Beclomethasone Dipropionate Treatment Research Articles

Can the response to a single dose of beclomethasone dipropionate predict the outcome of long-term treatment inchildhood exercise-induced bronchoconstriction?

Exercise-induced bronchoconstriction (EIB) is a frequent and highly specific symptom of childhood asthma. Inhaled corticosteroids (ICS) are the mainstay of controller therapy for EIB and asthma; however, a proportion of asthmatic children and adolescents is less responsive to ICS. We hypothesized that a single dose response to ICS could function as a predictor for individual long-term efficacy of ICS. To assess the predictive value of the bronchoprotective effect of a single-dose beclomethasone dipropionate (BDP) against EIB for the bronchoprotective effect of 4weeks of treatment, using an exercise challenge test (ECT). Thirty-two steroid-naïve children and adolescents aged 6 to 18years with EIB were included in this prospective cohort study. They performed an ECT at baseline, after a single-dose BDP (200µg) and after 4weeks of BDP treatment (100µg twice daily) to assess EIB severity. The response to a single-dose BDP on exercise-induced fall in FEV1showed a significant correlation with the response on exercise-induced fall in FEV1 after 4weeks of BDP treatment (r=.38, p=.004). A reduction in post-exercise fall in FEV1 of more than 8% after a single-dose BDP could predict BDP efficacy against EIB after 4weeks of treatment with a positive predictive value of 100% (CI: 86.1-100%) and a negative predictive value of 29.4% (CI: 11.7%-53.7%). We found that the individual response to a single-dose BDP against EIB has a predictive value for the efficacy of long-term treatment with BDP. This could support clinicians in providing personalized management of EIB in childhood asthma.

Effect of rhinophototherapy on nasal congestion in patients with seasonal allergic rhinitis.

SUMMARYObjectiveThe aim of the present study was to objectively and subjectively evaluate the effects of adding rhinophototherapy to intranasal beclomethasone dipropionate to treat nasal congestion in patients with seasonal allergic rhinitis.MethodSeventy-five seasonal allergic rhinitis patients were randomly divided into two groups. Patients in Group 1 received intranasal beclomethasone dipropionate for two weeks and patients in Group 2 had rhinophototherapy added to the same medical therapy as Group 1. The effectiveness of treatments was evaluated with the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Nasal Obstruction Symptom Evaluation scale (NOSE) questionnaires and active anterior rhinomanometry.ResultsAfter treatment, significant improvement was observed in Group 2 vs Group 1 in terms of RQLQ (p = 0.011) and NOSE (p = 0.001) scores. In Group 2, significant differences were observed between before and after treatment for inspiratory total nasal resistance (p = 0.004). However, no significant differences vs. baseline were observed in Group 1.ConclusionOur study shows that adding intranasal phototherapy with a combination of UVA, UVB and visible light therapy to nasal beclomethasone dipropionate treatment objectively improves nasal patency in patients with seasonal allergic rhinitis.

Breathomics in Asthmatic Children Treated with Inhaled Corticosteroids.

Background: “breathomics” enables indirect analysis of metabolic patterns underlying a respiratory disease. In this study, we analyze exhaled breath condensate (EBC) in asthmatic children before (T0) and after (T1) a three-week course of inhaled beclomethasone dipropionate (BDP). Methods: we recruited steroid-naive asthmatic children for whom inhaled steroids were indicated and healthy children, evaluating asthma control, spirometry and EBC (in asthmatics at T0 and T1). A liquid-chromatography–mass-spectrometry untargeted analysis was applied to EBC and a mass spectrometry-based target analysis to urine samples. Results: metabolomic analysis discriminated asthmatic (n = 26) from healthy children (n = 16) at T0 and T1, discovering 108 and 65 features relevant for the discrimination, respectively. Searching metabolomics databases, seven putative biomarkers with a plausible role in asthma biochemical–metabolic processes were found. After BDP treatment, asthmatic children, in the face of an improved asthma control (p < 0.001) and lung function (p = 0.01), showed neither changes in EBC metabolomic profile nor in urinary endogenous steroid profile. Conclusions: “breathomics” can discriminate asthmatic from healthy children, with prostaglandin, fatty acid and glycerophospholipid as putative markers. The three-week course of BDP—in spite of a significant clinical improvement—was not associated with changes in EBC metabolic arrangement and urinary steroid profile.

Inhaled steroid inhibits development of total and mite IgE

Serum levels of total immunoglobulin E (IgE) and allergen-specific IgE are related to asthma severity and risk factors for persistent asthma in childhood wheezing. Inhaled corticosteroids (ICS) have been the most effective therapy in children with asthma, as well as in adults. The serum levels of total and mite specific IgE in children with asthma and the effects on IgE levels of beclomethasone dipropionate (BDP) treatment on IgE levels in asthmatic children were investigated. First, a cross-sectional study of 255 children with asthma was carried out to measure IgE levels. Children under three years of age with asthma who were negative for Df-specific IgE were then treated with BDP or disodium cromoglycate (DSCG) as controls for one year. Serum IgE levels, numbers of eosinophils in peripheral blood and clinical variables were determined before and after treatment. After one-year DSCG treatment, the total IgE levels increased significantly, whereas the levels remained the same during BDP treatment. Five of 22 (23%) patients in the DSCG-treated group became positive for Df-specific IgE; however, only one of 13 (8%) in the BDP-treated group became positive. Taken together, ICS therapy may modulate the levels of total IgE and allergen-specific IgE.

IL-33/ST2 axis controls Th2/IL-31 and Th17 immune response in allergic airway diseases

IL-33 targeting ST2 receptor (T1/ST2), expressed on Th2 cell surface, regulates the production of cytokines like IL-17A and IL-31.We studied the role of IL-33/ST2 axis in IL-31 and IL-17A production in patients with allergic rhinitis (AR) and with concomitant allergic asthma and rhinitis (AAR).20 healthy control subjects (HC), 14 AR and 17 AAR subjects were recruited and blood samples collected. IL-33, soluble ST2 (sST2), IL-17A and IL-31 plasma concentrations were measured by ELISA method. T1/ST2, IL-31 and IL-17A cellular expression were studied in peripheral blood mononuclear cells (PBMC) from HC, AR and AAR (n=6 for each group) by flow-cytometry. In vitro, we also evaluated the effect of beclomethasone dipropionate (BDP) on T1/ST2, IL-31 and IL-17A expression in CD3+T-cells from PBMC of AAR (n=6).Plasma levels of IL-33, IL-31 and IL-17A were significantly higher and sST2 was lower in patients with AR and AAR than in HC. IL-31 and IL-17A intracellular levels significantly increased, whereas T1/ST2 expression was significantly lower, in CD3+T-cells from AR and AAR compared to HC. Positive correlations were observed between plasmatic components of IL-33/ST2 axis and IL-31 in both AR and AAR and IL-17A in AAR. In vitro IL-31 and IL-17A intracellular levels decreased after BDP treatment, whereas T1/ST2 expression increased in cultured CD3+T-cells obtained from AAR.IL-33/ST2 axis is involved in Th2/IL-31 and Th17 immune response during the progression of allergic airway disease. In vitro BDP is able to control Th2/IL-31 and Th17 immune response in PBMC from allergic patients.

Beclomethasone dipropionate and formoterol reduce oxidative/nitrosative stress generated by cigarette smoke extracts and IL-17A in human bronchial epithelial cells

Interleukin-17A (IL-17A), cigarette smoke and oxidative/nitrosative stress are involved in inflammatory airway diseases, and the mechanisms behind these processes are still poorly understood. We investigated whether recombinant human IL-17A (rhIL-17A), in combination with cigarette smoke extracts (CSE), increases the levels of inducibile nitric oxide synthase (iNOS), reactive oxygen species, nitrotyrosine (NT) and the activation of signal transducer and activator of transcription 1 (STAT-1) in normal human bronchial epithelial cells (16HBE). The effect of beclomethasone dipropionate (BDP), formoterol and their combination was also evaluated. We demonstrated that rhIL-17A or CSE alone increases iNOS expression, reactive oxygen species and NT production and STAT-1 downstream signalling activation in terms of STAT-1ser727 and STAT-1tyr701 phosphorylation. The combination of both stimuli further increased iNOS, ROS, NT and STAT-1ser727 phosphorylation. The silencing of STAT-1 expression partially reduced the levels of iNOS, reactive oxygen species and NT generated by rhIL-17A and inhibited the effect of CSE alone in 16HBE cells. The treatment of the cells with the MEK1/2 inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis (o-aminophenylmercapto butadiene) abolished the expression of iNOS and STAT-1ser727 phosphorylation generated by rhIL-17A. 16HBE treated with BDP or formoterol alone partially suppressed the effect of IL-17A or CSE on ROS, NT, and STAT-1 activation. Furthermore the use of the drugs in combination showed an additive effect in 16HBE. Our findings demonstrate that IL-17A increases oxidative/nitrosative markers, likely via ERK1/2 downstream signalling and STAT-1 pathway activation in human bronchial epithelial cells. BDP and formoterol treatment reduces this effect showing an additive effect used in combination.

Oral high dose Beclomethasone dipropionate for treatment of active ulcerative colitis

Oral corticosteroids (CS) have been widely used for treatment of ulcerative colitis (UC) at the price of systemic side effects. Role of topically active oral beclomethasone dipropionate (BDP) in clinical practice is still unclear. The aim of this paper is to investigate efficacy and tolerability of a high dose BDP regimen in mild to moderately active UC. Twenty-five patients (9 males, aged 25-40 years) with mild to moderately active UC, unresponsive to oral and topical 5-ASA (4.8 gr daily) and BDP (5 mg daily), were enrolled. All patients continued 5-ASA plus high dose oral BDP (15 mg od for 4 weeks and than tapered). Clinical, endoscopic, histological and laboratory parameters were monitored. Mean disease activity index (DAI) score at study entry was 8.82±4. Response to treatment was observed in all patients after 2 weeks. Remission was observed in all patients within 4-6 weeks from entering the study (mean DAI score: 2.34±0.5) and maintained throughout 6-month follow-up. No major adverse events were documented. Quality of life global evaluation score improved. This study provides the first evidence of efficacy and safety of high dose oral BDP-scheme in UC demonstrating excellent tolerability and favourable acceptability profile. This new BDPscheme might be a valid alternative to conventional oral CS when standard dose BDP is not effective. Future studies are needed to explore further clinical indications.

Short term efficacy of nebulized beclomethasone in mild-to-moderate wheezing episodes in pre-school children

BackgroundFew data are available on the usefulness of short term treatment with low-medium dose of inhaled corticosteroids (ICS) in pre-school children with wheezing exacerbations.MethodsTo compare the efficacy of one week treatment with 400 μg b.i.d. nebulized beclomethasone dipropionate (BDP), plus nebulized 2500 μg prn salbutamol (BDP group), versus nebulized b.i.d. placebo, plus nebulized prn 2500 μg salbutamol (placebo group), a post-hoc analysis was performed on data obtained in 166 pre-school children with multiple-trigger wheezing, recruited during an acute wheezing episode.ResultsThe percentage of symptom-free days (SFDs) was significantly higher in the BDP group (54.7%) than in the placebo group (40.5%; p = 0.012), with a 35% relative difference. Day-by-day analysis showed that the percentage of SFDs was already higher in the BDP group after 2 days (7.4%), the difference reaching statistical significance at day 6 (12.3%; p = 0.035). Cough score was also reduced in the BDP group (0.11) as compared with the placebo group (0.39; p = 0.048), the difference reaching statistical significance after 5 days of treatment (0.18 and 0.47 respectively; p = 0.047). The mean number of nebulizations per day of prn salbutamol was lower in the BDP group as compared to the placebo group (0.26 and 0.34, respectively), but the difference was not significant (p = 0.366). There were no differences in positive effects of BDP treatment between children with and without risk factors for asthma.ConclusionsA 1-week treatment with nebulized BDP and prn salbutamol is effective in increasing SFDs and improving cough in children with wheezing, providing a clinical rationale for the short term use of ICS in episodic wheeze exacerbations in pre-school children.Trial RegistrationClinicalTrials.gov (NCT00497523)

Oral Beclomethasone Dipropionate Monotherapy as An Initial Treatment for Stage 1-2 Gastrointestinal Tract Acute Graft-Versus-Host Disease Following Unrelated Cord Blood Transplantation.

Abstract 1153Poster Board I-175 IntroductionSystemic corticosteroid has been used as initial treatment for gastrointestinal tract acute graft-versus-host disease (GI-aGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, the response remains far from satisfactory, and adverse events caused by prolonged immunosuppression are significant problem. Oral beclomethasone dipropionate (BDP) is a topically active corticosteroid with low bioavailability. Although several studies demonstrated that BDP as monotherapy or in combination with systemic corticosteroid is safe and effective for treatment of GI-aGVHD, there has been not much data available regarding this issue in unrelated cord transplantation (UCBT). Design and MethodsThis study was approved by the institutional review board and started since January 2006. BDP was administered as a single agent in patients who developed stage 1-2 GI-aGVHD following UCBT, were able to swallow the drug, and gave written informed consent. BDP was administered orally as one enteric-coated cellulose capsule and an aqueous suspension every 6h for a total daily dose of 8mg. Response was evaluated on days 3, 7, 14, 21, and 28 after the beginning of BDP treatment. Patients who had worsening GI symptoms at day 3, or who had no improvement at day 7 were classified as nonresponders, and systemic corticosteroid was started. ResultsForty patients were included in this analysis from Jan 2006 through April 2009. Median age was 53.5 years (range 22-82). Twenty-eight (70%) had advanced disease (relapse or refractory disease), and 12 (30%) had history of prior transplantation. All but one patient received fludarabine-based preparative regimen. GVHD prophylaxis consisted of tacrolimus plus mycophenolate mofetil in 27, and tacrolimus alone in 13. Single cord blood units, matched at 4/6 in 35, 5/6 in 3, and 6/6 in 2, were infused. GI-aGVHD developed at a median of 32.5 days (range, 8-80 days) post-transplant. Twenty-five (62.5%) had stage 1 and 15 had stage 2 GI-aGVHD. Twenty (50%) had only GI involvement and the others had mild skin involvement. BDP was started at a median of 36 days (range, 8-86 days) post-transplant. Thirty-three (82.5%) responded to BDP treatment. Response occurred at a median of 4 days (range, 2-7 days) after BDP treatment. Response rate was suggestively higher in patients with stage 1 GI-aGVHD (88%) compared with those with stage 2 (73%), although not statistically significant (P=0.1). The median duration of BDP treatment was for 51 days (range, 7-343 days). Three patients progressed and 4 patients did not respond. Twenty-seven (67.5%) developed infectious episodes during BDP treatment; bacterial sepsis in 9, CMV reactivation in 10, CMV gastroenteritis in 2, Fungal pneumonia in 3, and others in 3 patients. Two patients developed symptomatic adrenal insufficiency during BDP treatment, and required systemic steroid hormone replacement. Transplant-related mortality was 15% at 100 days post-transplant. Three patients died due to sepsis associated with GVHD, 2 died from idiopathic pneumonia syndrome, and 1 died from invasive fungal infection. At median follow-up of 475 days (range, 132-1368 days), overall survival at 2 years was 35.7%. Conclusions: In this study, we evaluated the efficacy and safety of BDP as a single agent in a series of patients with stage 1-2 GI-aGVHD following UCBT. The response rate was 82.5%, which compares favorably with previously reported response rate using BDP as monotherapy or in combination with systemic corticosteroid after allogeneic HSCT. Furthermore, BDP treatment was not associated with the increased risk of severe opportunistic infections. We conclude that BDP as a single agent could become an ideal therapeutic approach for stage 1-2 GI-aGVHD following UCBT DisclosuresNo relevant conflicts of interest to declare.

Oral Beclomethasone Dipropionate for the Treatment of Steroid-refractory Gastrointestinal Acute Graft-versus-host Disease

Acute graft-versus-host disease (GVHD) is one of the most severe complications following allogeneic stem cell transplantation (SCT), and involvement of the gut has been associated with increased mortality and a poorer response to high-dose systemic corticosteroids. For over a decade, oral beclomethasone dipropionate (BDP) has been studied in the treatment of acute gastrointestinal GVHD, as a monotherapy, or in combination with systemic corticosteroids. Here we report, for the first time in Korea, the efficacy of oral BDP (8 mg/day for 25 days) in 3 adults with acute lymphoblastic leukemia who developed steroid-refractory gastrointestinal GVHD (grade III) after myeloablative conditioning SCT (1 matched sibling transplant, 2 matched unrelated transplants). All patients responded completely to oral BDP treatment. Oral BDP is safe and effective for the control of steroid-refractory acute gastrointestinal GVHD.

Prevalence of allergic rhinitis and its impact on the use of emergency care services in a group of children and adolescents with moderate to severe persistent asthma

To assess the prevalence of allergic rhinitis and the factors associated with the use of emergency care services by children and adolescents with acute asthma submitted to inhaled corticosteroid therapy. A cross-sectional study was conducted with 126 patients treated with beclomethasone dipropionate for 3 years. The factors associated with emergency care services in the third year of beclomethasone dipropionate treatment were assessed using logistic regression models. The prevalence of allergic rhinitis amounted to 74.6% (95%CI 65.9-81.7). The presence of allergic rhinitis (OR = 2.98, 95%CI 1.10-8.06) and asthma severity (OR = 2.09, 95%CI 1.05-4.44) were independent factors for emergency care services. The prevalence of allergic rhinitis was high and that, combined with asthma severity, constituted the major risk factor for the necessity of emergency care services. Health professionals should attempt to make an early diagnosis of allergic rhinitis in asthmatic patients.

Oral Beclomethasone Dipropionate for the Treatment of Gastrointestinal Acute Graft-versus-Host Disease (GVHD)

Acute graft-versus-host disease (aGVHD) remains one of the most severe complications after allogeneic transplantation; in particular, the presence of gut involvement has been related to increased mortality and poorer response. The use of systemic steroids remains the standard for first-line treatment despite its severe secondary effects. Beclomethasone dipropionate (BDP) is a topically active corticosteroid with low absorption, thereby avoiding many of the deleterious side effects associated with systemic steroids. In the present study we analyzed the efficacy of BDP in a series of 26 patients who were diagnosed with grade 1 and 2 gastrointestinal aGVHD. Twenty patients (77%) responded to BDP treatment, 17 (65.5%) reached complete remission (CR), and 3 (11.5%) showed partial response. Among those patients who reached CR, 5 relapsed, although 1 of them reached second CR after a second course of BDP; therefore, 13 (50%) of the 26 patients did not require systemic steroids to treat gastrointestinal aGVHD. CR rates in those showing gastrointestinal symptoms were 68% for patients with persistent nausea, 50% for those with vomiting, and 54% for those with diarrhea ( P = .2). No patient included in the study developed any symptom related to adrenal axis suppression. Thirteen patients (50%) developed ≥1 infectious episode during the first 100 days after transplantation. Transplant-related mortality was 0% at 100 days, and overall transplant-related mortality was 30%, with only 2 patients dying due to infectious complications. Therefore, our study shows that monotherapy with oral BDP is an effective initial therapeutic approach for mild to moderate intestinal GVHD, which avoids complications related to systemic steroids.

Initial Improvements in Lung Function and Bronchial Hyperresponsiveness Are Maintained During 5 Years of Treatment With Inhaled Beclomethasone Dipropionate and Terbutaline

Treatment with inhaled corticosteroids reduces bronchial hyperresponsiveness and relieves airways obstruction in patients with asthma. Up to now, it is unknown whether initial improvements are maintained over a long period of time. Therefore, we assessed whether initial improvements in FEV(1), provocative concentration of histamine causing a 20% fall in FEV(1) (PC(20)), and peak expiratory flow (PEF) persist with a constant dose of inhaled corticosteroids. Furthermore, we investigated whether FEV(1), PC(20), PEF indexes, and symptom scores improve after increasing the dose of inhaled corticosteroids in patients who did not respond sufficiently to treatment with beclomethasone dipropionate (BDP), 800 microg/d. Sixty-eight patients with bronchial hyperresponsiveness and airways obstruction completed a previous study on 3 years of treatment with terbutaline, 500 microg qid, and BDP, 200 microg qid. Fifty-eight of these patients participated in the current extension of another 2.5 years of follow-up. Every 6 months, FEV(1) and PC(20) were measured. Five patients dropped out of the study, one for pulmonary reasons. Forty-four patients continued treatment with BDP, 800 microg/d (BDP-800 group), and 9 patients received a higher dose of BDP (500 microg tid; BDP-1,500 group) after the first 3 years because of a rapid decline in FEV(1) (> 50 mL/yr) despite BDP treatment during the previous study period. After the initial improvement, the mean slope of individual regression lines for FEV(1), PC(20), and morning PEF were - 28 mL/yr, - 0.01 doubling concentrations per year, and 0.6 L/min/yr, respectively, in the BDP-800 group. In the BDP-1,500 group, there were no statistically significant improvements in FEV(1), PC(20), PEF indexes, and symptom scores after increasing the dose of BDP. We conclude that initial improvements in FEV(1), PC(20), and PEF are well preserved over 5 years in patients with obstructive airways diseases who are treated with terbutaline and BDP. In the patients who responded sufficiently to 800 microg/d of BDP, there was no accelerated decline in FEV(1) compared with the general population. Increasing the dose of BDP in a small group of patients with an accelerated fall in FEV(1) (initially treated with a moderate dose of BDP) resulted in no significant improvement in FEV(1), PC(20), PEF indexes, and symptom scores.

Inhaled Beclomethasone Dipropionate Improves Acoustic Measures of Voice in Patients With Asthma

Inhaled corticosteroids have the potential to produce upper-airway side effects such as hoarseness. As new compounds and delivery devices are developed and compared, it is difficult to quantify their adverse upper-airway effects. We undertook the following study to test the ability of an acoustic analysis technique to quantify changes in vocal function in steroid-naive patients with asthma who receive inhaled beclomethasone dipropionate (BDP), 1,000 microg/d for 4 months. Patients self-administered one of four regimens of inhaled BDP. Group 1 patients received one 250-microg puff qid via metered-dose inhaler (MDI); group 2 patients received one 250-microg puff qid via MDI with a holding chamber; group 3 patients received two 250-microg puffs bid via MDI; and group 4 patients received two 250-microg puffs bid via MDI with a holding chamber. A smaller cohort of nonsmoking asthmatic patients was managed without steroid intervention for 4 months. At baseline and again at 8 weeks and 16 weeks after the initiation of BDP treatment, patients underwent spirometry and methacholine challenge. At baseline and again at 2, 4, 8, 12, and 16 weeks, patients underwent voice recording for analysis of voice parameters. The recorded vowels were low-pass filtered (10 KHz), digitized (22 KHz), and analyzed by software to obtain two acoustic measures: (1) jitter, the cycle-to-cycle variation in the time period of the voice signal; and (2) shimmer, the cycle-to-cycle variation in voice signal amplitude. We recruited 77 patients for randomization to inhaled steroid therapy and 10 patients who continued to receive only occasional inhaled bronchodilator therapy. In all active treatment groups, FEV(1), FVC, and provocative concentration of methacholine causing a 20% fall in FEV(1) improved significantly after BDP treatment. Mean jitter scores, a measurement of variation in voice pitch, were not significantly influenced by BDP treatment. However, mean shimmer scores, a reflection of perturbation in vocal amplitude, fell significantly (p < 0.05) in the active treatment groups. These reductions in shimmer scores were not significantly different in the active treatment groups. Shimmer scores in the bronchodilator-treated group were unchanged during the 16 weeks of follow-up. Our data show that a simple and noninvasive acoustic analysis of voice is sensitive to subclinical changes associated with inhaled corticosteroid therapy. We have shown that 1,000 microg/d of inhaled BDP actually improves specific acoustic measures of voice in patients with inadequately controlled asthma. These improvements were uninfluenced by dosing schedule and whether a spacing chamber was used.

Effects of Inhaled Corticosteroid and Short Courses of Oral Corticosteroids on Bone Mineral Density in Asthmatic Patients: A 4-Year Longitudinal Study

It is not certain whether inhaled corticosteroid (ICS) therapy reduces bone mineral density (BMD) in asthmatic patients. In addition, the potential risk of osteoporosis associated with the rescue use of short courses of oral corticosteroids (SC-OCS) is unclear. To evaluate the effect of inhaled beclomethasone dipropionate (BDP) and SC-OCS on BMD in asthmatic patients. A 4-year longitudinal study. Lumbar BMD was measured twice by dual-energy x-ray absorptiometry at a mean (+/- SD) interval of 4.2 +/- 0.1 years in 35 asthmatic adults (15 men and 20 postmenopausal women; mean age at the second evaluation, 60.6 +/- 11.5 years) who had been treated with BDP and SC-OCS. The average period of BDP treatment was 7.7 +/- 2.2 years (range, 4.8 to 13.0 years) at the second evaluation. During the study period, the daily dose of BDP was 765 +/- 389 microg (range, 100 to 1,730 microg), and the frequency of SC-OCS was 1.9 +/- 2.7 courses per year (range, 0.0 to 8.9 courses per year). As a whole, lumbar BMD was unchanged during the course of the study, whereas the Z score (ie, the percentage of normal value predicted from age and sex) increased significantly. Changes in BMD and Z scores in patients receiving high doses of BDP (ie, > 1,000 microg/d; n = 9) were not significantly different from those of patients receiving lower doses (ie, <or= 1,000 microg/d; n = 26). However, patients receiving frequent SC-OCS (ie, > 2.5 courses per year; n = 9) showed a significantly greater loss in BMD and Z score compared with those receiving sporadic courses (ie, <or= 2.5 courses per year; n = 26) (p = 0.002 and p = 0.035, respectively). ICS therapy per se does not affect BMD, whereas frequent SC-OCS may do so.

Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma

Increased vascularity in airway mucosa is a distinctive feature of airway remodelling in asthma. While corticosteroids have proved most effective in modifying airway inflammation, the effect of inhaled corticosteroids on increased airway mucosal vascularity in asthmatics has been little studied. We examined the effect of inhaled corticosteroid on airway vascularity in bronchial biopsy specimens taken from asthmatic patients. We studied bronchial biopsies from 28 asthmatic patients before and after treatment with inhaled beclomethasone dipropionate (BDP) 800 microg/daily, or placebo, for 6 months in a double-blind manner. Biopsy specimens were evaluated for number of vessels and percentage of area occupied by vessels, using computerized image analysis after staining for type IV collagen in vessel walls. Specimens were also examined for extent of collagen III in the subepithelial basement membrane. In addition, we compared asthmatic specimens with biopsy specimens taken from non-asthmatic control subjects. There was a significant increase in number of vessels (P < 0.01) and percent vascularity (P < 0.001) in the submucosa of asthmatic patients compared with control subjects. After 6 months of treatment, we observed significant improvements in forced expiratory volume in 1 s (FEV1), FEV1% and airway responsiveness (P < 0.05, each) in the BDP treatment group compared with the placebo group. This was accompanied by significant decreases in both vessel number and percent vascularity in the airways of BDP-treated patients (P < 0.05, each). We also observed a significant correlation between change in percent vascularity and change in collagen III thickness in the BDP-treated patients (rs = 0.90, P < 0.001). Furthermore, the change in percent vascularity was inversely correlated with both FEV1 (rs = -0.49, P < 0.05) and airway responsiveness (rs = -0.36, P < 0.05). These findings suggest that inhaled corticosteroid treatment of asthma reduced airway wall vascularity during airway remodelling.

Efficacy of budesonide Turbuhaler® compared with that of beclomethasone dipropionate pMDI in Japanese patients with moderately persistent asthma

Objective: The aim of the study was to compare the efficacy and safety of budesonide Turbuhaler® with that of beclomethasone dipropionate (BDP) pMDI.Methodology: Three hundred and fifty adult asthma patients (mean age 52.7 years, mean baseline morning peak expiratory flow (PEF) 294 L/min (&lt; 80% predicted normal)), taking BDP via pressurized metered‐dose inhaler (pMDI), 400 μg daily for at least 2 months, were randomized in an open 6 week study to receive daily doses of either budesonide 100 μg or 400 μg twice daily via Turbuhaler or continued treatment with BDP, 100 μg four times daily. The primary efficacy variable was the mean change in morning PEF from baseline to the end of treatment. Outcome was also assessed using symptom scores and investigators' assessments employed in Japanese clinical trials.Results: At the end of the 6 week treatment period, mean morning PEF improved significantly from baseline in both budesonide groups, 16 L/min and 33 L/min in the 200 μg and 800 μg groups, respectively, but not in the BDP group, 5 L/min. There was no significant difference between 200 μg budesonide and 400 μg BDP treatment in the effect on PEF (P = 0.29), but 800 μg budesonide was significantly superior to BDP (P &lt; 0.001). Final assessment of improvement and usefulness ratings showed that both budesonide treatments were significantly superior to BDP (P &lt; 0.001). All treatments were well tolerated.Conclusion: Budesonide Turbuhaler (200 μg) was as effective as 400 μg BDP pMDI. The efficacy of budesonide was improved significantly by increasing the dosage to 800 μg daily. The study design shows the importance of including a higher dose treatment group when comparing two formulations of inhaled corticosteroids in order to determine whether the treatments to be compared are on the steep part of the dose–response curve. Without that information, comparative studies are usually inconclusive.

A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma

Background: Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few. Objective: We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 μg twice daily and 220 μg twice daily) with 2 doses of beclomethasone dipropionate (168 μg twice daily and 336 μg twice daily) in subjects with persistent asthma. Methods: Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV 1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards. Results: Fluticasone propionate treatment resulted in significantly ( P ≤ .034) greater improvements in objective pulmonary function parameters than did beclomethasone dipropionate treatment and significantly greater reductions in daily albuterol use ( P ≤ .010) and asthma symptoms ( P ≤ .027). Both low-dose (88 μg twice daily) and medium-dose (220 μg twice daily) fluticasone propionate significantly increased FEV 1 compared with higher doses of beclomethasone dipropionate ( P = .006). Low-dose and medium-dose fluticasone propionate improved FEV 1 by 0.31 L (14%) and 0.36 L (15%), respectively, compared with improvements of 0.18 L (8%) and 0.21 L (9%) with low-dose and medium-dose beclomethasone dipropionate. The adverse event profiles were similar for both medications. Conclusion: Fluticasone propionate provides greater asthma control at roughly half the dose of beclomethasone dipropionate, with a comparable adverse event profile. (J Allergy Clin Immunol 1999;103:796-803.)

The Effect of High-Dose Inhaled Beclomethasone Dipropionate in Patients With Stable COPD

The benefits of inhaled corticosteroids in the management of COPD are less apparent than they are in asthma therapy, and the potential for adverse systemic effects of high-dose inhaled corticosteroids has been recognized recently. It is therefore essential to know the maximal obtainable benefits in order to assess the risk/benefit ratio of this treatment. The aim of this study was to investigate the maximal obtainable benefits of high-dose inhaled corticosteroids, 3 mg/d of beclomethasone dipropionate (BDP), when used in combination with adequate doses of regular bronchodilators in patients with stable COPD. Thirty patients with stable COPD completed a randomized, double-blind, placebo-controlled cross-over trial with either 3 mg/d of BDP or with a matching placebo using a metered-dose inhaler with a spacer device for 4 weeks during each treatment period. All of the patients continued to inhale both 400 microg of salbutamol qid and 80 microg of ipratropium bromide qid. The mean prebronchodilator FEV1 was 0.97+/-0.35 L during the placebo period and 1.08+/-0.38 L during the BDP period (p < 0.001). While on BDP, five patients demonstrated a response in their FEV1 of more than 8.5% of the predicted value, which was above the range that covered 95% of the distribution of the placebo response. The mean absolute improvement in the FEV1 in these 5 objective responders was 0.34+/-0.10 L, compared to 0.06+/-0.09 L in the 25 objective nonresponders. Symptom scores for wheezing and dyspnea were significantly better with BDP than with placebo. Hoarseness and sore throat were associated more with BDP treatment. Although a considerable minority of patients benefited substantially from this treatment, the overall outcome does not seem to justify the widespread use of this treatment in the light of increasing recognition of the potential adverse systemic effects of high-dose inhaled corticosteroids.

Effects of inhaled corticosteroid on bone turnover in children with bronchial asthma

Long-term usage of systemic steroids is associated with multiple side effects. One of the major morbidities is due to its effect on bone metabolism leading to bone loss and resulting in skeletal fractures. This study was conducted to determine the effects of inhaled steroids on bone mineral density (BMD) and biochemical bone markers. Twenty-four children with frequent episodic or mild persistent asthma who satisfied the clinical criteria for starting on inhaled corticosteroids (ICS) were enrolled into the study. The BMD scan was done using dual energy X-ray absorptiometry, prior to starting ICS therapy and 6 months later. Biochemical markers of bone metabolism, (i) serum osteocalcin as a bone formation marker, and (ii) urinary deoxypyridinoline (Upd) as a bone resorption marker, were taken prior to ICS treatment and at 2 monthly intervals. The biochemical markers were all taken in the morning. Twenty-four, age- and sex-matched children with mild episodic asthma, not requiring ICS, were used as controls for the BMD measurements. The BMD scan was done upon enrollment into the study and 6 months later. Twenty-four children on ICS and 24 controls completed the study. The subjects were on a mean dose of beclomethasone dipropionate (BDP) 0.4 mg/day. One subject needed a short course of Prednisolone in the early treatment period. None of the controls needed oral steroid therapy. One child in the control group sustained a greenstick fracture after an accidental fall. The mean rate of change of BMD was 1.8% +/- 12.3 in the subjects on BDP. This was lower than the 6.1% +/- 10.6 among the control subjects. However, this difference did not reach statistical significance (P = 0.16). There was a significant increase in serum osteocalcin level after 6 months of BDP treatment from 66.83 +/- 22.71 ng/mL to 81.61 +/- 24.66 ng/mL (P < 0.005). There was a decline in Upd from 36.2 +/- 47.1 nmol/mmol creatinine to 21.4 +/- 6.92 nmol/mmol creatinine. However, this did not reach statistical significance. There was no difference in the statural gain between the subjects on ICS and their controls. This study showed that 6 months of ICS therapy (mean dose 0.4 mg/day) had no significant adverse effect on bone metabolism in asthmatic children.