Comparative Efficacy of Budesonide/Formoterol Versus Fluticasone/Salmeterol in Patients With Moderate-to-Severe Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVE: To compare the efficacy of budesonide/formoterol (BF) versus fluticasone/salmeterol (FS) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for studies comparing BF versus FS in the treatment of COPD from inception to July 17, 2023. Outcomes, including exacerbations, hospitalizations, pneumonia, emergency department (ED) visits for COPD, length of hospitalization, and number of exacerbations, were compared using risk ratio (RR) with corresponding 95% confidence interval (CI) or weighted mean difference (WMD) with 95% CI. All statistical analyses were performed using Stata version 12.0. RESULTS: Ten studies comprising a total of 136,369 participants were included. Compared with those treated with FS, patients with COPD treated with BF experienced a reduced number of exacerbations (RR 0.91 [95% CI 0.83-1.00]; p = 0.040), hospitalizations (RR 0.77 [95% CI 0.67-0.88]; p < 0.001), and frequency of pneumonia (RR 0.77 [95% CI 0.64-0.92]; p = 0.05). However, no significant difference was observed between BF and FS in terms of ED visits for COPD (RR 0.87 [95% CI 0.69-1.10]; p = 0.243), length of hospitalization (WMD -0.18 [95% CI -0.62-0.27]; p = 0.437), and number of exacerbations (WMD -0.06 [95% CI -0.28-0.16]; p = 0.602). Notably, no significant heterogeneity was noted in length of hospitalization between the two groups, whereas clear heterogeneity was observed in other outcomes (I2 > 50%, p < 0.05). CONCLUSION: Compared with FS, BF therapy appears to be a more promising treatment strategy for patients with moderate-to-severe COPD; however, this should be verified in further high-quality studies.

Budesonide/Formoterol or Budesonide/Albuterol as Anti-Inflammatory Reliever Therapy for Asthma.

Overuse of reliever as short-acting beta-agonist and associated underuse of controller as inhaled corticosteroid (ICS) administered via separate inhalers results in worse asthma outcomes. Such discordance can be obviated by combining both controller and reliever in the same inhaler. So-called anti-inflammatory reliever (AIR) therapy comprises the use of a single inhaler containing an ICS such as budesonide (BUD) in conjunction with a reliever as either albuterol (ALB) or formoterol (FORM), to be used on demand, with variable dosing driven by asthma symptoms in a flexible patient-centered regimen. Global guidelines now support the use of BUD-ALB as AIR therapy to reduce exacerbations, either on its own in mild asthma or in conjunction with fixed-dose maintenance ICS-long-acting beta-agonist in moderate to severe asthma. Using BUD-FORM on its own allows patients to seamlessly move in an intuitive flexible fashion between AIR and maintenance and reliever therapy, by stepping up and down the dosing escalator across a spectrum of asthma severities. Head-to-head clinical studies are indicated to compare BUD-FORM versus BUD-ALB as AIR in mild asthma, and also BUD-FORM as maintenance and reliever therapy versus BUD-ALB as AIR plus maintenance ICS-long-acting beta-agonist in moderate to severe asthma. Patients should be encouraged to make an informed decision in conjunction with their health care professional regarding the best therapeutic option tailored to their individual needs, which in turn is likely to result in long-term compliance and associated optimal asthma control.

Effect of Individual Patient Characteristics and Treatment Choices on Reliever Medication Use in Moderate-Severe Asthma: A Poisson Analysis of Randomised Clinical Trials.

INTRODUCTION: Even though increased use of reliever medication, including short-acting beta agonists (SABA), provides an indirect measure of symptom worsening, there have been limited efforts to assess how different patterns of reliever use correlate with symptom control and future risk of exacerbations. Here, we evaluate the effect of individual baseline characteristics on reliever use in patients with moderate-severe asthma on regular maintenance therapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). METHODS: A drug-disease model describing the number of 24-h puffs and overnight occasions was developed with data from five clinical studies (N = 6212). The model was implemented using a nonlinear mixed effects approach and a Poisson function, considering clinical and demographic baseline characteristics. Goodness of fit and model predictive performance were assessed. Heatmaps were created to summarise the effect of concurrent baseline factors on reliever utilisation. RESULTS: The final model accurately described individual patterns of reliever use, which is significantly increased with time since diagnosis, smoking, higher Asthma Control Questionnaire (ACQ-5) score and higher body mass index (BMI) at baseline. Whilst the number of puffs decreases slowly after an initial drop relative to the start of treatment, exacerbating patients utilise significantly more reliever than those who do not exacerbate. The mean effect of FP/SAL (median dose: 250/50 µg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5 µg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively. CONCLUSIONS: The availability of individual-level patient data in conjunction with a parametric approach enabled the characterisation of interindividual differences in the patterns of reliever use in patients with moderate-severe asthma. Taken together, individual demographic and clinical characteristics, as well as exacerbation history, can be considered an indicator of the degree of asthma control. High SABA reliever use suggests suboptimal clinical management of patients on maintenance therapy.

In this study, we tried to understand how patients with moderate to severe asthma use their quick-relief inhalers (like albuterol), how it relates to their symptoms and the risk of having asthma attacks. To evaluate whether differences in reliever inhaler use between patients are associated with factors like smoking or their asthma symptoms at the beginning of treatment, we gathered data from five clinical studies (n = 6212 patients). These data allowed us to create a model that predicts how often patients use their reliever inhalers (expressed as number of puffs in 24 h) during maintenance therapy with inhaled corticosteroids alone or in combination with long-acting beta agonists. The final model showed that reliever inhaler use is higher in patients who have been diagnosed with asthma for > 10 years, are smokers, have higher asthma symptom scores, and are obese or extremely obese. Patients who had asthma attacks also used their reliever inhalers more often. In addition, to understand how relief inhalers are used in real-life situations, we also created heatmaps that include a wide range of patient characteristics. By using individual patient data together with this model, we have learned that smoking, asthma control, BMI, long history of asthma and previous asthma attacks significantly influence reliever use. This information can help physicians and healthcare professionals understand know how well someone's asthma is managed. A patient who uses their reliever inhaler often is likely not to have their asthma well controlled by their regular medications.

Cost-effectiveness of budesonide-formoterol vs inhaled epinephrine in US adults with mild asthma.

BACKGROUND: The management of mild asthma has lacked an over-the-counter (OTC) option aside from inhaled epinephrine, which is available in the United States. However, inhaled epinephrine use without an inhaled corticosteroid may increase the risk of asthma death. OBJECTIVE: To compare the cost-effectiveness of OTC as-needed budesonide-formoterol as a plausible alternative to inhaled epinephrine. METHODS: We developed a probabilistic Markov model to compare OTC as-needed budesonide-formoterol inhaler use vs inhaled epinephrine use in adults with mild asthma from a US societal perspective over a lifetime horizon, with a 3% annual discount rate (2022 US dollars). Inputs were derived from the SYmbicort Given as-needed in Mild Asthma (SYGMA) trials, published literature, and commercial costs. Outcomes were quality-adjusted life-years (QALY), costs, incremental net monetary benefit (INMB), severe asthma exacerbations, well-controlled asthma days, and asthma-related deaths. Microsimulation was used to evaluate underinsured Americans living with mild asthma (n = 5,250,000). RESULTS: Inhaled epinephrine was dominated (with lower QALYs gains at a higher cost) by both as-needed budesonide-formoterol (INMB, $15,541 at a willingness-to-pay of $100,000 per QALY) and the no-OTC inhaler option (INMB, $1023). Adults using as-needed budesonide-formoterol had 145 more well-controlled asthma days, 2.79 fewer severe exacerbations, and an absolute risk reduction of 0.23% for asthma-related death compared with inhaled epinephrine over a patient lifetime. As-needed budesonide-formoterol remained dominant in all sensitivity and scenario analyses, with a 100% probability of being cost-effective compared with inhaled epinephrine in probabilistic sensitivity analysis. CONCLUSION: If made available, OTC as-needed budesonide-formoterol for treating mild asthma in underinsured adults without HCP management improves asthma outcomes, prevents fatalities, and is cost-saving.

Benefit of Prompt Vs Delayed Initiation of Triple Therapy Following an Exacerbation in Patients with COPD in Japan: A Retrospective Cohort Study.

Purpose: There is currently limited evidence for the optimal timing of triple therapy initiation in Japan, which is crucial for optimizing strategies for the effective treatment of chronic obstructive pulmonary disease (COPD). This study assessed the impact of prompt vs delayed initiation of triple therapy following a COPD exacerbation on clinical and economic outcomes in patients in Japan. Patients and Methods: Retrospective cohort study of patients in the Medical Data Vision Co., Ltd. database initiating triple therapy as single-inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol or budesonide/glycopyrronium/formoterol) or multiple-inhaler triple therapy within 180 days of a moderate-to-severe exacerbation (index). For the main analysis, patients were categorized as prompt or delayed initiators, initiating triple therapy within 0-30 days or 31-180 days of index, respectively. Inverse probability of treatment weighting based on propensity scores was used to adjust for measured confounders between prompt and delayed cohorts. Results: For the main analysis, 610 (60.3%) and 402 (39.7%) patients were prompt and delayed initiators, respectively. The rate of subsequent moderate-to-severe exacerbations following index exacerbation was numerically lower in prompt vs delayed initiators (weighted rate ratio 0.95, 95% confidence interval [CI]: 0.74-1.21; P = 0.6603). Time-to-first subsequent moderate-to-severe exacerbation increased significantly in prompt vs delayed initiators (weighted hazard ratio 0.77, 95% CI: 0.64-0.93; P = 0.0053). In patients indexed on a severe exacerbation, delayed initiation resulted in significantly higher 90-day all-cause readmissions vs prompt initiation (42.1% vs 30.6%; P = 0.0329 [weighted estimates]). Weighted healthcare resource utilization rates were numerically lower in prompt vs delayed initiators, and weighted direct costs (all cause and COPD-related) were significantly lower in prompt initiators. Conclusion: This real-world study demonstrated that earlier initiation of triple therapy resulted in several benefits in clinical outcomes for COPD and may also reduce the economic burden of COPD management in Japan.

Evaluating the affordability of asthma, chronic obstructive pulmonary disease, and cystic fibrosis medicines in a middle-income country.

BACKGROUND: A heavy financial burden is imposed on patients suffering from chronic diseases due to medicine out-of-pocket payments. OBJECTIVES: This study focuses on assessing the affordability of medications used for chronic respiratory diseases (CRDs) such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) in Iran, specifically on the category R medicines listed in the 2017 Iran drug list (IDL) that are used for the treatment of these diseases, based on the anatomical therapeutic chemical (ATC) drug code. METHODS: The affordability of medicines in mono and combination therapy approaches was assessed in CRDs using the World Health Organization/Health Action International (WHO/HAI) methodology. Accordingly, if out-of-pocket payment for 30-days of pharmacotherapy exceeds one day for the lowest-paid unskilled government worker (LPGW), it's considered non-affordable. RESULTS: Based on the monotherapy approach, our finding demonstrates that all generic medicines of category R were affordable. However, branded drugs such as Symbicort®, Pulmicort Respules®, Flusalmex®, Seretide®, Fluticort Plus®, Seroflo®, and Salmeflo® cost between 1.2 and 2.5 days' wage of LPGW and considered unaffordable despite 70% insurance coverage. Moreover, based on the affordability ratio in the combination therapy approach, all medicines used in asthma, COPD, and CF patients with mild respiratory problems are affordable except omalizumab (inj), which is non-affordable due to its high price and no insurance coverage. CONCLUSION: Results showed that the existing insurance coverage does not protect households from hardship, so more considerations are needed such as different insurance schedules and patient support programs.

Budesonide/formoterol maintenance and reliever therapy in childhood asthma: Real-world effectiveness and economic assessment.

INTRODUCTION: The study aims to compare the real-world effectiveness and economy of the budesonide/formoterol reliever and maintenance therapy (SMART) with fixed-dose inhaled corticosteroids (ICS)/long-acting b-agonist (LABA) or ICS alone plus as-needed, short-acting ß2 agonists (SABA) in pediatric patients. METHODS: The outpatient data warehouse of a hospital in China was used. A total of 103 patients under 18 years old in the SMART group and 63 patients in the control group were included from January 1, 2020 to December 31, 2021. The effectiveness was assessed using asthma attacks and lung function at baseline, 6 months and 12 months follow-up. Cost-effectiveness analysis was performed with a three-state Markov model from the healthcare system perspective. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to check the robustness of the results. RESULTS: The SMART regimen was more effective than other strategies in reducing the risk of mild and severe attacks in the real-life management of childhood asthma. Patients in both groups showed significant improvement in lung function at 6 and 12 months in contrast to baseline. Compared with other strategies, the forced expiratory volume in 1 s (FEV1 ) level in the SMART group was markedly improved at 6 months. The total cost of outpatient service using the SMART regimen was lower than that of other strategies, while the drug costs were similar in different groups. Incremental cost-effectiveness analysis results showed that using the SMART regimen reduced the total cost by approximately CNY 10,516.11 per year with a 0.12 quality-adjusted life year (QALYs) increase. Sensitive analyses supported that the SMART regimen was the dominant choice at the willingness-to-pay threshold of CNY 85,698, per capita GDP in China. CONCLUSIONS: Collectively, our findings indicate that the real-world effectiveness and economy of the SMART regimen are superior to the traditional strategies in pediatric asthma patients.

Should all asthma patients be switched to single maintenance and reliever therapy?

ABSTRACT: Recent data indicate that overuse of short-acting beta2-agonists (SABAs) results in an increased risk of asthma exacerbations and mortality. The use of inhaled corticosteroid-formoterol as both maintenance and reliever therapy has become a preferred regimen for asthma management. Clinicians should be aware of the pharmacology, dosing, and prescribing considerations regarding the use of budesonide-formoterol as the available combination in the United States.

Efficacy of inhaled tiotropium add-on to budesonide/formoterol in patients with bronchiolitis obliterans developing after hematopoietic stem cell transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We assessed whether inhaled tiotropium add-on to the combination regimen including budesonide/formoterol improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS. METHODS: Post-HSCT patients diagnosed as BOS in Seoul St. Mary's Hospital were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled. RESULTS: Total of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase, and a significant decrease in the RV/TLC ratio compared to the no-response group. CONCLUSIONS: Inhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.

Understanding the Clinical Implications of Individual Patient Characteristics and Treatment Choice on the Risk of Exacerbation in Asthma Patients with Moderate-Severe Symptoms.

INTRODUCTION: The assessment of future risk has become an important feature in the management of patients with asthma. However, the contribution of patient-specific characteristics and treatment choices to the risk of exacerbation is poorly understood. Here we evaluated the effect of interindividual baseline differences on the risk of exacerbation and treatment performance in patients receiving regular maintenance doses of inhaled corticosteroids (ICS) or ICS/long-acting beta-agonists (LABA) combination therapy. METHODS: Exacerbations and changes to asthma symptoms 5-item Asthma Control Questionnaire (ACQ-5) were simulated over a 12-month period using a time-to-event and a longitudinal model developed from phase III/IV studies in patients with moderate-severe asthma (N = 16,282). Simulations were implemented to explore treatment performance across different scenarios, including randomised designs and real-world settings. Treatment options included regular dosing with ICS monotherapy [fluticasone propionate (FP)] and combination therapy [fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR)]. Exacerbation rate was analysed using the log-rank test. The cumulative incidence of events was summarised stratified by treatment. RESULTS: Being a woman, smoker, having higher baseline ACQ-5 and body mass index (BMI) and lower forced expiratory volume in the first second (FEV1) are associated with increased exacerbation risk (p < 0.01). This risk is bigger in winter because of the seasonal variation effect. Across the different scenarios, the use of FP/SAL resulted in a 10% lower annual incidence of exacerbations relative to FP or regular dosing BUD/FOR, independently of baseline characteristics. Similar differences in the annual incidence of exacerbations were also observed between treatments in obese patients (BMI ≥ 25-35 kg/m2) (p < 0.01) and in patients who do not achieve symptom control on FP monotherapy. CONCLUSIONS: Individual baseline characteristics and treatment choices affect future risk. Achieving comparable levels of symptom control whilst on treatment does not imply comparable risk reduction, as shown by the lower exacerbation rates in FP/SAL vs. BUD/FOR-treated patients. These factors should be considered as a basis for personalised clinical management of patients with moderate-severe asthma.

The goal of this project was to demonstrate that individual baseline characteristics can affect the risk of exacerbation as well as the overall treatment response in patients receiving regular maintenance doses of inhaled corticosteroids, given as monotherapy or in combination with long-acting beta-agonists. Using computer simulations based on a drug­disease model previously developed from a large pool of patients with moderate­severe asthma symptoms (N = 16,282), we describe how demographic and clinical baseline patient characteristics at the time of treatment start correlate with the risk of exacerbation. Our results indicate that poor symptom control, limited lung function, obesity, smoking and sex are associated with significant increase in the incidence of asthma attacks. Such an effect is augmented in winter because of the contribution of seasonal variation. This analysis also allowed us to assess how different treatments modify or reduce the annual incidence of moderate to severe attacks. In addition, simulated scenarios showed that combination therapy with fluticasone propionate/salmeterol results in 10% fewer asthma attacks relative to budesonide/formoterol combination therapy. Such a difference may be associated with corticosteroid-specific properties, which vary between inhaled corticosteroids. Consequently, even though comparable level of immediate relief and symptom control may be achieved whilst on treatment, these effects do not imply the same long-term reduction in the risk of exacerbation. These factors should be considered as a basis for personalised clinical management of patients with moderate­severe asthma.

Effect of budesonide formoterol combined with tiotropium bromide on pulmonary function and inflammatory factors in patients with asthma-COPD overlap syndrome.

OBJECTIVE: To investigate the clinical efficacy of combining budesonide formoterol with tiotropium bromide for treating asthma-chronic obstructive pulmonary disease overlap syndrome (AOCS). METHODS: The data of 104 patients with AOCS admitted to our hospital from December 2019 to December 2020 were assessed, randomly and divided into an experimental group (comprising 52 patients, receiving drug combination therapy) and a conventional group (comprising 52 patients, receiving drug therapy alone). Patients' clinical efficacy, pulmonary function, fractioned exhaled nitric oxide (FeNO), immune function, endothelial function, serum lipid peroxidation injury indexes, adverse reactions, and quality of life scores were compared. RESULTS: Prior to treatment, no significant differences were observed in various pulmonary function indicators, FeNO, immune function, endothelial function, and lipid peroxidation injury indexes between the two groups (P > 0.05). However, after treatment, all observation indexes in both groups improved to different levels, with the experimental group -demonstrating -significantly superior improvement, compared to the conventional group (P < 0.05). We also observed that adverse reactions in the experimental group were significantly lower than in the conventional group (P < 0.05). CONCLUSION: The combination of budesonide formoterol to tiotropium bromide in treating asthma-COPD overlap syndrome may significantly improve pulmonary function, endothelial function, and immune status of patients and encourage the recovery of serum lipid peroxidation injury; therefore, this may deserve widespread adoption and application.

Effects of omalizumab combined with budesonide formoterol on clinical efficacy, pulmonary function, immune function, and adverse reactions in children with moderate and severe allergic asthma.

OBJECTIVE: To evaluate the clinical efficacy and safety of combining omalizumab with budesonide formoterol to treat children with moderate and severe allergic asthma, and investigate the effect of this combination therapy on pulmonary and immune functions. METHODS: The data of 88 children with moderate and severe allergic asthma, who were admitted to our hospital between July 2021 and July 2022, were included in the study. The patients were randomly assigned either to control group (n = 44; received budesonide formoterol inhalation therapy) or experimental group (n = 44; received omalizumab subcutaneous injection + budesonide formoterol inhalation therapy) using computer-generated randomization. The clinical efficacy, asthma control (measured using childhood Asthma-Control Test [C-ACT] score), pulmonary function (forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow), immune function (cluster of differentiation 3 cells [CD3+ cells], cluster of differentiation 4 cells [CD4+ cells], immunoglobulin G, immunoglobulin A, and immunoglobulin E), and adverse reactions were observed and compared between both groups. RESULTS: After treatment, the experimental group had improved levels of pulmonary function and immune function indexes, higher C-ACT scores, and a higher overall response rate than the control group (P < 0.05). In addition, the incidence of adverse reactions was not significantly different between both groups (P > 0.05). CONCLUSION: The combination of omalizumab with budesonide formoterol for treating moderate and severe allergic asthma in children demonstrated promising clinical efficacy and improved their pulmonary and immune functions, leading to more rational asthma control. The combined regimen demonstrated satisfactory clinical safety and deserved clinical promotion.

Assessing the Effects of Changing Patterns of Inhaled Corticosteroid Dosing and Adherence with Fluticasone Furoate and Budesonide on Asthma Management.

INTRODUCTION: Pharmacological asthma management focuses on the use of inhaled corticosteroid (ICS)-containing therapies, which reduce airway inflammation and provide bronchoprotection, improving symptom control and reducing exacerbation risk. ICS underuse due to poor adherence is common, leading to poor clinical outcomes including increased risk of mortality. This article reviews efficacy versus systemic activity profiles for various adherence patterns and dosing regimens of fluticasone furoate (FF)-containing and budesonide (BUD)-containing asthma therapies in clinical trials and real-world studies. METHODS: We performed a structured literature review (1 January 2000-3 March 2022) and mathematical modelling analysis of FF-containing and BUD-containing regular daily dosing in patients with mild-to-severe asthma, as-needed BUD/formoterol (FOR) in mild asthma, and BUD/FOR maintenance and reliever therapy (MART) dosing in moderate-to-severe asthma, to assess efficacy (bronchoprotection) and systemic activity (cortisol suppression) profiles of dosing patterns of ICS use in multiple adherence scenarios. RESULTS: A total of 22 manuscripts were included in full-text review and 18 in the model simulations. Focusing on FF-containing or BUD-containing treatments at comparable adherence rates, regular daily FF or FF/vilanterol (VI) dosing provided more prolonged bronchoprotection and fewer systemic effects than daily BUD, daily BUD/FOR, or BUD/FOR MART dosing, especially in low adherence scenarios. In model simulations and the real-world setting, FF/VI generally provided longer bronchoprotection, lower systemic activity, and greater clinical benefits over BUD/FOR as well as consistently higher adherence. CONCLUSION: In this literature review and modelling analysis, FF/VI was found to show clinical advantages on asthma control over BUD/FOR. These findings have implications for helping clinicians select the most suitable inhaled therapy for their patients with asthma.

Patterns of Asthma Medication Use in New Zealand After Publication of National Asthma Guidelines.

BACKGROUND: In June 2020, the New Zealand (NZ) adolescent and adult asthma guidelines recommended budesonide/formoterol, taken as maintenance and/or reliever therapy, as the preferred therapeutic approach. OBJECTIVE: To investigate whether these recommendations were associated with changes in clinical practice indicated by asthma medication use trends. METHODS: NZ national dispensing data for inhaler medications from January 2010 to December 2021 were reviewed. Monthly "dispensings" of inhaled budesonide/formoterol, inhaled corticosteroid (ICS), other ICS/long-acting ß2-agonists (LABA), and inhaled short-acting ß2-agonists (SABA), for the 12+ age group, were displayed graphically with piecewise regression used to produce plots of rates by time with a July 1, 2020, break point. The number of dispensings in the last 6 months that data were available (July-December 2021) was compared with the corresponding period, July-December 2019. RESULTS: Budesonide/formoterol dispensing increased markedly after July 1, 2020 (regression coefficient 41.1 inhalers dispensed/100,000 population per month [95% confidence interval (CI): 36.3-45.6, P < .0001]; 64.7% increase in the number of dispensings between July-December 2019 and July-December 2021), in contrast to "other ICS/LABA" (regression coefficient: -15.9 [95% CI: -22.2 to -9.6, P < .0001]; -1.7% decrease) and SABA (regression coefficient: -14.7 [95% CI: -29.7 to 0.3, P = .055]; -10.6% decrease), respectively. CONCLUSION: In NZ, a progressive increase in budesonide/formoterol dispensing, accompanied by a reduction in SABA and "other ICS/LABA" dispensing, occurred after publication of the 2020 NZ asthma guidelines. While acknowledging the limitations in the interpretation of temporal associations, these findings suggest that the transition to ICS/formoterol reliever-based therapy can be achieved if recommended and promoted as the preferred therapeutic approach in national guidelines.

Beginning to Address an Implementation Gap in Asthma: Clinicians' Views of Prescribing Reliever Budesonide-Formoterol Inhalers and SMART in the United States.

BACKGROUND: The Global Initiative for Asthma and National Asthma Education and Prevention Program recently made paradigm-shifting recommendations regarding inhaler management in asthma. The Global Initiative for Asthma now recommends that combination inhaled corticosteroid (ICS)-formoterol inhalers replace short-acting ß-agonists as the preferred reliever therapy at all steps of asthma management. Although the most recent guidelines of the National Asthma Education and Prevention Program did not review reliever ICS-formoterol usage in mild asthma, they similarly recommended single maintenance and reliever therapy (SMART) at steps 3 and 4 of asthma management. Despite these recommendations, many clinicians-particularly in the United States-are not prescribing new inhaler paradigms. Clinician-level reasons for this implementation gap remain largely unexplored. OBJECTIVE: To gain an in-depth understanding of the facilitators and barriers to prescribing reliever ICS-formoterol inhalers and SMART in the United States. METHODS: Community and academic primary care providers, pulmonologists, and allergists who reported regularly caring for adults with asthma were interviewed. Interviews were recorded, transcribed, qualitatively coded, and analyzed using the Consolidated Framework for Implementation Research. Interviews were continued until theme saturation. RESULTS: Among 20 interviewed clinicians, only 6 clinicians described regularly prescribing ICS-formoterol inhalers as a reliever inhaler (either alone or within SMART). Significant barriers to new inhaler approaches included concerns surrounding a lack of Food and Drug Administration labeling for ICS-formoterol as a reliever therapy, a lack of awareness regarding a patient's formulary-preferred ICS-long-acting ß-agonist choices, the high cost of combination inhalers, and time constraints. Facilitators to using new inhaler approaches included clinicians' beliefs that the latest inhaler recommendations are simpler and more congruent with real-world patients' behavior, and that a potential change in management strategy would offer a valuable opportunity for shared decision making. CONCLUSIONS: Although new guidelines exist in asthma, many clinicians described significant barriers to using them including medicolegal issues, pharmaceutical formulary confusion, and high drug costs. Nonetheless, most clinicians believed that the latest inhaler approaches would be more intuitive for their patients and would offer an opportunity for patient-centered collaboration and care. Stakeholders may find these results useful in future attempts to increase the real-world adoption of recent asthma recommendations.

Budesonide/formoterol maintenance and reliever therapy versus fluticasone/salmeterol fixed-dose treatment in patients with COPD.

BACKGROUND: Maintenance and reliever therapy (MART) with inhaled corticosteroid (ICS)/formoterol effectively reduces exacerbations in asthma. We aimed to investigate its efficacy compared with fixed-dose fluticasone/salmeterol in chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD and ≥1 exacerbation in the previous 2 years were randomly assigned to open-label MART (Spiromax budesonide/formoterol 160/4.5 µg 2 inhalations twice daily+1 prn) or fixed-dose therapy (Diskus fluticasone propionate/salmeterol combination (FSC) 500/50 µg 1 inhalation twice daily+salbutamol 100 µg prn) for 1 year. The primary outcome was rate of moderate/severe exacerbations, defined by treatment with oral prednisolone and/or antibiotics. RESULTS: In total, 195 patients were randomised (MART Bud/Form n=103; fixed-dose FSC n=92). No significant difference was seen between MART and FSC therapy in exacerbation rates (1.32 vs 1.32 /year, respectively, rate ratio 1.05 (95% CI 0.79 to 1.39); p=0.741). No differences in lung function parameters or health status were observed. Total ICS dose was significantly lower with MART than FSC therapy (budesonide-equivalent 928 µg/day vs 1747 µg/day, respectively, p<0.05). Similar proportions of patients reported adverse events (MART Bud/Form: 73% vs fixed-dose FSC: 68%, p=0.408) and pneumonias (MART: 5% vs FSC: 1%, p=0.216). CONCLUSIONS: This first study of MART in COPD found that budesonide/formoterol MART might be similarly effective to fluticasone/salmeterol fixed-dose therapy in moderate to severe patients with COPD, at a lower daily ICS dosage. Further evidence is needed about long-term safety.

Therapeutic Response to Single-Inhaler Triple Therapies in Moderate-to-Severe COPD.

BACKGROUND: COPD is characterized by progressive and irreversible air flow limitations. Single-inhaler therapies (SITTs) incorporating an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting ß2-agonist have been shown to effectively alleviate symptoms and improve lung function. Fluticasone-furoate/umeclidinium/vilanterol (F/U/V) and budesonide/glycopyrronium/formoterol (B/G/F) are available as SITT in Japan. However, the clinical differences between these 2 combinations and the predictors of their proper use have not been established. This study aimed to identify the subject characteristics that could predict the effectiveness of inhaler therapy. METHODS: We assessed the pulmonary function test results of subjects with COPD before and one month after using F/U/V and B/G/F as SITT. Subjects with a difference of 100 mL or more in the FEV1 after treatment with pre-SITT were extracted and divided into the F/U/V effect and no-effect group and B/G/F effect and no-effect group to examine the factors associated with positive outcomes with each inhaler. RESULTS: F/U/V and B/G/F significantly improved the inspiratory capacity (IC), %IC, FVC, and %FEV1 when compared to pre-intervention values (P < .001, P = .001, P = .007, P = .009, respectively, for F/U/V; and P = .006, P = .008, P = .038, P = .005, respectively, for B/G/F). Factors associated with FEV1 improvement in F/U/V included lower %IC (odds ratio 0.97 [95% CI 0.94-0.99], P = .03) and a higher modified Medical Research Council (mMRC) dyspnea score (2.36 [1.27-4.70], P < .01). In addition, a higher %IC (1.03 [1.00-1.06], P = .02) and lower mMRC dyspnea score (0.55 [0.28-0.99], P = .041) were predictors for the effectiveness of B/G/F. CONCLUSIONS: Our results showed that SITT significantly improved the IC, %IC, FVC, and %FEV1 when compared to pre-intervention and that F/U/V was more effective in subjects with severe symptoms, whereas B/G/F was more effective in subjects with mild symptoms.

Effectiveness and quality of life in asthmatic patients treated with budesonide/formoterol via Elpenhaler® device in primary care. The "SKIRON" real world study.

Aim: Inhaled corticosteroid (ICS)/long-acting ß2 agonist (LABA) combination therapy is used for the effective control of asthma. Aim of this study was to collect data on the effectiveness, safety, quality of life, and patient satisfaction from a fixed dose combination of budesonide/formoterol administered with the Elpenhaler® device following 3-months' treatment.Methods: A 3-month real-life, multicentre, one-arm, prospective observational study (SKIRON study-NCT03055793) was conducted, using the following questionnaires: Asthma Control Questionnaire (ACQ-6) for asthma control assessment, MiniAQLQ questionnaire for QoL assessment, and Feeling of Satisfaction with Inhaler questionnaire (FSI-10) for patients' satisfaction with the inhaler device. Comorbidities and safety data were also recorded during the study.Results: We enrolled 1,174 asthmatic patients following standard clinical practice in primary care from 126 sites in urban and rural areas of Greece. The majority of patients (71.5%) had at least one comorbidity. A statistically significant improvement in the ACQ-6 score was noted at 3 months compared to the baseline evaluation (mean ± SD 2.19 ± 0.97 at baseline vs. 0.55 ± 0.56 at 3 months; mean change -1.64 (95%CI -1.69, -1.57), p < 0.0001). MiniAQLQ score was statistically and clinically significantly improved, compared to baseline, (4.55 ± 1.04 at baseline vs. 6.37 ± 0.64 at 3 months; mean change 1.82 (95%CI 1.75, 1.87), p < 0.0001). The mean FSI-10 score of 44.2 ± 5.4 indicated patient satisfaction and ease-of-use of the Elpenhaler® device.Conclusions: In this large real-world study of inadequately-controlled asthma patients in primary care settings, the treatment with budesonide/formoterol FDC with the Elpenhaler® device was associated with significant improvement in patients' asthma control and quality of life.

Effect of budesonide formoterol combined with tiotropium bromide on pulmonary function and inflammatory factors in patients with asthma–COPD overlap syndrome

Objective: To investigate the clinical efficacy of combining budesonide formoterol with tiotropium bromide for treating asthma–chronic obstructive pulmonary disease overlap syndrome (AOCS). Methods: The data of 104 patients with AOCS admitted to our hospital from December 2019 to December 2020 were assessed, randomly and divided into an experimental group (comprising 52 patients, receiving drug combination therapy) and a conventional group (comprising 52 patients, receiving drug therapy alone). Patients’ clinical efficacy, pulmonary function, fractioned exhaled nitric oxide (FeNO), immune function, endothelial function, serum lipid peroxidation injury indexes, adverse reactions, and quality of life scores were compared. Results: Prior to treatment, no significant differences were observed in various pulmonary function indicators, FeNO, immune function, endothelial function, and lipid peroxidation injury indexes between the two groups (P > 0.05). However, after treatment, all observation indexes in both groups improved to different levels, with the experimental group -demonstrating -significantly superior improvement, compared to the conventional group (P < 0.05). We also observed that adverse reactions in the experimental group were significantly lower than in the conventional group (P < 0.05). Conclusion: The combination of budesonide formoterol to tiotropium bromide in treating asthma–COPD overlap syndrome may significantly improve pulmonary function, endothelial function, and immune status of patients and encourage the recovery of serum lipid peroxidation injury; therefore, this may deserve widespread adoption and application (AU)