The role of antileukotrienes in the treatment of asthma.

OBJECTIVE: This article reviews the literature on the role of antileukotrienes (anti-LTs), specifically montelukast, zafirlukast, and zileuton, in the treatment of asthma. DATA SOURCES: Relevant and appropriate controlled clinical studies were used. Only literature in the English language was reviewed. STUDY SELECTION: Material was taken from academic/scholarly journals, appropriate reviews, and published abstracts. RESULTS: In guidelines established by the National Asthma Education and Prevention Program and the National Heart, Lung, and Blood Institute, a stepwise approach to asthma management is recommended, with recommendations varying depending on degree of disease severity. The anti-LTs, the newest class of drugs for the treatment of asthma, play a circumscribed role in the guidelines as they were only recently available when the latest guidelines were published. Subsequently, however, extensive clinical experience with the anti-LTs has been amassed. Multiple clinical studies have demonstrated that the anti-LTs improve pulmonary function and quality of life, and reduce asthma symptoms, asthma exacerbations, and use of beta2-agonists and oral steroids. The anti-LTs may be particularly useful in asthma patients with aspirin sensitivity or concomitant allergic rhinitis, as well as in pediatric patients. These agents have additive effects with inhaled corticosteroids and may permit a reduction in inhaled corticosteroid dosages. CONCLUSIONS: The anti-LTs have several features that are likey to promote adherence to treatment and are generally well tolerated. The available clinical data suggest that anti-LTs should be considered as a therapeutic option or as additive therapy in patients with mild to severe asthma.

Effect of age on response to zafirlukast in patients with asthma in the Accolate Clinical Experience and Pharmacoepidemiology Trial (ACCEPT).

BACKGROUND: The Accolate Clinical Experience and Pharmacoepidemiology Trial (ACCEPT), evaluated zafirlukast in a wide spectrum of patients from a variety of clinical practices. OBJECTIVE: To determine the effect of age on the response to zafirlukast 20 mg twice daily in 3759 patients with mild, moderate, or severe asthma. METHODS: Patients received open-label administration of zafirlukast 20 mg twice daily (bid) for 4 weeks. Pulmonary function was measured twice daily, and overall asthma symptom scores, number of nighttime awakenings, severity of morning asthma symptoms, and beta2-agonist use were recorded daily. Trial results were analyzed to compare the efficacy of zafirlukast in 263 adolescent (12 to 17 years old), 2602 adult (18 to 65 years old), and 321 elderly (66 years old and older) patients (the evaluable population). RESULTS: After 4 weeks of zafirlukast therapy, improvements in pulmonary function decreased with age and were significant for all measures in adolescents and adults and for morning peak expiratory flow in elderly patients. Improvements in symptom response were statistically significant across age groups. Reduction in beta2-agonist rescue was similar in adolescents and adults but significantly less in elderly patients. CONCLUSIONS: Zafirlukast is an effective treatment for asthma in all patients, regardless of age. In elderly patients, improvement in asthma symptoms rather than pulmonary function may represent a primary marker for efficacy with zafirlukast.

Zafirlukast in clinical practice: results of the Accolate Clinical Experience and Pharmacoepidemiology Trial (ACCEPT) in patients with asthma.

BACKGROUND: Zafirlukast is an oral leukotriene receptor antagonist used in the treatment of patients with mild to moderate asthma. To investigate its effects in a clinical practice setting, we evaluated zafirlukast in a heterogeneous group of patients who had asthma of different degrees of severity and who were receiving concomitant asthma medications. METHODS: A total of 3759 patients were enrolled at 924 sites. Patients received zafirlukast 20 mg twice a day for 4 weeks. Pulmonary function was measured twice a day, and overall asthma symptom scores, number of nighttime awakenings, severity of morning asthma symptoms, and beta2-agonist use were recorded daily. RESULTS: In the efficacy analysis (3207 evaluable patients), all parameters showed statistically significant improvement that continued throughout the 4 weeks of the trial. A total of 71% of patients had improved pulmonary function and 72% had improved asthma symptoms. Improvement was consistent regardless of asthma severity category and regardless of concomitant asthma medication category. More than 70% of both physicians and patients indicated there was clinical improvement in pulmonary measures as well as in asthma symptoms. Common adverse events reported were headache (3.7%), nausea (1.4%), pharyngitis (1.4%), and sinusitis (1.1%). CONCLUSIONS: Zafirlukast 20 mg twice a day is well tolerated and improves pulmonary function and asthma symptoms, regardless of asthma severity category and regardless of concomitant asthma medication category.

Effect of fluticasone propionate aqueous nasal spray versus oral prednisone on the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Fluticasone propionate is a glucocorticoid with negligible oral bioavailability and very low intranasal bioavailability that is used as an intranasal spray for the treatment of rhinitis. OBJECTIVE: The purpose of this study was to evaluate the hypothalamic-pituitary-adrenal (HPA)axis effects of fluticasone propionate aqueous nasal spray (FP ANS) compared with oral prednisone and placebo by using a 6-hour cosyntropin infusion test. METHODS: In a 4-week, randomized, double-blind, double-dummy, placebo-controlled parallel-group study, 105 adult patients with allergic rhinitis were randomly assigned to receive FP ANS 200 microg once daily, FP ANS 400 microg twice daily, oral prednisone 7.5 mg once daily, oral prednisone 15 mg once daily, or placebo. HPA-axis function was assessed at the screening visit and after 4 weeks of treatment by measuring morning plasma cortisol concentrations and poststimulation concentrations of plasma and urinary cortisol. RESULTS: There was no evidence of altered HPA-axis response to cosyntropin by the end of treatment with FP ANS 200 microg once daily or FP ANS 400 microg twice daily when compared with placebo. In contrast, 4 weeks of treatment with oral prednisone 7.5 or 15 mg once daily was associated with significant (p < 0.05 vs placebo) reduction in HPA-axis function, as evidenced by lower plasma cortisol concentrations (area under the plasma concentration-time curve and peak concentrations) after cosyntropin stimulation and reduced mean 24-hour urinary cortisol excretion. FP ANS 400 microg twice daily and both prednisone regimens were associated with a significant (p < 0.05 vs placebo) reduction in mean morning plasma cortisol concentrations. CONCLUSION: These results indicate that a 4-week course of FP ANS at four times the recommended dose does not suppress adrenal function in response to a 6-hour cosyntropin stimulation test.

Limited coronal CT: an alternative screening examination for sinonasal inflammatory disease.

Coronal CT is the definitive procedure for radiologic evaluation of sinonasal inflammatory disease, yet many clinicians rely on the less expensive plain film sinus series. We designed a limited four slice coronal CT and prospectively compared it with conventional coronal CT and plain film sinus series in 25 patients to determine whether a limited CT examination is a suitable alternative to these other radiologic procedures in screening for sinonasal inflammatory disease. The presence, amount, and location of mucous membrane disease, opacification, air fluid levels, retention cysts, erosions, and anomalies were recorded for each technique. The limited CT agreed with the complete CT in 82% of the 200 sinus compartments reviewed. Localized disease, usually mucosal thickening of 3 mm or less and missed on the limited CT, but detected on the complete CT, accounted for 22 of 36 errors of interpretation. Underestimation of mucosal disease, usually 2 mm or less, accounted for eight errors and misinterpretation of partial volume effect for three errors. Using complete CT a s the established standard, plain film missed 37 instances of disease detected on the limited CT; 73% involved an error of mucosal thickening 4 mm or greater. A limited coronal CT of the paranasal sinuses offers a potentially lower cost alternative to complete CT in screening for sinonasal inflammatory disease. It is more accurate than plain film series. Localized disease and osteomeatal disease is underestimated with the current protocol, and so a limited CT should not be used for evaluating potential cancer patients or for surgical planning.

Common variable immunodeficiency in a renal transplant patient with severe recurrent bacterial infection: a case report and review of the literature.

The second reported case of common variable immunodeficiency (acquired agammaglobulinemia) after renal transplantation is presented. Agammaglobulinemia presumably resulted from long-standing immunosuppression. This case and our review of the literature indicate that agammaglobulinemia is a rare event after transplantation but can be treated successfully with intravenous immunoglobulin. Additionally, hypogammaglobulinemia occurs frequently after transplantation and should be monitored and treated in appropriate clinical situations. The treatment of our patient with intravenous immunoglobulin also suggests that patients with common variable immunodeficiency can undergo renal transplantation.

Triamcinolone acetonide Aqueous nasal spray in patients with seasonal ragweed allergic rhinitis: a placebo-controlled, double-blind study.

Because some patients may prefer aqueous nasal sprays and once-daily dosing for relief of seasonal allergic rhinitis symptoms, a new aqueous formulation of triamcinolone acetonide (TAA Aqueous) was developed. We conducted a randomized, placebo-controlled, double-blind study to compare the efficacy and safety of once-daily administration of 220 micrograms/d of TAA Aqueous for 1 week, followed by either 220 micrograms/d or 110 micrograms/d for an additional 2 weeks, with that of placebo in 429 patients with seasonal allergic rhinitis. Patients recorded the severity of symptoms (nasal stuffiness, discharge, sneezing, nasal index [the sum of the first three variables], nasal itching, and eye symptoms) on daily diary cards. Patients' and physicians' global evaluations of efficacy were made at the end of the 3-week study period. Both regimens of TAA Aqueous significantly improved symptoms compared with placebo at most time points. Patients demonstrated significant improvements in nasal symptoms as early as the first day of treatment (within 12 to 16 hours based on treatment in the morning and symptom assessment at bedtime). Although TAA Aqueous 220 micrograms/d provided numerically greater reductions in nasal symptoms compared with 110 micrograms/d, these differences in efficacy over the last 2 weeks were not statistically significant. The incidence of adverse effects with both TAA Aqueous regimens was low and comparable to that of placebo. In summary, during the first week of therapy, TAA Aqueous 220 micrograms/d significantly reduced nasal symptoms. During the last 2 weeks of therapy, the 110 micrograms/d regimen of TAA Aqueous was effective as continued therapy for most patients. Both the 110 micrograms/d and 220 micrograms/d regimens of TAA Aqueous provided significantly better relief of nasal symptoms than did placebo.

Systemic mastocytosis presenting as osteoporosis: a clinical and histomorphometric study.

Ten patients with systemic mastocytosis (SM) were evaluated for their metabolic bone disease (4 men and 6 women; mean +/- SD, 59 +/- 13 yr). All patients presented with generalized osteopenia and/or atraumatic vertebral compression fractures. Three patients had long-standing urticaria pigmentosa; in these, the diagnosis of cutaneous mastocytosis had been established by skin biopsy. One of the 3 and 2 of the other 7 individuals had symptoms suggestive of SM. Although six patients had previously undergone decalcified bone marrow trephine core biopsy (DBMB), findings were consistent with SM in only 2 of them. X-Ray survey revealed generalized osteopenia in all 10 patients and vertebral compression fractures in 9. No patient had sclerotic bone lesions. Histological findings of undecalcified transiliac crest biopsy (UTBB) specimens from 9 patients (5 patients underwent both DBMB and UTBB, 4 underwent only UTBB, and 1 had only DBMB) disclosed bone marrow that contained nodules characteristic of mast cell granulomas and numerous scattered oval- and spindle-shaped mast cells. The trabecular bone contained abundant newly synthesized bone matrix and a significant increase in osteoblastic, osteoclastic, and resorptive surfaces. Dynamic histomorphometric parameters revealed a significantly increased mineral apposition rate. Our study suggests that SM may be a more frequent cause of osteoporosis than previously recognized. Generalized osteopenia with compression fractures may be the only presentation of SM. Undecalcified bone biopsy is useful in the diagnosis of SM. Accelerated bone remodeling is a characteristic histomorphometric feature of SM with diffuse osteopenia.

Hypersensitivity reaction to desipramine.

Adverse reactions to the tricyclic antidepressant drugs imipramine and desipramine have been described and include eosinophilia, pulmonary infiltrates with eosinophilia, and elevated total serum IgE levels. The immunologic mechanism accounting for these adverse reactions has not been elucidated. This article describes a patient manifesting bronchospasm, profound eosinophilia, and elevated serum IgE levels after therapy with desipramine that resolved rapidly after withdrawal of the drug. Immunologic investigations failed to demonstrate specific IgE directed against a protein conjugate of desipramine but demonstrated the ability of desipramine to induce mast cell degranulation with direct intradermal skin challenges.