Inhaled corticosteroid reduction and elimination in patients with persistent asthma receiving salmeterol: a randomized controlled trial. A long-term study of the antiinflammatory effect of low-dose budesonide plus formoterol versus high-dose budesonide in asthma. Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma. Salmeterol reduces the need for inhaled corticosteroid in steroid-dependent asthmatics. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group.
Inhaled long-acting beta(2)-agonists improve asthma control when added to inhaled corticosteroid (ICS) therapy.
                To determine whether ICS therapy can be reduced or eliminated in patients with persistent asthma after adding a long-acting beta(2)-agonist to their treatment regimen.
                A 24-week randomized, controlled, blinded, double-dummy, parallel-group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 through January 1999.
                One hundred seventy-five patients aged 12 through 65 years with persistent asthma that was suboptimally controlled during a 6-week run-in period of treatment with inhaled triamcinolone acetonide (400 microg twice per day).
                Patients continued triamcinolone therapy and were randomly assigned to receive add-on therapy with either placebo (placebo-minus group, n = 21) or salmeterol xinafoate, 42 microg twice per day (n = 154) for 2 weeks. The entire placebo-minus group was assigned and half of the salmeterol group (salmeterol-minus group) was randomly assigned to reduce by 50% (for 8 weeks) then eliminate (for 8 weeks) triamcinolone treatment. The other half of the salmeterol group (salmeterol-plus group) was randomly assigned to continue both salmeterol and triamcinolone for the remaining 16 weeks (active control group).
                Time to asthma treatment failure in patients receiving salmeterol.
                Treatment failure occurred in 8.3% (95% confidence interval [CI], 2%-15%) of the salmeterol-minus group 8 weeks after triamcinolone treatment was reduced compared with 2.8% (95% CI, 0%-7%) of the salmeterol-plus group during the same period. Treatment failure occurred in 46.3% (95% CI, 34%-59%) of the salmeterol-minus group 8 weeks after triamcinolone therapy was eliminated compared with 13.7% (95% CI, 5%-22%) of the salmeterol-plus group. The relative risk (95% CI) of treatment failure at the end of the triamcinolone elimination phase in the salmeterol-minus group was 4.3 (2.0-9.2) compared with the salmeterol-plus group (P<.001).
                Our results indicate that in patients with persistent asthma suboptimally controlled by triamcinolone therapy alone but whose asthma symptoms improve after addition of salmeterol, a substantial reduction (50%) in triamcinolone dose can occur without a significant loss of asthma control. However, total elimination of triamcinolone therapy results in a significant deterioration in asthma control and, therefore, cannot be recommended. Adding inhaled long-acting beta(2)-agonists to a low dose of inhaled corticosteroids (ICS), results in better clinical asthma control than increasing the dose of ICS. However, this approach may mask underlying airway inflammation. In a double-blind parallel-group study, we evaluated the effect of adding formoterol to a low dose of budesonide, compared with a higher dose of budesonide, on the composition of induced sputum. After a 4-wk run-in period of treatment with budesonide (800 microg, twice daily), 60 patients with moderate asthma were randomly assigned to a 1-yr treatment with 400 microg of budesonide plus placebo, twice daily (BUD800), or 100 microg of budesonide plus 12 microg of formoterol, twice daily (BUD200+F). All drugs were administered via Turbuhaler. Budesonide (800 microg, twice daily) during run-in significantly reduced median sputum eosinophils from 4.5 to 0.68%. No significant changes in the proportion of eosinophils, EG2(+) cells, other inflammatory cells, or ECP levels in sputum were observed over the ensuing 1-yr treatment with BUD200+F or BUD800. Clinical asthma control was not significantly different between both groups. In conclusion, no significant differences in sputum markers of airway inflammation were observed during a 1-yr treatment with a low dose of inhaled budesonide plus formoterol compared with a higher dose of budesonide. To compare the efficacies of medium-dose fluticasone propionate (FP), medium-dose triamcinolone acetonide (TAA), and combined low-dose FP plus salmeterol (SL).
                Randomized, double-blind, triple-dummy, multicenter, 12-week clinical trial.
                Allergy/respiratory care clinics.
                Six hundred eighty patients with asthma previously uncontrolled with low-dose inhaled corticosteroids.
                FP, 220 microg bid; TAA, 600 microg bid; or FP, 88 microg plus SL, 42 microg bid.
                Outcome measures included FEV1, peak expiratory flow (PEF), supplemental albuterol use, nighttime awakenings, asthma symptoms, and physician global assessment. Compared with TAA, 600 microg bid, treatment with FP 220, microg bid, significantly increased FEV1, morning and evening PEF, and percent symptom-free days, and significantly reduced rescue albuterol use, number of nighttime awakenings, and overall asthma symptom scores (p < or = 0.035). Improvements with low-dose FP, 88 microg, plus SL, 42 microg bid, were significantly (p < or = 0.004) greater than TAA, 600 microg bid, in all the aforementioned efficacy measures as well as percent of rescue-free days. Combined low-dose FP, 88 microg, plus SL, 42 microg bid, also significantly increased FEV1 and percent of rescue-free days, and significantly reduced albuterol use compared with medium-dose FP, 220 microg bid (p < or = 0.018). At endpoint, both FP, 220 microg bid, and FP, 88 microg, plus SL, 42 microg bid, significantly increased FEV1 by 0.48 L and 0.58 L, respectively, compared with 0.34 L with TAA, 600 microg bid.
                In patients who are symptomatic while taking low-dose inhaled corticosteroids, medium-dose FP (440 microg/d) and combination treatment with low-dose FP (176 microg/d) plus SL (84 microg/d) are both more effective than medium-dose TAA (1200 microg/d) in improving pulmonary function and asthma symptom control. 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. The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide.
                After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days.
                The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater.
                In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.
In adults with asthma, using moderate to high maintenance doses of ICS, the addition of LABA has an ICS-sparing effect.  The addition of LABA permits more participants on minimum maintenance ICS to reduce ICS. The precise magnitude of the ICS dose reduction requires further study.