthmatic patients demonstrated Mg deficiency, and that the low Mg concentration in erythrocytes reflected decreased Mg stores in patients with bronchial asthma. Some studies, however, did not find any significant difference in Mg concentrations (both intracellular and extracellular) between asthmatics and normal subjects. This includes the studies by Kazaks et al. [28] . Although these studies do not agree with our results, they were conducted on adolescents and adults and focused mainly on milder degrees of exacerbations, which might explain the different findings. Bede [22] found a significant decrease in daytime asthma symptoms was experienced at 8 weeks in the Mg-treated patients with moderate asthma. This decrease persisted at the end of the study. A significant change was also observed at 12 weeks in the placebo-treated patients with moderate asthma. No significant differences in any symptom scores were observed between the Mg-treated and the placebo-treated children with mild asthma. He concluded that the significant reduction in bronchodilator use in children with moderate asthma versus the placebo group suggests the benefit of Mg supplementation [Figure 1] [Figure 2] [Figure 3] [Figure 4] and [Table 1], [Table 2], [Table 3], [Table 4], [Table 5].
Figure 1: Clinical presentation of the asthmatic group

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Figure 2: Comparison between two studied groups according to radiographic findings

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Figure 3: Comparison between cases and controls with regard to intracorpuscular and plasma magnesium level

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Figure 4: Comparison between children with mild, moderate, and severe asthma, and control, with regard to red blood cell and plasma magnesium level

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Table 1 Clinical presentation of the asthmatic group

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Table 2 Comparison between cases and controls with regard to radiographic findings

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Table 3 Comparison between cases and controls with regard to intracorpuscular and plasma magnesium level

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Table 4 Comparison between children with mild, moderate, and severe asthma, and controls, with regard to red blood cell and plasma magnesium level

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Table 5 Correlation between asthma severity and intracorpuscular and plasma magnesium level

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  Conclusion Top


The present study demonstrated that intracellular Mg level may be a more accurate method to assess Mg level in children with asthma. In addition, Mg may play a role in the regulation of disease activity.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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