An inhaled steroid improves markers of airway inflammation in patients with mild asthma. Auranofin in the treatment of steroid dependent asthma: a double blind study. Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid. Short course of steroids in home treatment of children with acute asthma. Need for theophylline in severe steroid-requiring asthmatics. Salmeterol reduces the need for inhaled corticosteroid in steroid-dependent asthmatics. Comparison of oral-steroid sparing by high-dose and low-dose inhaled steroid in maintenance treatment of severe asthma. Steroid-dependent asthma treated with inhaled beclomethasone dipropionate. A long-term study. An evaluation of azathioprine in severe chronic asthma.
Airway inflammation can be demonstrated in mildly asthmatic patients who are not treated with inhaled steroids. Current guidelines recommend that inhaled steroids should be introduced in mild asthmatics who use an inhaled beta2-agonist more than once daily. It was postulated that inhaled steroids can have anti-inflammatory effects in patients with even milder disease. The effect of 4 weeks of treatment with budesonide (800 microg twice daily by Turbohaler) was studied in 10 steroid-naive mildly asthmatic patients (forced expiratory volume in one second (FEV1) = 96+/-1.4% predicted) who required an inhaled beta2-agonist less than one puff daily, in a double-blind, placebo-controlled, crossover fashion. Spirometry, exhaled nitric oxide (NO), bronchial responsiveness (provocative concentration causing a 20% fall in FEV1 (PC20)), and sputum induction were performed before and after each treatment period. Following budesonide treatment, there were significant improvements in FEV1, and PC20, in association with a significant reduction in the percentage of eosinophils in induced sputum. Exhaled NO levels tended towards reduction, but the change was nonsignificant. There were also nonsignificant reductions in sputum eosinophil cationic protein and tumour necrosis factor-alpha levels. In conclusion inhaled budesonide can lead to improvements in noninvasive markers of airway inflammation, in association with a small improvement in lung function, even in mildly asthmatic patients who require an inhaled beta2-agonist less than once daily. This suggests a potential benefit of inhaled corticosteroids, even in relatively asymptomatic asthma. Long term administration of oral corticosteroids in patients with asthma may be associated with serious side effects. Non-steroidal anti-inflammatory drugs, including gold salts, have been shown to reduce the need for systemic corticosteroid treatment in uncontrolled studies. The effect of oral gold (auranofin) on asthma symptoms, lung function, and the need for oral prednisone treatment was investigated.
                A 26 week randomised, double blind, placebo controlled, parallel group trial of auranofin was performed in 32 patients with moderately severe chronic asthma who required an oral corticosteroid dose of at least 5 mg prednisone a day (or equivalent) or 2.5 mg/day prednisone plus more than 800 micrograms/day inhaled corticosteroids. Auranofin was given orally in a dose of 3 mg twice daily. Asthma symptoms, lung function, and adverse effects were assessed at regular intervals. After 12 weeks of treatment prednisone dosage was tapered down by 2.5 mg every two weeks if the patient was clinically stable. Asthma exacerbations were treated with short courses of high doses of oral steroids.
                Twenty eight of the 32 patients, 13 in the placebo group and 15 in the auranofin group, completed the study. The total corticosteroid reduction achieved after 26 weeks of treatment was significantly greater (4 mg) in the auranofin group than in the placebo group (0.3 mg). The number of exacerbations requiring an increase of steroids was greater in the placebo group (2.1) than in the active group (0.9). A significant increase in FEV1 of 6.4% predicted occurred in the auranofin group during the study and there was a reduction of asthma symptoms such as wheezing and cough. There was no difference between the groups in peak flow measurements or in the number of asthma attacks. The incidence of side effects of auranofin was low, but exacerbations of constitutional eczema were noticeable.
                Auranofin provides an effective adjunct to treatment for steroid dependent asthma, leading to a reduction of oral steroid dose. To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma.
                Randomised, double blind, placebo controlled, crossover trial.
                Twenty eight children aged 6-14 years with asthma of mild to moderate severity were studied for six months. Eighteen pairs of exacerbations were available for analysis, during which subjects took an increased dose of inhaled steroids or continued on the same dose.
                There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow variability, or symptom scores in the two weeks following an asthma exacerbation. Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (-3.5% to 10.4%) and -0.9% (-4.7% to 2.9%) for inhaled steroid and placebo, respectively. Spirometric function and the parents' opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo.
                This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans. A double blind, randomised, placebo controlled study of the treatment of children with acute asthma at home showed that a three day course of prednisolone hastened improvement of both asthmatic symptoms and peak expiratory flow rates. Thus all asthmatic children who present with an acute attack should be considered for treatment with corticosteroids in addition to bronchodilators not only to prevent possible deterioration but also to speed recovery. Concern about side-effects of theophylline prompted us to investigate whether this drug could be eliminated from the multi-medication regimen of severe asthmatics. We studied patients with a demonstrated requirement for systemic steroids who were taking most other available anti-asthma medications in an attempt to reduce systemic steroids while maintaining clinical stability. Five in-patients, 12-15 years old, completed a double-blind, cross-over trial of theophylline vs placebo. All were stable for 4 weeks prior to the study with normal spirometry and mildly elevated lung volumes. Regular medications consisted of long-acting theophylline with levels between 12 mcg/ml and 16 mcg/ml, and prednisone 10-30 mg on alternate days. In addition, they were all taking inhaled metaproterenol, cromolyn sodium, atropine sulphate, and beclomethasone dipropionate four times daily (qid). Patients received either theophylline or placebo during two drug periods. All other medications were unchanged. Parameters measured were symptom score, number of extra respiratory treatments (prn RTs), increase in steroid dosage, and daily spirometry. During the placebo period, all five patients required increased steroids, daily spirometry decreased and three patients developed severe exacerbations unrelated to viral infection. A marked increase in symptom score occurred within 48 hr of discontinuing theophylline in all. These findings emphasize that theophylline is beneficial in a subset of severe asthmatics who cannot be controlled with all other available bronchodilators, cromolyn, and inhaled and systemic steroids. Previous results have demonstrated addition of long-acting beta2-adrenergic agonists to be beneficial in asthma patients already receiving inhaled corticosteroid. The purpose of this study was to determine, qualitatively as well as quantitatively, the steroid-sparing properties of salmeterol in stable asthma patients receiving maintenance inhaled corticosteroids (800-1600 microg day(-1)). In these patients, the daily dose of beclomethasone dipropionate was reduced by 200 microg each week until asthma deteriorated, with the minimal acceptable dose (MAD) being defined as the dose one step above deterioration (sensitivity period). Following this, patients received three times the MAD for 2 weeks. Patients were randomized to receive either salmeterol 50 microg twice daily or placebo and the MAD was again determined (treatment period). Forced expiratory volume in 1 sec (FEV1) was measured each week. Morning and evening peak expiratory flow (PEF), symptom score and use of bronchodilator were recorded each day. Fifteen patients received salmeterol and 19 placebo. The MAD was significantly lower in the salmeterol group compared with placebo during the treatment period (P<0.01). A 50% reduction of the MAD was achieved by more patients treated with salmeterol than placebo (P = 0.001). Salmeterol caused a significantly greater reduction in daytime symptom score and use of as-needed beta2-agoinist therapy between sensitivity and treatment periods compared with placebo (P<0.05 for both). The results demonstrate, that the addition of salmeterol to corticosteroid treatment offers a clinically relevant potential for reduction of inhaled corticosteroid dose in steroid sensitive asthmatics. It is not clear whether high doses of inhaled steroids have a greater sparing effect than low doses on the requirement for systemic steroids. In a randomised, double-blind, multicentre study, we compared the effects of high-dose (1500 micrograms/day) and low-dose (300 micrograms/day) inhaled beclomethasone dipropionate (BDP) in patients with severe asthma requiring a daily oral prednisolone dose of 10-40 mg. During a 3-month run-in period, we tried to achieve optimum asthma control by means of oral steroid and inhaled BDP 300 micrograms/day. The patients were then allocated to high-dose (n = 71) or low-dose (n = 72) treatment by an independent observer who took into account various prognostic factors. BDP was administered by means of an aerosol inhaler with a spacer device. The dose of systemic steroid was reduced as much as possible during the 6-month study period while keeping the peak expiratory flow (PEF) constant and asthma clinically stable. There was no difference between the low-dose and high-dose treatment groups in the mean reduction in oral prednisolone dose achieved by the end of the study (5.2[ SD 7.9] vs 5.0 [9.4] mg/day). The maximum response to inhaled steroid was seen, however, only after several months' therapy in both groups. There were no differences between the groups in use of on-demand beta-agonist inhalations or in asthma symptoms, and PEF values were constant throughout the study. Both doses of BDP were well tolerated. High doses of inhaled steroid offer no further benefit over low doses in the maintenance treatment of severe steroid-dependent asthma when the inhaled steroid is administered with a spacer device. The efficacy of inhaled beclomethasone dipropionate has been examined in 44 steroid-dependent asthmatics observed for 9 months to 2 years. A 3-month double-blind trial found that subjects treated with beclomethasone had a significant diminution in symptoms, were able to reduce their use of medication, and had improved maximum expiratory flow rates. Approximately one half were able to discontinue the use of oral prednisone within 9 months after starting beclomethasone, and a further one third reduced their dose by at least 50%. No characteristics could be defined to predict responsiveness to beclomethasone. The effectiveness of beclomethasone was sustained for as long as 2 years and was not associated with any abnormal urine, blood, or serum values or chest X-ray findings. Candidiasis of the palate appeared in approximately one third of the subjects and was usually transient. The chronic use of beclomethasone did not result in endocrine suppression. nan
Currently there is a clear lack of evidence to support the use of azathioprine in the treatment of chronic asthma as a steroid sparing-agent. Large, long-term studies with pre-defined steroid reducing protocols are required before recommendations for clinical practice can be made.