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Journal of Clinical Medicine Nov 2023In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (β2-agonist use associated to an inhaled corticosteroid... (Review)
Review
In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (β2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population.
PubMed: 38068322
DOI: 10.3390/jcm12237270 -
Therapeutic Advances in Gastroenterology 2023Low bioavailability steroids, including beclomethasone dipropionate (BDP) and budesonide MMX, have been developed to ensure colonic targeting and low systemic activity...
BACKGROUND
Low bioavailability steroids, including beclomethasone dipropionate (BDP) and budesonide MMX, have been developed to ensure colonic targeting and low systemic activity than systematic corticosteroids in treating patients with ulcerative colitis (UC).
OBJECTIVES
This systematic review and meta-analysis evaluated the efficacy and safety of BDP and budesonide MMX® compared with 5-aminosalicylic acid (5-ASAs) or placebo, in patients with mild-to-moderate UC.
DESIGN
Systematic review and meta-analysis.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials from inception to December 2021. We included all available randomized controlled trials (RCTs) comparing oral BDP or budesonide MMX with 5-ASAs or with placebo in induction of remission of mild-to-moderate UC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.
RESULTS
We identified two RCTs comparing BDP 5 mg with 5-ASA, one RCTs comparing BDP 10 mg with 5-ASA, two RCTs BDP 5 mg placebo, one RCT BDP 10 mg placebo, two RCTs budesonide MMX 9 mg 5-ASA, and six RCTs budesonide MMX 9 mg placebo. In terms of achieving clinical remission or improvement, BDP 5 mg, BDP 10 mg, and budesonide MMX 9 mg were more effective than placebo (OR 2.36, 95% CI 1.37-4.08; OR 2.23, 95% CI 1.02-4.87; and OR 2.03, 95% CI 1.45-2.85, respectively). The drugs were also more effective than placebo in achieving endoscopic remission. Regarding the comparisons with 5-ASA, we found no differences between 5-ASA and BDP 5 mg or BDP 10 mg or budesonide MMX 9 mg in achieving clinical remission or improvement (OR 0.90, 95% CI 0.51-1.57; OR 1.54, 95% CI 0.42-5.64; and OR 1.17, 95% CI 0.82-1.66). However, 5-ASA was more effective than budesonide MMX 9 mg in achieving histological remission (OR 0.33, 95% CI 0.16-0.70). Overall, all the drugs were safe and well tolerated.
CONCLUSION
Low bioavailability steroids were more effective than placebo in achieving clinical remission, clinical and endoscopic remission, and histological remission. No differences were found between 5-ASA and BDP or budesonide MMX. Surely, more RCTs, also comparing BDP and budesonide MMX, are mandatory to confirm or not these results.
PubMed: 37538919
DOI: 10.1177/17562848231188549 -
World Journal of Diabetes Aug 2023Inhaled corticosteroids (ICS) and intranasal corticosteroids (INS) are the mainstays of treatment for chronic respiratory diseases like asthma, chronic obstructive... (Review)
Review
Inhaled corticosteroids (ICS) and intranasal corticosteroids (INS) are the mainstays of treatment for chronic respiratory diseases like asthma, chronic obstructive pulmonary disease, and allergic rhinosinusitis. In addition, these localized forms of steroid therapy are generally considered to have fewer systemic side effects compared to long-term oral corticosteroids. However, concern and controversy remain over the impact of ICS and INS on the incidence and control of diabetes mellitus (DM). Given the widespread use of ICS and INS, even small individual effects on DM could lead to large consequences for the global popu-lation. Multiple large observational studies suggest that high dose ICS is associated with increased incident DM and worsened DM control, though the contribution of other risk factors is less certain. In addition, only two studies were done to investigate the association of INS and DM, with both studies demon-strating a short-term association of INS use with hyperglycemia. While more research evaluating the risk of ICS/INS for DM-related adverse events is needed, high doses of ICS/INS should be avoided when possible. The following strategies for ICS/INS dose minimization can be considered: Use of non-pharmacological measures (trigger avoidance, smoking cessation, vaccination to avoid infection), control of comorbid conditions, use of non-ICS-containing medications, inter-mittent rather than regular ICS dosing, and appropriate de-escalation of high ICS doses.
PubMed: 37664474
DOI: 10.4239/wjd.v14.i8.1202 -
Acta Otorhinolaryngologica Italica :... Apr 2024Intranasal corticosteroids (INCs) are the first line of therapy for chronic sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most... (Review)
Review
INTRODUCTION
Intranasal corticosteroids (INCs) are the first line of therapy for chronic sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most frequently used is beclomethasone dipropionate (BDP). Over the years many studies have evaluated the efficacy of BDP as part of therapy for chronic rhinosinusitis (CRS) and allergic rhinitis (AR) along with nasal washes, which seems to be very well tolerated.
OBJECTIVE
To analyse the data in the literature regarding the various therapeutic regimens of BDP in different sinonasal disease and their efficacy and tolerability.
MATERIALS AND METHODS
Using different search engines, the posology, efficacy, and tolerability of BDP were reviewed and a total of 64 full-length articles were examined for eligibility. After applying inclusion and exclusion criteria, 4 articles were reviewed.
RESULTS
BDP is among the group of INCs with significant improvement of nasal symptoms and has good efficacy and safety.
CONCLUSIONS
BDP nasal spray is one of the most frequently prescribed INC for rhinitis and rhinosinusitis. Treatment with BDP resulted in significant and clinically meaningful improvements in nasal symptoms associated with AR and CRS. BDP is well tolerated, and the safety profile is similar to that of placebo in most patients. These results, in conjunction with the significant benefit reported in subjects with CRS and AR, provide convincing evidence of the overall effectiveness of BDP for the treatment of the full spectrum of sinonasal disease.
Topics: Humans; Randomized Controlled Trials as Topic; Administration, Intranasal; Rhinitis; Sinusitis; Beclomethasone; Adrenal Cortex Hormones; Glucocorticoids; Chronic Disease
PubMed: 38651550
DOI: 10.14639/0392-100X-N2745 -
Pharmaceuticals (Basel, Switzerland) Apr 2024The introduction of inhaled corticosteroids (ICSs) changed over a few decades the treatment focus of mild-to-moderate asthma from bronchodilation to reduction in... (Review)
Review
The introduction of inhaled corticosteroids (ICSs) changed over a few decades the treatment focus of mild-to-moderate asthma from bronchodilation to reduction in inflammation. This was achieved by inhaling a suitable corticosteroid (CS), giving a high, protracted airway concentration at a low total dose, thereby better combining efficacy and tolerance than oral therapy. Successful trials with the potent, lipophilic "skin" CS beclomethasone dipropionate (BDP) paved the way, suggesting that ICSs require a very low water solubility, prolonging their intraluminal dissolution within airways. The subsequent ICS development, with resulting clinical landmarks, is exemplified here with budesonide (BUD), showing that a similar efficacy/safety relationship is achievable by partly alternative mechanisms. BUD is much less lipophilic, giving it a 100-fold higher water solubility than BDP and later developed ICSs, leading to its more rapid intraluminal dissolution and faster airway and systemic uptake rates. In airway tissue, a BUD fraction is reversibly esterified to intracellular fatty acids, a lipophilic conjugate, which prolongs airway efficacy. Another mechanism is that the rapidly absorbed bulk fraction, via short plasma peaks, adds anti-inflammatory activity at the blood and bone marrow levels. Importantly, these plasma peaks are too short to provoke systemic adverse actions. Controlled clinical trials with BUD changed the use of ICS from a last resort to first-line treatment. Starting ICS treatment immediately after diagnosis ("early intervention") became a landmark for BUD. An established dose response made BUD suitable for the treatment of patients with all degrees of asthma severity. With the development of the budesonide/formoterol combination inhaler (BUD/FORM), BUD contributed to the widely used BUD/FORM maintenance and reliever therapy (MART). Recent studies demonstrated the value of BUD/FORM as a generally recommended as-needed therapy for asthma ("anti-inflammatory reliever", AIR). These abovementioned qualities have all influenced international asthma management and treatment guidelines.
PubMed: 38675463
DOI: 10.3390/ph17040503 -
Respiratory Medicine Nov 2023Incorrect inhaler use and poor treatment adherence have a negative impact on COPD outcomes. This multi-centre, single arm, non-interventional, phase IV study... (Observational Study)
Observational Study
OBJECTIVE
Incorrect inhaler use and poor treatment adherence have a negative impact on COPD outcomes. This multi-centre, single arm, non-interventional, phase IV study investigated whether inhalation technique, treatment adherence and patient outcomes change in patients who evolve from dual therapy or multiple inhaler triple therapy to single inhaler extrafine triple therapy (beclomethasone dipropionate (BDP, 87 μg), formoterol fumarate (FF, 5 μg) and glycopyrronium (G, 9 μg)) in combination with inhalation technique training.
METHODS
A total of 126 COPD patients were included in the per protocol set. Inhalation technique and treatment adherence were assessed at baseline and at two visits at approximately 3 and 6 months of treatment with extrafine BDP/FF/G. In addition, lung function, symptom score, patient satisfaction and exacerbations (exploratory) were followed up.
RESULTS
Before switching to single inhaler extrafine BDP/FF/G (baseline), any device errors and critical errors were detected for 28.8% and 9.6% of patients, respectively. After switching to BDP/FF/G, the percentage of patients with any device errors decreased to 14.0% (visit 2) and 16.3% (visit 3), without critical errors at the two follow-up visits. Treatment adherence increased from 67.5% at baseline to 75.8% (visit 2) and 80% (visit 3). In addition, lung function, symptom and patient satisfaction scores improved, whilst exacerbation rates substantially decreased.
CONCLUSIONS
This observational study demonstrates that in eligible COPD patients in a real-life setting, the switch from dual therapy or multiple inhaler triple therapy to single inhaler extrafine BDP/FF/G in combination with inhalation technique training is associated with improved inhalation technique and adherence.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Administration, Inhalation; Treatment Outcome; Formoterol Fumarate; Beclomethasone; Nebulizers and Vaporizers; Patient Care; Drug Combinations
PubMed: 37562659
DOI: 10.1016/j.rmed.2023.107368 -
BMJ Open Dec 2023To study if early initiation of inhaled beclomethasone 1200 mcg in patients with asymptomatic, mild or moderate COVID-19 reduces disease progression to severe COVID-19. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To study if early initiation of inhaled beclomethasone 1200 mcg in patients with asymptomatic, mild or moderate COVID-19 reduces disease progression to severe COVID-19.
DESIGN
Double-blinded, parallel-groups, randomised, placebo-controlled trial.
SETTING
A hospital-based study in Sri Lanka.
PARTICIPANTS
Adults with asymptomatic, mild or moderate COVID-19, presenting within the first 7 days of symptom onset or laboratory diagnosis of COVID-19, admitted to a COVID-19 intermediate treatment centre in Sri Lanka between July and November 2021.
INTERVENTIONS
All participants received inhaled beclomethasone 600 mcg or placebo two times per day, for 10 days from onset of symptoms/COVID-19 test becoming positive if asymptomatic or until reaching primary endpoint, whichever is earlier.
PRIMARY OUTCOME MEASURE
Progression of asymptomatic, mild or moderate COVID-19 to severe COVID-19.
SECONDARY OUTCOME MEASURES
The number of days with a temperature of 38°C or more and the time to self-reported clinical recovery.
RESULTS
A total of 385 participants were randomised to receive beclomethasone(n=193) or placebo(n=192) stratified by age (≤60 or >60 years) and sex. One participant from each arm withdrew from the study. All participants were included in final analysis. Primary outcome occurred in 24 participants in the beclomethasone group and 26 participants in the placebo group (RR 0.90 ; p=0.763). The median time for self-reported clinical recovery in all participants was 5 days (95% CI 3 to 7) in the beclomethasone group and 5 days (95% CI 3 to 8) in the placebo group (p=0.5). The median time for self-reported clinical recovery in patients with moderate COVID-19 was 5 days (95% CI 3 to 7) in the beclomethasone group and 6 days (95% CI 4 to 9) in the placebo group (p=0.05). There were no adverse events.
CONCLUSIONS
Early initiation of inhaled beclomethasone in patients with asymptomatic, mild or moderate COVID-19 did not reduce disease progression to severe COVID-19.
TRIAL REGISTRATION NUMBER
Sri Lanka Clinical Trials Registry; SLCTR/2021/017.
Topics: Adult; Humans; Middle Aged; Beclomethasone; COVID-19; Disease Progression; Double-Blind Method; Hospitals; SARS-CoV-2; Sri Lanka; Treatment Outcome; Male; Female; Aged
PubMed: 38101843
DOI: 10.1136/bmjopen-2023-075803 -
Respiratory Research Oct 2023This study, in patients with symptomatic chronic obstructive pulmonary disease (COPD), explored switching therapy from non-extrafine high-dose inhaled...
The effect of inhaled extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide on distal and central airway indices, assessed using Functional Respiratory Imaging in COPD (DARWiIN).
BACKGROUND
This study, in patients with symptomatic chronic obstructive pulmonary disease (COPD), explored switching therapy from non-extrafine high-dose inhaled corticosteroid/long-acting β-agonist (ICS/LABA; fluticasone propionate/salmeterol [FP/SLM]) to extrafine medium-dose beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium (BDP/FF/G), both via dry-powder inhaler. Functional Respiratory Imaging, a quantitative computed tomography method with 3D reconstructions of pulmonary anatomy, was used to assess airway geometry and lung function.
METHODS
Patients receiving a stable ICS/LABA regimen for ≥ 8 weeks were switched to FP/SLM 500/50 µg, one inhalation twice-daily (high-dose ICS) for 6 weeks. After baseline assessments (Visit 2 [V2]), therapy was switched to BDP/FF/G 100/6/10 µg, two inhalations twice-daily (medium-dose ICS) for 6 weeks, followed by V3. The primary endpoints were percentage changes in specific image-based airway volume (siV) and resistance (siR) from baseline to predose at V3 (i.e., chronic effects), assessed at total lung capacity (TLC) in central and distal lung regions. Secondary endpoints included siV and siR changes from pre-dose to post-dose at V2, and from pre-dose to post-dose at V3 at TLC (i.e., acute effects), and chronic and acute changes in siV and siR at functional residual capacity (FRC). Pre-dose forced expiratory volume in 1 s (FEV) and COPD Assessment Test (CAT) were also assessed.
RESULTS
There were no significant changes in pre-dose siV or siR at TLC from baseline to V3, although at FRC there was a significant decrease in mean siR in the distal airways (- 63.6%; p = 0.0261). In addition, in the distal airways there were significant acute effects at TLC on mean siV and siR (siV: 39.8% and 62.6%; siR: - 51.1% and - 57.2%, V2 and V3, respectively; all p < 0.001) and at FRC at V2 (siV: 77.9%; siR: - 67.0%; both p < 0.001). At V3, the mean change in pre-dose FEV was 62.2 mL (p = 0.0690), and in CAT total score was - 3.30 (p < 0.0001).
CONCLUSIONS
In patients with symptomatic COPD receiving high-dose ICS/LABA, adding a long-acting muscarinic antagonist while decreasing the ICS dose by switching to medium-dose extrafine BDP/FF/G was associated with improved airway indices, especially in the distal airways, together with improvements in respiratory health status. Trial registration ClinicalTrials.gov (NCT04876677), first posted 6th May 2021.
Topics: Humans; Formoterol Fumarate; Glycopyrrolate; Beclomethasone; Pulmonary Disease, Chronic Obstructive; Muscarinic Antagonists; Administration, Inhalation; Fluticasone-Salmeterol Drug Combination; Drug Combinations; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents
PubMed: 37803368
DOI: 10.1186/s12931-023-02549-5 -
Respiratory Medicine Jun 2023The extrafine single inhaler triple therapy (efSITT) containing beclometasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 μg has proved to be efficacious in... (Observational Study)
Observational Study
"Extrafine single inhaler triple therapy effect on health status, lung function and adherence in COPD patients: A Panhellenic prospective non-interventional study - The TRIBUNE study".
The extrafine single inhaler triple therapy (efSITT) containing beclometasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 μg has proved to be efficacious in patients with Chronic Obstructive Pulmonary Disease (COPD) in randomized control trials. TRIBUNE study aimed to assess the efSITT effectiveness on health status, lung function, adherence and rescue medication use in COPD patients in Greece in a real-world setting. This was a 24-week prospective, multicenter, observational study in 1,195 patients with moderate/severe COPD and history of at least one exacerbation during the previous year despite dual therapy. Health status (COPD Assessment Test/CAT), lung function parameters and rescue medication use were recorded at baseline, 3 (Visit 2/V2) and 6 months (Visit 3/V3) after treatment. Adherence (Test of Adherence to Inhalers/TAI) and self-reported overall impression of health condition change (Visual Analogue Scale/VAS) were recorded at V2 and V3. Mean CAT score decreased from 20.9 points at V1, to 15.1 at V2 and 13 at V3 (p < 0.001, all pair comparisons). 85.9% of patients achieved a CAT decrease of minimal clinically important difference (MCID) or more (≥2) at V3, compared to V1. Mean FEV1 increased from 1.4 ± 0.5 L on V1, to 1.6 ± 0.5 L on V3 (p < 0.001, N = 275). The percentage of patients with "good adherence" increased from 58.4% (V2) to 64.0% (V3). Rescue medication use and VAS also significantly improved. The efSITT achieves improved outcomes on health status, lung function and rescue medication use as well as satisfactory adherence and patient-reported improvement of health condition, in moderate/severe COPD patients previously treated with a dual combination in a Greek real-world setting.
Topics: Humans; Prospective Studies; Adrenergic beta-2 Receptor Agonists; Administration, Inhalation; Forced Expiratory Volume; Formoterol Fumarate; Pulmonary Disease, Chronic Obstructive; Nebulizers and Vaporizers; Lung; Health Status; Bronchodilator Agents; Drug Combinations
PubMed: 36965590
DOI: 10.1016/j.rmed.2023.107219 -
Pharmaceutics Jun 2023Medical composites derived from Gamma-cyclodextrin (-CD) and beclomethasone dipropionate-gamma-cyclodextrin (BDP--CD) are synthesized over supercritical-assisted...
Medical composites derived from Gamma-cyclodextrin (-CD) and beclomethasone dipropionate-gamma-cyclodextrin (BDP--CD) are synthesized over supercritical-assisted atomization (SAA) herein. Carbon dioxide, which serves the dual function of spraying medium and co-solute, is incorporated in this process along with the ethanolic solvent. Results indicate that, for fine spherical particles, optimized aerosol performance could be obtained with 50.0% (/) ethanolic solvent, precipitator, and saturator at 373.2 K and 353.2 K, respectively, and carbon dioxide-to--CD flow ratio of 1.8 in the presence of 10 wt% leucine (LEU) as dispersion enhancer. It is also noted that -CD solution at low concentration typically renders better aerosol performance of the particles. During drug particle-derivation, the solubility of drug BDP elevated considerably due to the formation of inclusion complexes, further assisted by the ethanolic solvent which increases the lipophilicity of BDP. Meanwhile, the in vitro aerosolization and dissolution performance of drug composites derived from varied -CD-to-BDP mass ratio () were also evaluated. It was found that high promises higher fine particle fraction in the obtained drug composite while the dissolution rate of active ingredient (BDP) exhibits positive correlation to the content of water-soluble excipient (-CD) in the formulation. This study offers a new avenue for instant drug formulation with promising pulmonary delivery over the SAA technique.
PubMed: 37376188
DOI: 10.3390/pharmaceutics15061741