Beclomethasone Diproprionate Research Articles

The buck stops with us

In this volume of The Journal, Bickel et al compare 2 time epochs bracketing a change made by a public insurance payer that eliminated coverage of beclomethasone diproprionate, or BDP, by metered-dose inhaler (MDI) in favor of mometasone furoate (MF), available as MDI or dry powder inhaler (DPI).

Beclomethasone dipropionate and formoterol fumarate synergistically interact in hyperresponsive medium bronchi and small airways

BackgroundCorticosteroids increase the expression of β2-adrenoceptors (β2-ARs) and protect them against down-regulation. Conversely, β2-AR agonists improve the anti-inflammatory action of corticosteroids. Nevertheless, it is still uncertain whether adding a long-acting β2-AR agonist (LABA) to an inhaled corticosteroid (ICS) results in an additive effect, or there is true synergy.Therefore, the aim of this study was to pharmacologically characterize the interaction between the ICS beclomethasone diproprionate (BDP) and the LABA formoterol fumarate (FF) in a validated human ex vivo model of bronchial asthma.MethodsHuman medium and small airways were stimulated by histamine and treated with different concentrations of BDP and FF, administered alone and in combination at concentration-ratio reproducing ex vivo that of the currently available fixed-dose combination (FDC; BDP/FF 100:6 combination-ratio). Experiments were performed in non-sensitized (NS) and passively sensitized (PS) airways. The pharmacological interaction was assessed by using Bliss Independence and Unified Theory equations.ResultsBDP/FF synergistically increased the overall bronchorelaxation in NS and PS airways (+ 15.15% ± 4.02%; P < 0.05 vs. additive effect). At low-to-medium concentrations the synergistic interaction was greater in PS than in NS bronchioles (+ 16.68% ± 3.02% and + 7.27% ± 3.05%, respectively). In PS small airways a very strong synergistic interaction (Combination Index: 0.08; + 20.04% ± 2.18% vs. additive effect) was detected for the total concentrations of BDP/FF combination corresponding to 10.6 ng/ml.ConclusionBDP/FF combination synergistically relaxed human bronchi; the extent of such an interaction was very strong at low-to-medium concentrations in PS small airways.Trial registrationNot applicable.

The consequences of exposure to mixtures of chemicals: Something from ‘nothing’ and ‘a lot from a little’ when fish are exposed to steroid hormones

Ill-defined, multi-component mixtures of steroidal pharmaceuticals are present in the aquatic environment. Fish are extremely sensitive to some of these steroids. It is important to know how fish respond to these mixtures, and from that knowledge develop methodology that enables accurate prediction of those responses. To provide some of the data required to reach this objective, pairs of fish were first exposed to five different synthetic steroidal pharmaceuticals (one estrogen, EE2; one androgen, trenbolone; one glucocorticoid, beclomethasone dipropionate; and two progestogens, desogestrel and levonorgestrel) and concentration-response data on egg production obtained. Based on those concentration-response relationships, a five component mixture was designed and tested twice. Very similar effects were observed in the two experiments. The mixture inhibited egg production in an additive manner predicted better by the model of Independent Action than that of Concentration Addition. Our data provide a reference case for independent action in an in vivo model. A significant combined effect was observed when each steroidal pharmaceutical in the mixture was present at a concentration which on its own would produce no statistically significant effect (something from ‘nothing’). Further, when each component was present in the mixture at a concentration expected to inhibit egg production by between 18% (Beclomethasone diproprionate) and 40% (trenbolone), this mixture almost completely inhibited egg production: a phenomenon we term ‘a lot from a little’. The results from this proof-of-principle study suggest that multiple steroids present in the aquatic environment can be analysed for their potential combined environmental risk.

Differences in physical chemistry and dissolution rate of solid particle aerosols from solution pressurised inhalers

Solution composition alters the dynamics of beclomethasone diproprionate (BDP) particle formation from droplets emitted by pressurised metered dose inhalers (pMDIs). The hypothesis that differences in inhaler solutions result in different solid particle physical chemistry was tested using a suite of complementary calorimetric techniques. The atomisation of BDP-ethanol solutions from commercial HFA-pMDI produced aerodynamically-equivalent solid particle aerosols. However, differences in particle physico-chemistry (morphology and solvate/clathrate formation) were detected by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and supported by hot stage microscopy (HSM). Increasing the ethanol content of the formulation from 8 to 12% (w/w), which retards the evaporation of propellant and slows the increase in droplet surface viscosity, enhanced the likelihood of particles drying with a smooth surface. The dissolution rate of BDP from the 12% (w/w) ethanol formulation-derived particles (63% dissolved over 120 min) was reduced compared to the 8% (w/w) ethanol formulation-derived particles (86% dissolved over 120 min). The addition of 0.01% (w/w) formoterol fumarate or 1.3% (w/w) glycerol to the inhaler solution modified the particles and reduced the BDP dissolution rate further to 34% and 16% dissolved in 120 min, respectively. These data provide evidence that therapeutic aerosols from apparently similar inhaler products, including those with similar aerodynamic performance, may behave non-equivalently after deposition in the lungs.

Adherence rate to beclomethasone dipropionate and the level of asthma control

There are only a few studies assessing the relationship between adherence rate to ICS, as assessed by electronic monitoring, and the level of asthma control in childhood. The present study was carried out to examine the relationship between adherence to beclomethasone diproprionate (BDP) as well as other factors related to poor asthma control. In this prospective cohort study, 102 steroid naïve randomly selected subjects with persistent asthma, aged 5-14 years were prescribed 500-750μg daily of BDP-CFC and followed during one year. Adherence to BDP was measured electronically in the 4th, 8th and 12th months of study. The level of asthma control was classified as either controlled or uncontrolled instead of the current three categories recommended by the Global Initiative for Asthma (GINA). Mean adherence rate was higher in patients with controlled asthma during follow-up, but went down from 60.4% in the 4th month to 49.8% in the 12th month (p=0.038). Conversely, among patients with uncontrolled asthma, the mean adherence rate decreased from 43.8% to 31.2% (p=0.001). Multivariate analysis showed that the level of asthma control was independently associated to the adherence rate in all follow-up visits (p-values equal or lower than 0.005). The level of asthma control was directly proportional to adherence rate. Our results suggest that a BDP daily dose by 300μg seems to be enough to attain control over mild and moderate persistent asthma, including exercise induced asthma.

A pediatric asthma management program in a low‐income setting resulting in reduced use of health service for acute asthma

The effectiveness of pediatric asthma management programs in reducing health services utilization during exacerbations in developing countries is not widely studied. This study was carried out to assess the effectiveness of an asthma management program to reduce the overall health services utilization by acute asthma in children and adolescents. In this historical population-based real-life cohort study, we selected 582 patients with asthma aged 4-15 living in deprived areas in the town of Itabira, Brazil, of which 470 cases were assisted by the asthma management program and 112 were controls. The end point was the first physician-diagnosed asthma exacerbation occurring after study enrollment and within 12 months after admission. All 470 cases received a written plan about exacerbation self-management, including the use of inhaled albuterol at home. Three hundred and seventeen out of 470 cases (67.4%) were also treated with beclomethasone diproprionate (BDP). Both groups were comparable regarding gender, age group, and place of residence. At the end of the study, only 5% of cases vs 34% of controls did seek health services because of acute asthma (P < 0.01). Statistical difference also remained when comparing the 112 controls with the 153 cases not treated with com BDP (Hazard Ratio = 0.04, 95% CI, 0.01-0.14, P < 0.01). Results have demonstrated the effectiveness of the pediatric asthma management program in reducing dependence on the health services for acute asthma. Effectiveness was also observed in subjects with no use of BDP.

O impacto do tratamento fonoaudiológico no controle da asma e da rinite alérgica em crianças e adolescentes respiradores orais

OBJETIVO: Detectar o impacto do tratamento fonoaudiologico no controle da asma e da rinite alergica em criancas e adolescentes respiradores orais. METODOS: Trata-se de um estudo quase-experimental; foram randomizados 24 pacientes com asma, rinite alergica e respiracao oral, idade de 6 a 15 anos. Todos os pacientes usavam dipropionato beclometasona inalacao oral. No momento em que aceitaram participar da pesquisa, a inalacao oral foi substituida pela inalacao exclusivamente nasal na inspiracao e, apos 1 mes, associou-se ao tratamento fonoaudiologico em metade dos pacientes. Esses receberam 16 sessoes de tratamento fonoaudiologico em 8 semanas, alem do dipropionato de beclometasona inalacao exclusivamente nasal (grupo DBF). O grupo de comparacao recebeu somente dipropionato beclometasona inalacao exclusivamente nasal (grupo DBI). Os dois grupos foram avaliados em cinco tempos. Utilizou-se o escore clinico da rinite alergica, da asma, o protocolo de avaliacao miofuncional orofacial adaptado de Marchesan (2003), a observacao dos responsaveis, dados de espirometria, de pico de fluxo inspiratorio e de pico de fluxo expiratorio. RESULTADOS: Houve melhora significativa do grupo DBF: escores clinicos da asma no tempo 5 (p = 0,046); valores do pico de fluxo inspiratorio no tempo 4 (p = 0,030); pico de fluxo expiratorio no tempo 3 (p = 0,008); modo respiratorio e postura de labios (p = 0,000) a partir do tempo 3; observacao dos responsaveis, no tempo 2, tempo 4 e tempo 5 (p = 0,010; p = 0,027; p = 0,030). CONCLUSOES: O tratamento fonoaudiologico associado ao dipropionato beclometasona por inalacao exclusivamente nasal promoveu um controle clinico e funcional mais precoce e duradouro da asma, da rinite alergica e da respiracao oral entre os grupos estudados.

The impact of speech therapy on asthma and allergic rhinitis control in mouth breathing children and adolescents

To determine the impact of speech therapy on asthma and allergic rhinitis control in mouth breathing children and adolescents. This was a quasi-experimental randomized study of 24 mouth breathing patients with asthma and allergic rhinitis, aged from 6 to 15 years. All patients were taking beclomethasone diproprionate through oral inhalation at the start of the study. At enrollment on the study, oral inhalation was substituted with exclusively nasal inhalation and 1 month later half of the patients began speech therapy. They attended 16 speech therapy sessions in 8 weeks and continued taking beclomethasone dipropionate through exclusively nasal inhalation (BDT group). The comparison group received only beclomethasone diproprionate through exclusively nasal inhalation (BDI group). Both groups were assessed five times. Clinical scores were calculated for allergic rhinitis and asthma, an adapted version of the Marchesan orofacial myofunctional assessment protocol was applied, and parents/guardians' observations were recorded, in addition to spirometry measurements of peak inspiratory and peak expiratory flow. There were significant improvements in the BDT group: clinical asthma score at T5 (p = 0.046); peak inspiratory flow at T4 (p = 0.030); peak expiratory flow at T3 (p = 0.008); breathing mode and lip position (p = 0.000) from T3 onwards; and parents/guardians' observations at T2, T4, and T5 (p = 0.010; p = 0.027; p = 0.030). Speech therapy in combination with beclomethasone diproprionate through exclusively nasal inhalation resulted in earlier and longer-lasting clinical and functional control of asthma, allergic rhinitis, and mouth breathing than was achieved in the group that only took beclomethasone diproprionate.

Oral Beclomethasone Dipropionate in Pediatric Active Ulcerative Colitis: A Comparison Trial With Mesalazine

The objective of the study was to evaluate the clinical efficacy of oral beclomethasone diproprionate (BDP) in inducing clinical and endoscopic remission in children with mild to moderate active ulcerative colitis (UC). Thirty patients with active UC (pancolitis or left-sided colitis) were enrolled in an open-labeled, randomized, head-to-head study. Group 1 (n = 15) received oral BDP (5 mg/day) for 8 weeks, followed by maintenance therapy with oral mesalazine, 5-aminosalycilate (5-ASA); group 2 (n = 15) received oral 5-ASA (80 mg . kg . day). Assessments were carried out (at 4, 8, and 12 weeks) for clinical scores and for endoscopy (at 12 weeks), together with a final clinical assessment after 1 year follow-up. Patients treated with BDP showed a significant reduced clinical activity within 4 weeks (P < 0.001 vs pretreatment values) with 80% achieving clinical remission compared with 33% treated with only 5-ASA (P < 0.025). A significant reduction in clinical activity was achieved by 5-ASA after 8 weeks. Comparing clinical activity between BDP and 5-ASA, the former did significantly better at 8 (P < 0.003) and at 12 weeks (P < 0.015). In 73% of BDP-treated patients colonoscopy showed remission compared with 27% of 5-ASA (P < 0.025). Both treatments led to better scores compared with pretreatment values (P < 0.001, both). Erythrocyte sedimentation rate was significantly reduced (P < 0.025 or less) with both treatments, whereas C-reactive protein dropped significantly (P < 0.02) only in BDP. Oral BDP was well tolerated and acts significantly faster and more effectively than 5-ASA in inducing clinical remission and endoscopic improvement in pediatric mild-to-moderate UC.

Optimisation of spray-drying process variables for dry powder inhalation (DPI) formulations of corticosteroid/cyclodextrin inclusion complexes

This study aims to develop and characterise a beclomethasone diproprionate:γ-cyclodextrin (BDP:γ-CYD) complex and to optimise the variables on the spray-drying process, in order to obtain a powder with the most suitable characteristics for lung delivery. The spray-dried powder – in a mass ratio of 2:5 (BDP:γ-CYD) – was physically mixed with three carriers of different particle sizes and in different ratios. Particle-size distribution, shape and morphology, moisture content, and uniformity in BDP content of formulations were studied. In vitro aerolisation behaviour of the formulations was evaluated using the Rotahaler, and the performance was characterised based on the uniformity of emitted dose and aerodynamic particle-size distribution (respirable fraction (RF), as a percentage of nominal dose (RFN) and emitted dose (RFE)). The most suitable conditions for the preparation of BDP:γ-CYD complexes were obtained with the solution flow of 5 ml/min, T in of 70 °C and T out of 50 °C. Statistically significant differences in the aerodynamic performances were obtained for formulations containing BDP:γ-CYD complexes prepared using different solution flows and different T in ( p < 0.05). RFN and RFE vary in direct proportion with T in, while an inverse relationship was observed for the solution flow. A direct correlation between the RFE and the T out was identified. Performance of the formulations was compared with an established commercial product (Beclotaide Rotacaps 100 μg) with improved performance of RF: formulations with respitose carrier attained RFN and RFE twofold greater, and formulations based on 63–90 μm fraction lactose and trehalose achieved a threefold improvement; also, all formulations showed that the percentage of dose of BDP deposited in the “oropharynx” compartment was reduced to half.

Rapid Effects Of Inhaled Beclomethasone On Hyperpnea-Induced Bronchoconstriction And Mast Cell Mediator Release In Athletes

Exercise provokes bronchoconstriction in most asthmatics. Asymptomatic elite athletes also report exercise-induced bronchoconstriction (EIB). Although the bronchial response following exercise is similar in these two groups, the underlying mechanism responsible for the transient airway narrowing might differ. Whilst an inflammatory process is involved in asthmatics, non-inflammatory mediated vascular engorgement and mucosal oedema may mediate EIB in athletes. PURPOSE: To determine if a single dose of inhaled beclomethasone diproprionate (BDP), through its acute vasoconstrictive and antioedematous properties, has a protective effect on EIB in athletes. METHODS: 6 trained athletes with EIB and 8 untrained mild asthmatics performed two eucapnic voluntary hyperpnea (EVH) tests (a surrogate for exercise) at 41/2h interval on the same day, the first 0.25h after placebo, and the second 3h after BDP (1500jj.g). Pulmonary function was recorded and urine was collected 60min before and for 90min after EVH for measurements by immunoassay of the mast cell marker 9?,11?-prostaglandin (PG)F2. RESULTS: BDP provided significant protection against post-EVH bronchoconstriction in both groups (P=0.0001): mean FEV1 fall (±SEM) in athletes 21.5±4.9% after placebo vs 14.3±2.8% after BDP; in untrained asthmatics 23.3±3.7% after placebo vs 14.0±3.2% after BDP. Urinary 9α, 11β-PGF2 increased post-EVH after placebo only (P=0.0462) with no significant difference between groups (Fig. 1).Fig 1: Mean ± SEM urinary excretion of 9α, 11β-PGF2 in asthmatics (o) and athletes (δ) at baseline and during the 90min period after EVH after administration of placebo (closed black symbols) or BDP (open grey symbols).CONCLUSIONS: A single dose of BDP has an acute protective effect on the bronchial response to hyperpnea in both untrained asthmatics and trained athletes with EIB. This effect seems at least partly mediated by an inhibition of the release of mast cell mediators.

Beclomethasone dipropionate versus mesalazine in distal ulcerative colitis: A multicenter, randomized, double-blind study

Background Topical beclomethasone diproprionate has shown efficacy in ulcerative colitis. Aim To assess, in a multicenter, randomized, double-blind study, the tolerability and safety of topical beclomethasone diproprionate (3 mg) enema and foam versus mesalazine (2 g) enema and foam in mild–moderate distal ulcerative colitis. Patients In 15 referral gastrointestinal units, 99 patients with distal ulcerative colitis were enrolled. This number was lower than planned according to the statistical analysis, due to a low recruitment rate. Methods Patients were randomly assigned to random preparations (beclomethasone diproprionate enema, beclomethasone diproprionate foam, mesalazine enema, mesalazine foam) once nightly for 8 weeks, with clinical and endoscopical assessment (Disease Activity Index score) at baseline ( T0), 4 ( T4) and 8 weeks ( T8). Results were expressed as median and range (95% confidence interval). The efficacy was assessed by comparing the Disease Activity Index value at T4 and T8 by using the Student's t-test or the Wilcoxon–Mann–Whitney test. Results Efficacy was comparable in the beclomethasone diproprionate or mesalazine groups at both T4 and T8 (response at T4: beclomethasone diproprionate 78% [95% confidence interval 0.6–0.8] versus mesalazine 79% [95% confidence interval 0.6–0.8]; T8: beclomethasone diproprionate 84% [95% confidence interval 0.7–0.9] versus mesalazine 90% [95% confidence interval 0.7–1.0]; p = n.s.; remission at T4: beclomethasone diproprionate 24% [95% confidence interval 0.1–0.3] versus mesalazine 28% [95% confidence interval 0.1–0.3]; remission at T8: beclomethasone diproprionate 36% [95% confidence interval 0.2–0.5] versus mesalazine 52% [95% confidence interval 0.3–0.6]; p = n.s.).The Disease Activity Index lowered at T4 and T8 versus T0 in the four groups ( T4 versus T0: beclomethasone diproprionate foam Disease Activity Index 2 versus 6 p < 0.0001; beclomethasone diproprionate enema 4 versus 6, mesalazine enema 3 versus 6, mesalazine foam 3.5 versus 7, p < 0.001 for all three groups; T8 versus T0: p < 0.01). The Disease Activity Index lowered at T8 versus T4 in the beclomethasone diproprionate enema and foam (Disease Activity Index: 2 versus 4 and 1 versus 4, respectively; p < 0.05) and in the mesalazine enema (Disease Activity Index: 1.5, range 0–4 versus 3, range 0–12; p < 0.01), but not in the mesalazine foam group (Disease Activity Index: 1, range 0–9 versus 3.5, range 0–8; p = n.s.). The safety profile was favourable for all groups. Conclusions Beclomethasone diproprionate and mesalazine enema and foam show a comparable tolerability and efficacy in mild active distal ulcerative colitis.

Hidrofluoralcano como propelente dos aerossóis pressurizados de dose medida: histórico, deposição pulmonar, farmacocinética, eficácia e segurança

To review the literature about hydrofluoroalkane as a propellent of pressurized metered-dose inhalers containing anti-asthma drugs. Bibliographic search in electronic databases (MEDLINE, MDConsult, HighWire, Medscape and LILACS) and direct search referring to the past 15 years, using the key words hydrofluoroalkane, asthma and childhood were carried out. 43 original articles on the replacement of chlorofluorcarbon by hydrofluoralkane were selected. Hydrofluoralkane showed to be a safe propellent, with pulmonary deposition ranging from 50 to 60%, and to have significant efficacy, when compared with placebo (p < or = 0.003) in controlled clinical trials. Most works using hydrofluoralkane included beclomethasone diproprionate. Approximate annual cost of a treatment with beclomethasone diproprionate/hydrofluoralkane was lower than with beclomethasone diproprionate/clorofluorcarbon. Some studies assessed salbutamol, fluticasone, flunisolide and the association fluticasone-salmeterol, with hydrofluoralkane as propellent in pressurized metered-dose inhalers. Efficacy and safety of hydrofluoralkane as propellent of bronchodilators and inhaled corticosteroids in adults was evidenced. In general, there was a better pulmonary deposition of particles. However, literature data on the use of hydrofluoralkane in the pediatric age group are still scarce and further studies with children and adolescents would be of great importance.

Reticular basement membrane thickening in airways of lung transplant recipients is not affected by inhaled corticosteroids

Chronic rejection is a major problem for all lung transplant programmes, which is functionally manifested by fixed airflow limitation, Bronchiolitis Obliterans Syndrome (BOS). The inclusion of a Pre-BOS category, BOS(0 approximately p), in newly revised guidelines, recognizes the potential importance of early changes. We have previously demonstrated reticular basement membrane (Rbm) thickening in clinically stable lung transplant recipients free from BOS. The present study extends this, testing the hypothesis that inhaled corticosteroid (ICS) therapy will lead to a decrease in Rbm thickness in lung transplant recipients. A parallel group, bronchoscopic intervention study of clinically stable lung allograft recipients, free from BOS, but with evidence of airway inflammation. Following baseline assessment of Rbm thickening, subjects were randomized to 3 months of either chlorofluorocarbon-driven beclomethasone diproprionate (BDP) 400 microg b.i.d., or a formulation designed to yield at least an equivalent dose, hydrofluoroalkane-driven BDP, 200 microg b.i.d. Three months treatment with a moderate dose of ICS, including a formulation designed for preferential small airway deposition, had no effect on Rbm thickening (13+/-3 vs. 14+/-5 microm post-ICS). Our data would suggest that airway remodelling can occur early in lung allografts and is not affected by moderate dose ICS therapy. Longitudinal studies are required to describe the pathophysiological processes involved in BOS, and specifically to elucidate potential relationships between airway remodelling, airflow obstruction and allograft failure.

Dilated cardiomyopathy with mural thrombus presenting with asthma-like symptoms

Rationale We report a case of dilated cardiomyopathy with mural thrombus presenting in an atopic patient with symptoms of reactive airways disease. Methods A 47 year-old female presented to the Allergy Clinic during the spring season with rhinitis, ocular pruritus, cough, chest tightness and wheeze. Allergy skin testing showed reactivity to tree pollens and dust mites. A chest film showed a mild lingular infiltrate. Pulmonary function test showed mild obstructive airway disease. She was treated with azithromycin, beclomethasone diproprionate 80 ug, 2 puffs twice daily, albuterol as needed and a short Prednisone taper. Her symptoms improved. Four weeks later, she experienced a recurrence of cough, nocturnal wheeze, dyspnea and tachycardia. When her symptoms persisted despite the use of fluticasone proprionate,220 ug, salmeterol and monteleukast, a repeat chest film was obtained. Results The chest film showed a mild cardiomegaly compared with her previous chest x-ray. An echocardiogram revealed a dilated cardiomyopathy with a left ventricular mural thrombus. D-Dimer was positive. Doppler study of the lower extremities was normal. She was started on digoxin, furosemide, warfarin sodium and lisinopril and has done well off all asthma medications. Conclusions Allergists should maintain a high index of suspicion in cases where symptoms suggestive of reactive airway disease may be masquerading as another unexpected disease entity.

LOW-DOSE INHALED CORTICOSTEROID THERAPY AND RISK OF EMERGENCY DEPARTMENT VISITS FOR ASTHMA

Sin DD, Man SFP. Arch Intern Med. 2002;162:1591–1595To determine if inhaled corticosteroid (IC) therapy prescribed after discharge from the emergency department (ED) prevents relapse of asthma exacerbations.Twelve hundred ninety-three residents of Alberta, Canada, who were enrolled in a government drug plan and visited an ED for asthma exacerbations between April 1, 1997, and March 31, 1999.The study cohort was identified using the Ambulatory Care Classification System database. Patients 5 to 60 years of age who had at least 1 ED visit for asthma were included in the cohort if they were enrolled in the government-sponsored drug plan. The cohort was followed from the time of the first identified ED visit to the date of a subsequent ED visit. Information regarding prescribed asthma medications was obtained through the Alberta Blue Cross database. The study population was stratified into nonusers and users of IC as well as into low- (<500 μg/day beclomethasone diproprionate or equivalent per day), medium- (501–1000 μg/day), and high-dose (>1000 μg/day) users. Rates of subsequent ED visits for asthma were compared between the IC users and nonusers and between the low-, medium-, and high-dose groups using the Cox proportional hazard regression.Six hundred fifty-eight (50.9%) of the cohort were not prescribed IC. Of those who were prescribed IC, 241 (18.6%) received low-dose, 96 (7.4%) received medium-dose, and 122 (9.4%) received high-dose IC. Corticosteroid users were older and were more likely to have used other asthma medications during the first 100 days of follow-up than nonusers. Inhaled corticosteroid use was associated with a decreased risk (relative risk [RR]: 0.64; 95% confidence interval [CI]: 0.52–0.79) of a subsequent ED visit. After adjusting for age, sex, use of other asthma medications, comorbidity and hospitalization, IC users still had a significantly reduced risk of a repeat ED visit (RR: 0.55; 95% CI: 0.44–0.69). Patients in all 3 dose categories had significantly reduced risks of repeat ED visit (low-dose: RR: 0.52; 95% CI: 0.39–0.68; medium-dose: RR: 0.51; 95% CI 0.39–0.68; high-dose: RR: 0.67; 95% CI: 0.47–0.94). However, medium- and high-dose IC did not reduce the rate of repeat ED visits to any greater extent than did low-dose IC.In this cohort with recent ED visits for asthma, IC reduce the risk of subsequent ED visits. The results suggest that this risk reduction is similar across all 3 dose groups and thus high-dose IC may not afford any greater protection than low-dose IC.Although ICs have been shown to improve lung function and reduce symptoms, the effect on ED visits and hospitalizations has been more difficult to ascertain because of the relative rarity of these outcomes as compared with symptom-based outcomes. The authors circumvented this issue by selecting a cohort of patients who had visited an ED for asthma thereby enriching the study population for those with more severe disease. This study underscores the significant role ICs play in preventing ED visits for asthma and suggests that the next step is to define the optimal dose range so that the risk:benefit ratio can be minimized.

Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease

Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined. A double-blind, randomized placebo controlled trial. Level-III neonatal intensive care unit. Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study. Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age. Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness. Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.

Equivalence of Two Steroid-Containing Inhalers: Easyhaler Multidose Powder Inhaler Compared with Conventional Aerosol with Large-Volume Spacer

Background and Objectives: An equivalence study was conducted in which the efficacy and safety of a daily dose of 800 μg of beclomethasone diproprionate administered via a multidose powder inhaler, Easyhaler, and via a metered-dose inhaler (MDI) with a large-volume spacer were compared in adult, newly diagnosed, steroid-naive asthmatic patients. Acceptability of the medications was also compared. Methods: One hundred and forty-four patients were recruited into the double-blind, double-dummy, randomised, parallel-group multicentre study. The study treatment period was 8 weeks. It was preceded by a 2-week run-in period. Morning and evening peak expiratory flow (PEF), numbers of inhalations of a sympathomimetic and asthma symptoms were recorded daily. Spirometry and histamine challenge were performed, and health-related quality of life and morning serum cortisol levels measured during control visits. Results: Criteria indicating treatment equivalence were met. The mean of the primary outcome variable, morning PEF, increased significantly, from 426 to 461 litres/min in the Easyhaler group and from 436 to 467 litres/min in the MDI+spacer group. Similar improvements between groups were also seen in relation to all secondary variables. Changes in serum cortisol levels were minor. In 6 out of 10 questions about device acceptability, the majority of patients rated Easyhaler as better than the MDI+spacer combination. Conclusion: It was concluded that the devices tested were equivalent in terms of efficacy and safety.

Improved targeting of beclomethasone diproprionate (250 μg metered dose inhaler) to the lungs of asthmatics with the Spacehaler™

The Spacehaler™(Evans Medical Ltd, Leatherhead, U.K.) is a new, compact, inhaler device containing the same aerosol canister as a conventional metered dose inhaler (MDI). However, the design of the Spacehaler™has been shown to reduce the velocity of the aerosol, thus reducing the proportion of non-respirable particles delivered to the patient. This study compared radioaerosol deposition patterns following inhalation of 250μg of beclomethasone dipropionate from the Spacehaler™and a conventional MDI (Beclazone™, Norton Health Care, Harlow, U.K.).After rigorous in vitro validation of the radiolabelling technique, 12 asthmatic subjects (seven men aged 20–69 years, mean baseline FEV12·59l (sd 0·55l) received one dose of99mTc-labelled beclomethasone dipropionate 250μg via either a Spacehaler™or MDI on each of two study days in a randomized cross-over manner. All subjects had been taught the required inhalation technique before the dose was administered. Inhalation details were recorded using a spirometer connected in series with the device. Lung and oropharyngeal depositions were measured by gamma scintigraphy.The mean percentage of the metered dose deposited in the lungs was 23·0% (sd 8·3%) for the Spacehaler™and 12·8% (sd 6·8%) for the MDI (P<0·01). However, there was no significant difference in the distribution patterns within the lungs between the two devices. Oropharyngeal deposition was significantly lower (P<0·01) for the Spacehaler™than for the MDI [mean (sd) 27·9% (16·4%) and 73·6% (8·7%), respectively] whilst the percentage of the metered dose remaining on the Spacehaler™actuator was significantly greater than that on the MDI actuator [mean (sd) 48·0% (11·8%) and 12·4% (8·5%) respectively, P<0·01]. There was evidence from the inhalation recordings that some patients experienced the ‘cold Freon effect’ whilst using the metered dose inhaler which may have contributed to the lower lung deposition seen with this device.This study demonstrates that the proportion of a 250μg dose of beclomethasone dipropionate that is delivered to the lungs is significantly greater with the Spacehaler™than the MDI. The Spacehaler™also reduces the proportion of the does that is deposited in the oropharynx to less than half that observed with the MDI, and reduces the total dose of drug received by the patient.

BECLOMETHASONE DIPROPRIONATE INHALATION AS A TREATMENT FOR POST‐INTUBATION TRACHEAL STENOSIS

SUMMARYA 67‐year‐old man was intubated for one week and suffered from wheeze and dyspnoea three months after the extubation. Bronchoscopy revealed tracheal stenosis by a web, which subsequent biopsy showed to be granulation tissue. The stenosis was removed by laser therapy but the stenosis soon returned. As cardiac function was poor, beclomethasone diproprionate (BDP) inhalation therapy (1200 μg daily) was started and proved successful. Discontinuation of inhalation therapy resulted in restenosis. Steroid inhalation therapy may be able to control post‐intubation tracheal stenosis caused by granulation tissue.