The role of magnesium in the treatment of acute asthma in adults and its effects on beta-2 adrenergic receptor function
Date
2019
Authors
Busuttil, Maureen
Editors
Advisors
Clifton, Vicki
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Thesis
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Abstract
Asthma is a common respiratory condition that affects adults and children. Treatment options for acute exacerbations are limited. Magnesium could provide additional benefit when used in conjunction with β-2 agonists however, the evidence for its efficacy is lacking. Meta-analysis suggests that severity is an important factor in response to magnesium. The results of published clinical trials are heterogeneous, suggesting that individual factors may influence response to treatment with magnesium. The literature also shows that there are sex differences in aetiology of asthma which could influence treatment response. Phenotypes also vary with ethnicity and atopy and these factors could also influence treatment response. The aims of the thesis were; to examine the effects of magnesium on β-2 agonist stimulation of the β-2-adrenergic receptor (β-2AR) on lymphocytes collected from asthmatics and compare these effects with non-asthmatics in vitro, and to determine if cellular responsiveness to magnesium is altered by asthma severity and patient sex or other factors such as atopy; to examine effects of the addition of intravenous magnesium to optimal standardised treatment in acutely exacerbating adult asthmatics in the emergency department; and to re-analyse 3M trial data to examine the effects of magnesium between severity subgroups and in relation to patient sex. The interpretation of the results of the in vitro studies is limited by small sample sizes. The in vitro studies suggested that there are sex differences in β-2AR function which could influence treatment response. The in vitro studies found that β-2ARs in lymphocytes of healthy females were more responsive to agonist stimulation relative to healthy males however, lymphocytes of asthmatic females were less responsive to agonist stimulation relative to asthmatic males. Magnesium was more effective in male asthmatics relative to female asthmatics, in augmenting β-2 agonist stimulation of the receptors, as indicated by the difference in cAMP elevations. This suggests that magnesium may be more effective in improving β-2AR responsiveness in males. The sample size was too small to assess the effects of atopy on β-2AR responses and the effects of magnesium on those responses. I was unable to determine a benefit from the use of magnesium for the treatment of acute asthma relative to standard care alone, due to the small numbers recruited to the trial. The small sample prevented me from determining any subgroup benefits. In my re-analysis of the 3M trial data, I found that there was a benefit from magnesium in those with severe asthma, as defined by PEF 33-50% predicted. The data also showed that there were sex differences in response to magnesium. Magnesium’s effect on reducing admission rates compared to placebo was greater for males relative to females. When the sexes were assessed separately, the sample size was too small to show a statistically significant benefit in males. Individual differences in β-2AR responses may account for differences in efficacy of magnesium. These may relate to differences in sex, and possibly atopic status and ethnicity, with potential interactions between sex and atopy. Further study may be warranted to confirm the initial findings and to further explore the effects of sex-atopy and ethnicity in a larger sample of asthmatics. It is likely that magnesium is a safe and inexpensive optional addition to the treatment of acute asthma in those patients failing to respond to standard treatment however, its utility and effectiveness may be limited in Caucasian populations, to males with severe asthma.
School/Discipline
Adelaide Medical School
Dissertation Note
Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2019
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