Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: a randomized, placebo-controlled clinical trial.

BACKGROUND: Nasal challenge studies have suggested histamine and cysteinyl leukotrienes are important proinflammatory mediators in allergic rhinitis. This study was designed to determine the efficacy of montelukast, a cysteinyl leukotriene receptor antagonist, administered alone or concomitantly with loratadine, an H(1)-receptor antagonist, in seasonal allergic rhinitis. OBJECTIVE: The purpose of this study was to determine the effect of concomitant use of montelukast and loratadine in the treatment of seasonal allergic rhinitis. METHODS: In this multicenter (N = 12) double-blind, randomized, parallel-group, placebo-controlled 2-week trial, 460 men and women, aged 15 to 75 years, with spring seasonal allergic rhinitis were randomly allocated to receive 1 of the following 5 treatments: montelukast 10 or 20 mg, loratadine 10 mg, montelukast 10 mg with loratadine 10 mg, or placebo, once daily in the evening. The primary end point was daytime nasal symptoms score (average of congestion, rhinorrhea, itching, and sneezing). Other end points were eye symptoms, nighttime symptoms, individual daytime nasal symptoms, global evaluations (patient's and physician's), and rhinoconjunctivitis quality-of-life scores. RESULTS: Concomitant montelukast with loratadine improved the primary end point significantly (P <.001) compared with placebo and each agent alone. Compared with placebo, montelukast with loratadine also significantly improved eye symptoms, nighttime symptoms, individual daytime nasal symptoms, global evaluations, and quality of life. Montelukast alone and loratadine alone caused modest improvements in rhinitis end points. All treatments were similarly well tolerated. CONCLUSIONS: Concomitant montelukast with loratadine provided effective treatment for seasonal allergic rhinitis and associated eye symptoms with a safety profile comparable with placebo.

Expression of the plasminogen activation system in kidney cancer correlates with its aggressive phenotype.

Malignant tumors contrast with benign ones in their ability to invade adjacent tissue and to metastasize. The urokinase plasminogen activator is a proteolytic enzyme that can facilitate these processes. In many carcinomas, the concentration of the urokinase plasminogen activator system is high. The high expression of these enzymes is related to tumor grade. In this study, we have investigated whether secretion of the urokinase plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor 1 in normal kidney tissue and kidney cancer tissue follows this pattern. We have found that urokinase plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor 1 were expressed in higher levels in kidney cancers (squamous cell carcinoma and renal cell carcinoma) than in normal kidney tissue and that these differences were statistically significant (P < or = 0.05). In renal cell carcinomas, we have observed differences between normal kidney tissue and renal cell carcinomas in males and Caucasians but not in females and African Americans (P < or = 0.05). Expression of the urokinase plasminogen activator system was also higher in grade III tumors when compared with lower-grade tumors or normal tissue.

Effectiveness of fluticasone propionate in patients with moderate asthma: a dose-ranging study.

This study was undertaken to evaluate the efficacy and safety of fluticasone propionate, an inhaled corticosteroid, in adolescents and adults with moderate asthma who were previously taking inhaled corticosteroids. After a 2-week, open-label screening period, a double-masked, randomized, parallel-group, dose-ranging study was conducted over 12 weeks in 21 outpatient centers throughout the United States. Patients (N = 304) > or = 12 years of age with moderate asthma previously treated with inhaled corticosteroids and beta-sympathomimetic bronchodilators were enrolled. Patients were assigned to receive placebo or fluticasone propionate 100, 250, or 500 micrograms twice daily via a metered-dose inhaler without a spacer device. These doses refer to the amount of fluticasone propionate released from the valve of the metered-dose inhaler; the corresponding doses released from the activator of the metered-dose inhaler are 88 micrograms, 220 micrograms, and 440 micrograms, respectively. Between baseline and end point, mean values of forced expiratory volume in 1 second decreased 0.31 L in the placebo group and improved 0.39 L, 0.30 L, and 0.43 L in patients receiving 100-micrograms, 250-micrograms, and 500-micrograms fluticasone propionate, respectively. The differences between placebo and all treatment groups were statistically significant. More patients were withdrawn from placebo (72%) than from fluticasone propionate (13% to 16%) because of failure to meet predetermined asthma stability criteria. Differences in baseline-to-end point changes in morning peak expiratory flow rate, physician overall assessments and patient-rated assessment of symptoms, and albuterol use for symptom control also significantly favored each fluticasone propionate group over placebo. There were essentially no differences in efficacy among the three fluticasone propionate groups. Treatment-related adverse events occurred in 8% of placebo-treated patients and 13% to 15% of fluticasone propionate-treated patients; these events were mainly localized to the oropharynx/ larynx. A 12-week course of fluticasone propionate (100, 250, and 500 micrograms twice daily) was well tolerated and more effective than placebo based on maintenance of asthma stability, pulmonary function tests, physician and patient assessments, and rescue bronchodilator use. No dose-related effects were observed with the dosages of fluticasone propionate used in this study.

Comparison of albuterol and metaproterenol syrup in the treatment of childhood asthma.

This study compared the acute and chronic effects of albuterol syrup (2 mg) and metaproterenol syrup (10 mg) three times a day over 28 days in 65 children, aged 6 to 9 years, with mild to moderate asthma. Wright peak flow, symptom scores, and rescue medication use were recorded twice daily during the 28 days; the acute cardiopulmonary effects of these syrups were compared over 8 hours on treatment days 1 and 28. Albuterol syrup produced a significantly greater peak magnitude of bronchodilation than metaproterenol, 29% vs 20% above baseline, respectively, on treatment day 1. Albuterol syrup had a duration of action of at least 8 hours and produced greater bronchodilation than metaproterenol syrup from 2 to 8 hours on both treatment days 1 and 28. The chronotropic effect of metaproterenol was greater than that of albuterol at 1 to 1 1/2 hours postdose on treatment days 1 and 28. There was a trend toward higher morning and evening Wright peak flow measurements during 28 days of treatment in the albuterol group. Side effects of both drugs were comparable. These findings imply therapeutic advantages of albuterol syrup over metaproterenol syrup in currently recommended doses with respect to improvement in pulmonary function, chronotropic effects, and frequency of dosing required to maintain optimum bronchodilation over a 24-hour period.

Once versus twice daily dosing of terfenadine in the treatment of seasonal allergic rhinitis: US and European studies.

Terfenadine was compared for efficacy in treatment regimens of 120 mg once daily (qd) and 60 mg twice daily (bid) in patients with seasonal allergic rhinitis in double blind, randomized, parallel 1-week studies, three in Europe (one multicenter study, three sites; n = 191) and one in the US (single center; n = 201). Patients had moderate or severe symptoms for 2 or more years and positive skin tests to relevant pollen antigens. On entry and final visit individual symptoms were rated by physicians on a visual analog scale in Europe and a numerical scale in the US. Most patients filled out daily symptom diaries during the studies. Individual symptom scores and total symptom scores, (calculated by adding individual symptom scores together) as assessed by physicians and patients, were similar at baseline for both treatment regimens on entry, with improvement during the week. There were more patients with complete and marked relief in Europe than in the US. (Total symptom scores as assessed by physicians, for instance, improved from baseline ratings of 407 for the 60 bid regimen and 431 for the 120 qd regimen in Europe to 102 and 95 at final visit, and in the US from 8.8 for 60 bid and 8.5 for the 120 qd to 4.5 and 4.1). There was no statistical difference between the two treatment regimens in Europe or the US. Terfenadine, 120 mg once daily, is as effective as the currently approved dosage of 60 mg twice daily in the treatment of seasonal allergic rhinitis, and terfenadine, 120 mg once daily, has the added convenience of allowing the patient once a day dosing.

Comparison of the acute cardiopulmonary effects of oral albuterol, metaproterenol, and terbutaline in asthmatics.

The acute cardiopulmonary effects of oral albuterol, 4 mg, metaproterenol sulfate, 20 mg, and terbutaline sulfate, 5 mg, were compared over eight hours in 20 moderate to severe asthmatics. The magnitude and time course of bronchodilation following albuterol and terbutaline were comparable. Albuterol and terbutaline had a duration of action of at least eight hours and produced significantly greater bronchodilation than metaproterenol from six to eight hours. Metaproterenol produced a greater degree of bronchodilation than albuterol and terbutaline 30 minutes after drug dosing. Significantly fewer patients receiving albuterol experienced one or more central nervous system or musculoskeletal side effects than patients receiving terbutaline. These findings imply possible therapeutic advantages of oral albuterol and terbutaline with respect to dosing frequency, while the more rapid onset of oral metaproterenol suggests that it may have an advantage when used on an as-needed basis.

Abnormal responses of wasted ventilation fraction (VD/VT) during exercise in patients with pulmonary vascular abnormalities.

The finding of a rise in VD/VT or failure of VD/VT to fall during exercise has been proposed as a useful noninvasive indicator of pulmonary vaso-occlusive disease in patients with unexplained dyspnea. However, we previously reported a normal fall in VD/VT during exercise in patients with pulmonary hypertension at rest and/or during exercise due to collagen vascular disease. To investigate further the relationship between pulmonary vascular abnormalities and VD/VT responses to exercise, we studied 4 subjects with severe hypoxemia due to cirrhosis or diffuse telangiectasia. We found an abnormal VD/VT response to exercise in these subjects despite normal pulmonary hemodynamics which effectively excluded hemodynamically significant pulmonary vascular obstruction. These findings provide further support for the lack of utility of the VD/VT measurement at rest and during exercise as a screening method for detecting pulmonary vaso-occlusive disease, since the VD/VT cannot only fall appropriately during exercise in patients with pulmonary hypertension but can also remain unchanged or rise during exercise in patients with normal pulmonary hemodynamics.

Pulmonary manifestations of mycosis fungoides.

Three patients with mycosis fungoides who developed pulmonary abnormalities are described. These abnormalities are correlated with the findings at open lung biopsy and at autopsy. The roentgenographic changes consisted of bilateral, nodular pulmonary infiltrates in two patients, and interstitial infiltrate and plate-like atelectasis with hilar adenopathy in a third patient. Examination of lung biopsies and autopsy tissue revealed interstitial and/or intra-alveolar infiltrates composed of atypical lymphoid cells similar to those seem in the skin biopsies. The short survival after detection of an abnormal chest film suggests that dissemination of mycosis fungoides to the lung heralds a poor prognosis.

Bronchodilator effects of terbutaline and aminophylline alone and in combination in asthmatic patients.

In 17 patients with moderate to severe asthma, we compared acute bronchodilator effects of the following drugs or drug combinations using a double-blind crossover design: terbutaline, 5; aminophyline 400; terbutaline, 5, plus aminophyline, 400; terbutaline, 2.5; aminophylline, 200; terbutaline, 2.5, plus aminophyline, 200 mg; and placebo. The higher doses of terbutaline and aminophylline alone produced comparable bronchodilation and similarly frequent adverse side effects; low doses of each drug also had comparable effects. The high-dose combination produced significantly (P less than 0.05) greater bronchodilatation than either drug alone. The low dose combination had bronchodilator effects comparable to those produced by the higher dose of either drug alone. These findings suggest therapeutic advantages in combining high doses of theophylline and an oral beta adrenergic agonist (terbutaline) in asthma not well controlled on high doses of either drug alone and in combining these drugs in lower doses in patients experiencing intolerable side effects from a high dose of either drug.

Hemoptysis: diagnosis and management.

Hemoptysis is one of the most important symptoms of cardiopulmonary disease-first, because bleeding even in small amounts may indicate the presence of such serious diseases as bronchogenic carcinoma or active tuberculosis, and second, because untreated massive hemorrhage is associated with a high mortality rate. The cause of hemoptysis may be suggested by the history, physical examination or chest x-ray findings, but often diagnostic procedures such as bronchoscopy, bronchography and pulmonary angiography are needed for definitive diagnosis. The importance of early localization of the bleeding site and surgical intervention in patients with massive hemoptysis is stressed.

Fatal lung scan in a case of pulmonary hypertension due to obliterative pulmonary vascular disease.

A young woman with pulmonary hypertension due to sclerodermatous pulmonary vascular disease died immediately following the injection of macroaggregated albumin labeled with 99-TC for a perfusion lung scan. Review of the literature suggests that patients with chronic pulmonary hypertension due to an obliterative pulmonary vascular disease are at risk of developing a serious reaction to perfusion lung scanning. Important factors which predispose to an adverse reaction to lung scanning are the size and dose of macroaggregated albumin particles in relation to the total cross-sectional area of the pulmonary vascular bed and a critical arteriolar lumen size.