Medline Articles in the treatment of Disease
Trace elements Arguments in Asthma
Reduced
intracellular magnesium concentrations in asthmatic patients.
Emelyanov A, Fedoseev G, Barnes PJ.
Hospital Therapeutic Clinic, Pavlov's Medical University, St Petersburg, Russia.
Magnesium is important in the regulation of bronchomotor tone, and low dietary
intake of magnesium has been associated with airway hyperresponsiveness in
epidemiological studies. The concentration of magnesium in serum, erythrocytes
and urine in 49 patients with asthma (29 males, aged 15-65 yrs) and in 25 normal
subjects (15 males, aged 17-36 yrs) was studied by atomic absorption. Magnesium
concentrations were significantly lower in erythrocytes and urine in both atopic
(n = 26) and nonatopic (n = 23) asthmatic patients as compared with the control
group, whereas serum concentrations did not differ. The concentration of
magnesium in erythrocytes was not related to the degree of airway obstruction as
measured by forced expiratory volume in one second (FEV1) but was significantly
correlated with airway hyperresponsiveness measured as the provocative
concentration causing a 20% fall in FEV1 to inhaled acetylcholine (r = 0.64;
p<0.05). In addition, a magnesium tolerance test showed increased retention
of magnesium (58.9% of administered dose in asthmatic patients compared with
8.9% in normal subjects, p<0.05). In conclusion, the low cellular
concentration of magnesium may be associated with airway hyperresponsiveness in
asthmatic patients.
PMID: 10836320 [PubMed - indexed for MEDLINE]
A
randomized trial of magnesium in the emergency department treatment of children
with asthma.
Scarfone RJ, Loiselle JM, Joffe MD, Mull CC, Stiller S, Thompson K, Gracely
EJ.
Division of Emergency Medicine, Department of Community and Preventive Medicine,
MCP Hahnemann School of Medicine, St. Christopher's Hospital for Children,
Philadelphia, PA, USA. Scarfone@email.chop.edu
STUDY OBJECTIVE: Magnesium sulfate has been shown to benefit asthmatic children
and adults with poor responses to initial beta(2)-agonist therapy in the
emergency department. We sought to determine whether the routine early
administration of high-dose magnesium would benefit moderate to severely ill
children with acute asthma. METHODS: This was a randomized, double-blind,
placebo-controlled trial of 54 children 1 to 18 years of age who presented to
the ED of a tertiary care children's hospital with a moderate to severe asthma
exacerbation. After receiving a nebulized albuterol treatment (0.15 mg/kg) and
methylprednisolone (1 mg/kg), patients were randomly assigned to receive either
75 mg/kg of magnesium sulfate (maximum 2.5 g) or placebo. Thereafter, all
patients were treated with frequent nebulized albuterol following a structured
protocol. The main outcome was degree of improvement as assessed by Pulmonary
Index scores over 120 minutes. Secondary outcomes included hospitalization rates
and time required to meet discharge criteria. RESULTS: The mean change in
Pulmonary Index score from baseline to 120 minutes was 2.83 for the magnesium
group compared with 2.66 for the placebo group (95% confidence interval -1. 24
to 1.60). Eleven (46%) of 24 magnesium-treated patients were hospitalized
compared with 16 (53%) of 30 in the placebo group (95% confidence interval -19%
to 34%). There were no statistically significant differences between the groups
with respect to time required to meet discharge criteria. CONCLUSION: The
routine administration of high-dose magnesium to moderate to severely ill
children with asthma, as an adjunct to initial treatment with albuterol and
corticosteroids, was not efficacious.
Publication Types:
Double-blind
trial of pyridoxine (vitamin B6) in the treatment of steroid-dependent asthma.
Sur S, Camara M, Buchmeier A, Morgan S, Nelson HS.
National Jewish Center for Immunology and Respiratory Medicine, Denver,
Colorado.
Pyridoxine has been reported to largely correct an abnormality of tryptophan
metabolism present in patients with bronchial asthma and to reduce the symptoms
of asthma in long-term studies. We enrolled 31 patients requiring steroids (oral
or inhaled) for the treatment of their asthma in a double-blind,
placebo-controlled assessment of 9 weeks' treatment with pyridoxine 300 mg per
day (13) or placebo (18). Outcome variables included PEFR, FEV1, asthma symptom
scores, 24 hour urinary 5-HIAA, skin test reactivity to histamine and compound
48/80 and blood serotonin levels. Plasma pyridoxine levels indicated overall
patient compliance with a mean change from baseline to the end of the study of
82.5 +/- 27.7 ng/mL in patients on pyridoxine and -2.9 +/- 10.3 for those on
placebo (P = .0001). Furthermore, patients routinely treated with theophylline
had lower (10 +/- 8 ng/mL) plasma pyridoxine levels at baseline than those not
on it (19 +/- 6 ng/mL; P = .01), suggesting that theophylline may lower plasma
pyridoxine levels. There was no significant difference between the pyridoxine
and placebo groups in the change from baseline to the last 2 weeks of treatment
phase in any of the outcome variables. We conclude that under the conditions of
the study, treatment with oral pyridoxine failed to improve the outcome
variables in patients requiring steroids for the treatment of their asthma. The
results of this study suggest that prescription or usage of oral pyridoxine for
the treatment of asthma cannot be justified in such patients.
Publication Types:
Studies
of the effects of inhaled magnesium on airway reactivity to histamine and
adenosine monophosphate in asthmatic subjects.
Hill J, Lewis S, Britton J.
Division of Respiratory Medicine, City Hospital, Nottingham, UK.
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 after
saline, by 0.64 (0.12-1.16) doubling doses (P = 0.023), though this difference
was not statistically significant after adjustment for differences in baseline
FEV1 on the two study days. CONCLUSIONS: Inhaled magnesium did not protect
against the effects of these direct and indirect bronchoconstrictor stimuli in
subjects with asthma, and may have increased airway reactivity to histamine.
Publication Types:
Do
dairy products induce bronchoconstriction in adults with asthma?
Woods RK, Weiner JM, Abramson M, Thien F, Walters EH.
Department of Respiratory Medicine, Monash Medical School and Alfred Hospital,
Melbourne, Australia.
BACKGROUND: Dairy products have often been implicated as a cause of exacerbation
of asthma, but there is little scientific evidence to support this hypothesis.
OBJECTIVE: We sought to determine whether dairy products induce
bronchoconstriction in a group of adults with asthma. METHODS: Twenty subjects
with asthma (13 women and 7 men) were recruited from respondents who had
previously completed a food and asthma questionnaire. Ten subjects perceived
that their asthma became worse with ingestion of dairy products (positive
perceivers), whereas ten were negative perceivers. None of the subjects had
positive skin prick test results with cow's milk. The study was a randomized,
cross-over, double-blind, placebo-controlled trial. Subjects complied with a
dairy-free diet throughout the study. The active challenge was a single-dose
drink equivalent to 300 ml of cow's milk. A positive reaction was defined as a
15% reduction in both FEV1 and peak expiratory flow (PEF) on the active
challenge day compared with results obtained at the same time on the placebo
day. RESULTS: For both FEV1 and PEF there were no statistically significantly
differences in group means between active challenge and placebo challenge,
between sequence of administration, or between perceptions. Nine subjects showed
FEV1 or PEF changes that were greater than 15% of baseline values: four patients
showed changes after both active and placebo treatment; two after treatment with
placebo only; and three after active treatment alone. Of the latter group, two
subjects showed changes only in PEF, and when one of these subjects underwent a
further detailed study, no asthmatic reaction could be demonstrated. CONCLUSION:
It is unlikely that dairy products have a specific bronchoconstrictor effect in
most patients with asthma, regardless of their perception.
Publication Types:
Dose-response
relationship and time-course of the effect of inhaled magnesium sulphate on
airflow in normal and asthmatic subjects.
Hill J, Britton J.
Division of Respiratory Medicine, City Hospital, Nottingham, UK.
1. Magnesium is a dietary cation with a wide range of actions of potential
relevance to asthma. 2. To determine the dose-response relationship and
time-course of the effect of inhaled magnesium sulphate on the airway, we have
studied the effect of 0, 90, 135, 180 and 360 mg of magnesium sulphate given by
nebulizer on specific airways conductance (sGaw) in 20 normal subjects, and
forced expiratory volume in one second (FEV1), forced vital capacity (FVC), flow
at 25% forced vital capacity (Vmax25) and peak expiratory flow (PEF) in 19
asthmatic subjects. 3. On five occasions after baseline measurements of airway
calibre, one of the five doses of magnesium sulphate in 3 ml normal saline was
administered by nebulizer in a randomized, double-blind design. Measurements of
sGaw or FEV1, FVC, Vmax25 and PEF were made at 5 and 10 min after nebulization
and at 10 min intervals thereafter up to 90 min. 4. There was no significant
difference in the mean area under the curve (AUC) for change from baseline in
sGaw or maximum increase from baseline between doses in normal subjects. 5. In
asthmatic subjects there was no significant difference in the mean AUC for
change from baseline in FEV1, FVC or Vmax25 when compared between doses by
analysis of variance. There was a difference in the mean AUC for change from
baseline in PEF between doses (ANOVA P for all groups 0.052) but this can be
explained by a detrimental effect of the maximum dose of magnesium sulphate. 6.
It would appear that inhaled magnesium does not act as a bronchodilator in
normal or asthmatic subjects.
Publication Types:
Effect
of alterations of dietary sodium on the severity of asthma in men.
Carey OJ, Locke C, Cookson JB.
Glenfield General Hospital, Leicester.
BACKGROUND--There is some evidence of a positive association between increased
dietary salt consumption and both increased bronchial reactivity and mortality
from asthma in men. This study assesses the effects of alterations in dietary
salt consumption on the clinical severity of asthma in adult male asthmatic
patients. METHODS--A randomised, double blind, placebo controlled, crossover
design was employed. Twenty seven mild to moderate asthmatic patients were
established on a low sodium diet (80 mmol/day) at the end of a 4-5 day run in
period and then randomised to receive 200 mmol/day slow sodium or matching
placebo for five weeks, crossing over to the alternative regime for a further
five weeks. Patients used diary cards to record twice daily peak expiratory flow
rates, daily symptom scores, and bronchodilator consumption. Spirometry and
degree of bronchial responsiveness (methacholine challenge test) were measured
at screening and at the end of each treatment period. Twenty four hour urinary
sodium excretion was measured at screening and in duplicate for each treatment
period. RESULTS--Twenty two patients completed the study. For these patients the
mean (95% confidence interval (CI)) difference in 24 hour sodium excretion
between treatments was 204 (175 to 235) mmol. Compared with placebo, sodium
supplementation resulted in deleterious alterations of all measured parameters.
Bronchial reactivity rose on slow sodium with a 0.73 (0.2 to 1.3) doubling dose
methacholine difference compared with placebo. Estimated median (95% CI)
difference in bronchodilator consumption was 1.3 (0.4 to 2.1) puffs per day, the
estimated median difference in symptom score was 0.6 (0.2 to 0.9), and mean
forced expiratory volume in one second fell by 0.21 (0.05 to 0.37) 1. The peak
expiratory flow rate rose on placebo and fell on slow sodium. Median differences
between treatments were 5.6% (2.2% to 9.8%) for morning and 7.8% (3.9% to 12.9%)
for evening peak expiratory flow rate. CONCLUSIONS--Our results suggest that
large increases in dietary sodium result in physiological deterioration and
increased morbidity in male asthmatic patients.
Publication Types:
Effect
of intravenous magnesium sulphate on airway calibre and airway reactivity to
histamine in asthmatic subjects.
Hill JM, Britton J.
Division of Respiratory Medicine, City Hospital, Nottingham, UK.
In a randomized, double-blind, placebo controlled cross-over study we have
investigated the effect of intravenous magnesium on airway calibre and airway
reactivity to histamine in 20 subjects with mild to moderate asthma. After
baseline measurements of forced expiratory volume in one second (FEV1), subjects
received 100 ml normal saline with or without 2 g of magnesium sulphate by
infusion over 20 min. Measurements of FEV1 were repeated at 5 min intervals
throughout the infusion, and the provocative dose of histamine required to drop
the FEV1 by 20% from baseline (PD20FEV1) was determined at 20 min. The area
under the curve (AUC) in litre minutes for change from baseline in FEV1 between
0 and 20 min was significantly higher on the magnesium study day (mean
difference in AUC (95% CI) 1.71 (0.02-3.4), P = 0.049). The increase in FEV1
from baseline with magnesium relative to saline was maximal at 20 min (mean
difference (95% CI) 0.13 (0.02-0.23) l, P = 0.01). Log PD20FEV1 to histamine was
not significantly different after magnesium and saline (mean difference in log
PD20FEV1 (95% CI) 0.04 (-0.19 to 0.27), P = 0.7). We conclude that intravenous
magnesium is a weak bronchodilator but does not alter airway reactivity at this
dose in stable asthmatic subjects.
Publication Types:
Role
of magnesium in regulation of lung function.
Landon RA, Young EA.
Department of Medicine, University of Texas Health Science Center, San Antonio
78284-7878.
Magnesium and calcium play multiple dynamic roles in pulmonary structure and
function. When magnesium is deficient, the action of calcium is enhanced. In
contrast, an excess of magnesium blocks calcium. These interactions are
important to the respiratory patient because the intracellular influx of calcium
causes bronchial smooth-muscle contraction. The possibility exists that
magnesium deficiency contributes to pulmonary complications. During the past few
years, there has been an increase in calcium consumption in the US population
but little change in magnesium intake, which has caused an imbalance in the
calcium:magnesium ratio. Although serum levels are used to assess magnesium
deficiency, cells can be deficient despite normal serum values. These findings
indicate that pulmonary patients should be monitored routinely for magnesium
deficiency.
Publication Types:
Skeletal
muscle magnesium and potassium in asthmatics treated with oral beta 2-agonists.
Gustafson T, Boman K, Rosenhall L, Sandstrom T, Wester PO.
Dept of Internal Medicine, Skelleftea Hospital, Sweden.
Dietary magnesium has been shown to be important for lung function and bronchial
reactivity. Interest in electrolytes in asthma has so far mainly been focused
upon serum potassium, especially linked to beta 2-agonist treatment. It is known
that serum levels of magnesium and potassium may not correctly reflect the
intracellular status. We therefore investigated whether asthmatics treated with
oral beta 2-agonists had low magnesium or potassium in skeletal muscle and
serum, and whether withdrawal of the oral beta 2-agonists would improve the
electrolyte levels. Magnesium and potassium levels in skeletal muscle biopsies,
serum and urine were analysed in 20 asthmatics before and 2 months after
withdrawal of long-term oral beta 2-agonists, and for comparison in 10 healthy
subjects. Skeletal muscle magnesium in the asthmatics was lower both before
(3.62 +/- 0.69 mmol.100 g-1 (mean +/- SD)) and after (3.43 +/- 0.60 mmol.100
g-1) withdrawal of oral beta 2-agonists compared with the controls (4.43 +/-
0.74 mmol.100 g-1). Skeletal muscle potassium and serum magnesium did not differ
between the groups. Serum potassium was significantly lower both before (4.0 +/-
0.2 mmol.L-1) and after (3.9 +/- 0.2 mmol.L-1) the withdrawal of oral beta
2-agonists compared with the control group (4.2 +/- 0.2 mmol.L-1). The
asthmatics had lower skeletal muscle magnesium and lower serum potassium than
the healthy controls, both with and without oral beta 2-agonists. Whether the
findings are related to asthma pathophysiology or treatment is currently being
investigated.
PMID: 8777958 [PubMed - indexed for MEDLINE]
Investigation of the effect of short-term change in dietary magnesium intake in asthma.
Dietary
antioxidants and magnesium in type 1 brittle asthma: a case control study.
Baker JC, Tunnicliffe WS, Duncanson RC, Ayres JG.
Brittle Asthma Unit, Birmingham Heartlands Hospital, UK.
BACKGROUND: Type 1 brittle asthma is a rare form of asthma. Atopy, psychosocial
factors and diet may contribute to this condition. As increased dietary
magnesium has a beneficial effect on lung function and selenium, vitamins A, C
and E have antioxidant properties, a study was undertaken to test the hypothesis
that patients with brittle asthma have diets deficient in these nutrients
compared with subjects with non-brittle asthma and healthy adults. METHODS: A
case control study of the dietary intakes of 20 subjects with brittle asthma, 20
with non-brittle asthma, and 20 healthy adults was performed using five day
weighed dietary records. Intake of magnesium was the primary outcome measure
with selenium and vitamins A, C and E as secondary outcomes. Serum levels were
measured at the same time as the dietary assessment. RESULTS: Sixty subjects (27
men) of mean age 49.5 years were recruited and completed the study. Subjects
with brittle asthma had statistically lower median dietary intakes of vitamins A
and E than the other groups (vitamin A: brittle asthma 522.5 micrograms/day,
non-brittle asthma 869.5 micrograms/day, healthy adults 806.5 micrograms/day;
vitamin E: brittle asthma 4.3 mg/day, non-brittle asthma 4.6 mg/day, healthy
adults 4.5 mg/day). Median dietary intakes for the other nutrients were not
significantly different between groups. Serum levels were within normal ranges
for each nutrient in all subjects. Intakes less than the reference nutrient
intake (RNI) for magnesium and vitamins A and C, and less than the safe intake (SI)
for vitamin E were more likely in patients with brittle asthma than in those
with non-brittle asthma. CONCLUSION: Nutrient deficiency and reduced antioxidant
activity may contribute to disease activity in type 1 brittle asthma, although a
prospective study of replacement therapy will be needed to confirm this
hypothesis.
PMID: 10325914 [PubMed - indexed for MEDLINE]
Dietary
magnesium, lung function, wheezing, and airway hyperreactivity in a random adult
population sample.
Britton J, Pavord I, Richards K,
Wisniewski A, Knox A, Lewis S, Tattersfield A, Weiss S.
Division of Respiratory Medicine, University of Nottingham, City Hospital, UK.
Magnesium is involved in a wide range of biological activities, including some
that may protect against the development of asthma and chronic airflow
obstruction. We tested the hypothesis that high dietary magnesium intake is
associated with better lung function, and a reduced risk of airway
hyper-reactivity and wheezing in a random sample of adults. In 2633 adults aged
18-70 sampled from the electoral register of an administrative area of
Nottingham, UK, we measured dietary magnesium intake by semiquantitative
food-frequency questionnaire, lung function as the 1-sec forced expiratory
volume (FEV1), and atopy as the mean skin-prick test response to three common
environmental allergens. We measured airway reactivity to methacholine in 2415
individuals, defining hyper-reactivity as a 20% fall in FEV1 after a cumulative
dose of 12.25 mumol or less. Mean (SD) daily intake of magnesium was 380 (114)
mg/day. After adjusting for age, sex, and height, and for the effects of atopy
and smoking, a 100 mg/day higher magnesium intake was associated with a 27.7
(95% CI, 11.9-43.5) mL higher FEV1, and a reduction in the relative odds of
hyper-reactivity by a ratio of 0.82 (0.72-0.93). The same incremental difference
in magnesium intake was also associated with a reduction in the odds of
self-reported wheeze within the past 12 months, adjusted for age, sex, smoking,
atopy, and kilojoule intake, by a ratio of 0.85 (0.76-0.95). Dietary magnesium
intake is independently related to lung function and the occurrence of airway
hyper-reactivity and self-reported wheezing in the general population. Low
magnesium intake may therefore be involved in the aetiology of asthma and
chronic obstructive airways disease.
PMID: 7914305 [PubMed - indexed for MEDLINE]
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Altern Ther Health Med 2000 May;6(3):85-91 |