Long-term safety of triamcinolone acetonide nasal aerosol for the treatment of perennial allergic rhinitis.

A 1-year, open-label extension of a 12-week, double-blind clinical trial was conducted to evaluate the long-term safety and efficacy of once-daily therapy with triamcinolone acetonide nasal aerosol (110, 220, or 440 micrograms) in 93 patients with perennial allergic rhinitis. All three doses of triamcinolone acetonide were associated with sustained improvement in allergic rhinitis symptoms over the course of 1 year, as evidenced by physicians' and patients' global evaluations, ratings of the nasal environment (appearance and color of the nasal mucosa, as well as the quality of nasal secretions), nasal eosinophil counts, and requirement for escape medication. Among patients who reported adverse clinical experiences, most were considered unrelated or remotely related to therapy. Few patients experienced nasal irritation or throat discomfort, and no serious adverse experiences were attributed to treatment. Among 6 patients who withdrew from the study because of adverse experiences, a possible drug relationship was cited in 2 individuals (1 with headache and 1 with nasal blood) and a remote relationship in 1 (with acne). No clinically meaningful changes in vital signs, physical examinations, or laboratory values were noted, and mean serum cortisol levels were not suppressed during long-term treatment. These findings demonstrate that both safety and efficacy are maintained during long-term once-daily therapy with triamcinolone acetonide nasal aerosol in patients with perennial allergic rhinitis.

A study of antibody levels in alcoholic, depressive and schizophrenic patients.

A study was undertaken to compare IgG, IgA, IgM, IgE and IgD antibodies in adult alcoholic, depressive and schizophrenic patients with healthy, adult controls. Total IgG, -IgA, -IgM, -IgE, and -IgD and specific-IgE antibodies were assessed using 33 allergens: 12 inhalant and 21 foods. There was no significant difference observed in the total immunoglobulin results between the patients and controls. There were, however, significant differences between the groups for allergen specific-IgE with the depressive patients exhibiting the greatest number of positive test results. The depressives had an over-all t-test value of 10.080 (5% = 1.960), the alcoholics t = 6.800 and the schizophrenics t = 6.015. The most often positive allergens were those from the perennial/mold group, although the most frequently positive single allergen was egg white and 100% of the depressives were sensitive to it. The data in this investigation suggest that psychiatric patients with alcohol dependence, depression and schizophrenia be studied further so that information on a causal relationship between allergen specific-IgE antibodies and these mental disorders can be evaluated.

Rapid onset of control with budesonide Turbuhaler in patients with mild-to-moderate asthma.

BACKGROUND: Budesonide (Pulmicort) is an inhaled corticosteroid with high topical potency but low systemic activity. Turbuhaler is a novel breath-actuated, multi-dose, dry-powder inhaler. OBJECTIVES: This study was conducted to determine the efficacy and safety of two different dose regimens of budesonide Turbuhaler, compared with placebo, in adult patients with mild-to-moderate asthma not well-controlled with bronchodilator therapy. METHODS: This double-blind, randomized, placebo-controlled, parallel-group, multicenter study compared the efficacy and safety of 200 microg and 400 microg of budesonide, administered twice daily via Turbuhaler, with placebo, in 273 adult patients (aged 19 to 70 years) with mild-to-moderate asthma (FEV1 67% of predicted normal), not well-controlled with bronchodilator therapy. Efficacy was assessed by pulmonary function tests and patient assessments of asthma symptom control. Safety was assessed in terms of adverse events, laboratory evaluations, and physical examinations. RESULTS: Two hundred and 400 microg of budesonide bid were significantly more effective than placebo at improving morning PEF (mean differences from placebo of 43.63 L/min and 40.10 L/min, respectively; P < .001) and FEV1 (mean differences from placebo of 0.44 L, and 0.50 L, respectively; P < .001) over the 12-week treatment period. Onset of action as assessed by morning PEF was within two days. Basal and stimulated plasma cortisol concentrations were not significantly affected by budesonide treatment compared with placebo. CONCLUSIONS: Treatment of adults suffering from mild-to-moderate asthma with budesonide Turbuhaler is well tolerated and results in a rapid onset of asthma control which is maintained over time.

Efficacy of once daily extended-release theophylline in decreasing the use of inhaled beta 2-agonists in stable, mild-to-moderate asthma patients.

BACKGROUND/OBJECTIVE: The purpose of this study was to determine whether the addition of extended-release theophylline to the daily treatment regimen of inhaled beta 2-agonist users would result in decreased use of beta 2-agonist while maintaining similar efficacy for treatment of asthma. METHODS: This was a single-blind, multicenter (six sites) study. Sixty-one patients with a history of mild-to-moderate asthma treated with inhaled beta 2-agonist were randomized to treatment with Theo-24 (anhydrous extended-release capsules) plus inhaled beta 2-agonist or placebo plus beta 2-agonist. Patients kept daily symptom diaries, measured peak flow rates, recorded puffs of inhaled beta 2-agonist, and adverse events during a 4-week treatment period. RESULTS: Fifty-five patients were included in the efficacy analysis. The primary efficacy variable in this study was the mean number of puffs (adjusted for baseline differences) of beta 2-agonist inhaled per day. In this study, the addition of theophylline to the daily regimen of inhaled beta 2-agonist for 4 weeks significantly reduced the total daily dose of inhaled beta 2-agonist at weeks 3 and 4 of treatment compared with placebo. The differences were significant at the P < .05 level. For patients in the theophylline group, the number of puffs decreased from an unadjusted mean of 9.81 at baseline to an adjusted mean of 6.78 after 4 weeks of treatment compared with 9.91 at baseline and 8.17 for the placebo group. There were no unexpected or serious adverse events. CONCLUSIONS: In this study, the addition of once daily, extended-release theophylline to the daily regimen of inhaled beta 2-agonist for 4 weeks significantly reduced the total daily dose of inhaled beta 2-agonist at weeks 3 and 4 of treatment compared with placebo, while maintaining acceptable asthma symptom scores.

Once daily intranasal fluticasone propionate is effective for perennial allergic rhinitis.

The efficacy of intranasal fluticasone propionate 200 micrograms once daily or 100 micrograms twice daily in treating perennial allergic rhinitis was evaluated in a randomized, double-blind, placebo-controlled study of 24 weeks' duration in 365 patients. Clinician-rated and patient-rated total nasal symptom severity scores were improved within 1 week of treatment with either regimen of fluticasone propionate and improvement was maintained over the 24-week treatment period. Clinician-rated overall evaluation indicated a significantly better response in the two fluticasone propionate groups compared with the placebo group. All efficacy evaluations indicated no difference in response between the fluticasone propionate 200 micrograms once-daily and 100 micrograms twice-daily groups. Patients in both fluticasone propionate groups had significantly less nasal obstruction upon awakening than the placebo group at all assessment periods. Fewer patients in either fluticasone propionate group used antihistamine rescue medication compared with the placebo group. The percentage of patients with nasal eosinophils and basophils at the end of the 24-week treatment period was significantly lower in both fluticasone propionate groups compared with the placebo group. Safety evaluations indicated that intranasal fluticasone propionate was as safe as placebo when given as 200 micrograms once daily or 100 micrograms twice daily. The incidence of drug-related adverse events was similar among the fluticasone propionate and placebo groups except for the incidence of epistaxis and blood in nasal mucus which was somewhat higher in the fluticasone propionate twice-daily group. There was no changes in the opthalmic examinations to suggest corticosteriod-induced posterior subcapsular cataract formation.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma.

BACKGROUND: An effective, long-acting bronchodilator could benefit patients with asthma who have symptoms not controlled by antiinflammatory drugs. We compared a new long-acting, inhaled beta 2-adrenoceptor agonist, salmeterol, with a short-acting beta 2-agonist, albuterol, in the treatment of mild-to-moderate asthma. METHODS: We randomly assigned 234 patients (150 male and 84 female patients 12 to 73 years old) to one of three treatment groups: one group received 42 micrograms of salmeterol twice daily, one received 180 micrograms of albuterol four times daily, and one received placebo. Treatment was assigned in a double-blind fashion, and all patients could use supplemental inhaled albuterol as needed during the 12-week treatment period. RESULTS: Measurements of the forced expiratory volume in one second, performed hourly for 12 consecutive hours, showed that a single dose of salmeterol produced a greater mean area under the curve than two doses of albuterol taken 6 hours apart (6.3 vs. 4.9 liter.hr, P < 0.05). The difference was significant on day 1 and at week 4 of the study, but not at week 8 or 12. Salmeterol was also more effective than albuterol or placebo (with albuterol taken as needed) in increasing the morning peak expiratory flow rate: salmeterol induced a mean increase of 24 liters per minute over the pretreatment values, as compared with a decrease of 6 liters per minute with albuterol (P < 0.001) and an increase of 1 liter per minute with placebo (P = 0.002). The mean overall symptom score was improved most by salmeterol treatment (P < 0.05), with the number of days with symptoms and of nights with awakenings decreasing by 22 percent and 52 percent, respectively; there were no differences in results between albuterol treatment and placebo administration. We found no evidence of tolerance to the bronchodilating effects of salmeterol, and adverse reactions to all the treatments were infrequent and mild. CONCLUSIONS: For the management of mild-to-moderate asthma, salmeterol given twice daily is superior to albuterol given either four times daily or as needed.

Dose ranging study of mometasone furoate (Nasonex) in seasonal allergic rhinitis.

BACKGROUND: Topical nasal corticosteroids are rapidly gaining acceptance as first-line therapy for seasonal allergic rhinitis, but there is a desire for effective corticosteroids with an improved safety profile over existing products. OBJECTIVE: A multicenter, double-blind dose ranging study was conducted to compare the activity and tolerance of four doses of mometasone furoate nasal spray (tradename Nasonex) and placebo in adult patients with seasonal allergic rhinitis. METHODS: Four hundred eighty patients with seasonal allergic rhinitis were enrolled and randomized to receive mometasone furoate nasal spray 50 micrograms (n = 96), 100 micrograms (n = 95), 200 micrograms (n = 98) or 800 micrograms (n = 95), or placebo vehicle (n = 95) once daily for 28 days. RESULTS: All of the doses of mometasone furoate nasal spray showed activity in reducing the severity of rhinitis. The 200-microgram dose reduced total nasal symptom scores and total symptom scores throughout the study (P < .05 versus placebo vehicle). The 50-microgram dose and the 100-microgram dose showed less consistent activity at early timepoints (days 3 and 7), while the 800 microgram dose did not provide significant additional benefits over the 200-microgram dose. All dose levels were well tolerated CONCLUSION: The results of this trial indicate that 200 micrograms once daily is the optimum dose of mometasone furoate nasal spray for the treatment of seasonal allergic rhinitis.

Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction.

BACKGROUND: Previous trials demonstrated the effectiveness of the leukotriene receptor antagonist zafirlukast in patients with mild-to-moderate asthma. OBJECTIVES: We sought to assess the efficacy and safety of zafirlukast and its effect on patients' quality of life (QOL) during a 13-week, double-blind, placebo-controlled, multicenter trial in adults and adolescents with moderate reversible airflow obstruction. METHODS: Patients (age range, 12 to 68 years) with total daytime asthma symptoms scores of 10 or greater over 7 consecutive days (maximum, 21/wk), FEV1 45% or greater but less than or equal to 80% of predicted value (>/=6 hours after beta2 -agonist), and reversible airway disease were randomized to 20 mg zafirlukast twice daily (nZ = 231) or placebo twice daily (nP = 223). Efficacy was assessed from changes in daytime and nocturnal symptoms, beta2 -agonist use, nasal congestion score, and pulmonary function. QOL was evaluated with a disease-specific Asthma Quality of Life Questionnaire. Safety was determined from adverse event information and clinical laboratory test results. RESULTS: Zafirlukast was significantly (P <.001) more effective than placebo, with reductions from baseline in the daytime asthma symptoms score (-23%), nighttime awakenings with asthma (-19%), and beta2 -agonist use (-24%) and improvements from baseline in morning (+25 L/min) and evening (+18 L/min) peak expiratory flow rates. Compared with placebo, zafirlukast significantly (P /=0.5-unit change from baseline; P