Biomedical subjects
P Chervinsky
Publications and source records attributed to P Chervinsky.
Fluticasone propionate reduces oral prednisone use while it improves asthma control and quality of life.
This study examined the ability of fluticasone propionate aerosol to reduce oral prednisone requirements in patients with severe asthma. Ninety-six patients dependent on oral prednisone were treated for 16 wk with placebo or fluticasone propionate aerosol (750 or 1,000 micrograms twice daily). Their dosage of oral prednisone was adjusted weekly according to predetermined criteria. A total of 69% and 88% of patients treated with fluticasone propionate 750 and 1,000 micrograms twice daily, respectively, compared with 3% of placebo-treated patients used no prednisone by the end of the study. In the fluticasone propionate groups, FEV1 and peak expiratory flow rates at the last evaluable visit/date improved and the number of night awakenings and symptomatic albuterol use declined relative to placebo values (p < 0.05). Patient-rated asthma symptoms improved in the groups receiving fluticasone propionate but not in the placebo group (p < 0.005). Fluticasone propionate aerosol was well-tolerated, and it improved some dimensions of health-related quality of life measured using a standard patient survey. Fluticasone propionate aerosol (750 or 1,000 micrograms twice daily) effectively and safely allowed most asthmatics dependent on oral corticosteroids to reduce or eliminate oral prednisone use while improving pulmonary function and quality of life.
Duration of action of a single dose of azelastine in patients with chronic asthma.
The aim of this double-blind, multicenter trial was to determine the duration of bronchodilating activity of a single 4-mg dose of azelastine in chronic asthmatics. Eligible patients had an FEV1 of 40-79% of predicted value with demonstrated reversibility of airway obstruction. A single dose of azelastine 4 mg resulted in rapid onset of bronchodilating activity with a 12-hr duration of action as demonstrated by a clinically and statistically significant mean percent improvement in FEV1, from hours 2-12. As an overall measure of improvement in FEV1, the area under the curve was statistically significantly greater for azelastine than for placebo. Mean improvements in symptom severity in the azelastine group exceeded those for placebo at all observation points. No serious adverse experiences were associated with azelastine.
Safety of salmeterol in the maintenance treatment of asthma.
BACKGROUND: Salmeterol is the first long-acting inhaled beta 2-agonist available in the US for the maintenance treatment of asthma. OBJECTIVE: To compare the safety of salmeterol with that of the short-acting beta 2-agonist albuterol. METHODS: Two identically designed, prospective, randomized, double-blind, parallel studies were conducted comparing salmeterol 42 micrograms twice daily, albuterol 180 micrograms four times daily, and placebo over 12 weeks in 556 patients (12 to 73 years old) with mild-to-moderate chronic asthma. Patients in each treatment group could use albuterol as needed to control acute symptoms. RESULTS: The incidence of potentially drug-related adverse events was similar among the treatment groups (range: 22% to 23%), with headache being the most commonly reported (range: 9% to 10%). No deaths occurred during the studies. Concomitant use of > 4 puffs of supplemental albuterol per day in the salmeterol group produced no increase in the incidence of adverse events either in general or of a cardiovascular nature. There were no statistically significant differences among treatment groups or clinically significant changes from pretreatment values in mean pulse rate, systolic/diastolic blood pressure, or clinical laboratory values after 12 weeks. There were no clinically significant differences among groups in heart rates nor were there differences in the frequency of supraventricular or ventricular ectopic beats during 24-hr Holter monitoring. The frequency of asthma exacerbations was lowest among patients receiving salmeterol (and highest among those who received placebo), and this rate did not increase over the 12 weeks. Asthma exacerbations were treated successfully with nebulized albuterol (2.5 mg), with no evidence of any increased risk of cardiovascular events. CONCLUSIONS: Salmeterol 42 micrograms twice daily is well-tolerated in patients with asthma, having a similar safety profile as that of albuterol 180 micrograms inhaled four times daily or placebo (plus as-needed albuterol). Concomitant use of albuterol, either by MDI or nebulization, did not affect the safety of salmeterol. Extensive cardiovascular monitoring revealed no significant cardiovascular adverse effects or arrhythmogenic effects associated with salmeterol over 12 weeks.
Fluticasone propionate aerosol for the treatment of adults with mild to moderate asthma. The Fluticasone Propionate Asthma Study Group.
BACKGROUND: Recent emphasis on the control of airway inflammation in asthma highlights the need for safe and effective antiinflammatory agents. Fluticasone propionate is one of the most potent antiinflammatory corticosteroids developed to date. OBJECTIVE: This study assessed the safety and efficacy of fluticasone propionate aerosol in the treatment of mild to moderate asthma. METHODS: Fluticasone propionate aerosol (25, 100, or 500 micrograms twice daily) or placebo was given for as long as 8 weeks to adults with mild to moderate asthma in a randomized, double-blind, parallel-group study. Patients were removed from the study if they showed predefined signs of worsening asthma. RESULTS: Sixty-three percent of placebo-treated patients and 23%, 13%, and 4% of patients treated with fluticasone propionate 25, 100, and 500 micrograms twice daily, respectively, were removed from the study. Mean forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow at midexpiratory phase at weekly visits throughout the study demonstrated that fluticasone propionate was more efficacious than placebo in maintaining asthma control. Measurements of peak expiratory flow and symptom scores significantly improved and nighttime awakenings and albuterol use to treat symptoms significantly declined in fluticasone propionate-treated groups relative to the placebo-treated group. Differences among fluticasone propionate groups for these variables were not statistically significant. Incidence and severity of adverse events were similar across groups. Fluticasone propionate did not affect morning or stimulated plasma cortisol concentrations, although slight, transient reductions in urinary free cortisol and urinary 17-hydroxy steroids occurred in the group receiving 500 micrograms fluticasone propionate twice daily. CONCLUSION: These data indicate that fluticasone propionate provides safe and effective treatment for mild to moderate asthma.
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.
Effectiveness of azelastine nasal solution in seasonal allergic rhinitis.
Azelastine is a novel antiallergy medication currently under investigation for the treatment of allergic rhinitis and asthma. Pharmacologic studies in laboratory animals and in vitro model systems indicate that azelastine exerts multiple actions including modulation of airways smooth muscle response, interference with inflammatory processes, and inhibition of allergic reactions. In a previous controlled clinical trial, azelastine nasal solution (ASTELIN N.S.) demonstrated effectiveness in controlling symptoms of seasonal allergic rhinitis (SAR). The objective of this 2-week double-blind, parallel-group study was to further assess the effectiveness of azelastine nasal solution in improving allergic rhinitis symptoms. Two hundred forty-seven patients (> or = 12 years) with symptomatic SAR who satisfied a minimum symptoms score during a 1-week, single-blind, baseline evaluation period were randomized to receive azelastine 2 sprays per nostril bid, azelastine 2 sprays per nostril qd, chlorpheniramine 12 mg bid, or placebo using a double-dummy technique to insure blinding. The primary efficacy variables were changes in Major Symptom Complex (nose blows, sneezes, runny nose/sniffles, itch nose, and watery eyes) and Total Symptom Complex (Major plus itchy eyes/ears/throat/palate, cough, and postnasal drip) severity scores. Patients treated with azelastine nasal solution qd and bid had mean percent improvements in the Total and Major Symptom Complex severity scores that were clinically significant (> or = 50% improvement over placebo) after both weeks, at endpoint, and overall. The improvements for the azelastine bid group were statistically significant (P < or = .05) at all evaluation points. Adverse experiences occurred infrequently, and none was considered serious or potentially limiting to the clinical utility of the nasal solution.(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.
Multicenter, double-blind, placebo-controlled trial of triamcinolone acetonide nasal aerosol in the treatment of perennial allergic rhinitis.
In a double-blind study involving 205 patients with perennial allergic rhinitis, statistically significantly greater symptomatic improvements were evident following the administration of 200 micrograms/day triamcinolone acetonide aerosol than following placebo. These improvements were evident as early as week 1 and were sustained throughout the 12-week study. They were accompanied by greater reductions in nasal eosinophils. Triamcinolone acetonide aerosol was well tolerated and had no effect on serum cortisol levels.
Pharmacist substitution of slow-release theophylline products.
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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.
Procaterol metered-dose inhaler: a multiclinic study evaluating the efficacy and safety in patients with asthma.
Procaterol hydrochloride aerosol, a potent beta 2-adrenergic bronchodilator, was evaluated in a double-blind, placebo-controlled study for efficacy and safety in 210 patients with documented mild to moderate reversible airway obstruction. Patients were randomized to receive procaterol in two inhalations (high dose) or one inhalation (low dose), 0.01 mg/inhalation, three times daily, or placebo. Pulmonary function tests were recorded at five and 30 minutes and hourly for eight hours after the first dose and following 1 and 2 weeks of treatment. Both doses of procaterol produced significantly greater improvement in PFTs at one hour and for up to seven hours after dosing compared with placebo (p less than 0.05). Mean percent increases in FEV1 were 35% in the high-dose group and 29% in the low-dose group at week 2. The high-dose group showed no loss of duration of bronchodilation with continued dosing. Improvement in PFTs and peak flow rates was significantly greater in the high-dose than in the low-dose group (p less than 0.05). Tremor was the most frequent side effect. Procaterol had no effect on electrocardiograms, heart rate, blood pressure, or clinical laboratory tests. The high dose of procaterol aerosol was shown to be an effective and well-tolerated bronchodilator with a rapid onset and long duration of action.
Twelve-hour bronchodilation in asthma with a single aerosol dose of the anticholinergic compound glycopyrrolate.
Anticholinergic aerosols provide effective bronchodilation in some patients with obstructive lung disease. Glycopyrrolate is a quaternary ammonium anticholinergic compound that is poorly absorbed from mucus membranes, thus reducing anticholinergic side effects. In 20 adult patients with asthma, we evaluated bronchodilation to a single administration of metered-dose glycopyrrolate aerosol (GA) to ascertain its onset and duration of action along with evaluation of safety. In this randomized, double-blind, placebo-controlled, single-dose, crossover trial, bronchodilation was evaluated on five separate occasions to either placebo or a GA dose of 80, 240, 480, or 960 micrograms. Baseline spirometry for each patient on each visit was similar (mean FEV1 +/- SD of 62.2 +/- 13.6% predicted). After aerosol dosing, spirometry was measured at 30 minutes and then at hourly intervals up to 12 hours. Compared to placebo, metered-dose aerosols of 240, 480 and 960 micrograms elicited significantly greater bronchodilation at each test time. Furthermore, significant bronchodilation was noted within 30 minutes of dosing and was sustained for at least 12 hours. Bronchodilation with the 480 and 960 micrograms dose was equal, and both were greater than 240 micrograms. A subset of four asthma patients with baseline FEV1 values less than 50% predicted did not have a bronchodilating response with GA. No notable side effects occurred. Thus, a single aerosol dose of GA provides clinically significant, safe 12-hour bronchodilation in patients with asthma without severe airway obstruction (i.e., FEV1 greater than 50% predicted).
A comparison of oral procaterol and albuterol in reversible airflow obstruction.
The efficacy and safety of orally administered procaterol hydrochloride, a potent beta 2-adrenergic bronchodilator, was compared with that of albuterol in an eight-center, double-blind study conducted in 223 patients with mild to moderate, reversible bronchial airway obstruction. After a 1-wk placebo washout period, patients were administered either procaterol 0.05 mg twice daily for 2 wk followed by 0.10 mg twice daily for 10 wk or albuterol 2 mg three times a day for 2 wk followed by 4 mg three times a day for 10 wk. Spirometry determinations 1.5 h postdose showed consistently greater percent improvements from predose in FVC, FEV1, and FEF25-75 with procaterol than with albuterol at Weeks 1, 2, 4, 8, and 12. Treatment differences were statistically significant (alpha = 0.05) after 2 wk, 2 months, and 3 months of treatment. Bronchodilatation was evident 0.5 h after dosing and peaked at 1.5 to 3 h postdose for both treatments. The duration of action (i.e., time until spirometry determinations were lower than those at 0.5 h postdose) was at least 5 h after procaterol but only 3 h after albuterol. There was no evidence of tolerance with continued procaterol treatment, whereas a diminished duration of response to albuterol was observed with long-term treatment. Tremor was reported statistically more frequently in patients receiving procaterol than in those receiving albuterol (alpha = 0.05); the frequencies of other adverse events were similar for the two groups. No statistically significant treatment differences were noted for asthma symptoms, global evaluations, ECG results, vital signs, or clinical laboratory measurements.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of inhaled albuterol powder and aerosol in asthma.
In this multicenter, randomized, double-blind study comparing the efficacy and safety of aerosolized albuterol with the dry powder formulation, 231 patients with chronic reversible obstructive airway disease were randomly allocated to receive either placebo albuterol aerosol followed immediately by active albuterol powder (200 micrograms) or active albuterol aerosol (two puffs, 180 micrograms) followed immediately by placebo lactose powder four times a day for a period of 12 weeks. No statistically significant differences were found between the powder and aerosol formulations with respect to pulmonary function, length of time mean FEV1 remained greater than or equal to 15% above baseline, physicians' assessments of patients' clinical response, or patients' subjective symptom scores. There were also no significant differences between treatment groups in cardiovascular effects, laboratory values, or adverse events. Among patients who expressed a preference for one of the delivery systems, half preferred using the powder. Results of this study demonstrate that 200 micrograms of albuterol powder is as safe and effective as 180 micrograms of albuterol aerosol.
Multicenter study of bitolterol and isoproterenol nebulizer solutions in nonsteroid-using patients.
Bitolterol mesylate, 1.0 mg, or isoproterenol hydrochloride, 1.5 mg, was administered three times daily for 3 months in a double-blind, multicenter study via closed-port, intermittent-flow, compressor-driven nebulizer system (CPIF) to 182 nonsteroid-using patients with asthma. Mean baseline FEV1 was approximately 60% of predicted normal for both groups. Pulmonary function tests and vital signs were measured before and for up to 8 hours after treatments on test days 1, 30, 60, and 90. Mean maximum increases in FEV1 were 51%, 54%, 52%, and 55% for bitolterol versus 48%, 46%, 50%, and 43% for isoproterenol on these monthly test days. The mean FEV1 response remained greater than 15% over zero time (baseline) for greater than or equal to 8 hours after medication with bitolterol on each of four monthly pulmonary function test days and 2 1/2 to 5 hours for isoproterenol. Median durations of bronchodilator activity for bitolterol were 7.3, 6.5, 6.5, and 6.0 hours versus 4.0, 1.7, 3.7, and 1.9 hours for isoproterenol on the monthly test days. On these test days, 37% to 49% of the patients treated with bitolterol had a duration of action of at least 8 hours compared with 16% to 29% after isoproterenol treatment. The onset of activity was within 5 minutes for both drugs. Bitolterol provided superior bronchodilator activity with fewer adverse effects compared with isoproterenol, and there was no evidence for drug tolerance during this 3-month study.
Comparison of the bronchodilator effects of nebulized bitolterol mesylate and isoproterenol hydrochloride in steroid-dependent asthma.
This study of 183 ambulatory patients with steroid-dependent asthma was conducted to evaluate the efficacy and safety of nebulized bitolterol mesylate solution (0.2%) compared to isoproterenol hydrochloride solution (0.3%). A double-blind, randomized, parallel-group, repetitive-dose design was followed at nine centers for 3 months. Patients received either 1.0 mg of bitolterol or 1.5 mg of isoproterenol three times a day with a closed, intermittent-flow nebulization system. Pulmonary function was evaluated on four 8-hour office visits at approximately 30-day intervals. Efficacy was based on a 15% increase in FEV1 over baseline. Both medications resulted in bronchodilatation within 5 minutes, whereas nebulized bitolterol was statistically superior (p less than 0.05) to nebulized isoproterenol in terms of duration of action and area under the curve. The mean FEV1 response to bitolterol therapy remained greater than 15% over baseline for 5 to 8 hours on the four test days compared to 2 to 4.75 hours for isoproterenol therapy. Both medications were well tolerated. Adverse reactions were transient, and most were mild to moderate. Tremor was the most frequent side effect occurring in approximately 30% of the patients in both groups. There were no clinically significant laboratory changes or electrocardiographic findings. Nebulized bitolterol mesylate was found to be a safe and effective bronchodilator in steroid-dependent patients with asthma.