Short-acting Β2-agonists Research Articles

A cost-utility analysis of single maintenance and reliever (SMART) therapy as compared to step 3 fixed-dose therapy in patients aged 12 years or more with uncontrolled asthma.

A significant percentage of patients with asthma appear to benefit from the addition of long-acting β2-agonists (LABAs) to ICS to achieve better control of their disease. The aim of the present study was to determine the cost-utility of single inhaler combination inhaled ICS/LABAs as both maintenance and reliever (SMART) versus remaining at the same treatment step with fixed-dose ICS-LABA maintenance with a short-acting β2-agonist (SABA) as reliever in patients aged 12 years or more with uncontrolled asthma. A Markov-type model was developed to estimate the costs and health outcomes of a simulated cohort of patients aged 12 years or more with uncontrolled asthma treated for 12 months. The effectiveness data and transition probabilities were obtained from a recent meta-analysis. Cost data were obtained from official databases provided by the Colombian Ministry of Health. The main outcome was the variable "quality-adjusted life-years" (QALYs). The base-case analysis showed that compared with remaining at the same GINA treatment step with ICS/LABA maintenance plus SABA reliever, ICS/LABAs as SMART was associated with lower costs, US$2,906.92 versus $4,462.02 average cost per patient, and the greatest gain in QALYs, 0.8540 versus 0.8258 QALYs on average per patient, thus leading to dominance. Compared with remaining at the same GINA treatment step with ICS/LABA maintenance plus SABA reliever, ICS/LABAs as SMART is more cost-effective in patients aged 12 years or more with uncontrolled asthma. This is because ICS/LABAs as SMART showed a greater gain in QALYs at lower total treatment costs.

Economic burden of short-acting beta-2 agonist (SABA) overuse among asthma patients in Türkiye: a cost analysis with respect to the updated GINA treatment recommendations.

This cost of illness study aimed to determine economic burden of short-acting β2-agonist (SABA) overuse in Türkiye from payer perspective with respect to the updated GINA 2022 treatment recommendations. A total of 3,034,879 asthma patients comprised the study population, via estimations extrapolated from the Türkiye arm of the global SABINA III study. The economic burden (costs related to the drug use and severe exacerbations) was compared in subgroups of overall (≥ 0 canisters/year) vs. GINA-recommended (0-2 canisters/year, hypothetical population) SABA use and in subgroups of appropriate use (0-2 canisters/year, real population) vs. overuse (≥ 3 canisters/year) of SABA with extrapolation of SABINA Türkiye data to the Türkiye asthma population. Recommended SABA use was predicted to prevent 127,505 of 157,512 severe exacerbations per year in mild asthma patients and 2,668,916 of 3,262,800 severe exacerbations per year in moderate-severe asthma patients. Annual cost burden of not applying recommended SABA use (overall [≥ 0 canisters/year] vs. GINA-recommended [0-2 canisters/year] SABA use) in mild asthma and moderate-severe asthma patients was calculated to be €20.43 million and €427.65 million in terms of severe exacerbations, and to be €829,352 and €7.20 million in terms of drug costs, respectively. The total annual economic burden arising from not applying recommended SABA use was estimated to be €456.11 million. Appropriate use (0-2 canisters/year) vs. overuse (≥ 3 canisters/year) of SABA was associated with decreased frequency of severe exacerbations per year in mild asthma (from 129,878 to 27,634) and moderate-severe asthma (from 2,834,611 to 428,189) patients. SABA overuse in mild and moderate-severe asthma patients was estimated to yield an additional annual cost of €16.38 million and €385.59 million, respectively in terms of severe exacerbations, and a total €11.30 million additional drug cost. The overall annual economic burden arising from SABA overuse was estimated to be €413.27 million. The estimated annual total economic burden arising from not applying recommended SABA use (€456.11 million) and SABA overuse (€413.27 million) with respect to the updated GINA 2022 treatment recommendations indicates the substantial cost burden of SABA overuse to the Turkish National Health System, corresponding up to 26% of the total direct cost of asthma reported in our country.

Asthma symptoms, severity, and control with and without a clinical diagnosis of asthma in early adolescence in sub-Saharan Africa: a multi-country, school-based, cross-sectional study.

Rapid urbanisation and population growth in sub-Saharan Africa has increased the incidence of asthma in children and adolescents. One major barrier to achieving good asthma control in these adolescents is obtaining a clinical diagnosis. To date, there are scant data on prevalence and severity of asthma in undiagnosed yet symptomatic adolescents. We therefore aimed to assess symptom prevalence and severity, the effect of symptoms on daily life, and objective evidence of asthma in young adolescents from sub-Saharan Africa with and without a clinical diagnosis of asthma by spirometry and fractional exhaled nitric oxide (FeNO). We designed a two-phase, multi-country, school-based, cross-sectional study to assess symptom prevalence and severity in sub-Saharan African adolescents. In phase 1 we surveyed young adolescents aged 12-14 years who were attending selected primary and secondary schools in Blantyre in Malawi, Durban in South Africa, Harare in Zimbabwe, Kampala in Uganda, Kumasi in Ghana, and Lagos in Nigeria. The adolescents were screened for asthma symptoms using the International Study of Asthma and Allergies in Children (ISAAC) questionnaire. Then, after opt-in consent, symptomatic adolescents were invited to complete a detailed survey on asthma severity, treatment, and exposure to environmental risk factors for phase 2. Adolescents performed the European Respiratory Society's diagnostic tests for childhood asthma. A positive asthma test was classified as a forced expiratory volume in 1 sec (FEV1) predicted under 80%, a FEV1 under the lower limits of normal, or FEV1 divided by forced vital capacity (FEV1/FVC) under the lower limits of normal; positive bronchodilator responsiveness or reversibility was defined as either an increase in absolute FEV1 of 12% or more, or an increase of 200 mL or more, or both, after 400 μg of salbutamol (shortacting β2 agonist) administered via a metered-dose inhaler and spacer, or FeNO of 25 parts per billion or higher, or any combination of these. The study was registered with ClinicalTrials.gov (NCT03990402) and is complete. Between Nov 1, 2018, and Nov 1, 2021, we recruited 149 schools from six regions in six sub-Saharan countries to participate in the study. We administered phase 1 asthma questionnaires from Jan 20, 2019 to Nov 11, 2021, and from 27 407 adolescents who were screened, we obtained data for 27 272 (99·5%). Overall, 14 918 (54·7%) adolescents were female and 12 354 (45·3%) adolescents were male, and the mean age was 13 years (IQR 12-13); nearly all recruited adolescents were of black African ethnicity (26 821 [98·3%] of 27 272). In phase 1, a total of 3236 (11·9% [95% CI 11·5-12·3]) reported wheeze in the past 12 months, and 644 (19·9%) of 3236 had a formal clinical diagnosis of asthma. The prevalence of adolescents with asthma symptoms ranged from 23·8% in Durban, South Africa to 4·2% Blantyre, Malawi. Using ISAAC criteria, severe asthma symptoms were reported by 2146 (66·3%) of 3236 adolescents, the majority of whom (1672 [77·9%] of 2146) had no diagnosis of asthma by a clinician. Between July 16, 2019, and Nov 26, 2021, we administered the phase 2 questionnaire to the 1654 adolescents who had asthma symptoms in phase 1 and consented to proceed to the second phase. In the phase 2 cohort, 959 (58·0%) were female and 695 (42·0%) were male, and the mean age was 13 years (IQR 12-14). One or more diagnostic tests for asthma were obtained in 1546 (93·5%) of 1654 participants. One or more positive asthma tests were found in 374 (48·8%) of 767 undiagnosed adolescents with severe symptoms, and 176 (42·4%) of 415 of undiagnosed adolescents with mild-to-moderate symptoms. Of the 392 adolescents in phase 2 with clinician-diagnosed asthma, 294 (75·0%) reported severe asthma symptoms, with 94 (32·0%) of those with severe symptoms not using any asthma medication. In general, findings in both phases 1 and 2 were consistent across sub-Saharan African countries. A large proportion of adolescents in sub-Saharan Africa with symptoms of severe asthma do not have a formal diagnosis of asthma and are therefore not receiving appropriate asthma therapy. To improve the poor state of asthma control in sub-Saharan Africa, potential solutions such as educational programmes, better diagnosis, and treatment and screening in schools should be considered. UK National Institute for Health and Care Research and UK Medical Research Council.

Clinical Effectiveness and Safety of Dupilumab in Chronic Obstructive Pulmonary Disease Patients: A 7-Year Population-based Cohort Study

BackgroundPrevious randomized controlled trials had established the efficacy of dupilumab among patients with chronic obstructive pulmonary disease (COPD) treated with triple therapy over 52 weeks of follow-up. ObjectiveThis population-based cohort study aimed to explore the long-term clinical effectiveness of dupilumab in COPD patients. MethodsThis population-based cohort study included U.S. patients with COPD between April 2017 and August 2024. Patients initiating dupilumab and therapies that incorporated long-acting β2-agonists (LABA) inhalers were included. Patients with asthma or lung cancer were excluded. The risk of outcomes after the initiation of dupilumab versus LABA-containing therapies was measured. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org. ResultsA total of 1,521 dupilumab initiators and 1,521 propensity score-matched patients receiving LABA-based therapies were included. Dupilumab recipients were associated with lower all-cause mortality (HR:0.53, 95% CI:0.43-0.65), emergency visits (HR:0.78, 95% CI:0.69-0.89), and acute exacerbation (AE) rates (HR:0.59, 95% CI:0.53-0.65). Dupilumab was also associated with reductions in the requirement of short-acting β2-agonists (HR:0.48, 95% CI:0.43-0.52), short-acting muscarinic antagonists (HR:0.43, 95% CI:0.37-0.49) for symptoms control. Additionally, dupilumab decreased subsequent pneumonia (HR:0.65, 95% CI:0.50-0.86), and COPD-relevant comorbidities including new-onset heart failure (HR:0.69, 95% CI:0.53-0.90) and new-onset anxiety (HR:0.70, 95% CI:0.53-0.93). ConclusionsDupilumab was associated with a lower rate of mortality, emergency visits, reduced risk of AEs, respiratory symptoms, and respiratory infections in COPD patients. More studies are required to validate the effectiveness of dupilumab among patients with COPD across various severities.

Single inhaler combination inhaled corticosteroid–formoterol as both maintenance and reliever (SMART) compared with a step up of treatment with fixed-dose inhaled corticosteroid–long-acting β2-agonist maintenance with a short-acting β2-agonist as reliever in adolescents and adults with poorly controlled asthma in Colombia: a cost-utility analysis

Objective The aim of the present study was to determine the cost-utility of single inhaler combination inhaled corticosteroid and a long-acting β2-agonist (ICS/LABAs) as both maintenance and reliever (SMART) compared with a step-up maintenance treatment with a fixed medium to high dose of ICS combined with LABA and a short-acting β2-agonist (SABA) as reliever (ICS-LABA maintenance plus SABA) among patients aged 12 years or more with poorly controlled asthma in Colombia. Methods A Markov-type model was developed to estimate the costs and health outcomes of a simulated cohort of patients aged 12 years or more with uncontrolled asthma treated for 12 months. The main effectiveness data were obtained from a recent meta-analysis. The main outcome was the variable ‘‘quality-adjusted life-years’’ (QALYs). Results The base-case analysis showed that the budesonide/formoterol (BUD/FORM) SMART strategy was associated with lower overall treatment costs (US $3,062.37 vs. $4,462.02 average cost per patient over 12 months) and the greatest gain in QALYs (0.8511 vs. 0.8258 QALYs on average per patient over 12 months) compared with ICS-LABA maintenance plus SABA at step 4, thus leading to dominance. Conclusions In patients aged 12 years or more with uncontrolled asthma at GINA step 3 or 4, the BUD/FORM SMART strategy at either step 3 or 4 is cost-effective compared with the ICS-LABA maintenance plus SABA at step 4 strategy, because it shows a greater gain in QALYs at lower total treatment costs.

The Analysis Study of Comparison of Effectiveness and Safety of Inhalers in Mild-to Moderate Asthma in Adults: A Comprehensive Systematic Review

Background: Asthma, a prevalent and potentially debilitating chronic disease, is traditionally managed using reliever medications such as short-acting β2-agonists (SABA) or low-dose inhaled corticosteroids (ICS). Recent evidence, however, indicates that a combination of as-needed ICS and a rapid-acting long-acting β2-agonist (LABA) provides superior outcomes compared to SABA alone. Furthermore, this combination therapy is at least as effective as regular ICS in mitigating the risk of exacerbations. This emerging evidence highlights a significant shift in treatment strategies for mild asthma, underscoring the potential for enhanced management and improved patient outcomes with the new therapeutic approach. Methods: Following PRISMA 2020 guidelines, this systematic review focused exclusively on full-text articles published in English between 2014 and 2024. Result: The study conducted a comprehensive review of over 400 publications sourced from reputable databases, including ScienceDirect, SagePub, and PubMed. Folowing an initial screening, eight publications were identified as warranting more in-depth analysis. Conclusion: The study found that as-needed ICS/LABA is effective in preventing exacerbations in mild-to-moderate asthma patients, but less effective than regular ICS in improving FEV1 and ACQ scores. Combining ICS/LABA with SMART regimen was highest for severe exacerbations prevention.

Preclinical Evaluation of Electronic Health Records (EHRs) to Predict Poor Control of Chronic Respiratory Diseases in Primary Care: A Novel Approach to Focus Our Efforts.

Background/Objectives: Managing chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) within the Spanish Sistema Nacional de Salud (SNS) presents significant challenges, particularly due to their high prevalence and poor disease control rates-approximately 45.1% for asthma and 63.2% for COPD. This study aims to develop a novel predictive model using electronic health records (EHRs) to estimate the likelihood of poor disease control in these patients, thereby enabling more efficient management in primary care settings. Methods: The Seleida project employed a bioinformatics approach to identify significant clinical variables from EHR data in primary care centers in Seville and Valencia. Statistically significant variables were incorporated into a logistic regression model to predict poor disease control in patients with asthma and COPD patients. Key variables included the number of short-acting β-agonist (SABA) and short-acting muscarinic antagonist (SAMA) canisters, prednisone courses, and antibiotic courses over the past year. Results: The developed model demonstrated high accuracy, sensitivity, and specificity in predicting poorly controlled disease in both asthma and COPD patients. These findings suggest that the model could serve as a valuable tool for the early identification of at-risk patients, allowing healthcare providers to prioritize and optimize resource allocation in primary care settings. Conclusions: Integrating this predictive model into primary care practice could enhance the proactive management of asthma and COPD, potentially improving patient outcomes and reducing the burden on healthcare systems. Further validation in diverse clinical settings is warranted to confirm the model's efficacy and generalizability.

Correction: Healthcare costs associated with short-acting β2-agonists in asthma: observational UK SABINA study.

Correction: Healthcare costs associated with short-acting β2-agonists in asthma: observational UK SABINA study.

The Impact of Eliminating Out-of-Pocket Payments on Asthma Medication Use.

High costs of controller therapies may be a barrier to guideline-recommended asthma treatment. We determined whether eliminating out-of-pocket (OOP) payments among low-income patients with asthma impacted controller medication use. We applied a controlled interrupted time series design to administrative claims data in British Columbia, Canada from 2017-2020. Cases were individuals with an annual household income <$13,750 in whom copays were eliminated on January 2019; there was no change in public coverage for the control group with annual income >$45,000. We evaluated trends in asthma medication costs, use, the ratio of inhaled corticosteroid (ICS)-containing medications to all asthma medications, excessive use of short-acting β-agonists (SABA) (>1 canister/month), and the proportion of days (PDC) covered by controller therapies. There were 12,940 cases (62% female, mean age 30.3 years, SD 14.9), and 71,331 controls (55% female, mean age of 31.3 years, SD 16.3). Removal of OOP payments increased monthly mean medication costs by $3.32 (95% CI $0.08 - $6.56, 2020 Canadian dollars), days supply of controller medications by 1.50 days (95% CI 0.61 - 2.40), and the ratio of ICS-containing medications to total medications by 4.20% (95% CI 0.73% - 7.66%) compared to the control group. The policy had no effect on PDC by controller therapies (0.01, 95% CI -0.01 - 0.04), but non-significantly decreased the percentage of patients with excessive SABA use (-6.37%; 95% CI -12.90% - 0.16%). Removal of OOP payments increased the dispensation of controller therapies, suggesting cost-related non-adherence could impair optimal asthma management.

Asthma: effect of excess short-acting β2-agonist (SABA) inhaler prescriptions on healthcare resource utilisation.

Asthma: effect of excess short-acting β2-agonist (SABA) inhaler prescriptions on healthcare resource utilisation.

Prescriptions of respiratory medications in children aged 0–10 years: A longitudinal drug utilization study in the POMME database

IntroductionRespiratory tract disorders are common in children. However, there is no available data on the prescription of respiratory medications for children in France. This study aimed to provide an overview of medications for obstructive airway diseases prescriptions for children during the initial ten years of their lives within POMME, a French population-based cohort of children. Material and methodsThis longitudinal, population-based study used data from the French POMME birth cohort, comprising children born in Haute Garonne between July 2010 and June 2011. Anonymous medical information, including medication reimbursement data, was collected between ages 0 and 10 years. Exposure was defined as at least one prescription for respiratory medications (ATC code R03*), focusing on specific subclasses. Data were analyzed by age, season, and prescribing physicians' specialties. ResultsOut of 5956 children, 4951 (83.1 %) received respiratory medication prescriptions. Inhaled corticosteroids (ICSs) were the most prescribed (95.3 %), followed by short-acting β2-agonists (68.8 %). The number of prescriptions increased with age, except for ICSs alone, which peaked between 6 months and 2 years. The average number of prescriptions per child was relatively low. DiscussionThis study highlighted high prescription rates of respiratory medications in children under 10 years, with ICSs being the most prevalent. While these medications are primarily intended for asthma management, the findings suggested a significant proportion of off-label prescriptions, especially in young children. Further research and clinical guidance are warranted to ensure appropriate medication use in the pediatric population.

Toward Personalized Salbutamol Therapy: Validating Virtual Patient-Derived Population Pharmacokinetic Model with Real-World Data.

Interindividual variability, influenced by patient-specific factors including age, weight, gender, race, and genetics, among others, contributes to variations in therapeutic response. Population pharmacokinetic (popPK) modeling is an essential tool for pinpointing measurable factors affecting dose-concentration relationships and tailoring dosage regimens to individual patients. Herein, we developed a popPK model for salbutamol, a short-acting β2-agonist (SABA) used in asthma treatment, to identify key patient characteristics that influence treatment response. To do so, synthetic data from physiologically-based pharmacokinetic (PBPK) models was employed, followed by an external validation using real patient data derived from an equivalent study. Thirty-two virtual patients were included in this study. A two-compartment model, with first-order absorption (no delay), and linear elimination best fitted our data, according to diagnostic plots and selection criteria. External validation demonstrated a strong agreement between individual predicted and observed values. The incorporation of covariates into the basic structural model identified a significant impact of age on clearance (Cl) and intercompartmental clearance (Q); gender on Cl and the constant rate of absorption (ka); race on Cl; and weight on Cl in the volume of distribution of the peripheral compartment (V2). This study addresses critical challenges in popPK modeling, particularly data scarcity, incompleteness, and homogeneity, in traditional clinical trials, by leveraging synthetic data from PBPK modeling. Significant associations between individual characteristics and salbutamol's PK parameters, here uncovered, highlight the importance of personalized therapeutic regimens for optimal treatment outcomes.

Short-acting β2-agonists (SABA) overuse in asthma and patients’ perceptions for this behavior

BackgroundShort-acting β2-agonists (SABA) overuse is associated with poor asthma control. The Global Initiative for Asthma (GINA) 2019-updated strategy report has therefore taken a paradigm shift in reliever therapy recommendations. Objectives(I) To investigate the status of SABA overuse and medication dispensing patters in asthma in the Netherlands (II) validate dispensing data for SABA overuse identification and (III) understand patients’ perspectives towards this SABA-taking behavior to inform future improvement strategies. MethodsAn annually repeated cross-sectional study was conducted from 2017 to 2021 using pharmacy dispensing data in a real-world setting, including asthma patients aged 18–45 with ≥1 inhaler. A following qualitative study was performed in identified SABA overusing patients with a questionnaire and semi-structured interviews, supported by theoretical frameworks. ResultsDispensing data was available from 87 % of all community pharmacies (n = 1994) in 2017 and 95 % (n = 2005) in 2021. SABA overuse prevalence was constant for the five study-years with 20.6 % (±0.5 %). Increased ICS-formoterol and decreased SABA dispenses were observed in starters of inhalation therapy in 2021. 53 asthma patients completed the questionnaire of whom 43 patients confirmed SABA overuse, generating a positive predictive value of 81 %. Key behavioral drivers covered 7 themes regarding capability (knowledge; skills; memory, attention and decision process) motivation (emotion; beliefs about-capabilities; consequences) and opportunity (environmental context). ConclusionSABA overuse remains in one-fifth of asthma patients across the Netherlands, requiring careful attention from healthcare professionals. Dispensing data is a valid measure for SABA overuse in a clinical setting, facilitating patient selection. To meet patients’ varied supporting needs, integration of tailored behavioral interventions is essential.

APPaRENT 3: Asthma Patients' and Physicians' Perspectives on the Burden and Management of Asthma in Seven Countries.

Asthma management is strongly dependent on physician and patient beliefs and perceptions about the disease and its long-term treatment. The APPaRENT 3 study was conducted to explore factors influencing treatment choice and to understand patients' and physicians' attitudes and perspectives on the use of controller inhalers in regular versus flexible dosing for asthma management. This cross-sectional survey of patients with asthma and treating physicians was conducted in seven countries: Indonesia, Malaysia, Philippines, Thailand, Vietnam (patient survey only), Saudi Arabia, and the United Arab Emirates. Assessment was carried out through an online/face-to-face questionnaire, where patients' viewpoints were focused on their attitudes and beliefs about asthma and treatment adherence, whereas physicians' viewpoints were gathered on their attitudes and beliefs about asthma management, knowledge of and adherence to asthma treatment guidelines, and asthma treatment regimens. Overall, 1400 patients (mean age, 34years) and 599 physicians (mean age, 43years) were included in the survey. Physicians similarly prioritised symptom control (39%) and exacerbation reduction (40%) in moderate asthma, whereas patients prioritised symptom control (41%) over exacerbation reduction (22%). Although both groups (physicians, 86%; patients, 84%) perceived asthma as well-controlled, poor management was evident based on Asthma Control Test (ACT) scores (mean, 15.7; standard deviation, 4.14; 82% had an ACT score<20) and high symptom burden (39% reported nighttime awakenings or early mornings≥2 nights/week). Most patients (76%) with moderate asthma were prescribed regular dosing, with the most common treatment being inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) with as-needed inhaled short-acting β2-agonist (SABA; 20%). Among patients on maintenance and reliever therapy, 93% of patients received a separate inhaled reliever. Despite high symptom burden, patients overestimated their level of asthma control. Physicians prioritised controlling symptoms and reducing exacerbations as treatment goals for moderate asthma, often prescribing regular dosing with ICS/LABA with as-needed inhaled SABA.

SABA prescriptions and asthma management practices in Singapore: results from a cross-sectional, observational SABINA III study

ObjectivesTo evaluate asthma characteristics and treatment patterns, including short-acting β2-agonist (SABA) prescriptions, in primary and specialist care in the Singapore cohort of the SABA use IN Asthma (SABINA III) study.DesignCross-sectional,...

SABINA + Hong Kong: a territory wide study of prescribing trends and outcomes associated with the use of short-acting β2 agonists in the Chinese population

BackgroundExcessive use of short-acting β2 agonists (SABA) in patients with asthma continues to be a notable concern due to its link to higher mortality rates. Global relevance of SABA overuse in asthma management cannot be understated, it poses significant health risk to patients with asthma and imposes burden on healthcare systems. This study, as part of global SABINA progamme, aimed to describe the prescribing patterns and clinical outcomes associated with SABA use in the Chinese population.MethodsRetrospective cohort study was conducted using anonymized electronic healthcare records of Clinical Data Analysis and Reporting System (CDARS) from Hong Kong Hospital Authority (HA). Patients newly diagnosed with asthma between 2011 and 2018 and aged ≥12 years were included, stratified by SABA use (≤2, 3–6, 7–10, or ≥11 canisters/year) during one-year baseline period since asthma diagnosis date. Patients were followed up from one-year post-index until earliest censoring of events: outcome occurrence and end of study period (31 December 2020). Cox proportional regression and negative binomial regression were used to estimate the mortality risk and frequency of hospital admissions associated with SABA use respectively, after adjusting for age, sex, Charlson Comorbidity Index (CCI), and inhaled corticosteroid (ICS) dose. Outcomes include all-cause, asthma-related, and respiratory-related mortality, frequency of hospital admissions for any cause, and frequency of hospital admissions due to asthma.Results17,782 patients with asthma (mean age 46.7 years, 40.8% male) were included and 59.1% of patients were overusing SABA (≥ 3 canisters per year). Each patient was prescribed a median of 5.61 SABA canisters/year. SABA overuse during baseline period was associated with higher all-cause mortality risk compared to patients with ≤2 canisters/year. Association was dose-dependent, highest risk in those used ≥11 canisters/year (adjusted hazard ratio: 1.42, 95% CI: 1.13, 1.79) and 3–6 canisters/year (adjusted hazard ratio: 1.22, 95% CI: 1.00, 1.50). Higher SABA prescription volume associated with increased frequency of hospital admissions with greatest risk observed in 7–10 canisters/year subgroup (adjusted rate ratio: 4.81, 95% CI: 3.66, 6.37).ConclusionsSABA overuse is prevalent and is associated with increased all-cause mortality risk and frequency of hospital admissions among the patients with asthma in Hong Kong.

Asthma control in the United States: Relationships between short-acting β2-agonist and systemic corticosteroid use

BackgroundAsthma control assessment is based on impairment (current symptoms) and risk (exacerbation history). ObjectiveTo understand the extent of uncontrolled asthma, we assessed relationships between prescription fills for systemic corticosteroids (SCS) and short-acting β2-agonists (SABA) as risk and impairment markers, respectively. MethodsAnnual SCS and SABA fills among US patients with asthma were evaluated by a retrospective analysis of the IQVIA Longitudinal Access and Adjudication Data. Patients' disease severity was assigned based on the Global Initiative for Asthma step-therapy level. Exacerbations were evaluated by SCS fills within 12 months of a first asthma prescription fill. Uncontrolled asthma was defined as 2 or more SCS and/or 3 or more SABA fills annually. Individual patient relationships between SCS and SABA fills were assessed using Pearson's correlation coefficients. ResultsA total of 4,506,527 patients were included; 15.1% had 2 or more SCS fills, 29.1% had 3 or more SABA fills, and 37.4% fulfilled either or both criteria. If only SCS use was assessed, 21.4% of cases that were treated as mild to moderate and 27.6% that were treated as severe asthma would have been misclassified as controlled. If only SABA use was evaluated, 7.8% of cases treated as mild to moderate and 11.2% treated as severe asthma would have been misclassified. Overall, 80.9% of uncontrolled asthma occurred in patients treated for mild to moderate disease. Among patients with 2 or more SCS fills, the mean SABA fills were 2.9; the correlation between SCS and SABA fills per patient was significant but weak (r = 0.18; P < .001). ConclusionHigh symptom burden and SCS exposures are not limited to severe asthma but are also characteristic of patients treated for mild to moderate disease. Both impairment and risk assessments are required to understand the full extent of uncontrolled asthma across disease severities.

Real-world use of inhaled corticosteroid/formoterol as needed in adults with mild asthma: the PRIME study.

Inhaled corticosteroid/formoterol fumarate (ICS/FF) as needed is recommended by the Global Initiative for Asthma (GINA) as sole therapy in adults with mild asthma, with low-dose maintenance ICS plus short-acting β2-agonist (SABA) as an alternative. SABA alone is no longer recommended. Given these changes in recommendations, the observational PRIME study aimed to describe real-world treatment patterns in mild asthma in Europe. Adults with asthma receiving low-dose maintenance ICS, or as needed ICS/FF or SABA were followed for 6 months. Data collected included Asthma Control Test (ACT), Asthma Control Questionnaire 5-item (ACQ-5), forced expiratory volume in 1 s (FEV1) and asthma exacerbations. The study was conducted in 883 patients in Germany, Italy, Poland and Spain; 833 (94.3%) completed follow-up. At enrolment, 32.2% received maintenance ICS, 56.3% ICS/FF as needed and 11.6% SABA as needed; 57.4%, 61.2% and 54.9%, respectively, had well-controlled asthma (ACQ-5/ACT definition). After 6 months, changes in mean FEV1 were small in the maintenance ICS and ICS/FF as needed groups, whereas there was a decline in FEV1 in the SABA as needed group. ACQ-5 total score improved from baseline in all three groups; 0.4%, 0.4% and 2.0% patients, respectively, had a severe exacerbation during the study. More patients received ICS/FF as needed than SABA as needed, suggesting that physicians are aware of the latest treatment recommendations. This real-world study provides additional support to the use of ICS/FF as needed as preferred treatment for patients with mild asthma, whereas SABA as needed was associated with a fall in lung function and more severe exacerbations.

Characterization of Moderate and Severe Asthma Exacerbations in the CAPTAIN Study

BackgroundLimited data exist on the relative impact of moderate and severe exacerbations on asthma control and impairment. ObjectiveTo explore data from the CAPTAIN trial to evaluate the relationship between first moderate or severe exacerbation and changes in lung function, symptoms, physical activity limitation scores, and short-acting β2-agonist (SABA) usage to determine the clinical relevance of moderate events. MethodsCAPTAIN was a Phase IIIA 24–52-week, multicenter, international, randomized controlled trial evaluating efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in patients with uncontrolled asthma on inhaled corticosteroid/long-acting β2-agonist. Outcomes reportedinclude: first post-randomization exacerbation event by severity (Weeks 1–52), frequency and duration of moderate and severe exacerbations and time course of changes over ±14-day peri-exacerbation period for lung function, symptoms, limitations, and SABA use. ResultsOf the intent-to-treat population (N=2436), 550 patients (23%) continued to 52 weeks. There were 529 moderate and 546 severe exacerbations. Lung function changes were similar, but symptom, physical activity limitation scores, and SABA use were higher, for severe versus moderate exacerbations. Lung function decline preceded increases in symptom, physical activity limitation scores, and SABA use, irrespective of exacerbation severity. Lung function variables, limitation scores, and SABA use returned to pre-exacerbation baseline after ∼8–12 days for both exacerbation severities. ConclusionWhile severe events were associated with greater impact on symptoms, physical activity limitations, and SABA use, onset and time to resolution were generally similar for moderate and severe events. Both exacerbation severities represent clinically important deteriorations comprising clinical and functional changes. NCT02924688.

Budesonide/Glycopyrrolate/Formoterol for the Management of COPD in a UK Primary Care Population: Real-World Use and Early Medication Success.

Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the frequency of medication success among patients with COPD who initiated BGF using real-world data. Patients with a recorded diagnostic COPD code who started BGF with ≥2 prescriptions within 90-days were identified in the UK Optimum Patient Care Research Database and followed from first prescription until censoring at the end of follow-up (180-days), death, leaving database or end of data at 24/10/2022. The primary outcome was medication success at 90-days post-BGF initiation, defined as no major cardiac or respiratory event (ie no complicated COPD exacerbation, hospitalization for any respiratory event, myocardial infarction, new/hospitalized heart failure, and death) and no incidence of pneumonia. Medication success was also assessed at 180-days post-BGF initiation. Overall real-life medication success was claimed if the lower 95% confidence interval (CI) for the proportion of patients meeting the primary outcome was ≥70% (defined a priori). Two hundred eighty-five patients were included. Prior to BGF initiation, these patients often had severe airflow obstruction (mean ppFEV1: 54.5%), were highly symptomatic (mMRC ≥2: 77.9% (n = 205/263); mean CAT score: 21.7 (SD 7.8)), with evidence of short-acting β2-agonist (SABA) over-use (≥3 inhalers/year: 62.1%, n=179/285), repeat OCS prescriptions (≥2 courses/year: 33.0%, n = 95/285) and multiple primary care consultations (≥2 visits/year: 61.1%, n = 174/285). Overall, 39.6% of patients (n = 113/285) switched from previous triple therapies. Real-life medication success was achieved by 96.5% of patients (n = 275/285 [95% CI: 93.6, 98.3]) during 90-days treatment with BGF and by 91.8% (n = 169/184 [95% CI: 86.9, 95.4]) of patients at 180-days. The prescribed daily dose of SABA remained stable over the study period. The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events. These benefits were apparent after 90-days of treatment and sustained over 180-days.