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The aim of this study was to determine the output of salbutamol nebulised in combination with either flunisolide or beclometasone dipropionate (BDP) from two different nebulisers under simulated breathing conditions. The BimboNeb and Nebula nebulisers were used to nebulise 3.0 mL of the two drug mixtures (salbutamol, 5000 microg plus either flunisolide, 600 microg, or BDP, 800 microg). Particle size was determined by inertial impaction. Total outputs of all drugs from both nebulisers were measured using a sinus flow pump under simulated paediatric and adult breathing patterns. The mass median aerodynamic diameter (MMAD) of BDP particles from the mixture was 6.34 mum using the BimboNeb and 5.34 mum using the Nebula. Values for salbutamol in this mixture were 3.93 and 3.32 microm, respectively. The MMAD of flunisolide particles from the BimboNeb and Nebula were 3.74 and 3.65 microm, respectively, while for salbutamol were 3.79 and 3.74 microm, respectively. With the simulated adult breathing pattern, all drug outputs from both mixtures were greater from the BimboNeb than from the Nebula after 5 and 10 min' nebulisation. Drug delivery from the BimboNeb, but not the Nebula, was affected by the simulated breathing pattern. Outputs with the BimboNeb were lower with the paediatric breathing pattern than with the adult pattern. In the majority of cases, nebulising for 10 min produced significantly greater drug output than after 5 min. For the Nebula, outputs were generally similar at 5 and 10 min, irrespective of the breathing pattern. These results highlight the need to assess the amount of aerosolised drug available when drugs are combined, when different nebulisers are used and when they are used with patients of different ages.

Flunisolide hydrofluoroalkane (HFA) has efficacy equivalent to that of flunisolide chlorofluorocarbon (CFC) at one third the dose of the CFC formulation, a reduction from 250 microg/puff for flunisolide CFC to 85 microg/puff for flunisolide HFA. Flunisolide HFA delivers a smaller particle size (1.2 microm) in solution, resulting in improved lung deposition as compared with flunisolide CFC (3.8 microm), which is delivered in suspension. An added built-in spacer has reduced oropharyngeal deposition that may result in fewer adverse events and make it easier to use. The objective of this study was to compare the year-long safety of flunisolide HFA (daily dosage 340 microg) with that of CFC beclomethasone dipropionate (BDP) (daily dosage 336 microg) and cromolyn sodium (daily dosage 6,400 microg) in children 4-11 years old with mild-to-moderate asthma. The effects of these drugs on linear growth and growth velocity were also compared. The study was a 1-year open-label, parallel-group trial. Changes in physical examinations (including growth), adverse events, vital signs, electrocardiograms, cosyntropin stimulation tests, mouth and throat cultures for Candida albicans, and laboratory findings were analyzed. Patients 4-5 years old received flunisolide HFA only. In total, 235 children were evaluated (152 receiving flunisolide HFA, 39 BDP, and 44 cromolyn). The incidence of adverse events was comparable among treatment groups; most were mild or moderate and considered unrelated to treatment. Among patients 6-11 years old, mean changes from baseline height at week 52 were 6.2 cm for the flunisolide HFA and cromolyn groups and 5.1 cm for the BDP group. Thus growth in children receiving flunisolide HFA was unaffected by 1 year of treatment. Changes from baseline in other parameters, including response to cosyntropin stimulation, were insignificant and similar among the 3 treatment groups. At the dosages studied, and following 1 year of treatment, flunisolide HFA with its small particle size and built-in spacer is safe and well tolerated in children 4-11 years old. There are no adverse effects associated with hypothalamic pituitary axis (HPA) function of flunisolide HFA, including linear growth in children 6-11 years old when compared with BDP and cromolyn sodium.

SUMMARY. Airway nitric oxide (NO) production can be measured by chemiluminescence analyzer in children able to perform a single low exhalation. The aim of the present study was to evaluate whether exhaled NO (e-NO) peaks (first part of the exhalation) were as useful as e-NO plateaus (last part of the exhalation) in evaluating e-NO production in asthmatic children and in detecting responses to inhaled steroid treatment. E-NO peak, plateau, and rate of production values were measured in 100 atopic asthmatic children using a chemiluminescence analyser. Thirty-seven patients (mean age, 11.1 +/- 0.7 years) were receiving inhaled steroids (flunisolide, 0.8-1 mg daily) or beclomethasone (0.2-0.4 mg daily), while the remaining 63 (mean age, 12.0 +/- 0.4 yrs) were-steroid naive and treated only with inhaled beta(2)-agonists on an as-needed basis. Fifteen out of the 63 steroid-naive patients were reevaluated after a short course (3 weeks) of inhaled corticosteroid treatment (flunisolide, 0.8-1 mg daily, or beclomethasone, 0.2-0.4 mg daily). Regardless of the type of data analysis (peak, plateau, or rate of production), the e-NO values of the steroid-naive patients were significantly higher than those of inhaled steroid-treated patients (P < 0.01, each comparison). Similarly, in the subgroup of steroid-naive patients, the three methods were able to detect a decrease in e-NO levels by inhaled steroid therapy (P < 0.001, each comparison). Plotting the difference between e-NO peak and e-NO plateau values against their average, the peak e-NO concentrations were higher than e-NO plateau values. This difference was independent of the absolute e-NO concentration. The results of the two types of data analysis seems to agree more closely in steroid-naive patients than in steroid treated patients, or in the subgroup of steroid-naive patients who received a short course treatment with inhaled steroids. In steroid-treated subjects, the differences were up to five times higher for peak than plateau e-NO values. These data suggest that both e-NO plateau and e-NO peak values are useful in detecting airway NO production in atopic asthmatic children, but they cannot be used interchangeably. Because of possible nasal contamination in e-NO peak measurement, we prefer e-NO plateau levels for evaluating lower airway e-NO production., (Copyright 2001 Wiley-Liss, Inc.)

Inhaled corticosteroids are first-choice drugs in the treatment of chronic asthma. A metered dose inhaler (MDI) equipped with a spacer device is easier to use for patients with a poor inhalatory technique; it favors a reduction in the size of the particles delivered to the patient and thus a reduction in the incidence of local and systemic side effects of these drugs. The aim of this study was to determine the particle characteristics of fluticasone propionate (FP), flunisolide (FLUN), and beclomethasone dipropionate (BDP), each administered at a rate of 250 micrograms per puff and at inspiratory flow rates of 30 and 60 L/min in vitro, to estimate the particle characteristics of these drugs aspirated via an MDI alone and via a large-volume holding chamber (Volumatic). Compared with the MDI alone, at 30 L/min, the Volumatic (Glaxo Wellcome, Ware, UK) significantly reduced the mass median aerodynamic diameter (MMAD) and increased the fine particles (< 5 microns and < 2 microns) generated by all three drugs. At 60 L/min, the MMAD increased and the generation of fine particles decreased with both devices. These data suggest that the inspiratory flow applied by means of the devices may be a determinant for the deposition of the drug in the lower airways in that by increasing the inspiratory flow, the MMAD increases and the percentage of fine particles decreases, probably because of the reaggregation favored by the higher flows.

Asthma is a chronic inflammatory disorder of the airways that affects 10 to 17.5 million people and leads to more than $5 billion in treatment costs in the Unites States annually. This retrospective study is an initial step in understanding the beneficial economic outcomes of inhaled corticosteroid therapy by determining whether differences exist in healthcare utilization expenditures for three inhaled corticosteroids available for use in the United States: (1) beclomethasone dipropionate (Vanceril/Schering and Beclovent/Allan & Hanburys); (2) flunisolide (Aerobid/Forest); and (3) and triamcinolone acetonide (Azmacort/Rhône-Poulenc Rorer). This study was based on an analysis of 4,441 patients with at least one pharmaceutical claim for one of the study drugs, using inpatient, outpatient, and prescription drug claims data obtained from The MEDSTAT Group's MarketScan database for calendar years 1990 through 1993. We tested a null hypothesis for no differences in total asthma treatment costs, when drugs were excluded, using multivariate linear regression modeling controlling for patient demographic and clinical characteristics that might affect the study outcome. We found that, after excluding study drug payments and controlling for other contributing factors, total asthma healthcare expenditures to triamcinolone acetonide (Azmacort) users were higher than those for beclomethasone dipropionate (Vanceril and Beclovent) and flunisolide (Aerobid) users. When study drug costs were included in the expenditure measure, both triamcinolone acetonide (Azmacort) and flunisolide (Aerobid) users had higher expenditures than did beclomethasone dipropionate (Vanceril and Beclovent) users. No significant differences in expenditures were detected between Vanceril and Beclovent patients, a finding consistent with the fact that these drugs are the same type of inhaled corticosteroid. Other factors contributing to differences in total asthma healthcare costs included patient age, patterns of switching among and continuing with study drugs, prestudy asthma utilization or drug proxy severity, and comorbidities of precipitating illnesses.

Background: Comparisons of relative potency for the three inhaled corticosteroids in the United States are limited to assessment of skin blanching., Objective: Development of a method for comparing relative potencies of inhaled corticosteroids for topical effect on human airway and systemic effect., Methods: With use of partial suppression of immediate response to inhaled allergen and 24-hour urinary free cortisol output, three-point dose-response curves were constructed for beclomethasone dipropionate (50 micrograms/puff), triamcinolone acetonide (100 micrograms/puff), and flunisolide (250 micrograms/puff). A randomized, parallel, single-blind study design was used. Dosing began with one puff four times a day for flunisolide and two puffs four times a day for the others. Doses were doubled after 1 week and again after a second week., Results: Twenty-five patients completed the study. Dose-response relationships were shown for each inhaled corticosteroid for both topical and systemic effect. Dose-response curves for the three preparations were similar when response was plotted against delivered dose in micrograms., Conclusion: Within the limits of the assays, relative potencies of the three preparations appeared to be approximately equivalent for both topical and systemic effect when dose was expressed in micrograms. Relative potency per puff is therefore approximately proportional to the dose delivered. This method has potential for evaluation of relative potency of newer inhaled corticosteroids and the relative advantage of alternative delivery systems.

Inhalation corticosteroids (beclometasone dipropionate, budesonide, flunisolide) proved effective against bronchial asthma (BA) and safe as they induce no severe systemic side effects. Of these three drugs side effects arise most frequently in administration of beclometasone dipropionate, least frequently of flunisolide. These inhalation corticosteroids are indicated both in non-steroid-dependent and steroid-dependent BA to reduce the dose of oral steroids or, if possible, for their complete discontinuation. Flunisolide is the most potent and effective of all inhalation corticosteroids used in current practice.

A randomized, double-blind, crossover study of a new formulation of flunisolide nasal spray was performed comparing its acceptability and safety to that of aqueous beclomethasone dipropionate nasal spray. The single center study enrolled 100 adults with allergic rhinitis; of these, 99 provided valid data for analysis. Each study participant received a single dose of each study drug and assessed nasal burning/stinging and other adverse effects. Analysis of patient evaluations revealed no significant differences in nasal or pharyngeal irritation (P > .05); however, mild aftertaste was present with use of flunisolide (P = .059) compared with beclomethasone dipropionate. There was similar acceptance of both study drugs.

After a 2-week run-in period 23 atopics and non-atopics with perennial rhinitis were treated with intranasally nebulized aqueous flunisolide or aqueous beclomethasone dipropionate in a randomized, double-blind cross-over study, each treatment period being 4 weeks. Before and after each treatment period daily rhinitis symptoms were recorded, and additional determination of nasal airway resistance was performed by posterior rhinomanometry. No statistically significant difference between drugs was observed for any effect parameter recorded, and furthermore no difference in patient preference for either drug was found. It is concluded that both steroids are effective for the improvement of nasal airway in patients with perennial, atopic and non-atopic rhinitis.

In order to evaluate the effects of flunisolide and beclomethasone dipropionate nasal sprays on seasonal allergic rhinitis, 45 patients were included in an open parallel comparative trial. The study design was open because of the different dosage schedules for the two preparations. Strict criteria were set up for patient selection, and all patients were carefully examined and assessed before and after the 4-week trial period. Throughout the whole treatment each patient kept a detailed daily record. A substantial or complete control of symptoms was achieved in 18 of the 21 patients on flunisolide and in 20 of the 22 on beclomethasone dipropionate. No serious side effects were observed. Thus it can be concluded that both test drugs are effective and well tolerated in the treatment of seasonal allergic rhinitis.

Although three effective topical treatments for allergic rhinitis are available, little information to assist the clinician in choosing among them has been reported. Therefore, we conducted a randomized clinical trial to compare beclomethasone nasal solution, flunisolide, and cromolyn with placebo in 120 patients with hay fever during the ragweed season of 1984. We found that all three agents were superior to placebo (P less than 0.001) and that the glucocorticoids were more effective than cromolyn (P less than 0.001). Surprisingly, we also found that these intranasal treatments considerably reduced the symptoms of seasonal asthma. Further study of this therapeutic advantage is needed.

Sixty-nine patients were entered into a randomized, single-blind, parallel group study. Patients had a history of moderate to severe seasonal allergic rhinitis and all patients commenced treatment before the start of the pollen season. Treatment was with either flunisolide or beclomethasone dipropionate, both being administered as 2 sprays to each nostril twice daily for 7 weeks. Assessments of signs and symptoms of hay fever were made at admission and after 3 and 7-weeks' treatment. Patients were asked to keep a daily record of the severity of their symptoms. The overall effect of treatment was evaluated by both the patient and physician. Side-effects were elicited by indirect questioning. Sixty patients completed the study. Four patients from the flunisolide group and 2 from the beclomethasone group were lost to follow-up. Two further patients withdrew from the flunisolide group and 1 from the beclomethasone group. Analysis of results did not reveal any statistically significant differences between the treatments. Minor side-effects were reported by 1 patient from each treatment group. Both treatments proved to be effective in the treatment of hay fever and were equally well tolerated.

Twenty patients with asthma controlled by oral inhalations of beclomethasone dipropionate (400 micrograms/day) were treated for concurrent rhinitis by the addition of flunisolide nasal solution (300 micrograms/day) and its placebo for three weeks each in a randomized, double-blind, crossover trial. Flunisolide produced a statistically significant benefit for each symptom parameter: sneezing (p = 0.013), runny nose (p = 0.027), stuffy nose (p = 0.005 and over-all severity (p = 0.005). More concomitant rhinitis medication was used during placebo treatment (p = 0.069). Seventy percent of the patients had "total" or "substantial" control of nasal symptoms with flunisolide vs. 45% with placebo (p less than 0.01). Eighty percent felt that flunisolide was either the only active drug or the more active (p less than 0.01). Three morning plasma cortisol determinations during the last week of each treatment period showed no drug-related effect. No nasal cultures were positive for Candida; the incidence of positive pharyngeal; cultures did not vary significantly. Adverse reactions consisted primarily of nasal burning and stinging; none was serious. In this group of twenty patients using inhalations of beclomethasone dipropionate for asthma, accompanying perennial rhinitis was substantially controlled by 300 micrograms of flunisolide nasal solution per day without significant additive effect on plasma cortisol levels or the incidence of overgrowth of Candida.

A prospective, randomized study comparing the effectiveness of two nasal steroid sprays, flunisolide and beclomethasone dipropionate, in the treatment of nasal obstruction associated with allergic or vasomotor rhinitis has been conducted at New York University Medical Center-Bellevue Hospital. All patients underwent routine history and physical examinations and a modified radioallergosorbent test. Paranasal sinus films were used to exclude patients with sinusitis. The Rhinotest microprocessor rhinomanometer was used to quantify pretreatment and posttreatment total nasal air flow and resistance during a period of 2 months. These findings were assessed in conjunction with the patients' subjective complaints. Results demonstrated that anterior rhinomanometric assessment of the nasal airway during inhalant therapy correlated well with the patients' own subjective impressions of nasal air flow. Both steroid inhalants were effective; however, flunisolide provided for earlier and more substantial symptomatic relief. Beclomethasone dipropionate had milder side effects.

Because the simultaneous use of more than one form of topical corticosteroid involves higher cumulative doses and, therefore, more potential for absorption, this study was concerned primarily with effect on adrenal function. Seventeen adults whose asthma symptoms had been stable for at least three months on 100-400 microgram/day of beclomethasone dipropionate aerosol received flunisolide intranasal solution (200 microgram/day) combined with its intrabronchial form (1 mg/day) or with beclomethasone dipropionate bronchial aerosol (400 microgram/day). Utilizing a physician-blind, crossover design, each medication combination was administered for one month. Patient and physician evaluations revealed no significant differences in efficacy, adverse effects (complaints) or effect on adrenal function between the two combinations. Thus, the addition of intranasal flunisolide to intrabronchial flunisolide or beclomethasone did not appear to result in significant systemic absorption of corticosteroid above that which might have occurred as a result of the bronchial inhalation of corticosteroid medication alone during the pretrial period.

Ninety-nine patients, who had never previously taken inhaled steroids were enrolled in a randomized, single-blind, parallel study, the aim of which was to compare the efficacy and safety of flunisolide inhalation, 500 mcg twice daily, with beclomethasone dipropionate inhaler 100 mcg four times daily for the treatment of chronic asthma. The treatment period was for 6 weeks. The patients were examined clinically at entry, week 3 and week 6 and both treatment groups showed a marked improvement in almost all parameters during the course of the study. Flunisolide was statistically significantly superior to beclomethasone dipropionate for wheezing at week 6, coughing at week 6 and chest tightness at weeks 3 and 6. The number of asthma attacks per day decreased significantly more with flunisolide treatment than with beclomethasone dipropionate. The over-all evaluation of efficacy by both doctors and patients also showed flunisolide to be superior to beclomethasone dipropionate. In several other parameters there was a trend shown favouring flunisolide, and beclomethasone dipropionate did not show a superiority over flunisolide in any efficacy parameter. Both drugs were well-tolerated, with unpleasant taste being the most frequent complaint in the flunisolide group. No patient in either group withdrew from the study because of adverse events. In this study, flunisolide inhaler was more effective than beclomethasone dipropionate inhaler for the treatment of chronic asthma exhibited by patients who had never been treated with inhaled steroids.

Forty-seven informed out-patients with the diagnosis seasonal rhinitis of at least two years' duration took part in a controlled single blind, double observer, parallel four-center study for the purpose to compare efficacy and tolerance of two local corticosteroid nasal sprays: flunisolide 25 micrograms/dose and beclomethasone 50 micrograms/dose. The patients received for four weeks one of the two treatments; flunisolide 50 micrograms in each nostril twice daily or beclomethasone dipropionate 50 micrograms in each nostril four times daily. The study was conducted under the Declaration of Helsinki. Patients were assessed on admission and after two and four weeks. All patients completed the trial. The results showed that both drugs are highly effective in controlling nasal rhinitis symptoms, 21 out of 24 flunisolide treated patients and 21 out of 23 beclomethasone treated stated good to total control after four weeks' treatment during the pollen season. No statistical difference between the two could be discovered in any of the parameters measured. The only side effect recorded was mild transistory stinging in connection with application of the two different sprays. This occurred in a few patients in both groups. The results from the study indicate that the new corticosteroid flunisolide in a dose of 100 micrograms X 2 is comparable to beclomethasone dipropionate 100 micrograms X 4 concerning efficacy and tolerance in prophylactic treatment of seasonal rhinitis.

An open, parallel comparison of flunisolide and beclomethasone dipropionate nasal sprays is described. Sixty patients entered the study of whom fifty-six completed the full 4 weeks' therapy. The dosage of flunisolide was two actuations (25 micrograms/actuation) into each nostril twice a day (total 200 micrograms). The dosage of beclomethasone dipropionate was one actuation (50 micrograms) in each nostril four times a day (total 400 micrograms). Both drugs produced statistically significant improvements compared with admission values in sneezing, stuffiness, runny nose, nose blowing and post-nasal drip. Both drug significantly decreased the interference by symptoms with routine life and sleep. At the end of the trial both treatment groups showed total or good control of symptoms in the majority of patients. No statistically significant difference was shown between the effects of the two drugs. Side-effects did not cause withdrawal from the trial in any patient and were mostly confined to minor headache and nose and throat complaints. In neither treatment group was there any evidence of adrenal suppression or growths of Candida from nasal swabs.

Human nasal cilia were perfused with aqueous solutions of two corticosteroid aerosols, beclomethasone dipropionate (BPD) and flunisolide, with the main preservative of flunisolide, propylene glycol, and with placebo. The concentration used were BPD 0.1 mg/ml, 0.05 mg/ml, 0.005 mg/ml and 0.0005 mg/ml, flunisolide 0.25 mg/ml, 0.05 mg/ml, 0.025 mg/ml and 0.00025 mg/ml, and propylene glycol 20 mg/ml and 200 mg/ml. A dose-related decrease in ciliary beating frequency (CBF) was seen after perfusion with both BDP and flunisolide as well as propylene glycol. The decrease in CBF following perfusion with propylene glycol was partially reversible upon re-perfusion with medium alone, whereas the decrease seen after BDP and flunisolide was irreversible. Although previous studies have shown no adverse effect on the mucous membrane except for the areas hit by the impact of the sprays, our results suggest that caution should be taken when the dose and/or the length of treatment is considered, and that the effect of administration of these drugs on CBF in vivo needs to be investigated.

Steroid-dependent, chronic asthmatic patients with severe rhinitis or nasal polyps are often candidates for treatment with intranasal topical corticosteroids, such as flunisolide. The possibility of additive adrenal suppression, when flunisolide, beclomethasone and prednisone are given together, has not previously been studied. The need to asses the risk is suggested by reports of additive adrenal suppression when aerosol and oral steroids are used together to treat asthma, and by the demonstrably higher systemic availability of aerosol steroid given intranasally rather than via the lung. We performed a double-blind, placebo-controlled crossover assessment of the efficacy and safety of 3 weeks of intranasal flunisolide spray treatment (300 micrograms/day) in nineteen steroid-dependent chronic asthmatic subjects, who also had nasal polyps or severe rhinitis. During the study, their doses of prednisone and beclomethasone, used for asthma, were held stable. Morning serum cortisol levels and 24-hr urinary-free cortisol excretion were essentially the same after the placebo, and the flunisolide treatments. The intranasal flunisolide improved their nasal symptoms significantly (P less than 0.05). Local complications were negligible. Given conventional steroid doses like those used in this study, there appears to be no important risk to endogenous adrenal function from combining the use of intranasal, flunisolide spray with administration of other steroids by other routes, when this is deemed clinically necessary. If higher doses are used, the possibility of some additive adrenal suppressive effect cannot be excluded.

Flunisolide nasal spray has been compared with placebo and with beclomethasone dipropionate in the treatment of perennial rhinitis. A double-blind, cross-over study in 26 patients comparing intranasal flunisolide (total dose 300 microgram/day) with placebo showed superiority of the active preparation in the relief of sneezing, stuffiness and runny nose. Physicians and patients significantly preferred the active spray. Side-effects on both sprays were mainly confined to transient nasal irritation. Plasma cortisol levels did not change significantly during the trial. A single-blind, cross-over study in 34 patients comparing flunisolide and beclomethasone dipropionate showed relief of sneezing, stuffiness, runny nose and nose-blowing with both medications. There were no differences between the effects of the two preparations. Physicians and patients favoured the drugs equally. Side-effects were minor.

Sixty-seven asthmatic individuals treated with either beclomethasone diproprionate or flunisolide were sequentially evaluated for up to 32 months to determine the incidence of oropharyngeal candidiasis as well as laboratory parameters which might be predictive of this complication. Throat cultures and measurements of Candida antibody by immunodiffusion and radioimmunoassay were performed and compared over time and treatment groups. Unlike other studies, pre-treatment Candida precipitins did not predict increased risk for clinical thrush nor did quantitative determinations of Candida antibody. Those patients with positive cultures pre-trial, however, had a significantly higher incidence of clinical thrush than those with negative cultures (P less than 0.01). No significant changes occurred over time or between drugs for any of the parameters. Symptomatic thrush, however, was slightly more common in those patients treated with beclomethasone.