Magnesium in the management of asthma
The recognition of asthma as an inflammatory disease has led over the past 20 years to a major shift in its pharmacotherapy. The previous emphasis on using relatively short-acting agents for relieving bronchospasms and for removing bronchial mucus has shifted toward long-term strategies with the use of inhaled corticosteroids, which successfully prevent and abolish airway inflammation. Because some of the biological, chemical, and immunological processes that characterize asthma also underly arthritis and other inflammatory diseases, and because many of these conditions have been successfully treated for the past 40 years at the Dead Sea, we were not surprised to realize and record the significant improvement of asthmatic condition after a 4-week stay at the Dead Sea: lung function was improved, the number and severity of attacks was reduced, and the efficacy of beta2-agonist treatments was improved. After reviewing the acute and chronic treatments of asthma in the clinic (including emergency rooms) with magnesium compounds, and the use of such salts as supplementary agents in respiratory diseases, we suggest that the improvement in the asthmatic condition at the Dead Sea may be due to absorption of this element through the skin and via the lungs, and due to its involvement in anti-inflammatory and vasodilatatory processes.
Harari M, Barzillai R, Shani J
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Magnesium and airway reactivity
Asthma is the commonest chronic disease in most Western countries, and it is widely believed that the prevalence of asthma has increased over the last 25 years. Studies in economically developing countries and in migrant populations suggest that the prevalence of asthma is strongly dependent on environmental factors. Diet is one of the environmental factors which has been implicated in the increase in asthma prevalence, and magnesium is one of a number of dietary constituents that have been studied. Magnesium is lost rapidly in the cooking and refining of food and therefore a Western, economically developed society with a higher asthma prevalence may consume a diet which is low in magnesium. Britton demonstrated, in a large population-based epidemiological study, that a lower dietary magnesium intake was associated with impaired lung function, bronchial hyperreactivity and an increased risk of wheezing.
The study by Dominguez is the first to report a correlation between intracellular magnesium levels and airway reactivity. Magnesium is a dietary cation with several actions of potential benefit to the asthmatic airway, including inhibition of contraction of vascular and bronchial smooth muscle in vitro, inhibition of release of acetylcholine from cholinergic nerve terminals and histamine from mast cells, and promotion of nitric oxide and prostacyclin generation. Thus there are good reasons why magnesium might be relevant to the aetiology and treatment of asthma. However, to date, the studies assessing the bronchodilator and bronchoprotective properties of magnesium therapy in asthma have given conflicting results, and at best magnesium has performed as a weak bronchodilator.
It is not known whether intracellular magnesium levels can be increased by oral or intravenous supplementation, and whether this intervention would reduce bronchial hyperreactivity or improve airway calibre. The only study to date which assessed the effect of oral magnesium supplementation on asthma control failed to lead to increases in leucocyte magnesium levels, or to demonstrate improvements in lung function or airway reactivity. Improvements in asthma symptoms and bronchodilator use of borderline clinical significance were seen in the magnesium-supplemented group. It is not known whether a high dietary magnesium intake may have different effects on asthma control.
The study by Dominguez therefore reports an interesting observation, but further work to confirm its findings is required. It is important to clarify whether oral or intravenous magnesium therapy can alter intracellular magnesium levels and whether this leads to reductions in airway reactivity and improvements in lung function and asthma control. More work is clearly required in this area.
** Increased bronchial smooth muscle contractility with consequent bronchial hyperreactivity are characteristic physiopathological events of asthma. Since magnesium intervenes in calcium transport mechanisms and intracellular phosphorylation reactions, it constitutes an important determinant of the contraction/relaxation state of bronchial smooth muscle. In the present study we investigated the relationship between bronchial reactivity, assessed by methacholine-provocation test, and magnesium concentrations both at extracellular and intracellular levels measured by spectrophotometry. 2. The salient finding of our study is that there is a strong positive correlation between bronchial reactivity and the level of intracellular magnesium (r = 0.72, P < 0.0001), both when the groups are analysed separately or together. Intracellular magnesium concentrations in the group of patients with asthma were significantly lower (1.8±0.01 mmol/l; n = 22) when compared with levels in rhinitis subjects allergic to Parietaria (1.9±0.01 mmol/l; n = 24, P < 0.05), and with levels in rhinitis subjects allergic to Grass pollen (2.0±0.03 mmol/l; n = 14, P < 0.05). Serum levels of the ion were similar in all groups. 3. We conclude that the level of intracellular magnesium may be an important determinant of bronchial hyperreactivity, as supported by the significant positive correlation between these two parameters in allergic patients with known bronchial hyperresponsiveness. This finding, in addition to reports of the bronchodilating effects of magnesium administration in patients with asthma, confirms the proposed role of this ion in the pathogenesis and treatment of asthma.
Respiratory Medicine Department West Glasgow Hospital University Trust 1053 Gt. Western Road, Glasgow G12 0YN, U.K. Source by: www.clinsci.org
Intravenous magnesium sulfate in acute severe asthma not responding to conventional therapy
Objective: To evaluate the effectiveness of early administration of intravenous magnesium sulfate (IV MgSO4) in children with acute severe asthma not responding to conventional therapy. Design: Randomized double-blind, placebo-controlled trial. Setting: Pediatric emergency service of a large teaching hospital. Subjects: 47 children aged between 1-12 years with acute severe asthma showing inadequate or poor response to 3 doses of nebulized salbutamol given at an interval of 20 min each. Intervention: The MgSO4 group received 0.2 mg/kg of 50% MgSO4 as intravenous (IV) infusion over 35 minutes and the placebo group received normal saline infusion in the same dose and at the same rate. MgSO4 solution and normal saline were coded and dispensed in identical containers. Decoding was done at the completion of the study. All the patients received oxygen, nebulized salbutamol, IV aminophylline and corticosteroids. Results: MgSO4 group showed early and significant improvement as compared to placebo group in PEFR and SaO2 at 30 min and 1, 2, 3 and 7 hours after stopping the infusion (p ranging from < 0.05 to < 0.01). The clinical asthma score also showed significant improvement in the MgSO4 group 1, 2, 3 and 11 hours after stopping the infusion (p < 0.01). Conclusion: Addition of MgSO4 to conventional therapy helps in achieving earlier improvement in clinical signs and symptoms of asthma and PEFR in patients not responding to conventional therapy alone. Studies of the effects of inhaled magnesium on airway reactivity to histamine and adenosine monophosphate in asthmatic subjects.
Background: Magnesium is a cation with smooth muscle relaxant and anti- inflammatory effects and may therefore have a role in the therapy of asthma. Several studies have investigated the effects of intravenous magnesium in acute or stable asthma, but little is known about the effects of inhaled magnesium.
Objective: To measure the effects of a single inhaled nebulized dose of 180 mg magnesium sulphate on airway reactivity to a direct-acting bronchoconstrictor (histamine) and an indirect-acting bronchoconstrictor (adenosine monophosphate (AMP)) in asthmatic subjects.
Methods: Two separate randomized, double blind, placebo controlled crossover studies. each involving 10 asthmatic subjects. In the histamine study, airway reactivity to histamine was measured and lung function allowed to recover spontaneously over 50 min before administering nebulized magnesium sulphate or saline placebo. Airway reactivity to histamine was then measured at 5 and 50 min. In the AMP study, a single measurement of airway reactivity was made 5 min after magnesium or placebo. Results: In the histamine study, the provocative dose required to reduce FEV1 by 20% (PD20FEV1) was significantly lower after magnesium than after placebo, by a mean (95% CI) of 1.02 (0.22- 1.82) doubling doses at 5 min (P=0.018), and 1.0 (0.3-1.7) doubling doses at 50 min (P = 0.01). In the AMP study, PD20FEV1 was also significantly lower at 5 min after magnesium than alter saline, by 0.64 (0.12-1.16) doubling doses (P = 0.023), though this difference was not statistically significant.
Effect of inhaled magnesium sulfate on sodium metabisulfite-induced Bronchoconstriction in asthma
Background: Inhaled magnesium (Mg) seemed to have a mild protective (nonbronchodilator) effect against histamine and methacholine. Inhaled sodium metabisulfite (MBS) causes bronchoconstriction in asthma through indirect mechanisms that involve sensory, nerve stimulation, and it is extensively used to study airway hyperresponsiveness. We designed this double-blind, randomized, crossover, and placebo-controlled study to test the effect of nebulized Mg sulfate against indirect challenge with MBS.
Methods: Ten asthmatic subjects (three male) aged 38.8 (3.29, SEM) years came on three occasions to perform MBS challenges 5 min after inhalation of either normal saline solution as placebo or Mg sulfate (4 mL; 286 mOsm). Doubling increasing concentrations of MBS were administered by continuous nebulization at tidal breathing during 1 min starting at 0.3 to 80 mg/mL until a 20% fall in FEV1 (PC20) from post saline solution baseline value was achieved. PC20 values were logarithmically transformed before analysis. Results: The mean baseline FEV1 at control day was 2.52 (0.14) L and 88.46 (4.28) percentage predicted, while the geometric mean MBS PC20 was 1.95 (1.38, geometric SEM) mg/mL. After placebo, the geometric mean PC20 was 2.26 (1.26) mg/mL. Inhaled Mg increased significantly the PC20 to 5.06 (1.52) mg/mL; p < 0.05. Mg diminished the bronchoconstrictor response to MBS by 1.3 doubling doses (p=0.08). Conclusions: Inhaled Mg attenuates MBS-induced bronchoconstriction in these asthmatic subjects. This new feature of magnesium, even modest in magnitude, emphasizes the necessity of studying the potential role of this cation in modulating airway response.