Treatment with intranasal fluticasone propionate significantly improves ocular symptoms in patients with seasonal allergic rhinitis.

BACKGROUND: If monotherapy with an intranasal corticosteroid can alleviate both nasal and ocular symptoms of allergic rhinitis, treatment may be simplified and costs may be reduced. OBJECTIVE: The purpose of this study was to evaluate the efficacy of once-daily fluticasone propionate (FP) aqueous nasal spray 200 microg compared with vehicle placebo and oral loratadine (LOR) 10 mg in reducing ocular symptoms associated with seasonal allergic rhinitis. METHODS: A total of 471 patients received vehicle placebo, LOR, or FP in this multi-centre, double-blind, double-dummy, randomized study. Patients were > or =12 years old with a history of seasonal allergic rhinitis and a positive skin test for a relevant allergen. During the baseline and treatment periods, patients rated the severity of eye itching, tearing, and redness via visual analogue scales that ranged from 0 (no symptoms) to 100 (most severe symptoms). The three ocular ratings were added to derive the total ocular symptom score (TOSS). Patients with a TOSS > or =120 on at least 4 of the 7 days before the randomization visit were enrolled. The primary outcome was the difference between FP and vehicle placebo in the mean change from baseline in the reflective TOSS overall (averaged over the 28-day treatment period). A difference between FP and vehicle placebo of 25.5 was considered clinically significant. RESULTS: The overall mean change from baseline in the TOSS was significantly greater in the FP group compared with vehicle placebo (clinically significant difference of 28.8; P<0.001) and compared with LOR (difference of 16.2; P=0.028). Overall mean (SEM) changes were -59.9 (5.4) for the placebo group, -72.5 (5.4) for the LOR group, and -88.7 (5.3) for the FP group. The FP treatment group also showed significantly greater overall mean changes in ocular itching, tearing, and redness compared with vehicle placebo (P<0.001) and compared with LOR (P< or =0.045). CONCLUSION: Patients treated with intranasal FP had clinically and statistically significant decreases in ocular symptom scores compared with vehicle placebo. Data also suggest that FP reduced ocular symptoms more than or comparable with oral LOR. Patients experiencing ocular symptoms associated with allergic rhinitis may benefit from monotherapy with intranasal FP.

Comparison of fluticasone propionate-salmeterol combination therapy and montelukast in patients who are symptomatic on short-acting beta(2)-agonists alone.

The objective of this study was to determine whether initial maintenance therapy for the treatment of inflammation and bronchoconstriction associated with persistent asthma is more effective with a combination product (100 microg of fluticasone propionate and 50 microg of salmeterol [FSC]) administered twice daily through the Diskus device (GlaxoWellcome, Research Triangle Park, NC) or with montelukast at 10 mg once daily. A 12-wk, randomized, double-blind, double-dummy, multicenter study was conducted with 423 patients 15 yr of age and older with asthma and who were symptomatic while receiving short-acting beta(2)-agonists alone. At end point, FSC resulted in significantly greater increases in morning predose FEV(1) (0.54 +/- 0.03 vs. 0.27 +/- 0.03 L), morning peak expiratory flow (PEF) (89.9 +/- 6.7 vs. 34.2 +/- 4.7 L/min), evening PEF (69.9 +/- 5.8 vs. 31.1 +/- 4.5 L/min), the percentage of symptom-free days (48.9 +/- 2.9 vs. 21.7 +/- 2.5%), the percentage of rescue-free days (53.0 +/- 2.8 vs. 26.2 +/- 2.5%), and the percentage of nights with no awakenings (23.0 +/- 2.5 vs. 15.5+/-2.4%) compared with montelukast (p < or = 0.001, all comparisons). FSC significantly reduced asthma symptom scores (-1.0 +/- 0.1 vs. -0.6 +/- 0.1), rescue albuterol use (-3.3 +/- 0.2 vs. -1.9 +/- 0.2 puffs/d), and the number of exacerbations (0 vs. 11) compared with montelukast (p < 0.001). Both treatments were well tolerated. In summary, treatment of the two main components of asthma (inflammation and bronchoconstriction) with fluticasone propionate and salmeterol in a combination product was a more effective initial maintenance treatment strategy than treatment with montelukast, a single-mediator antagonist.

Improved asthma control after changing from low-to-medium doses of other inhaled corticosteroids to low-dose fluticasone propionate.

OBJECTIVE: To evaluate the efficacy and safety of changing from low-to-medium doses of other inhaled corticosteroids to low-dose fluticasone propionate. METHODS: Data from 11 randomized, double-blind, parallel-group trials in adults (>= 12 years; n = 1453; % predicted FEV1 = 42% to 89%) and 4 trials in children (4-11 years; n = 161; % predicted FEV1 = 50% to 112%) with chronic asthma were retrospectively analyzed. Symptomatic adults (n = 1181) treated with low-to-medium doses of beclomethasone dipropionate (168-672 mcg/day), triamcinolone acetonide (400-1200 mcg/day), or flunisolide (>=1000 mcg/day) were switched to low-dose fluticasone propionate (176 or 200 mcg daily) for 6-26 weeks. Patients (n = 272) remaining on low-dose beclomethasone dipropionate (336 mcg daily) served as controls. Pediatric patients previously treated with low doses of triamcinolone acetonide (4-8 puffs/day), or low-to-medium doses of beclomethasone dipropionate (4-8 puffs/day) or flunisolide (2-6 puffs/day), were changed to low-dose fluticasone propionate (100 mcg daily) for 12-52 weeks. RESULTS: Improvements in FEV1, morning and evening peak expiratory flow (PEF), rescue albuterol use, asthma symptom scores, and symptom-free days were significantly greater in adults who changed from low-to-medium doses of beclomethasone dipropionate or triamcinolone acetonide to low-dose fluticasone propionate (P <.001). Regardless of the degree of asthma severity, these improvements were 1.5- to 4-fold greater in adult patients changed to low-dose fluticasone propionate vs those remaining on low-dose beclomethasone dipropionate. Significant improvements in lung function, albuterol use, and asthma symptoms (P <=.002) were also seen in pediatric patients who changed from beclomethasone dipropionate, flunisolide, or triamcinolone acetonide to a much lower dose of an inhaled corticosteroid (100 mcg fluticasone propionate daily). Drug-related adverse events were low in adults and children, and were comparable among adults receiving low-dose fluticasone propionate or beclomethasone dipropionate. CONCLUSIONS: Results indicate that patients with persistent asthma can change from other inhaled corticosteroids to a lower dose of fluticasone propionate and still maintain or improve asthma control.

Comparison of inhaled salmeterol and oral zafirlukast in asthmatic patients using concomitant inhaled corticosteroids.

CONTEXT: For asthmatic patients who remain symptomatic on inhaled corticosteroids, augmenting the therapy with additional long-term control medication is advocated. Long-acting beta2-adrenergic agonists and leukotriene modifiers are 2 therapeutic alternatives in the long-term controller class. OBJECTIVE: To compare the addition of a long-acting beta2-adrenergic agonist to the addition of an oral leukotriene modifier for asthma therapy in patients who remain symptomatic on inhaled corticosteroids. DESIGN: Double-blind, double-dummy, parallel-group, multicenter clinical studies. SETTING: 54 outpatient clinical centers. PATIENTS: 429 male and female patients with asthma 12 years of age and older who were symptomatic while taking inhaled corticosteroids. INTERVENTIONS: Salmeterol xinafoate 42 mcg via metered dose inhaler twice daily or oral zafirlukast 20 mg twice daily. MAIN OUTCOME MEASURES: Pulmonary function, asthma symptoms, supplemental albuterol use, asthma quality of life scores, and adverse events. RESULTS: Inhaled salmeterol provided significantly greater improvement in pulmonary function as well as significantly greater relief of both daytime and nighttime asthma symptoms compared with oral zafirlukast in patients concurrently treated with inhaled corticosteroids. The use of supplemental albuterol was reduced to a greater extent with salmeterol compared with zafirlukast. Patients treated with salmeterol showed significantly greater improvement in Asthma Quality of Life Questionnaire (AQLQ) scores and were satisfied with how fast, how long, and how well the medication worked compared with patients in the zafirlukast group. Both treatments were well tolerated and demonstrated similar safety profiles. CONCLUSIONS: In patients with moderate to severe persistent asthma not sufficiently controlled with inhaled corticosteroids alone, the combination of inhaled salmeterol and inhaled corticosteroids is superior to the combination of oral zafirlukast and inhaled corticosteroids as stepwise therapy.

Salmeterol powder provides significantly better benefit than montelukast in asthmatic patients receiving concomitant inhaled corticosteroid therapy.

STUDY OBJECTIVES: Comparison of inhaled salmeterol powder vs oral montelukast treatment in patients with persistent asthma who remained symptomatic while receiving inhaled corticosteroids. DESIGN: Randomized, double-blind, double-dummy, parallel-group, multicenter trials of 12-week duration. SETTING: Outpatients in private and university-affiliated clinics. PATIENTS: Male and female patients > or = 15 years of age with a diagnosis of asthma (baseline FEV(1) of 50 to 80% of predicted) and symptomatic despite receiving inhaled corticosteroids. INTERVENTIONS: Inhaled salmeterol xinafoate powder, 50 microg bid, or oral montelukast, 10 mg qd. MEASUREMENTS AND RESULTS: Treatment with salmeterol powder resulted in significantly greater improvements from baseline compared with montelukast for most efficacy measurements, including morning peak expiratory flow (35.0 L/min vs 21.7 L/min; p < 0.001), percentage of symptom-free days (24% vs 16%; p < 0.001), and the percentage of rescue-free days (27% vs 20%; p = 0.002). Total supplemental albuterol use was decreased significantly more in the salmeterol group compared with the montelukast group (- 1.90 puffs per day vs - 1.66 puffs per day; p = 0.004) and nighttime awakenings per week decreased significantly more with salmeterol than with montelukast (- 1.42 vs - 1.32; p = 0.015). Patients treated with inhaled salmeterol were significantly more satisfied with their treatment regimen and how well, how fast, and how long it worked than were patients who were treated with oral montelukast. The safety profiles for the two treatments were similar. CONCLUSION: In patients with persistent asthma who remain symptomatic while receiving inhaled corticosteroids, adding inhaled salmeterol powder provided significantly greater improvement in lung function and asthma symptoms and was preferred by patients over oral montelukast.

Use of changes in symptoms to predict changes in lung function in assessing the response to asthma therapy.

BACKGROUND: The majority of adult patients with asthma are managed by primary care providers. Although there is no generally accepted gold standard for the assessment of asthma severity in general practice, treatment decisions and modifications to therapy are strongly influenced by patients' symptoms and history of asthma medication use. OBJECTIVES: The primary goal of this study was to determine whether there is a correlation between changes in asthma symptoms during treatment and changes in lung function, as measured by peak expiratory flow (PEF). A secondary goal was to compare the relative efficacy (in terms of improvement in asthma symptoms and lung function) of 3 commonly used asthma treatments: inhaled fluticasone propionate, inhaled salmeterol xinafoate, and oral zafirlukast. METHODS: This was a retrospective comparison employing regression analyses of asthma symptom and lung function data from 2890 male and female adolescent and adult patients with persistent asthma who were enrolled in 8 randomized, double-blind, double-dummy, parallel-group studies. Data on patients' self-rated symptoms, PEF, supplemental albuterol use, nighttime awakenings, and frequency of asthma exacerbations were used to ascertain whether there was a correlation between changes in asthma symptoms and changes in pulmonary function, and to compare treatment effects. RESULTS: Changes in patients' ratings of asthma symptoms after treatment with study medications showed a strong correlation with changes in lung function. Similarly, changes in lung function were strongly correlated with changes in supplemental beta-agonist use and quality of life. In addition, fluticasone or salmeterol treatment resulted in significantly greater increases in mean morning PEF (P < 0.001), significantly greater decreases in symptom scores (P < or = 0.004), significantly fewer nights with awakenings due to symptoms (P < or = 0.017), and significantly greater reductions in supplemental beta-agonist use (P < 0.001) compared with zafirlukast treatment or placebo. Patients treated with fluticasone or salmeterol also experienced significantly lower rates of asthma exacerbation (3%) during treatment than did those receiving zafirlukast (7%) or placebo (12%) (P < 0.001 and P = 0.015, fluticasone and salmeterol, respectively). CONCLUSION: These findings support the validity of primary care practitioners' basing asthma-management decisions on patients' symptoms.

Onset of therapeutic effect of fluticasone propionate aqueous nasal spray.

BACKGROUND: The effectiveness of fluticasone propionate (FP) aqueous nasal spray in the treatment of rhinitis has been demonstrated in multiple controlled clinical studies. The onset of therapeutic effect of FP in these clinical trials appears to occur within 12 hours after administration of the initial dose. OBJECTIVE: This article presents an analysis from previous clinical trials that examined the efficacy of intranasal FP in patients with rhinitis to ascertain whether the time to onset of the therapeutic effect of this medication could be determined. METHODS: Completed randomized, double-blind, placebo-controlled studies with FP were evaluated to determine whether onset of effect could be evaluated based on the study designs. A study was deemed acceptable for evaluation of onset of effect if at least one evaluation of the intensity of nasal symptoms was completed within 12 hours after the initial dose of study medication and daily evaluations were made thereafter. Adult patients were included in the onset analysis if they received an initial FP dose of 200 microg. Pediatric patients who received an initial FP dose of 100 microg were also included. Onset of effect was evaluated by 1) examining the timepoints at which statistically significant differences were observed between FP and placebo in mean change from baseline for total nasal symptom score (TNSS); and by 2) using a binary probability model of success/failure to determine statistically significant differences from placebo. RESULTS: Twenty-two studies met the criteria to evaluate onset of therapeutic effect; 3,605 patients with rhinitis received FP and 2,271 patients received placebo. This database represents the largest compilation of data ever assembled to determine the onset of therapeutic effect of a corticosteroid nasal spray. Two studies used a "park design" to examine onset of effect; statistically significant differences in TNSS favoring FP were achieved at hours 2 to 4 and at hour 12, respectively. Using a binary probability model of success/failure for analysis of TNSS in the remaining 20 studies not specifically designed to evaluate onset of effect, numerically greater improvements in TNSS for FP compared with placebo were found in 19 of the 20 studies within 12 hours of the administration of the first dose (P < .001). Pairwise comparisons showed statistically significant improvement for TNSS within 12 hours postdose in five of the studies for FP compared with placebo and in none for placebo compared with FP. CONCLUSIONS: Onset of therapeutic effect occurs within 12 hours, and as early as 2 to 4 hours in some patients, after administration of the first dose of FP aqueous nasal spray.

Low-dose inhaled fluticasone propionate versus oral zafirlukast in the treatment of persistent asthma.

BACKGROUND: Few studies have compared the efficacy of inhaled corticosteroids and leukotriene modifiers for the treatment of persistent asthma. OBJECTIVE: Our purpose was to compare the efficacy of a low dose of inhaled fluticasone propionate (FP) with that of oral zafirlukast in the treatment of persistent asthma previously treated with short-acting beta(2)-agonists alone. METHODS: A 12-week, randomized, double-blind, double-dummy, multicenter study was conducted in 451 patients aged 12 years and older with asthma who were symptomatic on short-acting beta(2)-agonists alone. After an 8- to 14-day run-in period, patients were randomized to treatment with FP 88 microg twice daily or zafirlukast 20 mg twice daily. RESULTS: Treatment with FP was more effective than treatment with zafirlukast in increasing morning FEV(1) (by 0.42 L vs 0.20 L over baseline, P <.001), morning peak expiratory flow (by 49.94 L/min vs 11.68 L/min over baseline, P <. 001), and evening PEF (by 38.91 L/min vs 10.50 L/min over baseline, P <.001). Statistically significant differences between the two treatments in FEV(1) were noted after the first observation (week 4) and in morning and evening peak expiratory flow by week 2. Mean change in percentage of symptom-free days was greater with FP than with zafirlukast (28.5% of days vs 15.6% of days, P <.001) and FP significantly increased the percentage of rescue-free days by 40.4% of days compared with 24.2% of days with zafirlukast (P <.001). Treatment with FP significantly reduced albuterol use by 2.39 puffs per day compared with 1.45 puffs per day (P <.001) and increased the percentage of nights with no awakenings by 21.2% of nights compared with 8.0% of nights with zafirlukast (P <.001). CONCLUSION: The clinical effectiveness of a low dose of FP as first-line therapy in patients with persistent asthma who are symptomatic on beta(2)-agonists alone is superior to that of zafirlukast.

Salmeterol added to inhaled corticosteroid therapy is superior to doubling the dose of inhaled corticosteroids: a randomized clinical trial.

This randomized, double-blind, double-dummy, parallel group clinical trial compared the efficacy and safety of adding salmeterol xinafoate to concurrent inhaled beclomethasone dipropionate therapy with doubling the dose of beclomethasone dipropionate in patients experiencing symptoms on low-dose beclomethasone. Salmeterol added to low-dose beclomethasone was superior (p < or = 0.05) to doubling the dose of beclomethasone in improving peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1), and in reducing symptoms of asthma, sleep loss, nighttime awakenings, and use of albuterol. Both treatment regimens had comparable safety profiles. In asthma patients inadequately controlled despite the use of low-dose inhaled corticosteroids (i.e., less than 400 microg per day), the addition of salmeterol may be a more effective treatment option than doubling the dose of inhaled corticosteroids.

Effect of long-term salmeterol therapy compared with as-needed albuterol use on airway hyperresponsiveness.

STUDY OBJECTIVES: To determine the effect of long-term salmeterol aerosol therapy on airway hyperresponsiveness measured by methacholine challenge. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. SETTING: Thirty-one clinical centers in the United States. PATIENTS: Four hundred eight asthmatic patients > or = 12 years of age with baseline FEV1 of > or = 70% of predicted values. Patients were not using inhaled corticosteroids. INTERVENTIONS: Twice-daily salmeterol aerosol, 42 microg, or placebo via metered-dose inhaler for 24 weeks. Backup albuterol was available. MEASUREMENTS AND RESULTS: Pulmonary function tests were performed before, during, and after treatment. Subjects recorded asthma-related symptoms, morning and evening peak expiratory flow (PEF) levels, and use of supplemental albuterol daily on diary cards. Methacholine challenges were performed 10 to 14 h postdose at weeks 4, 12, and 24, and 3 and 7 days posttreatment. Over 24 weeks of treatment, salmeterol provided significant (p < 0.001) protection against methacholine-induced bronchoconstriction of approximately one doubling dose of methacholine when compared to placebo with no evidence for a progressive decrease in protection. A rebound increase in airway hyperresponsiveness was not observed 3 and 7 days after cessation of salmeterol therapy. Salmeterol treatment resulted in sustained improvements of 0.21 to 0.26 L in morning premedication FEV1 and an improvement of 26.2 L/min in morning PEF when compared to placebo (p < 0.001). The use of salmeterol significantly reduced combined daytime asthma symptoms by 20% when compared to placebo (p = 0.005). A total of 34 and 48 exacerbations, respectively, were reported in the Salmeterol and placebo groups, and no evidence was present for a difference in the severity of asthma exacerbations between groups. Adverse event profiles were similar for the salmeterol and placebo groups. CONCLUSIONS: Regular long-term use of salmeterol aerosol resulted in sustained improvements in pulmonary function and asthma symptom control over the 24-week treatment period. There was no increase in bronchial hyperresponsiveness or loss of bronchoprotection at 24 weeks from that seen following 4 weeks of therapy. There was no evidence of rebound airway hyperresponsiveness after cessation of salmeterol treatment. Regular treatment with the long-acting beta-agonist salmeterol does not lead to clinical instability or vulnerability to unpredictable asthma attacks.

Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma.

OBJECTIVES: To compare the efficacies of medium-dose fluticasone propionate (FP), medium-dose triamcinolone acetonide (TAA), and combined low-dose FP plus salmeterol (SL). DESIGN: Randomized, double-blind, triple-dummy, multicenter, 12-week clinical trial. SETTING: Allergy/respiratory care clinics. PATIENTS: Six hundred eighty patients with asthma previously uncontrolled with low-dose inhaled corticosteroids. INTERVENTIONS: FP, 220 microg bid; TAA, 600 microg bid; or FP, 88 microg plus SL, 42 microg bid. MEASUREMENTS AND RESULTS: 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. CONCLUSION: 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.

Concurrent use of salmeterol with inhaled corticosteroids is more effective than inhaled corticosteroid dose increases.

This randomized, double-blind, parallel, multi-center study was designed to determine whether the addition of salmeterol to existing inhaled corticosteroid therapy provides greater therapeutic benefit than doubling the dose of inhaled corticosteroids in symptomatic patients with asthma. A total of 514 adults were randomized to either beclomethasone 168 micrograms plus salmeterol 42 micrograms twice daily or beclomethasone 336 micrograms twice daily for 24 weeks. Both treatments resulted in significantly improved symptom control and increased pulmonary function. However, beclomethasone plus salmeterol provided greater improvements than doubling the dose of beclomethasone (p < or = 0.05) in FEV1 and in daily-recorded measurements of morning (38 L/minute versus 20 L/minute after treatment with higher dose beclomethasone) and evening peak expiratory flow, asthma symptom scores, symptom-free days, supplemental albuterol use, and days and nights not requiring albuterol. There were no significant differences between treatment groups in the number of patients with abnormal response to corticotropin stimulation at Treatment Week 24. No treatment differences in asthma exacerbation and adverse event frequency rates were seen. Beclomethasone 168 micrograms plus salmeterol 42 micrograms administered twice daily was superior to beclomethasone 336 micrograms taken twice daily in patients symptomatic on beclomethasone 168 micrograms, with no added safety risks.

A six-month, placebo-controlled comparison of the safety and efficacy of salmeterol or beclomethasone for persistent asthma.

BACKGROUND: There is a paucity of data comparing the long-term safety and efficacy of long-acting inhaled beta2-agonists versus low-dose inhaled corticosteroids in the treatment of asthma. OBJECTIVE: To compare the safety and efficacy of salmeterol xinafoate, beclomethasone dipropionate (BDP), and placebo over a 6-month treatment period in patients with persistent asthma. METHODS: Salmeterol (42 microg twice daily), BDP (84 microg four times daily), or placebo was administered via metered-dose inhaler to 386 adolescent and adult inhaled corticosteroid-naive patients in a randomized, double-blind, double-dummy, parallel-group study. Eligible patients demonstrated a forced expiratory volume in 1 second (FEV1) from 65% to 90% of predicted values. Pulmonary function, symptom control, frequency of asthma exacerbations, bronchial hyperresponsiveness (BHR) to methacholine challenge, and adverse events were assessed. RESULTS: There were few statistically significant differences between the two active treatments over 6 months of therapy. Asthma symptoms and lung function were significantly improved with both salmeterol and BDP compared with placebo (changes from baseline in FEV1 of 0.28 L (SE = 0.04) and 0.23 L (SE = 0.04), respectively, compared with 0.08 L (SE = 0.04); P < or = .014). There were no significant differences among the treatment groups with respect to the distribution of asthma exacerbations over time. Both salmeterol and BDP significantly reduced BHR compared with placebo (P < or = .033; changes from baseline of 1.29 (SE = 0.26) and 1.42 (SE = 0.24) doubling doses at 6 months, respectively, compared with 0.24 (SE = 0.29) doubling dose for placebo). No rebound effect in BHR was seen upon cessation of any of the three treatment regimens. There were no clinically important differences in the safety profiles among the three treatments. CONCLUSIONS: Both salmeterol and BDP are effective and well-tolerated when administered for 6 months to inhaled corticosteroid-naive patients with persistent asthma.

Salmeterol vs theophylline: sleep and efficacy outcomes in patients with nocturnal asthma.

STUDY OBJECTIVES: To compare the efficacy, safety, and effects on sleep quality of salmeterol and extended-release theophylline in patients with nocturnal asthma. DESIGN: Randomized, double-blind, double-dummy, three-period crossover. SETTING: Outpatients at a single center. Patients spent 1 night during screening and 2 nights during each study period in a sleep laboratory for completion of sleep studies. PATIENTS: Male and female patients who were at least 18 years old with nocturnal asthma (baseline FEV1, 50 to 90% of predicted) and who required regular bronchodilator therapy. Patients on inhaled corticosteroids, cromolyn, and nedocromil were allowed into the study if their dosing remained constant throughout the study. INTERVENTIONS: Inhaled salmeterol (42 microg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 microg/mL), and placebo taken twice daily. MEASUREMENTS AND RESULTS: Efficacy measurements included nocturnal spirometry, nocturnal polysomnography, sleep questionnaires, and daily measurements of lung function and symptoms. Salmeterol was superior to theophylline (p < or = 0.05) in maintaining nocturnal FEV1 levels and was superior to placebo (p < or = 0.05) in improving morning and evening peak expiratory flow (PEF) and in decreasing nighttime albuterol use. The use of salmeterol significantly increased the percentage of days and nights with no albuterol use and decreased daytime albuterol use compared with theophylline and placebo (p < or = 0.05). Sleep quality global scores significantly improved with salmeterol and placebo (p < 0.001) but not with theophylline. The effects on sleep architecture were similar across treatment groups. CONCLUSIONS: Salmeterol (but not theophylline) was associated with sustained improvements in morning PEF, protection from nighttime lung function deterioration, reductions in albuterol use, and improvements in patient perceptions of sleep. No differences were seen in polysomnographic measures of sleep quality.

Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma.

BACKGROUND: Salmeterol, a long-acting beta2 -agonist, and zafirlukast, a leukotriene receptor antagonist, are both indicated for the treatment of asthma in adolescent and adult patients. OBJECTIVE: We sought to compare the effect of 4 weeks of treatment with inhaled salmeterol xinafoate versus oral zafirlukast in the treatment of persistent asthma. METHODS: This was a randomized, double-blind, double-dummy, parallel-group, multicenter clinical trial. Patients, over 80% of whom were on a concurrent inhaled corticosteroid regimen, were treated for 4 weeks with either inhaled salmeterol xinafoate 42 microgram twice daily administered by means of a metered-dose inhaler or oral zafirlukast 20 mg twice daily. The primary efficacy measure was morning peak expiratory flow (PEF); secondary efficacy measures included evening PEF, asthma symptom scores, supplemental albuterol use, nighttime awakenings, sleep symptoms, asthma exacerbations, and FEV1. RESULTS: Both inhaled salmeterol and oral zafirlukast resulted in within-group improvements from baseline in measures of pulmonary function, asthma symptoms, and supplemental albuterol use. Salmeterol treatment resulted in significantly greater improvements from baseline compared with zafirlukast for most efficacy measurements, including morning PEF (29.6 vs 13.0 L/min; P

Lack of subsensitivity to albuterol after treatment with salmeterol in patients with asthma.

The development of tolerance to the bronchodilator effects of beta2-agonists used in asthma therapy has been the subject of debate. We conducted two placebo-controlled crossover studies to assess the bronchodilator response to a short-acting beta2-agonist before and after chronic therapy with salmeterol. Patients in one study were corticosteroid-naive; patients in the other study were using inhaled corticosteroids. Changes in FEV1 after cumulative doubling doses of inhaled albuterol were assessed after a 2-wk beta-agonist washout period, before administering study medication on Day 1, and again after 28 d of therapy. Ipratropium bromide was provided as rapid-relief treatment for asthma, and use of any beta2-agonist except the study treatment was prohibited. On both assessment days for salmeterol, and during placebo administration periods, significant increases from predose FEV1 values were observed beginning with the lowest dose of albuterol and continuing throughout the dose-response assessment (p