Inhaled mometasone furoate reduces oral prednisone requirements while improving respiratory function and health-related quality of life in patients with severe persistent asthma.

BACKGROUND: Inhaled corticosteroid therapy in severe persistent asthma has been shown to reduce or eliminate oral corticosteroid (OCS) use while retaining effective asthma control. OBJECTIVE: We sought to evaluate the ability of mometasone furoate (MF) delivered by means of dry powder inhaler to reduce daily oral prednisone requirements in OCS-dependent patients with severe persistent asthma. METHODS: We performed a 12-week, double-blind, placebocontrolled trial (21 centers, 132 patients) comparing 2 doses of MF (400 and 800 microg administered twice daily) with placebo, followed by a 9-month open-label phase in which 128 patients received treatment with MF. RESULTS: At the endpoint of the double-blind trial, MF 400 and 800 mg twice daily reduced daily OCS requirements by 46.0% and 23.9%, respectively, whereas placebo increased OCS requirements by 164.4% (P <.01). Oral steroids were eliminated in 40%, 37%, and 0% of patients in the MF 400 and 800 mg twice daily and placebo groups, respectively. Pulmonary function and quality of life significantly increased for MF-treated patients. Further reductions in OCS requirements were achieved with long-term MF treatment in the open-label phase. CONCLUSION: MF inhaled orally as a dry powder is an effective alternative to systemic corticosteroids in patients with severe persistent asthma.

Onset of action of mometasone furoate nasal spray (NASONEX) in seasonal allergic rhinitis.

BACKGROUND: Mometasone furoate nasal spray (MFNS, NASONEX ), is a new synthetic corticosteroid with considerable efficacy in the treatment of seasonal and perennial rhinitis and less than 0.1% systemic absorption. This study was designed to evaluate the time of onset of action of MFNS. The subjects were evaluated over the course of 2 weeks during the spring allergy season. METHODS: The effects of MFNS 200 microg given once daily for 2 weeks were evaluated in a randomized, multicenter, double-blind, placebo-controlled study in 201 patients with seasonal allergic rhinitis. Clinically significant onset of action was assessed prospectively by special patient diary cards kept during the first 3 days of treatment. RESULTS: By 12 h after initial dosage (the earliest evaluation), 28% of patients in the MFNS group experienced clinically significant relief, compared with 13% of those given placebo (P = 0.01). Median time to at least moderate symptom relief in patients who received MFNS was 35.9 h, compared with more than 72 h in patients given placebo (P<0.01). By 72 h, 64% of the patients receiving MFNS experienced at least moderate relief, compared with 40% of those treated with placebo (P<0.01). Both patient and physician ratings of symptom severity, response to treatment, and overall condition of rhinitis indicated significant (P<0.01) superiority of MFNS over placebo. MFNS was well tolerated, with adverse events comparable to placebo. CONCLUSIONS: MFNS provided rapid onset of clinically significant symptom relief in patients with seasonal allergic rhinitis.

Comparative efficacy and safety of once-daily versus twice-daily loratadine-pseudoephedrine combinations versus placebo in seasonal allergic rhinitis.

The objective of this study was to compare the efficacy and safety of Claritin-D 24 Hour (once daily) with that of Claritin-D 12 Hour (twice daily) and placebo in the treatment of patients with seasonal allergic rhinitis (SAR). In this double-blind, placebo-controlled, multicenter study, 469 patients with moderate-to-severe SAR symptoms were treated for 2 weeks with one of the following: Claritin-D 24 Hour (a combination tablet formulation of loratadine 10 mg in the coating and pseudoephedrine sulfate 240 mg in an extended-release core), Claritin-D 12 Hour (a combination tablet formulation of loratadine 5 mg in the tablet coating and 120 mg pseudoephedrine sulfate, 60 mg in the coating and 60 mg in the core), or placebo. Claritin-D 24 Hour and Claritin-D 12 Hour were consistently superior to placebo (P < 0.01) in reducing total, nasal, and nonnasal symptom scores. Patients in the Claritin-D 24 Hour and Claritin-D 12 Hour groups also had significantly greater (P

Conversion from twice- to once-daily extended-release theophylline treatment in patients with reversible airway obstruction.

This multicenter, randomized, investigator-blinded, parallel group study compared the effects of converting patients from a q12h extended-release theophylline preparation (Theo-Dur) to a q24h extended-release product (Uni-Dur). Patients (n = 133) first received open-label Theo-Dur treatment with dosage titrated to achieve peak serum theophylline concentrations of 10-20 micrograms/ml. Patients then were randomized to continue Theo-Dur (n = 64) or to convert to Uni-Dur (n = 60) with peak serum theophylline concentrations maintained in the desired range. Pulmonary function tests were performed during the open-label and blinded periods; patients maintained diaries and performed peak flow measurements before each dose of study treatment. Adverse events were recorded throughout the study. Respiratory status during blinded treatment was rated as the same or improved compared with open-label treatment by > 87% of evaluable patients and physicians, regardless of treatment group. There were no significant differences in mean peak serum theophylline concentrations at baseline, at the final evaluation, or at any point during the study. Few dosage adjustments were necessary (5/52, Uni-Dur; 9/57, Theo-Dur). There were no significant changes in pulmonary function test results or patient diary entries between the open-label and blinded periods. Headache and nausea were the most commonly reported adverse events. In conclusion, converting patients from twice- to once-daily theophylline treatment resulted in no significant changes in any measures of pulmonary function, and there were no significant differences between the groups during the blinded treatment period.

When a sigh is just a sigh . . . and not asthma.

Sighing is a normal physiologic response, expanding the lungs to vital capacity, usually followed by a prolonged expiratory phase. Sighing dyspnea is a condition that may be mistaken for asthma, and should be considered in the atypical cases. Recognizing sighing dyspnea at the onset may save patients from having to undergo extensive diagnostic evaluations and treatments. This condition, once identified, can often be easily treated by explaining the benign nature and giving reassurance to the patient.

Comparison of a new sustained-release theophylline preparation, TheoBeads, with Theo-Dur tablets in children with asthma.

A new, slow-release theophylline formulation for children, TheoBeads, which has the potential for once-daily dosing, has become available. We report the results of a study of pediatric patients whose medication was changed from Theo-Dur tablets b.i.d. to TheoBeads q.d. Forty-nine children with asthma (aged 6-12 years) were treated with b.i.d. Theo-Dur to produce therapeutic maximum and minimum concentration levels (i.e., 8-20 micrograms/ml). Approximately half the patients were then transferred to TheoBeads given q.d. at the same total daily dose and retitrated; seven patients needed to be changed to b.i.d. dosing due to unacceptable fluctuations. The other half of the patients continued on b.i.d. Theo-Dur. Following at least 5 days of steady-state dosing, serum theophylline levels were assayed over a 24-hour period. It was found that: 1. Children changed to q.d. TheoBeads showed no change in their overall asthma control based on clinical diary entries and peak flow measurements. 2. Lower Cmax and Cmin theophylline levels and a smaller area under the curve were noted for patients taking q.d. TheoBeads compared to those taking b.i.d. Theo-Dur. 3. Administration of TheoBeads q.d. resulted in a significantly larger overall peak-to-trough fluctuation and a higher percentage of patients with subtherapeutic theophylline levels in the second 12-hour period than did b.i.d. Theo-Dur administration. In summary, when children receiving b.i.d. Theo-Dur were transferred to q.d. TheoBeads, they did not maintain even and sustained therapeutic theophylline levels, although asthma control was not adversely affected during the short period of observation.

Use of external expiratory resistance in intubated neonates to increase lung volume.

Ten intubated neonates (weights 0.90 to 2.58 kg) recovering from respiratory disease had lung mechanics, respiratory patterns, and functional residual capacity measured at 0 cmH2O continuous positive airways pressure and then after application of serially increasing levels of external expiratory resistance. At an external expiratory resistance greater than 40 cmH2O/1 per second, there was a significant increase in mean functional residual capacity compared with control levels. Immediately after the application of external expiratory resistance, there was a significant decrease in flow which returned to control values after a few breaths. Tidal volume and respiratory rate decreased for a few breaths after the application of the external expiratory resistance, but returned to control values after several seconds. Study age, gestational age, or study weight had no appreciable effect on the relationship between functional residual capacity and external expiratory resistance. Application of external expiratory resistance may be useful for stabilising lung volume in neonates recovering from respiratory disease.

Posterior subcapsular cataracts in steroid-requiring asthmatic children.

Slit-lamp examinations were performed on 24 children and adolescents with severe asthma, all of whom had received steroids for at least 365 days. Posterior subcapsular cataracts (PSCC) were detected in 7 (29.1%). None of the patients had been treated with beclomethasone. All 7 of the patients with PSCC were in the subgroup of 14 patients who had been on the highest doses of corticosteroid, 10 mg or more per day, for the longest period of time. The 7 children with PSCC were all below the fifth percentile for height and had fallen away from their normal growth curve. Of the 17 children in whom PSCC were not detected, only 1 was below the fifth percentile for height. It would seem from our results that the steroid-requiring asthmatic who is growth-suppressed is at an increased risk for developing PSCC. We have documented the reversal of PSCC in 2 children. Both of these children had been placed on beclomethasone, which allowed for the discontinuation of daily prednisone in one case and a reduction to less than 10 mg per day of prednisone in the other. The reversal occurred within 6 months of starting on beclomethasone.