Placebo-controlled, double-blind study of the efficacy and safety of triamcinolone acetonide aerosol nasal inhaler in pediatric patients with seasonal allergic rhinitis.

Triamcinolone acetonide (TAA) aerosol nasal inhaler has been shown to effectively relieve the symptoms of seasonal allergic rhinitis in adults and adolescents. We conducted a study to evaluate the efficacy and safety of once-daily administration of TAA aerosol nasal inhaler in pediatric patients aged 6 to 11 years with grass seasonal allergic rhinitis. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled 116 children who were treated with either TAA aerosol nasal inhaler (220 micrograms/d) or placebo once daily for 2 weeks. Patients evaluated the severity of rhinitis symptoms (nasal stuffiness, discharge, sneezing, and itching) daily according to a four-point scale (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Patients' and physicians' global evaluations of overall treatment efficacy were assessed at the end of the 2-week treatment period. Patients treated with TAA aerosol nasal inhaler had significantly greater reductions in all nasal symptom scores overall and in virtually all symptoms at the end of week 1 and week 2 compared with those in the placebo group. Both patients' and physicians' global evaluations of efficacy favored TAA aerosol nasal inhaler over placebo. This study demonstrated that once-daily administration of 220 micrograms of TAA aerosol nasal inhaler was well tolerated and effectively reduced the symptoms of seasonal allergic rhinitis in pediatric patients.

Cell-mediated immunity in vitro in atopic dermatitis.

The function of T cells in atopic dermatitis was studied by leukocyte migration agarose and lymphocyte transformation tests. We found that phytohemagglutinin (PHA)- and PPD-induced release of leukocyte migration inhibition factor (LIF) from lymphocytes is significantly decreased (P less than .001) in patients with atopic dermatitis as compared with healthy controls. Blastogenic response of lymphocytes induced by PPD was also decreased in atopic patients as compared with controls (P less than .01). No differences were found in spontaneous blastogenesis or in blastogenic response of lymphocytes in vitro to PHA, concanavalin A (ConA), or streptokinase-streptodornase (SK-SD) between patients with atopic dermatitis and controls.

Comparative efficacy of once daily loratadine versus terfenadine in the treatment of allergic rhinitis.

This 1 week study compared the efficacy of once daily administration of 10 mg loratadine with 120 mg terfenadine in out-patients with seasonal allergic rhinitis. It focussed on the efficacy of treatment at the end of the 24 h period following a daily dose. The study was designed as a double-blind, randomized, parallel-group trial, and 41 patients were enrolled and evaluated for efficacy. Patients took an initial dose at the study site and returned on days 2 and 8. At day 2 (24 h after the initial dose), according to the physician's evaluation 57% of loratadine-treated patients had a good or excellent response, compared to 50% of those given terfenadine. At day 8, 24 h after the final dose, 71% of the loratadine-treated patients and 35% of the terfenadine-treated patients had a good or excellent response (P = 0.03). At days 2 and 8, reductions in mean symptom scores measured 22, 23 and 24 h after the initial and final doses showed an indication of being greater with loratadine than with terfenadine (nonsignificant due to small sample size). The incidence of sedation was similar in both groups. It is concluded that 10 mg loratadine, administered once daily, controls the symptoms of rhinitis more effectively than 120 mg terfenadine given once daily in the last few hours of the 24 h dosing period.

Current review of anaphylaxis and its relationship to asthma.

Anaphylaxis is the most dramatic of hypersensitivity reactions with a two-fold relationship with asthma, in the immediate and late phases and drugs and immunotherapy may be triggers. There are many causes of anaphylaxis, with IgE-mediated reactions, especially those to some foods very common. Drug reactions are next most common, especially to beta-lactam antibiotics, sulphonamides, Dilantin and aspirin. Exercise-induced anaphylaxis is well documented and may be exacerbated by food. Careful examination of the etiology of anaphylaxis is essential. Anaphylaxis may occur during immunotherapy and skin testing and every physician who uses these techniques must have available for immediate use appropriate remedial measures. In a study of 25 patients three distinct clinical patterns were seen, uniphasic, biphasic and protected degree of anaphylaxis. Latex is now known to be responsible for immediate anaphylaxis, as well as Type IV and is found in a variety of clinical situations, including surgery. The world-wide AIDS epidemic has caused much greater use of latex with a concomitant rise in risk of anaphylaxis.

Efficacy of azelastine nasal spray in the treatment of vasomotor (perennial nonallergic) rhinitis.

BACKGROUND: Azelastine hydrochloride is an antihistamine with anti-inflammatory properties that is available in the United States in a nasal spray formulation for the treatment of seasonal allergic rhinitis. Vasomotor (perennial nonallergic) rhinitis (VMR) is a noninfectious, chronic rhinitis usually not associated with inflammatory cell infiltration. OBJECTIVE: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trials were conducted to determine whether patients with symptoms of VMR (rhinorrhea, sneezing, postnasal drip, and nasal congestion) could be effectively treated with azelastine nasal spray. METHODS: All of the patients who participated in the trials had a diagnosis of VMR, symptoms for at least 1 year, negative skin tests for a mixed panel of seasonal and perennial allergens, and a nasal cytology examination negative for eosinophils. After a 1-week, single-blind, placebo lead-in period, patients who met the symptom severity qualification criteria were randomized to receive either azelastine nasal spray (two sprays per nostril twice daily, 1.1 mg/day) or placebo nasal spray for 21 days. Patients recorded the severity of their VMR symptoms on diary cards each morning and evening of the trial using a four-point symptom rating scale (0 = none to 3 = severe). The primary efficacy variable was the overall reduction from baseline in the total vasomotor rhinitis symptom score (TVRSS) over the 21-day, double-blind treatment period. RESULTS: In both studies, azelastine nasal spray significantly (study 1, P = .002; study 2, P = .005) reduced the TVRSS from baseline when compared with placebo. Significant improvement was observed within the first week and improvement in all symptoms favored treatment with azelastine nasal spray. No serious or unexpected adverse events were reported in either study. Bitter taste (19% vs 2%) was the only adverse experience that occurred with a statistically significantly greater incidence in the azelastine group than in the placebo group. CONCLUSIONS: This is the first demonstration of the efficacy of an antihistamine in the therapy of VMR in two double-blind, placebo-controlled clinical trials.

Once-daily budesonide via Turbuhaler improves symptoms in adults with persistent asthma.

BACKGROUND: Previous studies have demonstrated the efficacy and safety of twice-daily budesonide Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Wilmington, DE) for the treatment of mild to severe asthma. OBJECTIVE: To compare the efficacy and safety of budesonide Turbuhaler administered once daily each morning with placebo in inhaled corticosteroid-naive adults with persistent asthma. METHODS: In this randomized, double-blind, placebo-controlled, multicenter study, 177 adults (aged 18 to 70 years) received placebo or once-daily budesonide Turbuhaler (400 microg) for 12 weeks. Efficacy variables included mean changes from baseline in forced expiratory volume in 1 second (FEV1) and AM/PM peak expiratory flow rate (PEFR), and nighttime/daytime asthma symptom scores, patient discontinuations, use of breakthrough medication (albuterol), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), and quality of life assessments. Safety was evaluated based on adverse events, physical examinations, vital signs, and laboratory tests. RESULTS: Demographic and baseline characteristics were comparable between study groups. The mean percentages of predicted FEV1 at baseline were 71.9 +/- 9.8 in patients receiving budesonide Turbuhaler and 70.6 +/- 11.0 in patients receiving placebo. Mean changes from baseline over the 12-week treatment period in FEV1 were significantly (P = 0.007) improved in patients receiving once-daily budesonide Turbuhaler compared with placebo (0.31 L and 0.17 L, respectively). Significant (P < or = 0.037) improvements over placebo also were observed in AM PEFR, nighttime/daytime asthma symptoms, and albuterol use with budesonide Turbuhaler treatment. Adverse events were generally mild or moderate in intensity and similar between study groups. CONCLUSIONS: Budesonide Turbuhaler 400 microg administered once daily in the AM is efficacious and safe for inhaled corticosteroid-naive asthmatic adults.

Beta2-agonist induced ventricular dysrhythmias secondary to hyperexcitable conduction system in the absence of a long QT syndrome.

BACKGROUND: The use of inhaled beta 2-agonists for bronchodilation in the treatment of lower airway obstruction is accepted worldwide. These agents are used for symptomatic relief of lower airway obstruction and, as well, can be employed prophylactically in exercise-induced bronchospasm. Cardiac dysrhythmias, specifically the long QT syndrome, have been associated with cardiac events precipitated by sympathomimetics. There are reports of documented long QT syndrome in association with syncope in children; however, there are no reports of beta 2-agonist-induced syncope in the absence of long QT syndrome. OBJECTIVE: To determine predisposing cardiac factors resulting in syncope associated with inhaled beta 2-agonist use. METHOD: Case report. The index case was evaluated for cardiac pathology through non-invasive techniques, cardiac catheterization, and electrophysiologic studies. Electrophysiologic studies included provocative challenge with parenteral adrenergic agents. RESULTS: Non-invasive studies were unremarkable. There was no evidence of prolonged QT syndrome or support for vasopressor syncope. Electrophysiologic studies revealed reproducible polymorphic ventricular tachycardia. This predisposition required a ventricular stimulation program of higher intensity while on mexilitine. CONCLUSIONS: This case of syncope associated with inhaled, short-acting beta 2-agonist resulted from a hyperexcitable conduction system rather than the presence of a long QT syndrome.

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)

SCH 434: a new antihistamine/decongestant for seasonal allergic rhinitis.

In a double-blind, multicenter study, we compared the effects of SCH 434 (Claritin-D; Schering Corp., Kenilworth, N.J.), a new sustained-release, combination antihistamine/decongestant medication, with the effects of its individual components and placebo in 435 patients with seasonal allergic rhinitis. SCH 434 contains 5 mg of loratadine, a nonsedating antihistamine, and 120 mg of pseudoephedrine as the decongestant component. Administered twice daily in this study, SCH 434 effected a 50% decrease in total symptom scores at day 4 and was significantly (p less than or equal to 0.03) more effective than the components alone or the placebo. Loratadine or pseudoephedrine alone, with 43% and 33% decline in symptom scores, respectively, also was more effective than placebo (p less than 0.05). As expected, pseudoephedrine alone was more effective than loratadine (p less than 0.01) in relieving nasal stuffiness; SCH 434 was more effective (p less than or equal to 0.01) than placebo and loratadine in relieving nasal stuffiness. All treatments were safe and well tolerated, although insomnia and dry mouth were noted in a significant number of patients who received either SCH 434 or pseudoephedrine. No serious side effects were noted. The incidence of sedation did not differ significantly among the four treatment groups. We conclude that SCH 434 is a safe and effective treatment for symptoms of seasonal allergic rhinitis. The combination drug (SCH 434) was better than its components for some, but not all, symptoms.

Comparative efficacy and safety of once-daily versus twice-daily loratadine-pseudoephedrine combinations versus placebo in seasonal allergic rhinitis.

The objective of this study was to compare the efficacy and safety of Claritin-D 24 Hour (once daily) with that of Claritin-D 12 Hour (twice daily) and placebo in the treatment of patients with seasonal allergic rhinitis (SAR). In this double-blind, placebo-controlled, multicenter study, 469 patients with moderate-to-severe SAR symptoms were treated for 2 weeks with one of the following: Claritin-D 24 Hour (a combination tablet formulation of loratadine 10 mg in the coating and pseudoephedrine sulfate 240 mg in an extended-release core), Claritin-D 12 Hour (a combination tablet formulation of loratadine 5 mg in the tablet coating and 120 mg pseudoephedrine sulfate, 60 mg in the coating and 60 mg in the core), or placebo. Claritin-D 24 Hour and Claritin-D 12 Hour were consistently superior to placebo (P < 0.01) in reducing total, nasal, and nonnasal symptom scores. Patients in the Claritin-D 24 Hour and Claritin-D 12 Hour groups also had significantly greater (P