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.

Validation of a pediatric asthma caregiver diary.

BACKGROUND: Young children are generally not able to consistently and reliably perform tests of airway function, and normative values are not available. Reliable and valid measures of parental reporting of asthma symptoms and functioning are needed to determine the efficacy of asthma interventions. OBJECTIVE: A pediatric asthma caregiver diary was developed and validated for use in interventional asthma studies. METHODS: A 3-week prospective study of 125 caregiver parents and their children, aged 2 to 5 years, with persistent asthma was conducted. At baseline, children were classified as either stable (no change to anti-inflammatory therapy) or unstable (anti-inflammatory therapy added or increased). RESULTS: A symptom scale and day without asthma symptoms (DWAS) were defined from pediatric asthma caregiver diary questions. The scale and DWAS statistically differentiated between the stable and unstable groups at week 1 and detected change between the 2 groups (P <.01). On average, caregivers reported low symptom scores. However, the frequency of DWAS was only 43% of days in the stable group and 22% in the unstable group. CONCLUSION: The pediatric asthma caregiver diary scale and DWAS have acceptable measurement characteristics for use in clinical trials of children with asthma symptoms. The DWAS indicates an opportunity for improvement in asthma control in this population.

Comparison of once- and twice-daily dosing of fluticasone propionate 200 micrograms per day administered by diskus device in patients with asthma treated with or without inhaled corticosteroids.

BACKGROUND: There are limited published data regarding the efficacy of once- versus twice-daily administration of flutica-sone propionate. OBJECTIVE: Our purpose was to evaluate the effectiveness of fluticasone propionate powder 200 microg/d administered as a once- or twice-daily dosage regimen in patients who were currently being treated with bronchodilators only (BD patients) and in patients who required inhaled corticosteroids for maintenance treatment of asthma (ICS patients). METHODS: Five hundred seventy patients were randomly assigned to receive one of the following inhaled treatments through the Diskus device (Glaxo Wellcome, Research Triangle Park, NC) for 12 weeks: fluticasone propionate 100 microg twice daily (FP100BID) or 200 microg once daily (FP200QD) or placebo. RESULTS: BD patients treated with FP100BID, FP200QD, and placebo had mean increases in FEV(1) from baseline to end point of 0. 49 L, 0.37 L, and 0.21 L, respectively (P <.001, FP100BID vs placebo; P =.05, FP200QD vs placebo). ICS patients treated with FP100BID and FP200QD had mean increases in FEV(1) of 0.27 L and 0.11 L, respectively, compared with a decrease in FEV(1) of -0.08 L with placebo (P <.001, FP100BID vs placebo; P =.023, FP200QD vs placebo). BD patients treated with FP100BID and FP200QD had mean increases in morning peak expiratory flow from baseline to end point of 31 L/min and 27 L/min, respectively, compared with a 1 L/min increase in patients treated with placebo. ICS patients treated with FP100BID had a mean increase in morning peak expiratory flow (from baseline to end point) of 18 L/min compared with mean decreases of -3 L/min and -12 L/min in the FP200QD and placebo groups, respectively. More patients were withdrawn from placebo (26% and 48%, in BD and ICS patients, respectively) than from fluticasone propionate (7%-9% [BID-QD] and 18%-32% [BID-QD], in BD and ICS patients, respectively) because of failure to meet predetermined asthma stability criteria. CONCLUSION: The efficacies of FP100BID and FP200QD were comparable with regard to improvement in pulmonary function and asthma stability in BD patients. In ICS patients, asthma control was maintained with FP200QD, whereas FP100BID provided greater improvements in pulmonary function and asthma stability.

Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray.

OBJECTIVE: Intranasal corticosteroids are used widely for the treatment of allergic rhinitis because they are effective and well tolerated. However, their potential to suppress growth of pediatric subjects with allergic rhinitis continues to be a concern, particularly in light of reports of growth suppression after treatment with intranasal beclomethasone dipropionate or intranasal budesonide (see the article by Skoner et al in this month's issue). A 1-year study of prepubertal patients between 3 and 9 years of age with perennial allergic rhinitis was conducted to assess the effects on growth of mometasone furoate aqueous nasal spray (MFNS), a new once-daily (QD) intranasal corticosteroid with negligible bioavailability. METHODS: This was a randomized, placebo-controlled, double-blind, multicenter study. Ninety-eight subjects were randomized to treatment with either MFNS 100 microg QD or placebo for 1 year. Each subject's height was required to be between the 5th and 95th percentile at baseline, and skeletal age at screening was required to be within 2 years of chronological age, as determined by left wrist x-rays. Washout periods for medications that affect either childhood growth or allergic rhinitis symptoms were established based on estimated period of effect, and these medications were prohibited during the study. However, short courses of either oral prednisone lasting no longer than 7 days or low-potency topical dermatologic corticosteroids lasting no longer than 10 days were permitted if necessary. Height was measured with a calibrated stadiometer at baseline and at 4, 8, 12, 26, 39, and 52 weeks, and the primary safety variable was the change in standing height. The rate of growth was also calculated for each subject as the slope (linear regression) of the change in height from baseline using data from all visits of subjects who had at least 2 visits. Hypothalamic-pituitary-adrenocortical- (HPA)-axis function was assessed via cosyntropin stimulation testing at baseline and at 26 and 52 weeks. All analyses were based on all randomized subjects (intent-to-treat principle). The change from baseline in standing height was analyzed by a 2-way analysis of variance that extracted sources of variation attributable to treatment, center, and treatment-by-center interaction. RESULTS: Demographic characteristics were similar at baseline. Eighty-two subjects completed the study (42 in the MFNS group and 40 in the placebo group), and 93% of subjects achieved at least 80% compliance with therapy. After 1 year of treatment, no suppression of growth was seen in subjects treated with MFNS, and mean standing heights were similar for both treatment groups at all time points. For the primary safety variable (change in height from baseline), both treatment groups were similar at all time points except for weeks 8 and 52. Subjects treated with MFNS had a slightly greater mean increase in height than subjects treated with placebo at these time points: the change in height was 6.95 cm versus 6.35 cm at the 1-year time point. However, the rate of growth (.018 cm/day) averaged for all time points over the course of the study was similar for both treatment groups. Additional analyses found that MFNS did not retard growth in any sex or age subgroup of subjects. The use of exogenous corticosteroids other than the study drug was also similar among the 2 treatment groups. Results from cosyntropin stimulation testing confirmed the absence of systemic effects of MFNS. The change from baseline in the difference between prestimulation and poststimulation levels was similar for both treatment groups after 1 year of treatment, with no evidence of HPA-axis suppression in MFNS-treated subjects at any time point. Incidences of treatment-related adverse events were similar for both treatment groups, with 16% of MFNS-treated subjects reporting adverse events, compared with 22% of placebo-treated subjects. CONCLUSIONS: (ABSTRACT TRUNCATED)

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.

Theophylline: is it obsolete for asthma?

Theophylline, despite its potential for causing gastrointestinal tract and central nervous system side effects, is still the major drug used to control symptoms of moderate asthma in children. Selection of patients who will benefit most from this treatment is based on asthma frequency, severity, and triggers; the cost and side effects of theophylline; the likelihood of compliance; and the wishes of both patient and parent. Theophylline's pharmacodynamics, metabolism, and proposed mechanisms of action are discussed, as are the use of specific preparations and possible side effects. Although theophylline can be used in the acute care setting, its major use is in daily continuous prophylaxis against events triggered by either allergic or nonallergic factors. In addition to dosage and titration, aspects of monitoring, compliance, and weaning are discussed.

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.

Pollen-specific IgG antibodies in the tears of patients with allergic-like conjunctivitis.

Specific-IgG antibodies to rye grass and/or AgE in the tear secretions were demonstrated in studies of patients with the clinical features of allergic conjunctivitis but negative immediate skin reactivity and absent IgE antibodies by RAST to the inhalant pollen allergens. Studies by use of transferrin as a marker for the vascular leakage of plasma proteins into the tear secretions indicated that more than 98% of these pollen-specific IgG antibodies were locally produced by the conjunctival tissues of the external eye. These findings suggest that IgG-mediated immune mechanism(s) are important in the pathogenesis of some patients with allergic-like conjunctivitis.

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.