Efficacy and safety of dry powder fluticasone propionate in children with persistent asthma.

BACKGROUND: Flovent Diskus is a powder formulation of the inhaled corticosteroid fluticasone propionate (FP) delivered via a breath-actuated, multidose inhaler. OBJECTIVE: To determine the efficacy and safety of dry powder FP administered once or twice daily (200 microg per day) to children with persistent asthma. METHODS: Twelve-week, randomized, double-blind, placebo-controlled, multicenter trial with a 52-week, open-label extension. Children aged 4 to 11 were required to have pulmonary function 50% to 85% of predicted values. The population was stratified for baseline therapy (inhaled corticosteroid/cromolyn or bronchodilators only). After a 2-week placebo run-in, 242 patients received dry powder FP 200 microg each morning, dry powder FP 100 microg BID, or placebo for 12 weeks; 192 were rerandomized to the QD or BID regimen for an additional 52 weeks of open-label treatment. Primary endpoints were mean changes in FEV1 and morning PEF recorded at clinic visits. RESULTS: Both dry powder FP regimens significantly improved FEV1, evening PEF, and asthma symptoms at the double-blind phase endpoint (P < or = .017 compared with placebo). The BID regimen also significantly improved morning PEF and nighttime awakenings due to asthma (P < or = .005). Among patients previously treated with inhaled corticosteroids/cromolyn, improvements observed with the QD and BID regimens were similar. Patients switched from BID to open-label QD treatment showed additional improvements at week 52 generally comparable to patients who received the BID regimen during both phases. Fluticasone propionate was well tolerated for up to 64 weeks with few reports of drug-related adverse events or morning plasma cortisol abnormalities. CONCLUSIONS: Once daily dosing of dry powder FP 200 microg is an effective and convenient alternative for children whose asthma is controlled with a more frequent dosing regimen of inhaled corticosteroids.

Placebo-controlled, double-blind study of the efficacy and safety of triamcinolone acetonide aerosol nasal inhaler in pediatric patients with seasonal allergic rhinitis.

Triamcinolone acetonide (TAA) aerosol nasal inhaler has been shown to effectively relieve the symptoms of seasonal allergic rhinitis in adults and adolescents. We conducted a study to evaluate the efficacy and safety of once-daily administration of TAA aerosol nasal inhaler in pediatric patients aged 6 to 11 years with grass seasonal allergic rhinitis. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled 116 children who were treated with either TAA aerosol nasal inhaler (220 micrograms/d) or placebo once daily for 2 weeks. Patients evaluated the severity of rhinitis symptoms (nasal stuffiness, discharge, sneezing, and itching) daily according to a four-point scale (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Patients' and physicians' global evaluations of overall treatment efficacy were assessed at the end of the 2-week treatment period. Patients treated with TAA aerosol nasal inhaler had significantly greater reductions in all nasal symptom scores overall and in virtually all symptoms at the end of week 1 and week 2 compared with those in the placebo group. Both patients' and physicians' global evaluations of efficacy favored TAA aerosol nasal inhaler over placebo. This study demonstrated that once-daily administration of 220 micrograms of TAA aerosol nasal inhaler was well tolerated and effectively reduced the symptoms of seasonal allergic rhinitis in pediatric patients.

A double-blind study of the efficacy of nedocromil sodium in the management of asthma in patients using high doses of bronchodilators.

The effects of nedocromil sodium were assessed in 110 patients with asthma who experienced asthma symptoms despite the use of high doses of inhaled bronchodilators. During the baseline period, antiinflammatory agents were not permitted, and patients were treated with inhaled beta-agonists on an as-needed basis. Patients who required 12 or more puffs of albuterol and experienced continuing asthma symptoms for 7 of the 14 baseline days were randomized to treatment groups. Subjects received either nedocromil sodium (4 mg) or placebo four times a day for 10 weeks. Statistically significant (p < 0.05) between-treatment differences (weeks 3 to 10), favoring nedocromil sodium, were determined for the asthma summary score, daytime asthma severity, asthmatic cough, morning peak flow rates, reduction of as-needed bronchodilator use, physician's assessment of asthma severity, and patient and physician opinions of treatment effectiveness. By trial end (week 10), sleep difficulty caused by asthma decreased 29% in the nedocromil sodium group and 4% in the placebo group (p = 0.006). Nedocromil sodium was well tolerated and improved asthma control while reducing the inhaled bronchodilator load of these patients with moderately severe asthma.

Comparative taste evaluation of aerosolized formulations of triamcinolone acetonide, flunisolide, and flunisolide with menthol.

The taste characteristics of aerosolized formulations of triamcinolone acetonide, flunisolide, and flunisolide with menthol flavoring were compared in 102 adult asthmatic patients. During a 2-hour test period, study participants evaluated the taste of each of the three inhaled corticosteroids, one at a time, in a randomly assigned sequence. The extent to which they liked the taste of each preparation and the taste intensity (strength of taste) of each product were rated on 100-point scales. Patients also characterized the predominant taste of each inhaled corticosteroid as "no taste," "salty," "sour," "sweet," or "bitter." Assessments were made immediately after inhalation and 2 minutes after inhalation. At both assessment times, subjects liked the taste of triamcinolone acetonide significantly more than the taste of flunisolide or flunisolide with menthol, and they liked the taste of flunisolide with menthol better than that of flunisolide without menthol. The taste intensity of triamcinolone acetonide was rated significantly less than that of the two flunisolide preparations at both evaluation times. There was no significant difference in the taste-intensity ratings for flunisolide with and without menthol. Triamcinolone acetonide was most frequently described as having no taste, whereas the taste of both flunisolide and flunisolide with menthol was most frequently described as bitter. Because of the possible adverse impact of an unpleasant taste on patient compliance with prescribed therapy, differences in the taste of inhaled corticosteroids should be an important consideration in selecting and recommending an aerosolized steroidal preparation for the control of asthma.

Aerobiology of the Colorado Rockies: pollen count comparisons between Vail and Denver, Colorado.

Pollen patterns were compared between Vail, CO (8,200 feet elevation), Aspen, CO (7,900 feet) and Denver, CO (5,280 feet) from 1984 through 1988. Counts were obtained at all sites with a volumetric intermittent cycling rotating impaction sampler. Aspen and Denver were compared in 1984, and Vail and Denver from 1985 through 1988. While counts were generally lower in the mountain sites than Denver, certain pollens, especially trees, were quite high. Ragweed was essentially absent from Aspen and Vail, and chenopod-amaranth counts were very low. Cedar, pine, and aspen frequently pollinated despite active snowfall.

Exercise-induced allergies: the role of histamine release.

Exercise is a physical cause of allergic reactions, including exercise-induced anaphylaxis (EIAna), exercise-induced urticaria (EIU), exercise-induced asthma (EIA), and exercise-induced rhinitis (EIR). Since its first description in 1979, EIAna has been reported with variable clinical manifestations, with exercise alone, and in combination with food ingestion. Elevated serum histamine levels and cutaneous mast cell degranulation have been noted. Exercise-induced urticaria appears as small, punctate lesions that differ from the classic coalescent type seen with EIAna. Variant forms of EIAna with cholinergic urticarial lesions manifesting systemic collapse and/or respiratory distress have been studied. Exercise-induced urticaria and cold-induced urticaria may cause elevated plasma histamine levels coincident with the onset of pruritus and hives. Theories accounting for EIA include respiratory heat loss, water loss, and mast cell activation. Although some studies have shown increased plasma histamine with EIA, others have not. Recently, bronchoalveolar lavage in atopic subjects with EIA has been evaluated preexercise and postexercise, with no significant differences in histamine or tryptase, suggesting a pathogenesis of EIA independent of the mast cell. Exercise-induced rhinitis, with varying degrees of rhinorrhea, congestion, and sneezing, has been increasingly recognized in athletes who run, cycle, and ski. Cold-air-induced rhinorrhea in laboratory challenges displays a mediator release pattern similar to that produced by allergen-induced nasal challenges. Therapeutically, H1 antihistamines are recommended for EIAna both as pretreatment and acute therapy. H1 antihistamines may be helpful in EIU, but are recommended for EIAna both as pretreatment and acute therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Champ Camp: the Colorado Children's Asthma Camp experience.

To encourage children with asthma to enjoy outdoor activities without physical or psychosocial impairment, children's asthma camps are established throughout the country sponsored by organizations including local and state allergy societies. We wish to describe our Colorado "Champ Camp" experience as a model and reference for future similar efforts and to encourage networking by medical leadership for information sharing and guidelines development nationally. Statistics from parents' satisfaction surveys over 8 years demonstrate a positive influence on attitudes toward asthma and confidence to enter activities and sports with children without asthma.

The skier's nose: a model of cold-induced rhinorrhea.

Cold-induced rhinorrhea (CIR) is a commonly experienced discomfort not previously addressed in the medical literature. In a 2-part study, we assessed the prevalence and described the characteristics of CIR and evaluated the efficacy of an anticholinergic nasal spray in its treatment. In Part 1, 90 general medical patients at a ski resort clinic were asked to describe their symptoms associated with cold exposure. Ninety-six percent reported some degree of CIR; 48% reported moderate to severe CIR. Fifty percent had some degree of nasal congestion and 33% reported sneezing. Allergic and nonallergic patients described similar degrees of rhinorrhea. In Part 2, 14 ski patrollers were given atropine sulfate in saline (AS/S) nasal spray before cold exposure in double-blinded placebo (P) controlled crossover fashion. Ninety-two percent noted improvement of CIR with AS/S and 8% experienced no change. None of the subjects noted worsening of symptoms, however, one subject reported excessive dryness at the AS/S concentration used. All 14 subjects receiving P experienced no change in CIR. We conclude that CIR is a distinct clinical syndrome frequently seen with cold temperature exposure, presenting primarily as rhinorrhea and sometimes involving nasal congestion and sneezing. Pretreatment with a 0.005% solution AS/S can effectively block CIR with only minimal short-term side effects.

Timed effects of an oral adrenergic bronchodilator on pulmonary function and measurements of plasma and leukocyte cyclic AMP: divergence in duration of drug action and development of tolerance.

The time course of response to initiation and withdrawal of treatment with terbutaline (5 mg orally, three times daily) was examined in eight normal subjects and 14 asthmatic patients. The various indices of response, examined simultaneously, yielded divergent estimates of the duration of drug action and the development of tolerance during continuous treatment. Bronchodilator responses were observed after each dose of terbutaline, but within 8 hr after a dose, pulmonary functions were similar to those observed in the absence of treatment. There was a suggestion of moderate tolerance to the bronchodilator effects of medication in that areas under the curve for increments in pulmonary function after terbutaline were lower during treatment than after the initial doses of medication; but the variations in magnitude of pulmonary response on different study days did not achieve statistical significance. Measurements of plasma cyclic AMP concentration suggested a much longer duration of drug action, with elevated levels observed 24 hr after a treatment dose; there was a progressive decrease in the plasma cyclic AMP responses to medication during the course of treatment. Conversely, leukocyte cyclic AMP responses to adrenergic stimulation were suppressed within 4 hr after the first dose of medication; the suppression persisted throughout treatment and for 1 to 3 days thereafter. These observations indicated that duration of drug action and induction of tolerance vary in different organ systems.