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Biomedical subjects

S L Spector

Publications and source records attributed to S L Spector.

At least 19 recordsLinked to original sources

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

Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with acute bacterial maxillary sinusitis.

PURPOSE: This multicenter study compared the clinical and bacteriologic efficacy of two oral antibiotics, cefuroxime axetil and amoxicillin/clavulanate, in the treatment of acute bacterial maxillary sinusitis. PATIENTS AND METHODS: Three hundred seventeen patients with clinical and radiographic evidence of acute maxillary sinusitis were enrolled at nine centers and were randomly assigned to receive 10 days of treatment with cefuroxime axetil 250 mg twice daily (n = 157) or amoxicillin/clavulanate 500 mg three times daily (n = 160). Patients were assessed for both clinical and bacteriologic responses once during treatment (5 to 7 days) and twice after treatment (1 to 3 days and 4 weeks). Bacteriologic assessments were based on needle aspirates of the maxillary sinus obtained pretreatment and, when possible, at the first posttreatment visit. RESULTS: Organisms were isolated from the pretreatment sinus aspirates of 198 of 317 (62%) patients, with the primary isolates being Streptococcus pneumoniae (22%), Haemophilus spp. (17%), Staphylococcus aureus (13%), and Haemophilus influenzae (10%). A satisfactory clinical outcome (cure or improvement) was achieved in 85% (98 of 115) and 82% (102 of 124) of the clinically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.446). With respect to the eradication of the bacterial pathogens, a satisfactory outcome (cure or presumed cure) was obtained in 84% (31 of 37) and 87% (34 of 39) of bacteriologically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (p = 0.567). Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events (13% versus 3%, p = 0.001), particularly diarrhea (8% versus 1%, p = 0.001). Two patients in the cefuroxime axetil group and three patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events. CONCLUSIONS: Our results indicate that cefuroxime axetil twice a day is as effective as amoxicillin/clavulanate three times a day in the treatment of acute bacterial maxillary sinusitis but produces fewer adverse effects.

Acute Disease

The role of allergy in sinusitis in adults.

Allergic sinus disease in adults has not been definitively established. On the other hand, sinusitis is more common in allergic individuals than control subjects. Nasal provocation studies with allergens produce clinical findings and radiographic evidence suggestive of allergic sinusitis. Studies that use single-photon emission computerized tomography do not confirm direct entry of pollens into the sinuses. Fungal sinusitis typically occurs in patients with allergic rhinitis and nasal obstruction for many years. Patients often have an elevated specific IgE and total IgE with positive skin tests to the fungus involved. The diagnosis is confirmed by computed tomographic scan or magnetic resonance imaging of the sinuses. There is no direct fungal invasion. Many patients who have chronic severe sinusitis, asthma, and frequently aspirin idiosyncrasy appear to have immunologic reactions in the sinuses (and bronchial tissue). Histologic findings of the sinus mucosa show infiltration with plasma cells and eosinophils. Immunofluorescent stains show IgE dispersed throughout the tissue possibly in plasma cells. An intense linear stain for IgD is found along the epithelial side of the basement membrane.

Acute Disease

Double-blind study of intranasal ipratropium bromide in nonallergic perennial rhinitis.

We undertook this trial to determine whether ipratropium bromide nasal spray 0.03% (IB) reduced the nasal hypersecretion associated with nonallergic perennial rhinitis (NAPR) without causing excessive dryness or irritation of the nasal mucosa. We compared two drug doses of IB (21 micrograms and 42 micrograms per nostril) to a placebo, administered as two sprays to each nostril twice daily. The study design consisted of a 1-week screening period without treatment, a 1-week single-blind placebo period, a 4-week double-blind treatment comparison period, and a 1-week follow-up period without medication to evaluate nasal rebound. One hundred fifty-two patients were entered and 140 completed the trial. Both doses of IB reduced the severity and duration of rhinorrhea compared with placebo (P = .05 and .03, respectively). Treatment differences were noticeable during the first week of therapy, continued to widen during the second week, and then remained stable throughout the next 2 weeks. There was no evidence of nasal rebound observed during the week after treatment. The drug was well tolerated with side effects limited to infrequent nasal adverse events of nasal dryness, blood-tinged mucus, and epistaxis occurring in 2% to 6% of patients. We conclude that IB is a safe and effective therapy for control of rhinorrhea associated with NAPR.

Administration, Intranasal

Common triggers of asthma.

Control of asthma is enhanced when careful consideration is given to underlying mechanisms. Patients can be advised of ways to avoid or minimize contact with offending allergens, and, in some cases, pharmacologic management may not be necessary. Care must be taken when treating patients with concomitant disorders, such as hyperthyroidism. Also, psychological factors may have a role in exacerbating symptoms in suggestible patients. Noncompliance, in some cases due to inability to pay for medication, may be an unrecognized cause of treatment failure.

Allergens