William F. Schoenwetter

Efficacy and Safety of Fexofenadine Hydrochloride for Treatment of Seasonal Allergic Rhinitis

BACKGROUND H1-receptor antagonists are effective for the treatment of seasonal allergic rhinitis. In rare circumstances, some second-generation H1-receptor antagonists have been associated with prolongation of the corrected QT interval (QTc), thus increasing the risk of ventricular arrhythmias. Fexofendine HCl, the carboxylic acid metabolite of terfenadine, is a new second-generation antihistamine that is nonsedating and does not cause electrocardiographic effects. OBJECTIVE To investigate the clinical efficacy and safety of fexofenadine HCl in the treatment of ragweed seasonal allergic rhinitis and to characterize the dose-response relationship of fexofenadine HCl at dosages of 60, 120, and 240 mg bid. METHODS A multicenter, 14-day, placebo-controlled, double-blind trial was conducted with patients suffering from moderate to severe ragweed seasonal allergic rhinitis who met symptom severity criteria after a 3-day placebo baseline period. Patients with minimal or very severe symptoms during the baseline period were excluded. Patients were randomized to receive fexofenadine HCl (60, 120, or 240 mg bid) or placebo at 12-hour dosing intervals (7:00 AM and 7:00 PM). The primary efficacy measure was patient-assessed 12-hour reflective total symptom score before the evening dose (trough). RESULTS Five hundred seventy patients completed the trial. Fexofenadine HCl at each dosage provided significant improvement in total symptom score (P < or = .003) and in all individual nasal symptoms compared with placebo. The frequency of adverse events was similar among fexofenadine HCl and placebo groups, with no dose-related trends. No sedative effects or electrocardiographic abnormalities, including prolongations in QTc were detected. CONCLUSIONS Fexofenadine HCl is both effective and safe for the treatment of ragweed seasonal allergic rhinitis. Because there was no additional efficacy at higher dosages, 60 mg bid appears to be the optimal therapeutic dosage for these patients.

The relationship between bronchiolitis and allergic asthma: A prospective study with allergy evaluation

Abstract A long-term prospective study has been made of twenty-four infants with the diagnosis of “bronchiolitis” in 1960–1961. Three to four years after the “bronchiolitis” episode, 50 per cent of the children were still wheezing. A very strong correlation was found between the persistence of wheezing and (a) family history of allergy and (b) presence of other allergies in the patients. There was also a strong correlation between the persistence of wheezing and increased number of eosinophils in the nasal secretions. In those patients available for study, there was no statistically significant difference in the incidence of peripheral eosinophilia between the two groups of patients. The significance of these findings with etiologic and prognostic implications is discussed.

Patterns of allergic respiratory disease in children with a past history of bronchiolitis

Abstract Sequential annual examinations have been carried out in a group of children who were hospitalized 5 years previously for bronchiolitis. During the subsequent 5 year study period, 40 to 50 per cent of the children were observed to wheeze recurrently. These was a high incidence of positive family histories of allergy, atopic rhinitis and dermatitis, and increased eosinophils in the nasal secretions and peripheral blood. Strong skin test responses to allergens were seen predominantly in the wheezing subjects and increased in frequency during the 5 year period. Wheezing episodes were generally associated with respiratory infections but were also observed during exposure to skin test reactive antigens as the children became older. The relationship of the bronchiolitis episode to childhood asthma is discussed.

Double-blind comparison of terfenadine, chlorpheniramine, and placebo in the treatment of chronic idiopathic urticaria

The efficacy of terfenadine, a nonsedating H1 antihistamine, in the management of chronic idiopathic urticaria was compared with chlorpheniramine and placebo in a parallel multicenter trial. Subjects with symptoms of hives for 3 days per week for at least 6 weeks were initially screened and admitted if no identifiable cause for symptoms could be determined. Patients entered a single-blind placebo period, and if hives of moderate severity were present for at least 3 days during the week, they were randomly assigned in a double-blind fashion to take terfenadine, 60 mg twice daily, chlorpheniramine, 4 mg three times a day, or placebo for 6 weeks. Data were analyzed for 122 patients. Those patients receiving both active treatments noted significant improvement in symptoms: pruritus, redness, number of hives, and waking hours during which hives were present, at the end of the first day of therapy. Symptom control by terfenadine was statistically superior to placebo during all 6 weeks, as rated by both patients and investigators. However, statistical significance was not achieved for chlorpheniramine at all observation points. Diphenhydramine was permitted as a relief medication for refractory symptoms and was taken by 52% of subjects receiving placebo, 26% taking chlorpheniramine, and only 9% of patients who were receiving terfenadine. In addition to providing superior symptom control, terfenadine caused less drowsiness and fatigue than chlorpheniramine. Terfenadine is a useful therapeutic agent for primary management of chronic idiopathic urticaria.

Efficacy and safety of budesonide inhalation powder (Pulmicort Turbuhaler) during 52 weeks of treatment in adults and children with persistent asthma.

Background. Inhaled corticosteroids are the agents of choice for treating persistent asthma. Objective. To evaluate the long-term efficacy and safety of budesonide inhalation powder (Pulmicort Turbuhaler®) in patients with mild to severe persistent asthma. Methods. Patients (n = 1133) received open-label budesonide (dose range, 100–800 µg b.i.d.) for 52 weeks following 2 weeks to 5 months of treatment in one of four double-blind, placebo-controlled studies. Patients, identified before the double-blind studies, included adults (n = 249) not receiving corticosteroids, adults (n = 384) and children (n = 356) previously maintained on inhaled corticosteroids, and adults (n = 144) previously maintained on oral corticosteroids. Results. Mean forced expiratory volume in 1 sec was 68.2% of predicted normal (n = 1133) at baseline (mean from two visits before randomization), 74.4% (n = 1132) at the end of double-blind treatment, 81.3% (n = 971) at week 52, and 80.1% (n = 1125) at last observation (including patients who discontinued early). Sixty-four patients maintained on oral corticosteroids before double-blind treatment entered the open-label study off oral corticosteroids, 58 of whom (91%) remained oral corticosteroid–free throughout the study. There was no evidence of basal or cosyntropin-stimulated hypothalamic-pituitary-adrenal axis function suppression, and the most commonly occurring adverse events were respiratory infection, sinusitis, and pharyngitis. Conclusions. During this 52-week, open-label study, budesonide maintained the improved pulmonary function and decreased oral corticosteroid use observed during previous double-blind treatment and was well tolerated, supporting its long-term use in adults and children with mild to severe persistent asthma.

Fatal hypersensitivity pneumonitis.

BACKGROUND Hypersensitivity pneumonitis (HP) is an uncommon, non-IgE-mediated interstitial lung disease caused by the inhalation of a variety of organic dusts, most commonly from exposure at work or in the pursuit of hobbies. Typically, after the disease is recognized, the causative allergen or environment is identified and treatment initiated through avoidance measures and corticosteroids. Progression of the disease is then usually halted and even reversed. Fatal cases of HP are unusual. OBJECTIVE To report a case of progressive and deadly HP in a 40-year-old printer who developed subacute bird fanciers disease with its clinical characteristics and positive precipitins to pigeon proteins. METHODS Chest x-ray examinations and tests of lung function were performed in the patient. Two months after initial consultation, when the diagnosis was still elusive, an open lung biopsy was performed and the patient was treated with prednisone for 3 months. A subsequent chest x-ray examination was performed 4 months after the biopsy. RESULTS With avoidance of birds and treatment with corticosteroids, the patients symptoms resolved and lung function normalized. He was subsequently diagnosed as having asthma followed by bronchitis and 2 episodes of pneumonia. He did not fully recover from these but developed progressive dyspnea. After linking his symptoms to work by history, he underwent lung biopsy with findings consistent with chronic HP. Serum antibody titers were positive for Aspergillus but not pigeon proteins. Based on exposure to water-based coolants, he was suspected of having chronic occupational HP, although this could not be confirmed. Despite aggressive treatment, he developed a progressive course that was ultimately fatal. CONCLUSIONS This report details the progressive disease course in an individual who presented initially with subacute HP. Unfortunately, even after appropriate diagnosis and management, the course of the disease can be fatal.