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Biomedical subjects

S L Spector

Publications and source records attributed to S L Spector.

At least 37 records · Page 2Linked to original sources

Alternative treatments in the patient with intractable asthma.

Various medications have been suggested as alternative therapy for oral corticosteroids in the treatment of asthma, due to the known adverse effects of oral corticosteroids. Examples of such medications include methotrexate, gold, cyclosporin A, hydroxychloroquine, and dapsone, all of which have a significant side-effect profile. Intravenous gammaglobulin therapy used as an immuno-modulator has little if any side-effects, but it is very costly. The antileukotrienes represent a safe class of medications that may be of particular benefit to certain subgroups of asthmatic patients. Antileukotrienes have become commercially available in other countries.

Adrenal Cortex Hormones↗

Antileukotriene agents.

The antileukotriene agents, the first new class of asthma medications introduced in two decades, represent a promising new alternative in the continuing search for effective and safe therapy for chronic inflammation in asthma. The leukotrienes are inflammatory mediators whose effects on asthma include bronchoconstriction, increased vascular permeability, and increased mucus production. In chronic asthma, regular use of either leukotriene synthesis inhibitors or leukotriene receptor antagonists has improved pulmonary function and clinical symptoms significantly. Antileukotriene agents appear to be safe and well tolerated, although long-term studies will be needed to confirm this.

Anti-Asthmatic Agents↗

Leukotriene activity modulation in asthma.

Leukotrienes constitute a class of inflammatory mediators synthesised from arachidonic acid, a product of cell membrane metabolism. Synthesis occurs in the 5-lipoxygenase enzyme pathway, which produces several species of leukotrienes, each with characteristic biological activities. With regard to asthma, the leukotrienes are particularly important because of their ability to directly and potently mediate bronchoconstriction; in addition, they specifically stimulate the secretion of mucus into the airways and the extravasation of fluids and proteins into the airway tissues, both of which contribute to airway obstruction. A number of antileukotriene agents have been developed with the goal of modulating the inflammatory process in various disease states. These agents fall into 2 general classes: leukotriene receptor antagonists and leukotriene synthesis inhibitors. Results of antileukotriene agents in preclinical and clinical trials indicate that antileukotriene agents attenuate the response to challenges with inhaled leukotrienes, cold air, exercise, aspirin and allergen; in addition, they have shown efficacy in clinical asthma and have not been associated with serious adverse effects. Although results to date indicate that these medications are well tolerated and effective in the treatment of asthma, the recent approval by the FDA of 2 antileukotriene agents will give physicians further insight into how patients with asthma respond to them.

Asthma↗

Chronic cough.

Explore the source record for details and available documents.

Antitussive Agents↗

Management of asthma with zafirlukast. Clinical experience and tolerability profile.

This article reviews the literature on the use of zafirlukast in the treatment of asthma, with particular focus on its ability to attenuate the asthma-causing effects of leukotrienes. Leukotrienes produced by the 5-lipoxygenase enzyme pathway have various biological activities. These include the specific inflammatory effects associated with asthma, such as increased vascular permeability, enhanced mucus production and decreased mucociliary transport. Leukotriene receptors in the airways also mediate a potent bronchoconstriction and this is particularly important in asthma. Zafirlukast was developed with the goal of attenuating the inflammatory effects of leukotrienes in asthma. Zafirlukast attenuates the responses to inhaled leukotrienes and allergen challenges, and produces beneficial effects in cold air- and exercise-induced asthma. Zafirlukast has been compared with placebo and sodium cromoglycate in clinical trials involving asthma patients. Zafirlukast brings about a significant bronchodilation within 1 hour of administration that is additive to the effects of beta 2 agonists. These studies showed that zafirlukast improves pulmonary function and reduces the symptoms of asthma. Zafirlukast is well tolerated with an incidence of adverse events similar to that seen with the use of placebo. As an oral twice-daily formulation, zafirlukast may improve patient adherence to therapy. As an anti-inflammatory agent, zafirlukast may in the future find a role in the treatment of a variety of diverse inflammatory conditions.

Anti-Asthmatic Agents↗

Comparison of the bronchodilatory effects of cetirizine, albuterol, and both together versus placebo in patients with mild-to-moderate asthma.

BACKGROUND: Many potential users of the H1 antihistamine cetirizine are asthmatic and may be using inhaled albuterol. This study was conducted to assess the possible bronchodilatory effect of cetirizine in patients with mild-to-moderate asthma and to determine whether cetirizine interacts with albuterol. METHODS: In a randomized, double-blind, placebo-controlled, crossover study, the effects on pulmonary function of 5, 10, and 20 mg oral doses of cetirizine with and without inhaled albuterol (180 micrograms) were determined in 12 patients at 11 time points over 8 hours. The primary measure of efficacy was forced expiratory volume in 1 second (FEV1). RESULTS: Cetirizine with or without albuterol significantly increased FEV1, peak expiratory flow rate, and forced expiratory flow rate between 25% and 75% of vital capacity relative to baseline and placebo but did not have a significant effect on forced vital capacity. The effect of 20 mg of cetirizine on FEV1 was generally greater than that of 10 or 5 mg, but the difference was statistically significant only at the 30-minute time point (p < 0.05). All three cetirizine doses produced significantly greater increases than placebo in FEV1 and forced expiratory flow rate between 25% and 75% of vital capacity for 8 hours and in peak expiratory flow rate for 7 hours (p < 0.02). Albuterol alone had a significant effect on the four pulmonary function variables from 1 to 5 hours after baseline (p < 0.05), which is consistent with albuterol's recommended dosing frequency of every 4 to 6 hours. Albuterol alone increased FEV1 significantly more than 5 mg of cetirizine alone but not 10 mg or 20 mg of cetirizine alone at 60, 90, and 120 minutes after baseline, but all three doses of cetirizine increased FEV1 significantly more than albuterol 7 and 8 hours after baseline (p < 0.05), indicating that the bronchodilatory action of cetirizine lasts longer than that of albuterol. Cetirizine neither potentiated nor inhibited the bronchodilatory action of albuterol, but the two drugs appeared to have an additive bronchodilatory effect. None of the cetirizine treatments caused a worsening of pulmonary function, and all were well tolerated. CONCLUSIONS: Cetirizine has a significant bronchodilatory effect in patients with mild-to-moderate asthma and can be used to treat concomitant conditions (e.g., allergic rhinitis) without concern that it will interfere with the bronchodilatory effect of albuterol or cause worsening of asthma by itself.

Albuterol↗

The common cold: current therapy and natural history.

Despite its prevalence, the common cold is complicated and can be difficult to treat, even symptomatically. There is still no cure for the myriad of viruses that cause the common cold. Many of the most popular remedies are either ineffective or counterproductive. This paper reviews the causes and course of upper respiratory infections, and discusses treatment options, including a new anticholinergic aqueous formulation for controlling rhinorrhea.

Common Cold↗

Albuterol aerosol versus albuterol Rotacaps in exercise-induced bronchospasm in children.

The purpose of this study was to determine the safety and effectiveness of albuterol aerosol 180 micrograms and albuterol powder 200 micrograms in the prevention of exercise-induced bronchospasm in children. Forty-six patients aged 4-11 years with asthma and exercise-induced bronchospasm were enrolled in this randomized, double-blind, single-dose, three-way crossover study comparing albuterol aerosol, albuterol powder, and placebo. Exercise challenge was performed at the screening visit for qualifying and baseline determinations of pulmonary function and then 15 min after drug administration at each of three visits. Prevention of exercise-induced bronchospasm was assessed by comparing across all treatment groups the percentage change in FEV1 from pre- to postexercise, the percentage of patients protected by treatment, postexercise minimum FEV1, and postexercise change in FEV1. Safety was assessed by observation of clinical adverse events, laboratory tests, physical examination, electrocardiogram and rhythm strips, vital signs, and pulmonary auscultation. Forty-four patients completed the study. Mean postexercise FEV1 decreased 6% from preexercise values when patients were treated with either albuterol formulation; FEV1 decreased 23% when patients were treated with placebo. Exercise-induced bronchospasm was prevented in 95% of patients when treated with albuterol powder, in 91% treated with albuterol aerosol, and in 57% treated with placebo. Patients maintained significantly higher mean minimum FEV1 values after treatment with albuterol powder and albuterol aerosol than when treated with placebo. Treatment with either albuterol formulation produced a significantly smaller decrease in mean FEV1 from pre- to postexercise than treatment with placebo. No drug-related adverse events were reported, and safety assessments were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Leukotriene inhibitors and antagonists in asthma.

OBJECTIVE: This article reviews the literature on the effects of leukotrienes in asthma. In particular, the ability of recently developed receptor antagonists and synthesis inhibitors to attenuate the asthma-causing effects of leukotrienes is examined. DESIGN: Published literature on the role of leukotrienes in asthma was reviewed. Reports of research on agents that inhibit the synthesis of leukotrienes or block leukotriene receptors were also studied. RESULTS: Leukotrienes are endogenous molecules formed by the breakdown of a membrane constituent, arachidonic acid, via the 5-lipoxygenase enzyme pathway. This pathway ultimately produces several species of leukotrienes with various biologic activities, including generalized inflammatory effects associated with asthma: increased vascular permeability, enhanced mucous production, and decreased mucociliary transport. Particularly important in asthma, leukotriene receptors on the airways mediate a potent bronchoconstriction. Two general types of drugs have been developed with the goal of attenuating the leukotrienes' effects in inflammation and asthma: the leukotriene receptor blockers and the leukotriene synthesis inhibitors (eg, 5-lipoxygenase inhibitors). CONCLUSIONS: The antileukotriene drugs attenuated the responses to inhaled leukotrienes and allergen challenges. These agents produced beneficial effects in cold-, exercise-, and aspirin-induced asthma, as well as clinical asthma. Many of these medications appear to be effective in the treatment of asthma; however, further clinical research is needed to determine which patients would benefit most from their use.

Aspirin↗

Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. ACCOLATE Asthma Trialists Group.

The efficacy of 6 wk of therapy with oral ICI 204,219, a selective leukotriene D4 (LTD4) receptor antagonist, was evaluated in subjects with moderate asthma during a multicenter, double-blind, randomized, placebo-controlled, dose-ranging study. Subjects who entered the trial had been chronically treated for asthma with beta agonist alone or in combination with theophylline. Subjects were randomized to treatment with twice daily doses of ICI 204,219 (5, 10, or 20 mg) or placebo if they had an FEV1 between 40 and 75% of predicted values without bronchodilator therapy and a daytime asthma score > 10 (range 0 to 21 per wk) for 7 consecutive d. Efficacy was evaluated from the results of symptom assessments, pulmonary function tests, and rescue medication use. Of 276 subjects randomized to treatment, 266 (10 mg, n = 66; 20 mg, n = 67; 40 mg, n = 67; placebo, n = 66) were analyzed for efficacy. Diary card assessments showed that treatment with increasing doses of ICI 204,219 linearly improved five efficacy criteria without increasing the number or severity of adverse events. The 40 mg dose was more effective than placebo (p < 0.05) in reducing nighttime awakenings, first morning asthma symptoms, the daytime asthma score, and albuterol use and in increasing evening peak expiratory flow (PEF) rates as well as FEV1. Compared with baseline measurements, the 40 mg dose decreased awakenings by 46%, albuterol use by 30%, and daytime symptoms by 26% and increased FEV1 by 11%. ICI 204,219 improves objective and subjective measures of asthma severity in moderately ill asthmatic subjects and may provide a new treatment option for the disease.

Administration, Oral↗

As-needed medication use in asthma usage patterns and patient characteristics.

Daily inhaled bronchodilator medication usage was recorded using an electronic device and airway obstruction by daily peak flow measurement. The demographic, clinical, and psychological characteristics of the subjects were noted. Subjects were allocated to as-needed (prn) medication usage groups according to the mean number of inhaler activations on days with zero, moderate, and severe airway obstruction. Segregation into arbitrary and nonarbitrary use, and into overuse, appropriate use, and underuse resulted in six usage groups. Appropriate use was observed in only 10 of 39 subjects. The major psychological variable to differ among groups was the MMPI variable Pt, representing general anxiety. Arbitrary users had a significantly higher mean score than nonarbitrary users. The variable Specific Internal Awareness, representing a perceived difficulty in recognizing the premonitory symptoms of an asthma attack, also differed among the usage groups, with arbitrary users having the lowest scores. These findings raise the possibility that reliance on an objective measurement of airway obstruction rather than on subjective symptomatology might enhance compliance with prn medication in some patients.

Adolescent↗

Update on exercise-induced asthma.

Exercise-induced asthma (EIA) is a temporary increase in airway resistance that occurs after several minutes of strenuous exercise, generally eight to 15 minutes after the patient has stopped exercising. Some individuals experience a secondary reduction in pulmonary function several hours later, the so-called late-phase response. Many physicians believe that EIA is caused by respiratory water loss or airway cooling. Others incriminate tissue mast cells of the lung. The role of histamine is uncertain because it is detected inconsistently in the serum after an attack. Recent studies suggest that the release of sulfidopeptide leukotrienes may play a major role in EIA. Although the exact pathophysiology has yet to be determined, several highly successful treatment regimens have been developed. Preventive pharmacologic treatment with aerosolized beta-agonists is more successful than treatment with cromolyn sodium; however, coadministration of these agents produces significant symptomatic improvement in more than 90% of patients. Other useful medications include antihistamines, anticholinergic agents, theophylline, oral beta-agonists, calcium channel blockers, alpha-adrenergic antagonists, nedocromil, and leukotriene antagonists. Exercise-induced asthma may be suppressed with warm humidified air. This environment can be simulated by swimming in a heated pool or wearing a scarf over the nose and mouth in cold weather.

Asthma, Exercise-Induced↗