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.

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 mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma.

BACKGROUND: Although inhaled glucocorticoids are recommended for all stages of persistent asthma, compliance with long-term therapy is often poor, leading to significant morbidity and mortality. A simplified, once-daily dosing regimen may foster improved compliance. OBJECTIVE: To compare the efficacy and safety of once-daily (AM) administration of mometasone furoate dry powder inhaler (MF DPI) 200 microg and 400 microg with placebo in patients with asthma previously maintained only on short-acting inhaled beta-adrenergic receptor agonists. METHODS: This was a 12-week, double-blind, placebo-controlled, parallel group study. The mean change from baseline to endpoint (last treatment visit) for FEV1 was the primary efficacy variable. RESULTS: At endpoint, both doses of MF DPI were significantly more effective than placebo (P < or = .05) in improving FEV1. Based on morning peak expiratory flow rate, once-daily MF DPI 400 microg was more effective than placebo (P < or = .001) at endpoint. Both active treatments also demonstrated improvement at endpoint in asthma symptom scores, physician-evaluated response to therapy and use of rescue medication. Although both MF DPI dosages were efficacious, MF DPI 400 microg provided additional improvement in some measures of pulmonary function (eg, morning PEFR) when these agents were administered once daily in the morning. Both doses of MF DPI were well tolerated and treatment-related adverse events occurred at a similar incidence among the three treatment groups. CONCLUSIONS: The results of this study indicate that once-daily (AM) MF DPI provides a convenient and effective treatment option for patients with mild or moderate persistent asthma.

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

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.

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.

Use of ipratropium bromide nasal spray in chronic treatment of nonallergic perennial rhinitis, alone and in combination with other perennial rhinitis medications.

To study the long-term safety and effectiveness of ipratropium bromide nasal spray 0.03% in the treatment of nonallergic perennial rhinitis, we administered this medication for 1 year in an open-label trial involving 285 patients. Our intention was to maintain the highest protocol dose possible to gain a clearer picture of the long-term side effect profile of the compound. Ipratropium bromide was well tolerated with no serious side effects in this patient population. It provided a significant improvement in rhinorrhea throughout the year-long trial; only 17 of 285 patients (6%) were considered treatment failures. There was an improvement in patient quality of life, as well as a substantial reduction in the need for other medications (antihistamines, decongestants, and nasal steroids) used to treat perennial rhinitis symptoms.

Ipratropium bromide nasal spray in non-allergic rhinitis: efficacy, nasal cytological response and patient evaluation on quality of life.

Intranasal fluorocarbon anticholinergic agents have been used to treat the nasal hypersecretion of perennial non-allergic rhinitis, but chronic use has been restricted either due to the potential for systemic anticholinergic adverse events or due to the irritating properties of the fluorocarbon metered dose formulations. This study evaluates a new aqueous nasal formulation of ipratropium bromide (Atrovent Nasal Spray 0.03%) in subjects with perennial non-allergic rhinitis in a double-blind, placebo-controlled trial. Two hundred and twenty-eight patients were randomized to receive two sprays per nostril of either ipratropium bromide (42 micrograms/nostril) or placebo-administered three times a day as an aqueous nasal spray over an 8-week interval. Patients were evaluated bi-weekly and maintained daily diaries for duration and severity of nasal symptoms. Ipratropium bromide reduced the mean severity and duration of rhinorrhoea within the first week and throughout the 8 weeks of active treatment compared with placebo (P < 0.05). Secondary endpoints of efficacy (patient and physician global assessments and a quality of life assessment) also supported the use of ipratropium bromide nasal spray for rhinitis symptom control. With the reduction in rhinorrhoea by the ipratropium bromide nasal spray, patients reported a marked improvement in daily moods vs placebo (P < 0.01). Both placebo and ipratropium bromide nasal spray induced a modest reduction of nasal congestion, sneezing and postnasal drip. This improvement in these other nasal symptoms was consistent with the known soothing effects of a nasal saline vehicle. There were no drug-related serious or systemic anticholinergic adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Once daily loratadine versus astemizole once daily.

This study was designed to compare the efficacy and safety of loratadine and astemizole for the treatment of seasonal allergic rhinitis. A total of 167 adult patients with seasonal allergic rhinitis was enrolled in a randomized double-blind, parallel group study. Patients were treated once daily for 2 months during a spring allergy season. Both treatment groups showed significant reduction of symptoms (P < .01) from baseline. The physicians' and patients' evaluations of response to treatment were generally higher for loratadine than astemizole but only reached statistical significance (P < .05) at the 1-week evaluation. Astemizole-treated patients showed statistically significantly more weight gain than did loratadine-treated patients. Loratadine and astemizole were comparable in reducing the signs and symptoms of seasonal allergic rhinitis. Both treatments were well tolerated, although less weight gain was observed in patients treated with loratadine.

Fluticasone propionate aqueous nasal spray is safe and effective for children with seasonal allergic rhinitis.

INTRODUCTION: Fluticasone propionate aqueous nasal spray, a new topical corticosteroid preparation, is effective when given as 200 micrograms once daily in patients (> 12 years of age) with seasonal allergic rhinitis. STUDY OBJECTIVE: To evaluate the efficacy and safety of fluticasone proprionate aqueous nasal spray in children aged 4 to 11 years with seasonal allergic rhinitis. STUDY DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group. PATIENTS: Two hundred fifty children aged 4 to 11 years with moderate-to-severe nasal symptoms, a positive skin test reaction to a late-summer or autumn allergen, a history of seasonal allergic rhinitis, and documentation of an unsatisfactory response to conventional treatment. INTERVENTIONS: Children were randomly assigned to receive fluticasone propionate, either 100 micrograms or 200 micrograms, or placebo, given by intranasal spray once daily in the morning for 14 days. MEASUREMENTS AND RESULTS: Severity of nasal symptoms (obstruction, rhinorrhea, itching, and sneezing) was recorded on visual analog scales by investigators at weekly visits and by patients (or adult guardian) daily in the evening. According to investigator and patient ratings, both fluticasone propionate 100 micrograms/d and 200 micrograms/d lowered total nasal symptom scores when compared with placebo. Both dosages of fluticasone propionate were more effective than placebo on the basis of investigator-rated overall clinical evaluation of efficacy at the end of treatment, with significant improvement (as opposed to moderate or mild improvement, no change or worsening) noted in 21% to 29% of the active-treatment groups vs 9% in the placebo group. There were no significant differences between the two fluticasone propionate dosages in any efficacy measurement. Morning plasma cortisol concentrations and frequency of drug-related adverse events were similar in the fluticasone propionate and placebo groups. CONCLUSION: In children as young as 4 years, 100 micrograms of fluticasone propionate aqueous nasal spray given once daily is as effective as 200 micrograms given once daily, the usual adult dose for the treatment of seasonal allergic rhinitis. Both fluticasone propionate dosages were well tolerated and neither dosage appears to interfere with the hypothalamic-pituitary-adrenal axis in children.

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.

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.