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Journal of Gastrointestinal and Liver... Mar 2013Systemic corticosteroids have been used to treat active inflammatory bowel disease for over 50 years by virtue of their unquestionable efficacy in inducing clinical... (Review)
Review
Systemic corticosteroids have been used to treat active inflammatory bowel disease for over 50 years by virtue of their unquestionable efficacy in inducing clinical remission rapidly in the vast majority of patients. Nevertheless, traditional corticosteroids are associated to a plethora of potentially serious side effects due to their systemic metabolism; for this reason, interest has lately been growing in newer steroid compounds characterized by a high topical anti-inflammatory activity and a low systemic bioavailability. These compounds, namely budesonide and beclomethasone dipropionate--regarding the treatment of inflammatory bowel disease--can be administered orally and thanks to sophisticated delivery systems are conveyed specifically to the inflamed gut mucosa where they exert their anti-inflammatory action. After intestinal absorption, these drugs are promptly and efficiently inactivated by the liver, so that only inactive molecules reach the systemic circulation. This review revises the main clinical trials, meta-analyses and observational studies conducted on traditional and newer steroids, and critically interprets the main results achieved by these studies.
Topics: Beclomethasone; Biological Availability; Budesonide; Glucocorticoids; Humans; Inflammatory Bowel Diseases
PubMed: 23539393
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2005Cough in isolation of other clinical features is known as non-specific cough, which has been defined as non-productive cough in the absence of identifiable respiratory... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cough in isolation of other clinical features is known as non-specific cough, which has been defined as non-productive cough in the absence of identifiable respiratory disease or any known aetiology. In children with non-specific cough the possibility of asthma being the underlying disorder is often raised (so called cough variant asthma). The proponents of cough variant asthma suggest a therapeutic trial of medications usually used to treat asthma.
OBJECTIVES
To determine the efficacy of inhaled corticosteroids in non-specific cough in children over the age of two years.
SEARCH STRATEGY
Searches were conducted on Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Searches were current as of March 2004.
SELECTION CRITERIA
All randomised (randomised and quasi-randomised) controlled clinical trials in which an inhaled corticosteroid (beclomethasone (BDP), fluticasone (FP), triamcinalone (TAA) or any other corticosteroid) were given for cough in children over two years of age were included. Two review authors independently assessed articles for inclusion and methodological quality.
DATA COLLECTION AND ANALYSIS
Data from trials was extracted by both review authors and entered into the Cochrane Collaboration software program RevMan Analyses 1.0.2.
MAIN RESULTS
Two trials met the inclusion criteria (123 participants). One compared inhaled beclomethasone dipropionate (400 micrograms per day) with placebo and the other compared fluticasone propionate (2 mg per day for 3 days followed by 1 mg per day for 11 days) with placebo. Both studies used metered dose inhalers via a spacer. With the lower dose of inhaled corticosteroid there was no significant difference between the beclomethasone and placebo groups. With the higher dose there was a significant improvement in nocturnal cough frequency after two weeks in children presenting with persistent nocturnal cough. However, a significant but smaller improvement was also seen with placebo.
AUTHORS' CONCLUSIONS
In one study beclomethasone dipropionate (400 micrograms per day) was no different from placebo in reducing the frequency of cough measured objectively or scored subjectively. There might be a small improvement with very high-dose inhaled corticosteroid but the clinical impact of this is unlikely to beneficial.
Topics: Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Cough; Fluticasone; Humans; Randomized Controlled Trials as Topic
PubMed: 16235355
DOI: 10.1002/14651858.CD004231.pub2 -
Journal of Medical Virology Feb 2021
Topics: Administration, Inhalation; Anti-Inflammatory Agents; Beclomethasone; Clinical Trials as Topic; Humans; Lung; Mometasone Furoate; COVID-19 Drug Treatment
PubMed: 32776550
DOI: 10.1002/jmv.26413 -
The Cochrane Database of Systematic... Apr 2006The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant.
OBJECTIVES
To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma.
SEARCH STRATEGY
The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of January 2006.
SELECTION CRITERIA
Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity.
MAIN RESULTS
Eight studies (1260 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event.
AUTHORS' CONCLUSIONS
There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.
Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Chronic Disease; Fluticasone; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic
PubMed: 16625634
DOI: 10.1002/14651858.CD005309.pub3 -
Biology of Blood and Marrow... Jul 2020Systemic glucocorticoids remain the standard treatment for gastrointestinal (GI) acute graft-versus-host disease (aGVHD) despite their toxicity and incomplete efficacy....
Systemic glucocorticoids remain the standard treatment for gastrointestinal (GI) acute graft-versus-host disease (aGVHD) despite their toxicity and incomplete efficacy. Controlled trials have tested poorly absorbable steroids as adjuncts with systemic glucocorticoids, but only small case series have reported treatment with poorly absorbed beclomethasone dipropionate (BDP) and budesonide (BUD) alone. Our team has adopted the practice of administering BDP or BDP+BUD without systemic glucocorticoids as first-line therapy for isolated upper GI (UGI) aGVHD. We report results in 76 patients treated with BDP alone and in 81 patients treated with BDP+BUD, with allocation by physician choice. Almost all patients received peripheral blood stem cells (92%) from a fully HLA-matched related or unrelated donor (80%) after myeloablative conditioning (76%) for acute leukemia (49%), myelodysplastic syndrome (17%), non-Hodgkin lymphoma (14%), or another hematopoietic disorders (20%). After 28 days of treatment with BDP, 46% of the patients had a complete response (CR) and 10% had a partial response (PR); after 200 days, 61 (80%) patients were alive, 34% maintained a CR, and 3% maintained a PR, whereas 53% required additional immunosuppression (IS). After 28 days of treatment with BDP+BUD, 67% had a CR and 10% a PR; after 200 days, 74 (91%) patients were alive, 46% maintained a CR, and 2% maintained a PR, whereas 43% required additional IS. Among the entire cohort of 157 patients, 66 (42%) were treated successfully without systemic glucocorticoids. This study reports the efficacy of poorly absorbable steroids alone for patients with isolated UGI aGVHD. Prospective trials should test for the potential advantages of BDP and BUD use over systemic glucocorticoids.
Topics: Adult; Aged; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Female; Graft vs Host Disease; Humans; Male; Middle Aged; Prospective Studies
PubMed: 32361010
DOI: 10.1016/j.bbmt.2020.04.023 -
The Cochrane Database of Systematic... 2002Beclomethasone dipropionate (BDP) and budesonide (BUD) are used widely in the treatment of chronic asthma. The two drugs have different in vitro pharmacokinetic... (Review)
Review
BACKGROUND
Beclomethasone dipropionate (BDP) and budesonide (BUD) are used widely in the treatment of chronic asthma. The two drugs have different in vitro pharmacokinetic characteristics. It is unclear whether this translates into clinically significant differences in efficacy or safety when treating children and adults with chronic asthma.
OBJECTIVES
To assess clinical outcomes in studies which have compared inhaled BDP and BUD in the treatment of chronic asthma.
SEARCH STRATEGY
We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997-1999).
SELECTION CRITERIA
Prospective, randomised trials comparing BDP to BUD in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.
DATA COLLECTION AND ANALYSIS
One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager 4.0.3 with Metaview 3.1.
MAIN RESULTS
24 studies met the criteria for inclusion (1174 subjects). Methodological quality was variable. A meta-analysis of crossover studies did not demonstrate a significant difference between BDP and BUD for FEV1, morning PEF, evening PEF, asthma symptoms or rescue beta2 agonist use, over a dose range of 400 to 1000 mcg/d. The majority of crossover trials had significant design flaws related to a lack of washout and/or failure to exclude carryover effects so the results must be viewed with caution. A single crossover study with adequate washout showed that BUD 400 mcg/d delivered via Turbohaler dry powder inhaler (DPI) may be more effective than BDP 400 mcg/d delivered via Rotahaler DPI in reducing histamine bronchial hyper-responsiveness: Weighted Mean Difference (WMD) 0.43 log10 PC20 FEV1 (95% Confidence Intervals (CI) 0.05, 0.81 log10 PC20 FEV1). A meta-analysis of two parallel group, dose down-titration studies (231 patients) showed that less BUD delivered via a Turbohaler DPI was required to maintain control in adults asthmatics compared to BDP delivered via metered dose inhaler with or without a spacer: WMD 444 mcg/d (95% CI 332, 556 mcg/d).
REVIEWER'S CONCLUSIONS
There is limited high quality randomised controlled trial data comparing the relative efficacy of BDP and BUD. Current guidelines (BTS 1997, GINA 1995, NHLBI 1997) assume BDP and BUD to have equal efficacy, such that for each defined level of asthma severity, the recommended doses BDP and BUD are the same. Although there is some data to suggest that BUD via Turbohaler is more effective than BDP via either Rotahaler or MDI (with and without spacer), these comparisons are confounded by use of different delivery devices, and are not sufficient to warrant a change in guideline recommendations.
Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Humans; Randomized Controlled Trials as Topic
PubMed: 11869673
DOI: 10.1002/14651858.CD003530 -
Respiratory Medicine Dec 2012Fixed-dose combinations of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) have been used to manage asthma for several years. They are the preferred... (Review)
Review
Fixed-dose combinations of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) have been used to manage asthma for several years. They are the preferred therapy option for patients who do not achieve optimal control of their asthma with low-dose ICS monotherapy. In Europe, four ICS/LABA products are commercially available for asthma maintenance therapy (fluticasone propionate/formoterol fumarate, fluticasone propionate/salmeterol xinafoate, budesonide/formoterol fumarate and beclometasone dipropionate/formoterol fumarate), and other combinations are likely to be developed over the next few years (e.g. mometasone/formoterol fumarate, fluticasone furoate/vilanterol, mometasone/indacaterol). Data from randomized, controlled, clinical trials do not demonstrate a clear overall efficacy difference among ICS/LABA combinations approved for asthma therapy. Conversely, pharmacological data indicate that there may be certain advantages to using one ICS or LABA over another because of the specific pharmacodynamic and pharmacokinetic profiles associated with particular treatments. This review article summarizes the pharmacological characteristics oft he various ICSs and LABAs available for the treatment of asthma, including the potential for ICS and LABA synergy, and gives an insight into the rationale for the development of the latest ICS/LABA combination approved for asthma maintenance therapy.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Evidence-Based Medicine; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Time Factors; Treatment Outcome
PubMed: 23273165
DOI: 10.1016/S0954-6111(12)70005-7 -
The Cochrane Database of Systematic... Oct 2014Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong evidence however, that the adequate control of asthma can improve health outcomes for mothers and their babies. Despite known risks of poorly controlled asthma during pregnancy, a large proportion of women have sub-optimal asthma control, due to concerns surrounding risks of pharmacological agents, and uncertainties regarding the effectiveness and safety of different management strategies.
OBJECTIVES
To assess the effects of interventions (pharmacologic and non-pharmacologic) for managing women's asthma in pregnancy on maternal and fetal/infant outcomes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 June 2014) and the Cochrane Airways Group's Trials Register (4 June 2014).
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing any intervention used to manage asthma in pregnancy, with placebo, no intervention, or an alternative intervention. We included pharmacological and non-pharmacological interventions (including combined interventions). Cluster-randomised trials were eligible for inclusion (but none were identified). Cross-over trials were not eligible for inclusion.We included multi-armed trials along with two-armed trials. We also included studies published as abstracts only.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed trial eligibility and quality and extracted data. Data were checked for accuracy.
MAIN RESULTS
We included eight trials in this review, involving 1181 women and their babies. Overall we judged two trials to be at low risk of bias, two to be of unclear risk of bias, and four to be at moderate risk of bias.Five trials assessed pharmacological agents, including inhaled corticosteroids (beclomethasone or budesonide), inhaled magnesium sulphate, intravenous theophylline, and inhaled beclomethasone verus oral theophylline. Three trials assessed non-pharmacological interventions, including a fractional exhaled nitric oxide (FENO)-based algorithm versus a clinical guideline-based algorithm to adjust inhaled corticosteroid therapy, a pharmacist-led multi-disciplinary approach to management versus standard care, and progressive muscle relaxation (PMR) versus sham training.The eight included trials were assessed under seven separate comparisons. Pharmacological interventionsPrimary outcomes: one trial suggested that inhaled magnesium sulphate in addition to usual treatment could reduce exacerbation frequency in acute asthma (mean difference (MD) -2.80; 95% confidence interval (CI) -3.21 to -2.39; 60 women). One trial assessing the addition of intravenous theophylline to standard care in acute asthma did not report on exacerbations (65 women). No clear difference was shown in the risk of exacerbations with the use of inhaled beclomethasone in addition to usual treatment for maintenance therapy in one trial (risk ratio (RR) 0.36; 95% CI 0.13 to 1.05; 60 women); a second trial also showed no difference, however data were not clearly reported to allow inclusion in a meta-analysis. No difference was shown when inhaled beclomethasone was compared with oral theophylline for maintenance therapy (RR 0.88; 95% CI 0.59 to 1.33; one trial, 385 women). None of these trials reported on neonatal intensive care admissions.
SECONDARY OUTCOMES
inhaled magnesium sulphate in acute asthma was shown to improve lung function measures (one trial, 60 women); intravenous theophylline in acute asthma was not associated with benefits (one trial, 65 women). No clear differences were seen with the addition of inhaled corticosteroids to routine treatment in three trials (374 women). While inhaled beclomethasone, compared with oral theophylline, significantly reduced treatment discontinuation due to adverse effects in one trial (384 women), no other differences were observed, except for higher treatment adherence with theophylline. Four of the five trials did not report on adverse effects. Non-pharmacological interventionsPrimary outcomes: in one trial, the use of a FENO-based algorithm was shown to significantly reduce asthma exacerbations (RR 0.61; 95% CI 0.41 to 0.90; 220 women); and a trend towards fewer neonatal hospitalisations was observed (RR 0.46; 95% CI 0.21 to 1.02; 214 infants). No exacerbations occurred in one trial assessing pharmacist-led management; this approach did not reduce neonatal intensive care admissions (RR 1.50; 95% CI 0.27 to 8.32; 58 infants). One trial (64 women) assessing PMR did not report on exacerbations or neonatal intensive care admissions.
SECONDARY OUTCOMES
the use of a FENO-based algorithm to adjust therapy led to some improvements in quality of life scores, as well as more frequent use of inhaled corticosteroids and long-acting β-agonists, and less frequent use of short-acting β-agonists (one trial, 220 women). The FENO-based algorithm was associated with fewer infants with recurrent episodes of bronchiolitis in their first year of life, and a trend towards fewer episodes of croup for infants. Pharmacist-led management improved asthma control scores at six months (one trial, 60 women); PMR improved lung function and quality of life measures (one trial, 64 women). No other differences between comparisons were observed.
AUTHORS' CONCLUSIONS
Based on eight included trials, of moderate quality overall, no firm conclusions about optimal interventions for managing asthma in pregnancy can be made. Five trials assessing pharmacological interventions did not provide clear evidence of benefits or harms to support or refute current practice. While inhaled magnesium sulphate for acute asthma was shown to reduce exacerbations, this was in one small trial of unclear quality, and thus this finding should be interpreted with caution. Three trials assessing non-pharmacological interventions provided some support for the use of such strategies, however were not powered to detect differences in important maternal and infant outcomes. While a FENO-based algorithm reduced exacerbations, the effects on perinatal outcomes were less certain, and thus widespread implementation is not yet appropriate. Similarly, though positive effects on asthma control were shown with PMR and pharmacist-led management, the evidence to date is insufficient to draw definitive conclusions.In view of the limited evidence base, further randomised trials are required to determine the most effective and safe interventions for asthma in pregnancy. Future trials must be sufficiently powered, and well-designed, to allow differences in important outcomes for mothers and babies to be detected. The impact on health services requires evaluation. Any further trials assessing pharmacological interventions should assess novel agents or those used in current practice. Encouragingly, at least five trials have been identified as planned or underway.
Topics: Adrenal Cortex Hormones; Algorithms; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Humans; Magnesium Sulfate; Muscle Relaxation; Nitric Oxide; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Theophylline
PubMed: 25331331
DOI: 10.1002/14651858.CD010660.pub2 -
Journal of Acquired Immune Deficiency... Jul 2013To identify an alternative inhaled corticosteroid to fluticasone propionate that can be safely coadministered with HIV protease inhibitors, the safety and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To identify an alternative inhaled corticosteroid to fluticasone propionate that can be safely coadministered with HIV protease inhibitors, the safety and pharmacokinetics of beclomethasone dipropionate (BDP) and its active metabolite, beclomethasone 17-monopropionate (17-BMP), in combination with ritonavir (RTV) and darunavir/ritonavir (DRV/r) were assessed.
DESIGN
Open-label, prospective, randomized pharmacokinetic and pharmacodynamic study in healthy volunteers.
METHODS
Thirty healthy volunteers received inhaled 160 μg bid BDP for 14 days and were then randomized (1:1:1) into 3 groups: group 1 (control) remained on BDP alone for 28 days, group 2 received 100 mg bid BDP + RTV for 28 days, and group 3 received 600/100 mg bid BDP + DRV/r for 28 days. Pharmacokinetic sampling for 17-BMP was performed on days 14 and 28, and pharmacokinetic parameter values were compared within patients and between groups. Cortisol stimulation testing was also performed on days 1, 14, 28, and 42 and compared within and between groups.
RESULTS
Geometric mean ratios (day 28:day 14) (90% confidence interval) for 17-BMP area under the concentration-time curve in groups 1, 2, and 3, respectively, were 0.93 (0.81 to 1.06, P = 0.27), 2.08 (1.52 to 2.65, P = 0.006), and 0.89 (0.68 to 1.09, P = 0.61). There were no significant reductions in serum cortisol levels within or between groups (P > 0.05).
CONCLUSIONS
DRV/r did not increase 17-BMP exposure, whereas RTV alone produced a statistically significant but clinically inconsequential 2-fold increase in 17-BMP exposure. Adrenal suppression was not observed in any of the study groups. These data suggest that BDP can be safely coadministered with DRV/r and likely other RTV-boosted protease inhibitors.
Topics: Adolescent; Adult; Anti-Inflammatory Agents; Beclomethasone; Darunavir; Drug Interactions; Female; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; Ritonavir; Sulfonamides; Young Adult
PubMed: 23535292
DOI: 10.1097/QAI.0b013e31829260d6 -
Archives of Disease in Childhood Nov 1986We compared nebulised beclomethasone dipropionate suspension against placebo in 16 children with moderately severe asthma in double blind crossover fashion. Three... (Clinical Trial)
Clinical Trial
We compared nebulised beclomethasone dipropionate suspension against placebo in 16 children with moderately severe asthma in double blind crossover fashion. Three children withdrew due to deterioration while on placebo. Of the remaining 13, eight were better on beclomethasone and five on placebo. These trends in favour of nebulised beclomethasone were not significant and do not suggest that the suspension is as effective as inhaled powder or aerosol topical steroid formulation.
Topics: Asthma; Beclomethasone; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Infant; Male; Nebulizers and Vaporizers; Suspensions
PubMed: 3539031
DOI: 10.1136/adc.61.11.1108