Oral versus intravenous corticosteroids in children hospitalized with asthma

BACKGROUND: Previous studies have demonstrated that in the emergency treatment of an asthma exacerbation, corticosteroids used in conjunction with beta-agonists result in lower hospitalization rates for children and adults. Furthermore, orally administered corticosteroids have been found to be effective in the treatment of outpatients with asthma. However, similar data in inpatients is lacking. OBJECTIVE: The purpose of this study was to determine the efficacy of oral prednisone versus intravenous methylprednisolone in equivalent doses for the treatment of an acute asthma exacerbation in hospitalized children. METHODS: We conducted a randomized, double-blind, double-placebo study comparing oral prednisone at 2 mg/kg/dose (maximum 120 mg/dose) twice daily versus intravenous methylprednisolone at 1 mg/kg/dose (maximum 60 mg/dose) four times daily in a group of patients 2 through 18 years of age hospitalized for an acute asthma exacerbation. All patients were assessed by a clinical asthma score 3 times a day. The main study outcome was length of hospitalization; total length of stay and time elapsed before beta-agonists could be administered at 6-hour intervals. Duration of supplemental oxygen administration and peak flow measurements were secondary outcome measures. RESULTS: Sixty-six patients were evaluated. Children in the prednisone group had a mean length of stay of 70 hours compared with 78 hours for the methylprednisolone group (P =.52). Children in the prednisone group were successfully weaned to beta-agonists in 6-hour intervals after 59 hours compared with 68 hours for the methylprednisolone group (P =.47). Patients receiving prednisone required supplemental oxygen for 30 hours compared with 52 hours for the methylprednisolone group (P =.04). CONCLUSION: There was no difference in length of hospital stay between asthmatic patients receiving oral prednisone and those receiving intravenous methylprednisolone. Because hospitalization charges are approximately 10 times greater for intravenous methylprednisolone compared with oral prednisone, the use of oral prednisone to treat inpatients with acute asthma would result in substantial savings.     

Safety of a specific COX-2 inhibitor in aspirin-induced asthma

In a subset of patients with asthma, aspirin and several other non-steroidal anti-inflammatory drugs (NSAID) that inhibit simultaneously cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) precipitate dangerous asthmatic attacks. We tested the hypothesis that in patients with aspirin-induced asthma the attacks are triggered by inhibition of COX-1 and not COX-2. In twelve asthmatic patients (seven men, five women, average age 39 years) oral aspirin challenge precipitated symptoms of bronchial obstruction with fall in FEV1 > 20%, and a rise in urinary leukotriene E4 (LTE4) excretion; also in five patients the stable metabolite of PGD2, 9alpha11betaPGF2, increased in urine. The patients then entered a double-blind, placebo-controlled, cross-over study in which they received either placebo or rofecoxib in increasing doses 1.5-25.0 mg for 5 consecutive days, separated by a 1-week wash-out period. No patient on rofecoxib developed dyspnoea or fall in FEV1 > 20%; mean urinary LTE4 and 9alpha11betaPGF2 urinary levels, measured on each study day for 6 h post-dosing, remained unchanged. Two patients on placebo experienced moderate dyspnoea without alterations in urinary metabolites excretion. At least 2 weeks after completion of the study, all patients received on an open basis 25 mg rofecoxib without any adverse effects. NSAID that inhibit COX-1, but not COX-2, trigger asthmatic attacks in patients with asthma and aspirin intolerance. Rofecoxib can be administered to patients with aspirin-induced asthma.     

Loss of response to treatment with leukotriene receptor antagonists but not inhaled corticosteroids in patients over 50 years of age.

BACKGROUND: There are limited published data describing the relative efficacy of available treatment options in younger versus older patients with persistent asthma. OBJECTIVE: To compare the efficacy of fluticasone propionate (FP) and zafirlukast (Z) in younger (12 to 49 years of age) versus older (50 years and older) patients with asthma. METHODS: A retrospective analysis of five randomized, double-blind, double-dummy studies 4 to 12 weeks in duration of 1,742 patients <50 years of age and 243 patients aged 50 years or older. Interventions were inhaled fluticasone propionate (FP) 88 microg, oral Z 20 mg, or placebo twice daily. RESULTS: Treatment with FP resulted in significantly greater improvements than Z in all efficacy measurements (except for nighttime awakenings) regardless of age. In older patients, treatment with FP significantly increased pulmonary function compared with Z: FEV (FP= +0.19 L; placebo = -0.34 L; Z = -0.06 L); AM peak expiratory flow rate [PEFR] (FP = +25 L/minute; placebo = -18 L/minute; Z = +4 L/minute); PM PEFR (FP = +24 L/minute; placebo = -24 L/minute; Z = +5 L/minute; P < or = 0.023; for all comparisons). Compared with Z, treatment with FP in older patients also resulted in significantly greater increases in the percentage of symptom-free days (25% vs 13%) and rescue-free days (35% vs 17%); and significantly greater reductions in albuterol use (-1.6 vs -0.3 puffs/day) and the percentage of patients with exacerbations (2.7% vs 14.3%; P < or = 0.031). CONCLUSIONS: Regardless of age, treatment with FP in patients with asthma significantly improved pulmonary function and overall asthma control. In contrast, treatment with Z in older patients with asthma resulted in small improvements in asthma symptoms, whereas lung function improved minimally or not at all, and exacerbations increased. These data suggest that FP effectively controls inflammation in older patients, whereas Z may mask inflammation and may not provide the level of bronchodilatory or anti-inflammatory activity needed for effective asthma control in older patients.     

Comparative efficacy and anti-inflammatory profile of once-daily therapy with leukotriene antagonist or low-dose inhaled corticosteroid in patients with mild persistent asthma.

BACKGROUND: Current guidelines advocate the use of preventative anti-inflammatory therapy for mild persistent asthma. OBJECTIVE: We compared the efficacy and anti-inflammatory profiles of a leukotriene receptor antagonist and a low dose of inhaled corticosteroid in patients with mild persistent asthma. METHODS: Twenty-one adult patients with mild asthma received 4 weeks of either once-daily inhaled hydrofluoroalkane triamcinolone acetonide (450 microg/day ex-actuator dose) or oral montelukast (10 mg/day) in a randomized, placebo-controlled, single-blinded crossover study. Measurements were made before and after 2 and 4 weeks of each treatment. RESULTS: At the endpoint (after 4 weeks), triamcinolone and montelukast had improved the primary outcome (provocative dose of methacholine required to produce a 20% fall in FEV(1)) in comparison with placebo (P <.05), there being no difference between the treatments (1.09-fold; 95% CI 0.73 to 1.63). Triamcinolone was better than placebo or montelukast for effects on all other surrogate inflammatory markers (P <.05), including exhaled nitric oxide, blood eosinophils, serum eosinophil cationic protein, plasma intracellular circulating adhesion molecule 1, and plasma E-selectin. Both treatments improved (P <.05) morning and evening peak flow, nighttime beta2-agonist use, and symptoms in comparison with placebo, though triamcinolone was better than montelukast (P <.05) with regard to peak flow. Triamcinolone produced suppression (P <.05) of overnight urinary cortisol/creatinine and serum osteocalcin. CONCLUSION: Once-daily inhaled corticosteroid and leukotriene antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree.     

Inhaled budesonide aerosols in treatment of childhood asthma

Twenty-six children with chronic bronchial asthma, 19 boys and 7 girls, aged between 6 and 16 years with duration of asthma ranging from 1-12 years, were studied by a control, oral prednisolone 5 mg twice a day and inhaled budesonide 200 micrograms twice daily, each for 3 weeks. The clinical efficacy assessed daily by day and night symptom scores of cough, wheeze, sleep disturbance, limitation of activity, symptomatic inhaled terbutaline usage, daily morning and afternoon Peak Expiratory Flow Rate (PEFR), and weekly PEFR and Forced Expiratory Volume in 1 second (FEV1) in percent of predict, showed statistically significant improvement during the inhaled budesonide aerosol and oral prednisolone treatment periods in comparison with the control. No side effect was observed during any study periods.     

Effect of a non-sedative antihistaminic (loratadine) in moderate asthma

Seventeen patients with perennial asthma, stable on a moderate dose of inhaled steroid, participated in a crossover study comparing the clinical effect of a non-sedative, potent and highly selective H1 antagonist (loratadine 10 mg) with placebo. Each treatment period began with 2 weeks run-in followed by 8 weeks on either antihistamine or placebo. During the 8-week periods inhaled steroid was gradually tapered according to a fixed scheme. One patient was withdrawn from active treatment and three from placebo periods because of decreasing lung function (P greater than 0.1). Among the remaining 13 patients there was a threefold (1.8-4.8) decrease in the bronchial sensitivity to histamine during treatment with antihistamine compared to placebo (P less than 0.01). There was a trend in favour of active treatment with regard to changes in all symptom scores, lung function and use of escape medication, but these differences were not statistically significant. The increase in FEV1 was less than 5% of predicted normal (P less than 0.05). We concluded that the bronchial response to histamine can be attenuated by loratadine, an oral H1 receptor antagonist, but further studies are necessary to assess the clinical usefulness and place of loratadine in the therapy of asthma.     

Methotrexate therapy in asthma increases T cell susceptibility to corticosteroid inhibition

BACKGROUND: Concomitant methotrexate (MTX) therapy of severe, oral corticosteroid-dependent asthmatics has been shown to be corticosteroid sparing, but the mechanism is unknown. We hypothesized that MTX therapy of these patients increases the susceptibility of their T cells to corticosteroid inhibition. OBJECTIVE: To measure prednisolone inhibition of lectin-induced proliferation of peripheral blood T cells from a group of these patients before, during and following MTX therapy. METHODS: Eighteen severe asthmatics (median (range) age 56 (33-68) years, FEV1 61 (38-69)% predicted, dependent on oral prednisolone 15 (7.5-25) mg/day in addition to high-dose, inhaled corticosteroids) were treated with MTX 15 mg intramuscularly, weekly for 28 weeks. After 12 weeks of MTX, oral prednisolone dosages were reduced systematically over 16 weeks, provided that asthma control did not deteriorate. Patients were followed for a further 12 weeks after MTX withdrawal. Concentration-dependent, prednisolone inhibition of lectin-induced proliferation of peripheral blood T cells was measured just prior to MTX therapy (week 1) and at weeks 12, 28 and 40, and IC50 concentrations were interpolated. RESULTS: By week 28 of MTX therapy, patients were able to reduce oral prednisolone dosages from (median, SIQR) 15 (10-20.5) to 5.9 (1.4-9.4) mg/day (P<0.01) without alteration of lung function and symptoms, while median IC50 values for prednisolone inhibition of peripheral blood T cell proliferation were reduced from 49 (21-144) to 4 (1-9) nm (P<0.0001). These increased again to 15 (9.4-25.7) mg/day and 36 (18-67) nm, respectively, following MTX withdrawal. A correlation (P<0.01) was observed between percentage reductions in prednisolone dosages in vivo and fold changes in prednisolone IC50in vitro between weeks 12 and 28. CONCLUSION: This effect of MTX may at least partly account for its oral corticosteroid-sparing effect in severe asthma.     

Long-term efficacy of dupilumab in asthma with or without chronic rhinosinusitis and nasal polyps

BackgroundCoexisting chronic rhinosinusitis and nasal polyps (CRS-NPs) substantially increases the disease burden of asthma. Dupilumab, a fully human monoclonal antibody, has established efficacy and an acceptable safety profile in asthma and CRS with NP.ObjectiveTo evaluate long-term dupilumab efficacy in TRAVERSE (NCT02134028) patients with uncontrolled, moderate-to-severe (QUEST) or oral corticosteroid (OCS)-dependent (VENTURE) asthma with or without coexisting CRS-NP.MethodsIn TRAVERSE, 317 of 1530 (21%) QUEST and 61 of 187 (48%) VENTURE patients had self-reported CRS-NP; they received subcutaneous 300 mg dupilumab every 2 weeks up to 96 weeks. Patients were categorized by parent study treatment group (placebo/dupilumab, dupilumab/dupilumab). End points included annualized asthma exacerbation rates and mean change from parent study baseline in prebronchodilator forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, Asthma Quality of Life Questionnaire score, and OCS dose.ResultsPatients with coexisting CRS-NP had higher OCS dose and a history of more exacerbations. Concluding TRAVERSE, exacerbation rates decreased from 2.39 to 0.32 and 2.32 to 0.35 in dupilumab/dupilumab and 2.36 to 0.41 and 2.36 to 0.45 in placebo/dupilumab by week 96 from QUEST and VENTURE baselines, respectively. Non-CRS-NP results were similar. Improvements in forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, and Asthma Quality of Life Questionnaire score during parent studies were maintained in TRAVERSE; placebo/dupilumab patients achieved similar improvements to dupilumab/dupilumab by week 48. By week 96, 71% and 39% of OCS-dependent patients with CRS-NP and 83% and 47% without CRS-NP treated with dupilumab/dupilumab and placebo/dupilumab, respectively, stopped OCS.ConclusionLong-term dupilumab efficacy was maintained in patients with asthma with or without self-reported coexisting CRS-NP, including OCS-sparing effects observed in OCS-dependent severe asthma.Clinical Trial RegistrationClinicalTrials.gov Identifiers: NCT02528214, NCT02414854, and NCT02134028.     

Step-down and step-up therapy in moderate persistent asthma

BACKGROUND: A step-down therapy may be more beneficial for the management of asthma than a step-up therapy. METHODS: Eighty-two asthmatic patients with moderate persistent asthma were enrolled in the study and randomized into three groups. One group of patients received 400 microg/day of beclomethasone dipropionate (BDP) for 4 weeks and then 800 microg/day for another 4 weeks (step-up group). The other two groups of patients received 1,200 microg/day of BDP for 4 weeks with or without short-term oral steroid (prednisolone, 0.5 mg/day for 1 week) and then 800 microg/day for another 4 weeks (step-down group). Severe exacerbation of asthma, asthma symptoms, respiratory function and rescue use of inhaled beta(2)-agonists were monitored. If asthma was well controlled, the dose of BDP was decreased every 3 months and if asthma was exacerbated, the dose of BDP was increased until 8 months after the initial treatment. RESULTS: Twenty-two patients during the run-in period, 4 patients in the step-up group, 2 patients in the step-down group treated with a high dose of BDP and no patients in the step-down group with oral steroids during first 4 weeks dropped out because of severe exacerbation of asthma. Although asthma symptoms and respiratory function significantly improved 8 weeks after the therapy in all groups, more significant and prompt improvements of these parameters were observed in patients of the step-down group than in patients of the step-up group after the first 2 weeks of treatment. Furthermore, step-down therapy with short-term oral steroid resulted in the lowest maintenance doses of BDP at 8 months of the three groups. CONCLUSIONS: These results suggest that step-down therapy starting with a high dose of inhaled steroid and short-term oral steroid is more effective in gaining prompt control of asthma and reducing the severe exacerbation of asthma and the maintenance dose of inhaled steroids than a step-up therapy starting with a low dose of inhaled steroids in patients with moderate persistent asthma.     

A trial comparing nedocromil sodium (Tilade®) and placebo in the management of bronchial asthma

Abstract. In a double-blind group comparative trial nedocromil sodium (Tilade®) at a dose of 4 mg four times daily was compared with placebo in the management of out-patients with bronchial asthma. Treatments were delivered by pressurized aerosol over a period of 28 days following a 2-week base-line during which patients continued on their usual therapy. Twenty-one patients entered the nedocromil sodium group and twenty entered the placebo group. All were using beclomethasone dipropionate aerosol as maintenance steroid therapy plus intermittent use of a bronchodilator taken by inhalation. The dose of steroid was reduced for all patients after 2 weeks of treatment and again for approximately half the patients after 3 weeks trial treatment. Patients in the nedocromil sodium treatment group improved in respect of Diary Card symptom scores and peak expiratory flow rate (PEFR), and in their requirements for inhaled bronchodilators. Patients in the placebo group were worse, particularly in respect of daytime asthma symptoms ( P < 0·01), bronchodilator use ( P < 0·05) and morning PEFR during the third week of trial treatment ( P < 0·05). More patients in the nedocromil sodium group than in the placebo group thought their treatment had been effective ( P < 0·05). Nedocromil was well tolerated. Despite the short duration of treatment imposed at this stage in the clinical evaluation of a new compound, our results were sufficiently encouraging to prompt further evaluation of nedocromil sodium over the longer period required (3–12 months) for the clinical assessment of a new treatment for chronic asthma.     

Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of bronchial responses to cat allergen and histamine.

Ten asymptomatic patients with normal pulmonary function were selected for a double-blind trial of immunotherapy in cat-induced asthma. Each patient had a positive prick test to cat pelt extract and also a positive bronchial challenge response to the same extract. Patients were randomly assigned to active treatment or placebo groups and received weekly or biweekly injections over a 3 to 4-month period. The 5 patients who received the active treatment received a cumulative dose of cat pelt extract that ranged from 16.4 to 44.8 mg of total solid containing 1.7 to 4.7 mg of cat allergen 1. Apparent systemic reactions were observed in 3 patients who received the placebo and 3 patients who received the active treatment. The 5 patients who received the active treatment showed a reduction in skin reactivity to cat pelt extract as well as a significant mean reduction in bronchial sensitivity to the same extract. The 5 patients who received the placebo showed no significant changes in skin reactivity or bronchial sensitivity to cat pelt extract. Bronchial response to histamine did not change significantly in either the active treatment of the placebo group.     

Methylprednisolone pulse therapy in acute severe asthma

Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.     

Tezepelumab improves patient-reported outcomes in patients with severe,uncontrolled asthma in PATHWAY

BackgroundPatients with severe, uncontrolled asthma experience frequent exacerbations and hospitalization, leading to poor health-related quality of life. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced exacerbations by up to 71% and improved lung function, asthma control, and health-related quality of life vs placebo.ObjectiveThis analysis further assessed the impact of tezepelumab on patient-reported outcomes (PROs) in PATHWAY.MethodsAdults with severe, uncontrolled asthma were randomized to subcutaneous tezepelumab (70 mg every 4 weeks, 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. PROs were assessed using the asthma control questionnaire–6 (ACQ-6) and the asthma quality of life questionnaire (standardized) for patients aged 12 years or older (AQLQ[S]+12). The proportions of responders (defined by improvements of ≥0.5 in ACQ-6 or AQLQ(S)+12 scores) and patients whose asthma was well-controlled, partially-controlled, or uncontrolled in the tezepelumab and placebo groups were identified. The Asthma Daily Diary questionnaire was used to assess changes in overall symptom severity.ResultsOverall, 550 patients were randomized. Up to 82% and 77% of tezepelumab-treated patients were ACQ-6 and AQLQ(S)+12 responders, respectively, compared with 70% and 64% of placebo-treated patients, respectively. The proportions of patients with well-controlled or partially-controlled asthma were higher in the tezepelumab-treated group than in the placebo group. In addition, tezepelumab improved the overall symptom severity.ConclusionTezepelumab treatment improved PROs vs placebo, as indicated by the higher proportion of ACQ-6 and AQLQ(S)+12 responders and improvements in symptom severity in the tezepelumab dose groups. These data further support the benefits of tezepelumab in patients with severe, uncontrolled asthma.     

Effect of mattress and pillow encasings on children with asthma and house dust mite allergy

BACKGROUND: House dust mite (HDM) allergy is a frequent cause of allergic asthma in children. Reduction of exposure seems to be the most logical way to treat these patients. OBJECTIVE: Our aim was to investigate whether mattress and pillow encasings resulted in an effective long-term control of HDM allergen levels, thereby reducing the need for asthma medication in children with asthma and HDM allergy. METHODS: In a prospective, double-blind, placebo-controlled study 60 children (age range, 6-15 years) with asthma and HDM allergy were randomized to active (allergy control) or placebo mattress and pillow encasings. After a 2-week baseline period, follow-up was performed every 3 months for 1 year. During the entire study period, the dose of inhaled steroids was tapered off to the lowest effective dose according to well-defined criteria. RESULTS: Fifty-two patients completed the trial, and 5 were excluded, leaving data from 47 children (26 in the active treatment group and 21 in the placebo group) for analysis. A significant perennial reduction in HDM allergen concentrations was seen only for the active treatment group. Also, a significant decrease in the dose of inhaled steroids (mean, 408 to 227 microg/d; P <.001) was found for the active treatment group only, with significant differences between groups after 9 and 12 months. After 1 year, the dose of inhaled steroids was reduced by at least 50% in significantly more children in the active treatment group than in the placebo group (73% vs 24%, P <.01). CONCLUSION: Encasing of mattresses and pillows resulted in a significant long-term reduction in HDM allergen concentrations in mattresses and in the need for inhaled steroids in children with asthma and HDM allergy.     

The effect of ketotifen on bronchial hyperreactivity in childhood asthma

Eighteen children with perennial bronchial asthma with an average age of 9.6 yr were studied with respect to the protective effect of ketotifen on bronchial hyperreactivity. All children included demonstrated bronchial reversibility after inhalation of salbutamol, and the methacholine challenge produced a decrease of the forced expiratory volume during the first second of at least 20% in the concentration interval of 0.25 mg/ml to 4.0 mg/ml. The study was double-blind with patients divided into two parallel groups treated for 12 wk with ketotifen or placebo. Methacholine provocation tests were performed every fourth week during this period. No differences between the challenges before and during the treatment period were found in either group, nor were any differences found between the ketotifen and placebo groups. Long-term treatment with ketotifen does not appear to alter the bronchial hyperreactivity in children with bronchial asthma.     

Long-term prognosis of asthmatic patients treated with low-dose beclomethasone dipropionate]

To clarify the prognosis of asthmatics treated with low-dose of inhaled beclomethasone dipropionate (BDP), we retrospectively assessed 43 patients treated with initial dose of 200 or 400 micrograms/day for 5 years, and obtained the following results. 1) 15 patients achieved step-down therapy (group A), 17 patients maintained initial dose of BDP (group B), and 11 patients required step-up therapy of BDP or daily use of oral prednisolone (group C). 2) There was no significant difference in age, sex, duration of disease, severity of disease, peripheral eosinophil counts, %FEV1 and histamine PC20 before BDP treatment among three groups. The percentage of atopic asthmatics was significantly higher in group C than in group A. 3) There was no significant difference in symptom and histamine PC20 between after 1 year state and after 5 years state in three groups. 4) After 1 year from the start of BDP treatment, only 18% patients got symptom free and neither patients exceeded 20,000 micrograms/ml of histamine PC20 in group C. Long-term treatment of low-dose BDP inhalation was effective on mild/moderate asthmatics. Patients requiring step-up therapy had not got sufficient improvement in bronchial hyperresponsiveness after one-year treatment.     

A double-blind trial of oral immunotherapy for Artemisia pollen asthma with evaluation of bronchial response to the pollen allergen and serum-specific IgE antibody

Eighteen asymptomatic Artemisia pollen asthma patients with normal pulmonary function were selected for a double-blind trial of oral immunotherapy. Each patient had a positive skin test to Artemisia pollen extract and also a positive bronchial challenge response to the same extract. The patients were randomly assigned to active treatment or placebo group and received intensive oral administration of Artemisia pollen extract over a 50-day course. The nine patients who received the active treatment ingested a cumulative dose of 396,652 PNU and showed a significant decrease in serum-specific IgE antibodies (P less than .05) and a significant reduction in bronchial sensitivity to the same extract (P less than .01). The changes in these two variables correlated well (r = .8787, P less than .01). The nine patients who received the placebo showed no significant changes in serum-specific IgE or bronchial sensitivity to Artemisia pollen extract. Follow-up of two cases with the same extract showed that the reductions in serum-specific IgE as well as bronchial sensitivity induced by oral immunotherapy were maintained for 3 months.     

Urinary magnesium excretion in asthmatic children receiving magnesium supplementation: a randomized, placebo-controlled, double-blind study.

The aims of this study were to establish whether a magnesium (Mg) deficit indicated by a decreased urinary excretion exists and to determine whether 12-week oral Mg supplementation affects the Mg status and bronchodilator use in children with stable bronchial asthma. The effects of long-lasting Mg supplementation were investigated in 89 children 4 to 16 years of age with mild or moderate persistent bronchial asthma in a randomized, double-blind, placebo-controlled, prospective study. Each subject received one capsule of Mg citrate per day (= 7 years: 200 mg, > 7 years: 290 mg) or one capsule of placebo containing 260 mg glucose during 12 weeks. Evaluation was performed at 4-week intervals. Venous blood serum total and free Mg and urine Mg levels were determined at the beginning and end of the 12-week period. Parents recorded the number of bronchodilator doses twice daily. A urinary Mg loss (6.81 +/- 3.9 versus 2.79 +/- 1.39 mmol/day, p = 0.01) was observed in the placebo-treated persistent moderate asthmatics. Bronchodilator use was significantly higher after 8 and 12 weeks in the placebo-treated than in the Mg-treated patients with moderate asthma (31.1 +/- 1.8 versus 29.5 +/- 1.2 puffs per patient/4 weeks, p < 0.05, and 31.0 +/- 2.3 versus 29.3 +/- 0.9 puffs per patient/4 weeks, p < 0.05, respectively). Long-lasting Mg supplementation is clearly of benefit in mildly to moderately asthmatic children and is recommended as a concomitant drug in stable asthma.     

A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma

BACKGROUND: Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy. OBJECTIVE: To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma. PATIENTS AND METHODS: A single-blind double-dummy placebo-controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 microg inhaled plus 200 microg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1-week placebo run-in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms. RESULTS: There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2-18.6) for placebo vs. budesonide, 2.9 (1.0-8.4) for placebo vs. montelukast, and 2.1 (1.1-4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms. CONCLUSION: Once-daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.     

Oxatomide modifies methacholine- and exercise-induced bronchoconstriction in asthmatic children.

Oxatomide is a potent inhibitor of both the release and effects of allergic mediators and is similar to calcium antagonists in chemical structure. It prevents histamine release by inhibiting not only the increase in calcium intake, but also intracellular calcium release. We investigated its effect on methacholine-induced and exercise-induced bronchoconstriction in asthmatic children. Methacholine challenges were performed after oral administration of 0.88 mg/kg oxatomide or placebo in nine asthmatic children in a double-blind placebo-controlled study. Respiratory thresholds were improved in seven patients and log PC20 in the oxatomide group (6.65 +/- 1.34 micrograms/mL) was significantly higher than that in the placebo group (5.74 +/- 1.04 micrograms/mL) (P < .05). Exercise challenges were performed after oral administration of 1.5 mg/kg oxatomide or placebo in eight asthmatic children in a double-blind placebo-controlled study. Oxatomide produced acute bronchodilatation with 6.1% improvement on an average in FEV1. The mean maximal % fall obtained by oxatomide was 13.5%, while that by placebo was 22% (P < .05). These results indicate that oxatomide reduces nonspecific bronchial hyperresponsiveness.