Background: For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids, addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines.Objective: To compare montelukast, a once-daily leukotriene receptor antagonist, and salmeterol, a twice-daily, long-acting beta-agonist, concomitantly administered with inhaled fluticasone, according to the percentage of patients without an asthma attack for 1 year.Methods: A randomized, double-blind, double-dummy, multicenter study was conducted. Adult patients with moderate-to-severe persistent asthma (ages 14-73 years) receiving inhaled fluticasone (220 mug/d) who remained symptomatic during a 4-week run-in period were randomized to the addition of salmeterol (84 mug/d) or montelukast (10 mg/d) for 48 weeks.Results: Of the 1,473 randomized patients, 743 were randomized to montelukast and 730 to salmeterol; 1,059 patients completed the study. Eighty percent of patients in the montelukast group and 83.3% of patients in the salmeterol group remained attack free during the 48 weeks of treatment (relative risk, 1.20; 95% confidence interval, 0.96-1.49). Montelukast significantly reduced blood eosinophil counts compared with salmeterol, whereas salmeterol significantly increased prealbuterol forced expiratory volume in 1 second, asthma-specific quality of life, morning peak expiratory flow rate, and decreased nocturnal awakenings compared with montelukast. Differences between treatments were small, and both treatments were generally well tolerated.Conclusions: Addition of montelukast or salmeterol to an inhaled corticosteroid similarly protected most patients from experiencing an asthma attack during a 1-year period, but, based on noninferiority limits, the study was inconclusive with regard to a difference between treatment groups.

Background: Although response to intranasal corticosteroid therapy has been reported in patients with nonallergic rhinitis with eosinophilic syndrome (NARES), efficacy specifically in non-NARES patients has not been fully characterized.Objective: To evaluate the efficacy of intranasal fluticasone propionate (FP) in the treatment of patients with perennial nonallergic rhinitis, with and without nasal eosinophilia.Methods: Data from 983 patients in three randomized, double-blind, placebo-controlled PNAR trials were integrated. Patients received a total daily dose of FP 200 mug (n = 332), FP 400 mug (n = 325), or placebo (n = 326) for 28 days. Patients were 12 years of age with perennial rhinitis and negative skin tests to all allergens relevant to the geographic region. Nasal eosinophils were evaluated using a five-point scale. Patients were classified as non-NARES with a point score of 0 (n = 674; 69%); patients with a point score between I and 4 were classified as NARES (n = 309; 31%). Efficacy of FP was evaluated by the mean change in total nasal symptom score (TNSS), a sum of patient ratings of nasal obstruction, postnasal drip, and rhinorrhea.Results: Patients with either NARES or non-NARES had similar statistically significant improvement with FP 200 mug or 400 mug compared with placebo, thus, the total group comprising both varieties of rhinitis responded to FP. In the total population, both FP treatment groups showed significantly greater improvement in TNSS compared with placebo during each week of treatment (P less than or equal to 0.002), with mean changes in TNSS for day 22 to day 28 ranging from -84 and -85 in the FP 200 mug and FP 400 mug groups, respectively, to -64 in the placebo group, The three study treatment groups had similar proportions of non-NARES (68 to 69%) and NARES (31 to 32%) patients at baseline. In the non-NARES subgroup, mean changes in TNSS for each treatment group were similar to changes seen in the total population. In the NARES subgroup, mean changes in TNSS for the FP 200 mug and placebo groups were similar to changes seen in die total population; mean change in TNSS for the FP 400 mug group was somewhat greater than changes seen in the total population.Conclusions: Intranasal FP is an effective treatment for perennial nonallergic rhinitis with or without nasal eosinophilia (NARES or non-NARES).

BACKGROUND Inhaled corticosteroid therapy in severe persistent asthma has been shown to reduce or eliminate oral corticosteroid (OCS) use while retaining effective asthma control. OBJECTIVE We sought to evaluate the ability of mometasone furoate (MF) delivered by means of dry powder inhaler to reduce daily oral prednisone requirements in OCS-dependent patients with severe persistent asthma. METHODS We performed a 12-week, double-blind, placebocontrolled trial (21 centers, 132 patients) comparing 2 doses of MF (400 and 800 microg administered twice daily) with placebo, followed by a 9-month open-label phase in which 128 patients received treatment with MF. RESULTS At the endpoint of the double-blind trial, MF 400 and 800 mg twice daily reduced daily OCS requirements by 46.0% and 23.9%, respectively, whereas placebo increased OCS requirements by 164.4% (P <.01). Oral steroids were eliminated in 40%, 37%, and 0% of patients in the MF 400 and 800 mg twice daily and placebo groups, respectively. Pulmonary function and quality of life significantly increased for MF-treated patients. Further reductions in OCS requirements were achieved with long-term MF treatment in the open-label phase. CONCLUSION MF inhaled orally as a dry powder is an effective alternative to systemic corticosteroids in patients with severe persistent asthma.

Background: Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use.Objective: This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma.Methods: Oral prednisone-dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 mu g administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study, Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria.Results: Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 mu g fluticasone propionate groups, respectively, versus 9% of the placebo group (P < .001). FEV1, morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance (P less than or equal to .009) primarily in the 1000 mu g twice daily group. Hypothalamic-pituitary-adrenal axis suppression observed at baseline improved when patients were weaned off oral prednisone to fluticasone propionate. Adverse events ascribed to drug treatment were primarily topical effects of inhaled corticosteroids or those associated with prednisone withdrawal. Patient quality of life assessed by means of the Asthma Quality of Life Questionnaire was clinically and significantly improved after fluticasone propionate treatment (P less than or equal to .003).Conclusion: Fluticasone propionate powder (500 or 1000 mu g twice daily) effectively improved lung function, adrenal function, and asthma-specific quality of life in patients with severe chronic asthma previously treated with oral prednisone while allowing most patients to be weaned off oral corticosteroid therapy.

A single-masked, randomized, controlled, multicenter, parallel-group study compared the efficacy, tolerability, and specific treatment-related side effects of 4 weeks of intranasal therapy with 220-μg once-daily triamcinolone acetonide aerosol versus 168-μg twice-daily beclomethasone dipropionate aqueous spray in 313 patients with perennial allergic rhinitis. Both treatments produced similar improvement in rhinitis symptoms (nasal congestion, rhinorrhea, postnasal drip, sneezing, and nasal itching) and in mean total nasal symptom scores. There were no clinically or statistically significant between-group differences in physician global evaluation of symptom relief or in the number of patients who withdrew prematurely from the study because of insufficient therapeutic effect. The onset of action during the first week of therapy was comparable for the two treatments. The frequency of two specific treatment-related complaints—medication running down the throat and medication running out of the nose—was statistically significantly less with triamcinolone acetonide than with beclomethasone dipropionate. The severity of these two complaints, plus one other—bad medication taste—was statistically significantly greater with beclomethasone dipropionate. The frequency of drug-related adverse events was similar in the two treatment groups. The results of this trial indicate that triamcinolone acetonide, 220 μg once daily, is comparable to beclomethasone dipropionate, 168 μg twice daily, in relieving the nasal symptoms of perennial allergic rhinitis. Both treatments were well tolerated, although some specific treatment-related events were significantly more frequent and severe in the beclomethasone dipropionate aqueous spray group than in the triamcinolone acetonide aerosol group.

In this double-blind, parallel, single-dose study, bitolterol mesylate aerosol (three sprays, 1.11 mg) and albuterol aerosol (two sprays, 180 mcg) were compared for efficacy of bronchodilation in 120 adolescent and young adult patients with moderate to severe asthma. All patients required regular medications for asthma control. None was steroid dependent. Both medications gave effective bronchodilation within 5 min with maximum effect at 30 to 60 min. Mean percent increase in forced expiratory volume in 1 sec (FEV,) over baseline was higher for bitolterol than for albuterol at all test times up to 8 hr after a dose at which time 20% mean percent increase of FEV, over baseline was still present in the bitolterol-treated patients. With albuterol mean percent increase in FEV, fell to 15% over baseline at 5 hr after a dose. Differences in FEV, increase between the two treatment groups were statistically significant at 4 to 8 hr after a dose. Patients with baseline FEV1 < 50% of predicted normal had a response to bitolterol that was higher than that observed with albuterol treatment (p < 0.1). Mean maximum percent increase in FEV, and median duration of bronchodilation were greater with bitolterol than with albuterol, but the differences were not statistically .significant. Bath bitolterol aerosol and albuterol aerosol were demonstrated to be safe, effective, and long-acting bronchodilating agents. Both bitolterol and albuterol administered by aerosol had a rapid onset, and the maximum degree of bronchodilation was comparable. However, at the doses studied, bitolterol produced significantly higher increase in FEV, over baseline at longer times after medication than did albuterol.

From the experience above, it may be concluded that corticosteroid therapy in allergic disease has become more effective than ever before. The expected variations in usage of new important pharmacologic agents is seen with special clarity in the use of corticosteroids. The wide acclaim for the "miracle drug of the 1950's", which followed penicillin of the 1940's, soon gave away to anguish about side-effects that threatened to abolish its use entirely in the late 1950's. The 1960's brought alternate day therapy for chronic usage and recognition that short term usage was relatively safe. The 1970's saw proliferation of topically active steroids similar to those so important to the practice of Dermatology in the previous decade. Results in treating asthma and nasal diseases have been excellent and extensive research for adverse effects has been largely unrevealing.

NUMBER 2with "infectious" asthmatic episodes, and 12 control individuals without respiratory disease~ by culture of transcrieothyroid aspirates (TCTA) and sputums (asthmatics only).Patients had been symptomatic over at least a 3 day period, were documented to have reversible airway obstruction~ and were not receiving antibiotics.Fourteen patients were "nonatopie" (no evidence of reagins to common inhalant or ingestant allergens); 11 had symptoms that could not be related to reagins.Twenty-one had one or more symptoms consistent with infection: coryza ( 19), change of volume, color, or consistency of sputum (13), fever/myalgias (3), or sore throat (2).Four had persisting unexplained asthma.All had been treated symptomatically and were in no respiratory distress when the aspirates were obtained.Bacteria were found in 13 of the 25 aspirates from asthmatics, 8 as single isolates; however~ they were sparse in number, more than 6 colonies per plate being obtained in only 5 instances.Aspergillus and Penicillium were cultured once each.The presence of microbial growth from the TCTA did not correlate with clinical or laboratory features of the asthmatic exacerbations.Bacteria were cultured from 9 of 15 TCTA from the 12 control iindividuals.Mycobacteria~ Mycoplasma, and virsuses were not cultured.Microbial isolates :[rom sputum cultures did not correspond with those obtained by TCTA.Inasmuch as organisms were found in small numbers in comparable frequency in TCTA :both from asthmatics and from individuals without respiratory distress, the findings do not suggest that overt infection of the lower respiratory tree contributed to the asthma.However, l:he few organisms isolated may conceivably pro~ide an agency for immunologic or other host reactions sufficient to contribute to the asthma.