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Background: The extrafine single inhaler triple therapy (efSITT) containing beclomethasone 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. Objective: TRIWIN study evaluated the effectiveness of efSITT delivering beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 μg in COPD patients previously treated with multiple-inhaler triple therapy (MITT) in a real-world study in Greece. Design: Prospective, multicenter, observational, non-interventional study was conducted over 24 weeks. Methods: A total of 475 eligible patients had moderate-to-severe COPD, an indication for treatment with efSITT, and were symptomatic despite receiving MITT. COPD Assessment Test (CAT) score, pulmonary function parameters, use of rescue medication, and adherence to inhaler use were recorded at baseline (Visit 1), 3 (Visit 2), and 6 months (Visit 3) after treatment. Results: Mean CAT score decreased from 21.4 points at Visit 1, to 16.6 at Visit 2 and 15.1 at Visit 3 (p < 0.001 for all pair comparisons). At Visit 3, 79.8% of patients reached a CAT improvement exceeding minimal clinically important difference (⩾2), compared to baseline. Mean forced expiratory volume in 1 s (%pred.) increased from 55.4% at Visit 1 to 63.5% at the end of study period (p < 0.001), while mean forced vital capacity (%pred.) increased from 71.1% at Visit 1, to 76.7% at Visit 3 (p < 0.001). The mean Test of Adherence to Inhalers score increased from 42.5 to 45.3 and 46.3 points, for the three visits, respectively (p < 0.001 comparing Visits 1/2 and Visits 1/3; p = 0.006 comparing Visits 2/3). The percentage of patients showing good adherence rose from 33.7% at baseline to 58.3% at Visit 3. The percentage of patients using rescue medication during the last month dropped from 16.2% to 7.4% at the end of study period (p < 0.001). Pulmonary function parameters also improved. Conclusion: The TRIWIN results suggest that extrafine beclomethasone dipropionate/formoterol fumarate/glycopyrronium is effective in improving health status, pulmonary function, and adherence and in reducing rescue medication use in COPD patients previously treated with MITT, in a real-world setting in Greece. [ABSTRACT FROM AUTHOR]

When selecting inhaled therapies, it is important to consider both the active molecules and the device. Extrafine formulation beclomethasone dipropionate plus formoterol fumarate (BDP/FF) has been available for some years delivered via pressurized metered-dose inhaler (pMDI). More recently, a breath-activated, multi-dose dry-powder inhaler (DPI), the NEXThaler, has been approved. The current study aimed to demonstrate the non-inferiority of BDP/FF delivered via the DPI vs. via the pMDI, in Chinese adults with asthma. After a four-week run-in period, when all patients received BDP/FF pMDI 100/6 µg, two inhalations twice daily (BID), patients were randomized equally to BDP/FF pMDI or DPI, both 100/6 µg, two inhalations BID for 12 weeks. The primary objective was to demonstrate non-inferiority of BDP/FF DPI vs. BDP/FF pMDI in terms of average pre-dose morning peak expiratory flow (PEF) over the entire treatment period. Of 252 and 242 patients in the DPI and pMDI groups, respectively, 88.5% and 88.8% completed the study. The primary objective was met, with no statistically significant difference between the treatments in average pre-dose morning PEF, and with the lower limit of the 95% CI above the −15 L/min non-inferiority margin (adjusted mean difference: 5.25 L/min [95% CI: −0.56, 11.06]). Adverse events were reported by 48.4% and 49.6% patients in the DPI and pMDI groups, respectively, most mild or moderate. The NEXThaler DPI is a similarly effective device to the pMDI for the administration of BDP/FF in adults, so extending the options available for the management of asthma. [ABSTRACT FROM AUTHOR]

Abstract Background A single-inhaler extrafine triple combination of beclometasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) has been developed for maintenance therapy of chronic obstructive pulmonary disease (COPD). This study evaluated the efficacy and safety of BDP/FF/G in patients in three eastern Asian areas: China, Republic of Korea and Taiwan. Methods TRIVERSYTI was a double-blind, randomised, active-controlled, parallel-group study in patients with COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1)

Background: Functional respiratory imaging (FRI) is a computational fluid dynamics-based technique using three-dimensional models of human lungs and formulation profiles to simulate aerosol deposition. Methods: FRI was used to evaluate lung deposition of extrafine beclomethasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB) and extrafine BDP/FF delivered through pressurized metered dose inhalers and to compare results with reference gamma scintigraphy data. FRI combined high-resolution computed tomography scans of 20 patients with moderate-to-severe chronic obstructive pulmonary disease (mean forced expiratory volume in 1 second 42% predicted) with in silico computational flow simulations, and incorporated drug delivery parameters to calculate aerosol airway deposition. Inhalation was simulated using profiles obtained from real-life measurements. Results: Total lung deposition (proportion deposited in intrathoracic region) was similarly high for both products, with mean ± standard deviation (SD) values of 31.0% ± 5.7% and 28.1% ± 5.2% (relative to nominal dose) for BDP/FF/GB and BDP/FF, respectively. Pairwise comparison of the deposition of BDP and FF gave a mean intrathoracic BDP/FF/GB:BDP/FF deposition ratio of 1.10 (p = 0.0405). Mean intrathoracic, central and peripheral deposition ratios for BDP were 1.09 (95% confidence interval [CI]: 1.05–1.14), 0.92 (95% CI: 0.89–0.96), and 1.20 (95% CI: 1.15–1.26), respectively, and for FF were 1.11 (95% CI: 1.07–1.15), 0.94 (95% CI: 0.91–0.98), and 1.21 (95% CI: 1.15–1.27), within the bioequivalence range (0.80–1.25) for intrathoracic and central regions, and slightly exceeding the upper boundary in the peripheral region. Mean ± SD central:peripheral deposition (C:P) was 0.48 ± 0.13 for BDP/FF/GB and 0.62 ± 0.17 for BDP/FF, indicating a higher proportion of drug deposition in the small airways than in the large airways. Conclusion: FRI demonstrated similar deposition patterns for extrafine BDP/FF/GB and BDP/FF, with both having a high lung deposition. Moreover, the deposition patterns of BDP and FF were similar in both products. Furthermore, the C:P ratios of both products indicated a high peripheral deposition, supporting small airway targeting and delivery of these two extrafine fixed combinations, with a small difference in ratios potentially due to mass median aerodynamic diameters. [ABSTRACT FROM AUTHOR]

Background: A single-inhaler extrafine triple combination of beclometasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) has been developed for maintenance therapy of chronic obstructive pulmonary disease (COPD). This study evaluated the efficacy and safety of BDP/FF/G in patients in three eastern Asian areas: China, Republic of Korea and Taiwan.Methods: TRIVERSYTI was a double-blind, randomised, active-controlled, parallel-group study in patients with COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1) < 50% predicted, ≥ 1 exacerbation in the previous 12 months, and receiving inhaled maintenance medication. Patients received either extrafine BDP/FF/G 100/6/10 µg via pressurised metered-dose inhaler, or non-extrafine budesonide/formoterol (BUD/FF) 160/4.5 µg via dry-powder inhaler, both administered as two puffs twice-daily for 24 weeks. The co-primary objectives (analysed in the overall population) were to demonstrate superiority of BDP/FF/G over BUD/FF for change from baseline in pre-dose morning and 2-h post-dose FEV1 at Week 24 (these were analysed as key secondary objectives in the China subgroup). The rate of moderate/severe COPD exacerbations was a secondary endpoint.Results: Of 708 patients randomised, 88.8% completed. BDP/FF/G was superior to BUD/FF for pre-dose and 2-h post-dose FEV1 at Week 24 [adjusted mean differences 62 (95% CI 38, 85) mL and 113 (87, 140) mL; both p < 0.001]. The annualised moderate/severe exacerbation rate was 43% lower with BDP/FF/G [rate ratio 0.57 (95% CI 0.42, 0.77); p < 0.001]. Adverse events were reported by 61.1% and 67.0% patients with BDP/FF/G and BUD/FF. Results were similar in the China subgroup.Conclusions: In patients with COPD, FEV1 < 50% and an exacerbation history despite maintenance therapy, treatment with extrafine BDP/FF/G improved bronchodilation, and was more effective at preventing moderate/severe COPD exacerbations than BUD/FF. Trial registration CFDA CTR20160507 (registered 7 Nov 2016, http://www.chinadrugtrials.org.cn/index.html ). [ABSTRACT FROM AUTHOR]

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of the current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation.

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., Competing Interests: Declaration of competing interest The authors have the following to declare: Konstantinos Porpodis reports no conflict of interest. Konstantinos Bartziokas reports no conflict of interest. Panagiotis Chatziapostolou reports financial support as principal investigator of this study by Chiesi Hellas S.A. Petros Efstathopoulos and Aliki Korkontzelou are employed by Chiesi Hellas S.A. Panos Katerelos reports financial support as statistical analyst of the present study. Petros Bakakos has nothing to declare in terms of the present study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Abstract: Despite the wealth of experience in the management of asthma, the disease remains inadequately controlled in some patients, who face long-term respiratory impairment and disability. The disease has been characterised as an inflammatory condition affecting first the larger airways and eventually the smaller airways, but there is evidence that peripheral airway involvement defines a particular and more severe phenotype of asthma. For this reason, assessing functional and biological parameters reflective of small airways involvement is important prognostically. No assessment method is universally and directly representative of peripheral airway function, but the traditional spirometric tests, including vital capacity, residual volume and forced vital capacity, are somewhat correlated with this function; useful methods for further assessment include the single-breath nitrogen wash-out test, impulse oscillometry, nitrous oxide and exhaled breath concentrate measurements, as well as computed tomography to reflect air trapping and response to treatment. Formulation advancements have made for easier treatment access to the smaller airways, with the new extrafine formulations resulting in better asthma control compared with non-extrafine formulations. [Copyright &y& Elsevier]

Background: Asthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting β2 agonist combination therapy. Methods: This was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100 μg) of fluticasone/salmeterol were randomly assigned to 6 months of open-label treatment with either 500/100 μg fluticasone/salmeterol Diskus daily or 400/24 μg extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency. Results: Four hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49 L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6 months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events. Conclusions: Stepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100 μg fluticasone/salmeterol daily or 400/24 μg extra-fine beclomethasone/ formoterol daily provides comparable maintenance of lung function and asthma control. [ABSTRACT FROM AUTHOR]

Background: Although patients have more problems using metered dose inhalers, clinical comparisons suggest they provide similar control to dry powder inhalers. Using real-life situations this study was designed to evaluate asthma control in outpatients with moderate to severe persistent asthma and to compare efficacy of fixed combinations of inhaled corticosteroids (ICS) and long acting beta-agonists (LABA). Methods: This real-life study had a cross-sectional design. Patients using fixed combinations of ICS and LABA had their asthma control and spirometry assessed during regular visits. Results: 111 patients were analyzed: 53 (47.7%) received maintenance therapy of extrafine beclomethasoneformoterol (BDP/F) pressurized metered dose inhaler (pMDI), 25 (22.5%) fluticasone-salmeterol (FP/S) dry powder inhaler (DPI), and 33 (29.7%) budesonide-formoterol (BUD/F) DPI. Severity of asthma at time of diagnosis, assessed by the treating physician, was comparable among groups. Asthma control was achieved by 45.9% of patients; 38.7% were partially controlled and 15.3% were uncontrolled. In the extrafine BDF/F group, asthma control total score, daytime symptom score and rescue medication use score were significantly better than those using fixed DPI combinations (5.8 ± 6.2 vs. 8.5 ± 6.8; 1.4 ± 1.8 vs. 2.3 ± 2.1; 1.8 ± 2.2 vs. 2.6 ± 2.2; p = 0.0160; p = 0.012 and p = 0.025, respectively) and the mean daily ICS dose were significantly lower. Conclusions: pMDI extrafine BDP/F combination demonstrated better asthma control compared to DPIs formulated with larger particles. This could be due to the improved lung deposition of the dose or less reliance on the optimal inhalation technique or both. [ABSTRACT FROM AUTHOR]

Exhaled nitric oxide (NO) is a noninvasive marker of airway inflammation. Beclomethasone dipropionate (BDP) is the only inhaled corticosteroid (ICS) available as both extrafine and nonextrafine hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) formulation. The present study was designed to evaluate whether the different patterns of lung deposition of two HFA BDP formulations are associated with a different effect on bronchial and alveolar NO. This was a prospective double-blind, randomized, controlled, crossover study. After a 2-week placebo run-in period without ICSs, asthmatic patients were randomized to extrafine BDP, 100 μg, b.i.d. or nonextrafine BDP, 250 μg, b.i.d. for two 2-week periods separated by a 2-week washout period. Fourteen patients (5 men) with a mean age 37 years and mean baseline forced expiratory volume in 1 second (FEV1) of 83% of predicted were analyzed. Exhaled bronchial NO was significantly (p < 0.001) reduced in both treatment groups when compared with the last week of run-in period, whereas alveolar NO was significantly (p < 0.001) reduced only with extrafine BDP. Moreover, extrafine BDP was superior to nonextrafine BDP in both parameters (p < 0.05). Extrafine but not nonextrafine BDP HFA formulation lowers both bronchial and alveolar exhaled NO in asthmatic patients. ICS distribution throughout the whole bronchial tree could be important in patients who do not gain optimal control of inflammation with conventional nonextrafine ICS. [ABSTRACT FROM AUTHOR]

Background: The fixed combination of extrafine beclometasone dipropionate 100 μg/formoterol 6 μg (extrafine BDP/F) delivered by NEXThaler has proved to be effective in patients with moderate-to-severe asthma in terms of lung function, symptoms and asthma control. The aim of this study was to investigate the usability/satisfaction of NEXThaler and adherence to treatment in asthma patients not well controlled by low-dose inhaled corticosteroids (ICS). Methods: This was a 6-month prospective, multicenter, open-label, observational study in 661 patients with asthma not well controlled by low-dose ICS according to the physician's clinical assessment, which have received regular treatment with extrafine BDP/F NEXThaler. Feeling of Satisfaction with Inhaler (FSI), treatment adherence with self-reported Morisky scale, asthma control, lung function and QoL were recorded at baseline, 3 and 6 months after treatment with extrafine BDP/F. Results: The percentage of patients at least "fairly" satisfied with NEXThaler usability (FSI-10 score 40 to 50) was 96.3%. The mean FSI-10 total score was 46.8 ± 4.4 on Visit 2 and increased to 48.1 ± 3.3 on Visit 3 (p < 0.001). Approximately 67% of the patients reported "high adherence" on Visit 2, and 70% of them reported "high adherence" on Visit 3. The percentage of patients with ACQ-6-uncontrolled asthma decreased from 79.1% on Visit 1 to 22.3% on Visit 2 and further decreased to 6.7% on Visit 3. Significant improvements were also observed in the total AQLQ score, predicted FEV1% and reduction in rescue medication use. Conclusions: The NEXThaler device, delivering a combination of BDP/F, achieves satisfaction and high adherence in patients with asthma not well controlled with low-dose ICS. Asthma control, QoL, lung function and rescue medication use were improved in a Greek real-world setting. [ABSTRACT FROM AUTHOR]

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of the current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation. [ABSTRACT FROM AUTHOR]

Abstract Background Although patients have more problems using metered dose inhalers, clinical comparisons suggest they provide similar control to dry powder inhalers. Using real-life situations this study was designed to evaluate asthma control in outpatients with moderate to severe persistent asthma and to compare efficacy of fixed combinations of inhaled corticosteroids (ICS) and long acting beta-agonists (LABA). Methods This real-life study had a cross-sectional design. Patients using fixed combinations of ICS and LABA had their asthma control and spirometry assessed during regular visits. Results 111 patients were analyzed: 53 (47.7%) received maintenance therapy of extrafine beclomethasone-formoterol (BDP/F) pressurized metered dose inhaler (pMDI), 25 (22.5%) fluticasone-salmeterol (FP/S) dry powder inhaler (DPI), and 33 (29.7%) budesonide-formoterol (BUD/F) DPI. Severity of asthma at time of diagnosis, assessed by the treating physician, was comparable among groups. Asthma control was achieved by 45.9% of patients; 38.7% were partially controlled and 15.3% were uncontrolled. In the extrafine BDF/F group, asthma control total score, daytime symptom score and rescue medication use score were significantly better than those using fixed DPI combinations (5.8 ± 6.2 vs. 8.5 ± 6.8; 1.4 ± 1.8 vs. 2.3 ± 2.1; 1.8 ± 2.2 vs. 2.6 ± 2.2; p = 0.0160; p = 0.012 and p = 0.025, respectively) and the mean daily ICS dose were significantly lower. Conclusions pMDI extrafine BDP/F combination demonstrated better asthma control compared to DPIs formulated with larger particles. This could be due to the improved lung deposition of the dose or less reliance on the optimal inhalation technique or both.

Introduction: Chronic obstructive pulmonary disease (COPD) management focuses on the alleviation of symptoms and prevention of exacerbations. Inhaled long acting bronchodilators and inhaled corticosteroids (ICS) are the main classes of treatment for COPD. Triple therapy with a long acting beta 2 -agonist (LABA), long acting muscarinic antagonist (LAMA), and ICS is commonly prescribed for symptomatic COPD patients experiencing regular exacerbations. Triple therapy is usually administered using separate inhalers; there is little clinical trial evidence of an effect on exacerbation prevention with this approach. Areas covered: This evaluation reviews the single inhaler extrafine combination containing beclometasone diproprionate (BDP), formoterol fumarate (FF), and glycopyrronium bromide (GB) which has been developed as a simplified triple regime. BDP/FF/GB significantly reduced exacerbation rates in three clinical trials (1-year duration) compared against LAMA monotherapy (20% exacerbation reduction), ICS/LABA combination (23% exacerbation reduction), and LAMA/LABA combination (15% exacerbation reduction). Expert opinion: The practical benefits of single inhaler triple therapy in the real world have not been studied. However, the robust clinical trial evidence that BDP/FF/GB reduces exacerbations compared to double combination treatments and LAMA monotherapy cements triple therapy positioning as an escalation step in COPD management pathways.

Unlabelled: This multicentre, double-blind, randomised, placebo-controlled, crossover study aimed to determine the dose-response of the long-acting muscarinic antagonist (LAMA) glycopyrronium bromide (GB) when added to beclometasone dipropionate plus formoterol fumarate (BDP/FF) in patients with COPD. Patients received extrafine GB 12.5, 25 or 50 μg twice daily (BID) or placebo for 7 days via pressurised metered dose inhaler (pMDI), and extrafine BDP/FF via pMDI throughout the study. The primary objective was to demonstrate superiority of GB plus BDP/FF versus BDP/FF in terms of FEV1 area under the curve from 0 to 12 h (AUC0-12h) on Day 7. Secondary endpoints included: FEV1 AUC0-12h on Day 1; peak FEV1 and FVC on Days 1 and 7; and trough (12 h post-dose) FEV1, FVC and inspiratory capacity (IC) on Days 1 and 7. Of 178 patients randomised (mean age 62.7 years, post-bronchodilator FEV1 48.9%), 172 (96.6%) completed. Mean FEV1 AUC0-12h on Day 7 was significantly higher (p < 0.001) for all GB doses plus BDP/FF compared to BDP/FF alone, with the difference for the 25 and 50 μg BID doses being clinically relevant (i.e., ≥100 mL). The results for the other spirometry endpoints were consistent with the primary endpoint. Adverse events were reported in 7.4, 5.7 and 8.0% of patients receiving GB 12.5, 25 and 50 μg BID, respectively, versus 11.0% of patients receiving BDP/FF alone. This study confirms the value of adding GB to BDP/FF to improve lung function in COPD patients. The dose of extrafine GB 25 μg BID was associated with the best efficacy/safety profile., Trial Registered at: ClinicalTrials.gov., Registration Number: NCT01476813., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Inhaled therapy is often considered the cornerstone of asthma management and international guidelines recommend combination therapy of inhaled corticosteroids (ICS) and long-acting-beta2-agonists (LABA) in a large proportion of asthmatic patients. The effectiveness of ICS/LABA is dependent on the correct choice of device and proper inhalation technique, this influences drug delivery and distribution along the bronchial tree, including the most peripheral airways. The fixed combination of beclometasone dipropionate/formoterol fumarate (BDP/FF) is the only extrafine formulation available in pressurized metered dose inhaler (pMDI) and in dry powder inhaler (DPI). Here, we focus on the recent significant advances regarding BDP/FF fixed combination for the treatment of asthma.

The small-particle inhaled corticosteroid might be a new available way to treat uncontrolled asthma. To evaluate the efficacy and safety of extrafine hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) versus budesonide (BUD) in patients with asthma, a meta-analysis was performed. A systematic search was made of PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov and Ovid, and a hand search of leading respiratory journals. Randomised controlled trials (RCTs) on treatment of asthma for 4 or more weeks with extrafine HFA-BDP, compared with BUD, were reviewed. Five studies involving 949 asthmatic patients met the inclusion criteria. There was no significant difference in FEV1 (SMD=-0.03L, 95% CI -0.15 to 0.10L, I(2)=0%, P=0.70), morning PEF (WMD=0.88 L/min, 95% CI -5.96 to 7.72 L/min, I(2)=0%, P=0.80), evening PEF (WMD=6.32 L/min, 95% CI -1.17 to 13.81 L/min, I(2)=33%, P=0.10) and use of rescue medication (WMD=-0.13, 95% CI -0.31 to 0.06, I(2)=41%, P=0.18) between extrafine HFA-BDP at half of the daily dose and BUD group. Individual studies reported no significant differences in asthma exacerbations and 7-point Asthma Control Questionnaire score (ACQ-7). There were no significant difference in total number of adverse events (OR=1.04, 95% CI 0.78 to 1.38, I(2)=0%, P=0.81) between the two groups. Our meta-analysis demonstrated that extrafine HFA-BDP at half of daily dose is equivalent to BUD in improving lung function and use of rescue medication, without increasing adverse events in patients with asthma. Long-term trials are required to assess the efficacy and safety of extrafine HFA-BDP.

Drugs for asthma and other chronic obstructive diseases of the lungs should be preferably delivered by the inhalation route to match therapeutic effects with low systemic exposure. Inhaled drugs are delivered to the lungs via different devices, mainly metered dose inhalers and dry powder inhalers, each characterized by specific inhaler technique and instructions for use. The patient-device interaction is part of the prescribed therapy and can have a relevant impact on adherence and clinical outcomes. The most suitable device should be considered for each patient to assure the correct drug intake and adherence to the prescribed therapy. The development of new drugs/devices in the past decades improved the compliance with inhaler and possibly drug delivery to the bronchi. The present review focuses on the recently developed beclomethasone/formoterol extrafine fixed combination and technical aspects of drug delivery to the lungs in patient's perspective.