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Biomedical subjects

E O Meltzer

Publications and source records attributed to E O Meltzer.

At least 91 records · Page 5Linked to original sources

Antihistamine- and decongestant-induced performance decrements.

Among the most common of health problems, allergies afflict more than one of every six Americans. In the allergic reaction, mast cells degranulate, releasing inflammatory mediators such as histamine. These mediators in turn cause smooth muscle contraction, itch, mucus secretion, and vascular leakage. A number of pharmacologic agents, including the H1 receptor antihistamines and the sympathomimetic decongestants, have been developed in an attempt to minimize such effects. Antihistamines were first used clinically 50 years ago. Currently taken by approximately 30 million Americans each year, they are grouped by structure into six classes. Until recently, all of the classes, or first-generation antihistamines, were thought to be relatively equal in efficacy and, because of their ability to cross the blood-brain barrier, they all caused varying degrees of sedation. The effects of antihistamines on psychomotor reflexes and driving skills, antihistamine-induced drowsiness, and the interaction of antihistamines with alcohol and tranquilizers are reviewed. The centrally acting first-generation agents, and the performance decrements these agents commonly induce, are compared with the newer, nonsedating, second-generation antihistamines (eg, terfenadine, astemizole, cetirizine, and loratadine). Although decongestants do not appear to cause impaired performance, this needs to be evaluated further, particularly with regard to decongestant-induced insomnia.

Histamine H1 Antagonists↗

Beta 2 adrenergic agonists--oral or aerosol for the treatment of asthma?

Beta 2 adrenergic agonists, especially in aerosol formulations, are often used as first-line medications for treating the symptoms of bronchial asthma. Although oral forms of these medications may result in greater improvement in small airway function, comparative studies of these two routes of administration show that inhaled beta 2 adrenergic bronchodilators have a more rapid onset of activity, are as long lasting, and as effective in improving pulmonary function as their oral forms. Moreover, they are equally effective at much lower dosages which results in fewer adverse effects. Their use in metered-dose inhalers, nebulizers, and breath-activated devices, is improving asthma therapy.

Administration, Inhalation↗

Evaluation of symptom relief, nasal airflow, nasal cytology, and acceptability of two formulations of flunisolide nasal spray in patients with perennial allergic rhinitis.

A new formulation of intranasal flunisolide containing less propylene glycol was compared with the original formulation for efficacy and acceptability in more than 200 patients with symptoms of perennial allergic rhinitis. In this multicenter, randomized, double-blind, parallel group study, symptomatic patients were treated with either the new or the original formulation of 0.025% solution of intranasal flunisolide for 4 weeks to provide 200 micrograms flunisolide daily. Both formulations were highly effective in decreasing symptom scores as evident from patient diary reports before and after treatment (P less than .001). Similarly, nasal airflow was improved with each treatment as measured by anterior rhinomanometry (P less than .0002) and the number of patients with nasal eosinophilia decreased (P less than .01). Finally, fewer patients using the new formulation reported nasal burning or stinging and the acceptability rating of the new formulation was higher.

Administration, Topical↗

A simplified screening test for the diagnosis of allergy.

The Quidel allergy screen is a relatively rapid (less than 2 hours) multiallergen dipstick method for detecting specific immunoglobin E antibodies in serum. It was developed to answer the need of primary physician nonspecialists in allergy for a convenient in-office screening test for diagnosing allergy. The new test was evaluated against the benchmark diagnostic skin tests and the radioallergosorbent serologic tests for sensitivity, specificity, accuracy, and technical feasibility in an office setting. It was found that while the Quidel allergy screen lacks the specificity of the standard tests, its overall sensitivity, as defined by the percentage of patients with positive skin reactions who also tested positive with the Quidel screen (68%), its ease of use, and its rapidity warrant its consideration as a screening tool for confirming a possible case of allergy.

Humans↗

The use of antihistamines for the treatment of airway disease.

This report reviews studies of the use of antihistamines for the treatment of allergic respiratory diseases. The cumulative results indicate that the nonsedative antihistamine terfenadine, given orally at a dosage of 60 mg twice daily, is effective in the treatment of seasonal allergic rhinitis in both adults and children. No major side effects have been reported, and sensitivity to this agent is not decreased after eight weeks of treatment. Preliminary data on the use of antihistamines for the treatment of asthma are also reviewed.

Astemizole↗

Efficacy of azelastine in perennial allergic rhinitis: clinical and rhinomanometric evaluation.

Azelastine is a chemically novel medication that has been demonstrated to be clinically effective for asthma and seasonal allergic rhinitis. In a 10-week, multicenter, double-blind, placebo-controlled, crossover study, the efficacy and safety of azelastine, 1 mg and 2 mg twice daily, were evaluated in 192 patients with symptoms of perennial allergic rhinitis. Patients maintained daily symptom and adverse-experience diaries and were evaluated every 2 weeks by the investigators. Pseudoephedrine, 30 mg, was provided as backup medication. Amelioration of most individual symptoms and a decrease in the total symptom scores were observed with both dosages of azelastine; greater improvement with 2 mg twice daily than with 1 mg twice daily, was observed. Nasal congestion, as a symptom and as reflected by rhinomanometric assessment, was the least improved parameter. Backup decongestant medication decreased during treatment with azelastine and increased during the placebo regimen. There were no major adverse effects.

Adolescent↗

Evaluating rhinitis: clinical, rhinomanometric, and cytologic assessments.

Allergic rhinitis is a common disease. Its diagnostic accuracy can be improved by quantifiable methods, such as scoring symptoms and signs, rhinomanometry, and the examination of nasal cytologic specimens. These methods are fast, easy to use, and well tolerated by patients. The same methods can also be used to follow changes as they occur with treatment. For example, improvements can be documented in patients with allergic rhinitis receiving topical corticosteroids, including flunisolide. Flunisolide therapy decreases the symptoms, improves the patency of the nasal airways, and leads to more normal nasal cytologic studies in patients with allergic rhinitis.

Chronic Disease↗

Comparison of a new sustained-release theophylline preparation, TheoBeads, with Theo-Dur tablets in children with asthma.

A new, slow-release theophylline formulation for children, TheoBeads, which has the potential for once-daily dosing, has become available. We report the results of a study of pediatric patients whose medication was changed from Theo-Dur tablets b.i.d. to TheoBeads q.d. Forty-nine children with asthma (aged 6-12 years) were treated with b.i.d. Theo-Dur to produce therapeutic maximum and minimum concentration levels (i.e., 8-20 micrograms/ml). Approximately half the patients were then transferred to TheoBeads given q.d. at the same total daily dose and retitrated; seven patients needed to be changed to b.i.d. dosing due to unacceptable fluctuations. The other half of the patients continued on b.i.d. Theo-Dur. Following at least 5 days of steady-state dosing, serum theophylline levels were assayed over a 24-hour period. It was found that: 1. Children changed to q.d. TheoBeads showed no change in their overall asthma control based on clinical diary entries and peak flow measurements. 2. Lower Cmax and Cmin theophylline levels and a smaller area under the curve were noted for patients taking q.d. TheoBeads compared to those taking b.i.d. Theo-Dur. 3. Administration of TheoBeads q.d. resulted in a significantly larger overall peak-to-trough fluctuation and a higher percentage of patients with subtherapeutic theophylline levels in the second 12-hour period than did b.i.d. Theo-Dur administration. In summary, when children receiving b.i.d. Theo-Dur were transferred to q.d. TheoBeads, they did not maintain even and sustained therapeutic theophylline levels, although asthma control was not adversely affected during the short period of observation.

Asthma↗

A dose-response study of the bronchodilator action of azelastine in asthma.

Azelastine is an orally effective inhibitor of mediator activity in allergic reactions and has also been demonstrated to have bronchodilator activity. In this randomized, double-blind, placebo-controlled, multicenter study, 150 patients, aged 12 to 60 years, with moderate to severe asthma, received a single oral dose of 2, 4, 8, 12, or 16 mg of azelastine or placebo. Theophylline was stopped 24 hours and other bronchodilators at least 8 hours before the study day. Patients were evaluated for 8 hours after dose by spirometry and were monitored for adverse effects. All doses of azelastine produced bronchodilation with 4 mg greater than 2 mg greater than placebo; higher doses did not increase magnitude or duration of effect. We conclude that azelastine produces significant bronchodilation of long duration. The optimal dose appears to be 4 mg for adolescent and adult patients with asthma.

Adolescent↗

Comparison of bronchodilator responses with bitolterol mesylate solution with the use of two different nebulizer systems in asthma.

Bitolterol mesylate is a beta 2-adrenergic bronchodilator that has been studied in a metered-dose inhaler formulation and as an aerosol in a closed, intermittent-flow nebulizer system. The optimum dose was found to be 1.0 mg in the closed system. In this dose-response study, 1.0 mg by closed-system nebulizer was compared with different doses delivered by an open, continuous-flow nebulizer system. Treatment with 2.5 mg of bitolterol mesylate in the open system is comparable to 1.0 mg in a closed system. Onset of bronchodilator activity occurred within 5 minutes for most patients, and median duration of action with different doses was 8 hours or longer. Mean maximum percent increases in FEV1 with 2.5, 3.5, and 4.5 mg of bitolterol mesylate with the open system were approximately 50% and comparable with that obtained with 1.0 mg with the closed system. Treatments with doses up to 3.5 mg in the open system were well tolerated with few side effects. We conclude that bitolterol mesylate is an effective, long-lasting bronchodilator when it is used as a nebulized aerosol by both open and closed delivery systems; a larger dose is optimal for the former system than for the latter. We believe that manufacturers' recommended doses should take into account the different efficiencies of open and closed nebulizer systems.

Adolescent↗

Clinical, rhinomanometric, and cytologic evaluation of seasonal allergic rhinitis treated with beclomethasone dipropionate as aqueous nasal spray or pressurized aerosol.

The currently available beclomethasone dipropionate (BDP) metered-dose nasal aerosol spray is considered uncomfortable by some patients because of the force of delivery. It was compared for efficacy and acceptability in a double-blind study with a new aqueous suspension BDP spray for the treatment of seasonal allergic rhinitis in 44 symptomatic patients aged 12 to 43 years. After 7 days of baseline evaluation, every patient was given both an aerosol canister and an aqueous spray bottle each containing either BDP, 42 mcg per spray, or placebo (P). For 15 days the patient sprayed each nostril twice a day with one spray of suspension (BDP or P) followed 5 minutes later by one spray of aerosol (P or BDP). Patients were evaluated before the study medications were started (day 1) and on days 4, 8, and 15 for nasal and eye symptoms. Nasal cytologic specimens were examined on days 1 and 15, and rhinomanometry was performed on days 1, 8, and 15 of the study. Topical BDP by both methods of delivery was rapidly effective in decreasing mean nasal obstruction, rhinorrhea, sneezing, and itching symptoms as well as mean eye symptoms with no statistically significant differences between them. Nasal airflow increased with both treatments; rhinomanometry significantly correlated with subjective nasal obstruction scores. Of 34 patients with nasal eosinophils, 74% had fewer eosinophils after treatment. Most patients (84%) preferred the aqueous spray over the pressurized aerosol.

Administration, Intranasal↗

Duration of action of oral albuterol in an asthmatic population.

In a randomized, double-blind, two-way crossover study in four centers, 124 patients received single doses of 4 or 6 mg of albuterol and placebo on two separate visits. Pulmonary function tests were performed at intervals up to ten hours. Both dosages produced peak bronchodilation responses which occurred at two hours and significant activity was maintained for at least eight hours. Adverse experiences were typical of adrenergic agents.

Administration, Oral↗

Inhaled albuterol powder for the treatment of asthma--a dose-response study.

Many patients are unable to obtain optimal benefit from inhaled bronchodilators as delivered by metered-dose aerosol spray because of difficulty in synchronizing release of medication with the start of inspiration. The Rotahaler is a flow-activated device that avoids this problem since the act of inspiration itself delivers medication to the lungs. In this randomized, double-blind, crossover study, each of 20 male patients with moderate to severe asthma, ages 12 to 23 yr, received a single treatment with 100, 200, or 400 mcg of albuterol powder or placebo by Rotahaler on 4 study days separated by 2 to 10 days. All patients stopped theophylline and inhaled beta-agonists as needed 24 and 12 hr, respectively, before study days. All patients emptied the Rotahaler with a single inhalation. Pulmonary functions were followed for 8 hr after medication. Statistical analyses of FEV1, FEF25-75, and FVC revealed that all doses of albuterol powder were superior to placebo within 5 min with a log dose-response trend for both degree and duration of bronchodilation.

Adolescent↗

Efficacy and tolerance of fluocortin butyl administered twice daily in adult patients with perennial rhinitis.

Fluocortin butyl (FCB) is a newly developed corticosteroid drug with no detectable systemic corticosteroid activity when it is used topically. Previous studies have demonstrated the therapeutic efficacy of FCB applied topically to the nasal mucosa three to four times a day for perennial rhinitis. The therapeutic efficacy of FCB used only twice daily, with total daily dosages similar to those previously found to be effective when these were applied more frequently, was studied in a multicenter, double-blind, placebo-controlled trial. This was a 4-week study with a 1-week observation (baseline) period and a 3-week period during which the response to three dosage regimens (2 mg per day, 4 mg per day, and 8 mg per day) of FCB and placebo were compared to baseline observations of rhinitis. Two hundred thirty-five patients from six centers were studied. Patients had perennial rhinitis of allergic, nonallergic, or combined etiology. Patients who received FCB exhibited significant amelioration of signs and symptoms of rhinitis as assessed by patients and physicians and had a greater reduction in the use of concomitant antihistamine and/or decongestant therapy compared to placebo-treated patients. Relief tended to occur early and was progressive during the 3 wk of therapy. There were no significant differences in response between the various dosages of FCB used. Side effects were minimal and insignificant and did not differ between FCB-treated and placebo-treated patients. FCB appears to be an effective well-tolerated topical steroid useful in the treatment of perennial rhinitis.

Adolescent↗

Effect of dosing schedule on efficacy of beclomethasone dipropionate aerosol in chronic asthma.

Fifty-two children 6 to 12 yr of age and 37 young adults 13 to 38 yr of age with moderate to severe extrinsic asthma requiring daily bronchodilators and who had been taking beclomethasone dipropionate (BDP) for at least 3 months were evaluated. All patients received their regular daily medications and BDP, 2 inhalations 4 times a day (q.i.d.) (total dose, 336 micrograms/day), for 2 wk; they were then randomized to receive either BDP or placebo aerosol, 4 inhalations twice a day (b.i.d.), with the same total dose/day as well as their regular medications, for 8 wk. Placebo patients deteriorated significantly by comparison with BDP patients in respiratory symptoms and pulmonary functions. More placebo than BDP patients ended participation in the study prematurely because of increasingly severe symptoms. In the 89 study patients, there were no significant differences in respiratory symptoms or pulmonary function measurements between the b.i.d. and q.i.d. dosage regimens in either pediatric or adult age groups. There were no significant changes in mean morning cortisol levels from baseline measurements to the end of the study period; at that time, all patients had a normal ACTH stimulation test. We conclude that BDP (336 micrograms/day) is as effective and safe for control of asthma symptoms with b.i.d. as with q.i.d. dosage schedules in pediatric and young adult patients.

Adolescent↗