Short-acting Β2-agonists Research Articles

Is overreliance on short-acting β2-agonists associated with health risks in the older asthma population?

Recent Global Initiative for Asthma (GINA) recommendations reduce the role of short-acting β2-agonist (SABA) premised on the associated exacerbation risk. The widely accepted SABA risk profile is based on limited data described 30 years ago. This GINA paradigm shift demands an examination of SABA risks in a modern therapeutic era. Recent studies confirm that SABA overuse is common and associated with adverse outcomes. This study aimed to determine associations between SABA use, all-cause mortality and asthma exacerbations in an older North American asthma population.In this population-based cohort study, individuals with prevalent asthma (2006–2015) aged ≥65 years, eligible for provincial drug coverage, were included. Annual SABA canisters filled (0, 1–2, 3–5, ≥6) was the primary exposure. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazard regression, adjusted for confounders.There were 59 533 asthma individuals; 14% overused SABA (≥3 canisters annually). Compared to those who used <3 canisters, the adjusted HRs of death for those who used 3–5 and ≥6 canisters were 1.11 (95% CI: 1.02–1.22, p=0.0157) and 1.56 (95% CI: 1.41–1.71, p<0.0001), respectively. Severe asthma exacerbation rates for ≥3 and <3 canisters/year were 7.5% and 2.1%, respectively. The adjusted HRs of severe asthma exacerbations were 1.59 (95% CI: 1.40–1.82, p<0.0001) and 2.26 (95% CI: 1.96–2.60, p<0.0001) in those who used 3–5 and ≥6 SABA canisters per year, respectively.In Canada, 1 in 7 individuals with asthma overused SABA associated with increased risks of severe asthma exacerbations and death. The adverse impacts of SABA overuse continue 30 years after early publications.

Demographics, Treatment Patterns, and Morbidity in Patients with Exercise-Induced Bronchoconstriction: An Administrative Claims Data Analysis.

PurposeExercise-induced bronchoconstriction (EIB) is generally treated with short-acting β2-agonists (SABA) before exercising, to prevent symptoms. Real-world data on treatments and outcomes for patients with EIB alone (EIBalone), or with asthma (EIBasthma), in the USA are limited. This study compared demographics, treatment patterns, morbidity, and costs of treating EIB between these two groups of patients.Patients and MethodsAdministrative claims from US IBM® MarketScan® Research databases were analyzed retrospectively. Patients aged ≥4 years filling a SABA claim between 1/1/2011 and 12/31/2016 were evaluated. Patients were indexed on a random SABA claim and required to have 12 months’ continuous eligibility pre- and post-index, ≥1 maintenance medication and/or SABA fill post-index, and were designated EIBalone or EIBasthma according to diagnostic codes (EIB only or EIB plus asthma, respectively). Descriptive statistics were used.ResultsIn total, 13,480 patients had EIBalone and 14,862 had EIBasthma. Compared with EIBasthma, the EIBalone group was older (mean[SD] 20.4[13.6] vs 17.8[13.6] years), had more females (60.7% vs 54.7%), and filled fewer SABA claims (1.9[1.4] vs 2.5[2.2]) (all p<0.001). A smaller proportion of patients in the EIBalone than EIBasthma group had maintenance therapy claims (79.9% vs 90.6%, p<0.001). The EIBalone group also had a lower proportion of patients with oral or injectable corticosteroid claims (29.4% vs 32.0%) and asthma and/or EIB-related emergency department (1.0% vs 13.0%) or outpatient visits (65.1% vs 72.3%; all p<0.0001). Annual days’ supply of oral corticosteroids was similar between groups (mean[SD] EIBalone: 20.7[30.8] vs EIBasthma: 19.8[28] days).ConclusionIndividuals with EIBalone or EIBasthma demonstrate considerable morbidity. New treatment paradigms may be needed to optimize outcomes for both patient groups.

Sensor-Based Electronic Monitoring for Asthma: A Randomized Controlled Trial

To assess whether sensor-based monitoring of daily inhaled corticosteroids and short-acting b-agonist medications can improve asthma outcomes in diverse populationsA socioeconomically and racially diverse population of caregiver and children dyads were randomly assigned to control (n = 127) or sensor-based electronic monitoring (n = 125) for asthma.This was a randomized controlled multicenter trial of socioeconomically and racially diverse caregiver and children pairs from 5 Chicago medical clinics. The primary outcomes measured were the Asthma Control Test (ACT) (≥19 score equivalent to controlled asthma) and health care use (emergency department visits, hospitalizations, and oral corticosteroid prescriptions). Caregiver quality of life (QoL) and adherence to inhaled corticosteroids were also evaluated with multitiered models to ascertain changes.The intervention group had a significant increase in adjusted mean ACT scores (19.1 [n = 123; SE = 0.3] to 21.8 [n = 102; SE = 0.4]). The control group also had an increase in adjusted mean ACT scores (19.4 [n = 126; SE = 0.3] to 19.9 [n = 118; SE = 0.4]), the change was less than that of the intervention group at all time points (P < .01 for all comparisons). There was no difference in terms of the reported number of asthma attacks, missed school days, and steroid prescriptions in the ED and/or hospital. However, more children in the intervention group were prescribed steroids for asthma attacks during the 12 month study than controls were (72.5% intervention versus 34.6% control; P < .01). Improved QoL was reported by caregivers of the intervention group; this change was greater that of seen in the control group at 1 month follow-up, but there was no difference at 12 months.The outcomes of the study reveal that sensor-based inhaler monitoring with clinical participant–provider feedback may enhance asthma control and caregiver QoL in racially and socioeconomically diverse populations. However this improvement in outcomes for child and caregiver comes at the price of higher health care use, so further improvement in the sensor and participant–provider feedback system is needed.The authors should be recognized for demonstrating that use of sensor monitoring for asthma medications in children can improve asthma control and caregiver QoL in diverse populations. However, these improvements may come at a price of increasing health care use (steroid prescriptions). The limitations of the study include that data had to be manually entered because the blue chip device did not fit the inhaler and the absence of documentation or quantification of participant–provider phone feedback and adherence in both study groups as well as cost-effectiveness analysis.

A comparison of administrative claims-based risk predictors for pediatric asthma.

Head-to-head comparisons are needed to determine the most accurate and appropriate administrative claims-based exacerbation risk predictor for emergency department (ED) visits and hospitalizations among children with asthma. Retrospective cohort study. We analyzed 2013-2014 MarketScan Medicaid data. Children aged 2 to 17 years were included. Seven risk predictors were compared for accuracy in predicting 3-month subsequent ED visits/hospitalizations for asthma: 3-month rolling asthma medication ratio (AMR), Healthcare Effectiveness Data and Information Set (HEDIS) criteria, revised HEDIS criteria, quarterly short-acting β-agonist (SABA) claims, prior ED visit, prior hospitalization, and prior ED visit or hospitalization. Sensitivity, specificity, positive and negative predictive value (NPV), and percentage of population identified as high risk were compared for each risk predictor utilizing the McNemar test to identify statistically significant differences in risk prediction accuracy. A total of 214,452 children were included; the mean age was 7.8 years. HEDIS and revised HEDIS identified prohibitively large cohorts as high risk (67% and 48%, respectively). For the remaining measures, the NPV range is narrow (97%-99%), indicating high performance at identifying patients who would not benefit from intervention. The ED visit and ED/hospitalization measures have superior sensitivities (44% and 49%, respectively) compared with pharmacy claims-based measures (AMR [5%] and SABA count [10%]). Pharmacy claims-based measures identify a smaller proportion of patients as high risk and maintain high NPV. Pharmacy-based asthma exacerbation risk predictors such as the AMR and SABA count can rule out low-risk patients with a high degree of specificity and NPV, which is a primary goal of real-time risk monitoring in pediatric asthma.

Association Between Early Antibiotic Treatment and Clinical Outcomes in Children Hospitalized for Asthma Exacerbation

To assess the impact of early antibiotic use in the treatment of asthma exacerbation without comorbid bacterial infection on clinical outcomes and resource use.A total of 48 743 children between 3 months and 15 years hospitalized for asthma exacerbation with no evidence of bacterial infection who were treated with intravenous corticosteroids and inhaled short-acting β-agonists.Cases were retrospectively identified from an inpatient database, including records from >1000 hospitals in Japan. Those who received antibiotics during the first 2 days of hospitalization were included in the early treatment group, whereas those who had antibiotic therapy after the first 2 days or not at all were considered the untreated group. The primary outcome was the mean length of hospital stay. Secondary outcomes included hospitalization cost, risk of mechanical ventilation, risk of readmission, and risk of probiotic use because of antibiotic-associated diarrhea.A total of 19 866 (40.8%) of 48 743 eligible children were included in the early treatment group. This group had a longer hospital stay (average difference: 0.21 days; 95% confidence interval [CI]: 0.17 to 0.25), higher cost of hospitalization (mean difference: $83.5; 95% CI: 62.9 to 104), and higher rate of probiotic use (rate ratio: 2.01; 95% CI: 1.81 to 2.23). The risk of 30-day readmission did not significantly differ between the 2 groups. The risk of mechanical ventilation was similar or slightly higher in the early treatment group, depending on the statistical model.Early antibiotic treatment in asthma exacerbation is associated with several negative outcomes without clear clinical benefit: slightly longer hospital stay, increased health care costs, increased risk of probiotic use, and possibly higher risk of mechanical ventilation.Despite the known association of viral respiratory tract infections with asthma exacerbations in children, there continues to be high rates of antibiotic use for pediatric asthma exacerbations in developed countries. There have been conflicting results of studies examining the utility of early antibiotic use, particularly macrolide therapy, for asthma exacerbation. With this study, the authors add to evidence illustrating that risks of antibiotic therapy outweigh benefits in the treatment of asthma exacerbation without evidence of bacterial infection.

State-of-the-art beta-adrenoreceptor agonists for the treatment of asthma

ABSTRACT Introduction Asthma, a heterogeneous disease, is characterized by chronic airway inflammation and hyperreactivity. β2-adrenoreceptor agonists (β2-agonists) remain pivotal for asthma management. Short-acting β2-agonists (SABAs) result in rapid symptomatic alleviation and bronchospasm prevention. Patients experience significant clinical benefits from therapy with long-acting β2-agonists (LABAs) with efficacy to bronchodilate, and prolonged lung function betterment. Recently discovered β2-agonists with longer half-lives offer once-daily dosing. Areas covered The authors provide a thorough review of the pharmacokinetics, pharmacodynamics, efficacy, tolerability, classification, and safety of β2-agonists through an in-depth review of current literature using these databases: U.S. National Institutes of Health’s National Library of Medicine (NIH/NLM), PubMed Central, and NLM clinical trials. Expert opinion β2- agonists act primarily on airway smooth muscle cells and are quintessential for adequate asthma management. Given their pharmacodynamic and pharmacokinetic properties, SABAs are used as rescue medication. Notably, the current Global Initiative for Asthma (GINA) strategy document recommends using LABA/inhaled corticosteroid combinations both as a daily controller and as a rescue medication. Clinicians should assess this new treatment plan on a per-case basis, making sure to evaluate inhaler adherence and treat modifiable risk factors. The development of next-generation β2- agonists is an exciting research area that could significantly improve patients’ adherence to treatment regimens and, consequently, asthma control and quality of life.

A real-world study of inhaled corticosteroid use in patients with severe eosinophilic asthma treated with mepolizumab

BackgroundMepolizumab is a humanized anti-interleukin-5, monoclonal antibody approved for the treatment of patients with severe eosinophilic asthma (SEA). There is limited evidence that mepolizumab can reduce inhaled corticosteroid (ICS) use in these patients. ObjectiveTo investigate changes in ICS use and clinical outcomes in patients with SEA who initiated mepolizumab treatment. MethodsThis retrospective cohort study (GlaxoSmithKline identification: 212695/HO-20-19951) used administrative claims data from the IBM Watson Health MarketScan Database (identification period: November 2015 to March 2018). Eligible patients had SEA and were receiving high-dose ICS and mepolizumab. Use of ICS, oral corticosteroid (OCS), and short-acting β2-agonist and exacerbation frequency were analyzed quarterly during the 12-month follow-up period after mepolizumab initiation. ResultsIn total, 351 patients were included. The proportion of patients using high-dose ICS decreased in quarters 1 to 4 after mepolizumab initiation (79.8%, 74.6%, 68.9%, 65.5%, respectively); 49.0% of patients reduced or discontinued ICS for one or more quarter. Comparing patients who discontinued ICS vs those who remained on high-dose ICS, a lower proportion had chronic OCS use (3.4%–9.2% vs 13.9%–16.8%) and OCS burst use (15.4%–20.8% vs 19.7%–26.1%) in quarters 1 to 4; similarly in quarters 3 and 4, a lower proportion of patients had exacerbations (16.9% and 20.3% vs 27.2% and 27.7%) and short-acting β2-agonist claims (35.4% and 39.2% vs 43.3% and 49.0%, respectively). ConclusionIn patients with SEA on high-dose ICS, a reduction in both ICS and OCS use was observed after initiating mepolizumab. These findings have important implications for clinical outcomes and follow-up care in this patient population.

Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting β2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS-formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS-formoterol (maintenance-and-reliever therapy, "MART") in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting β2-agonist (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11 years, new treatment options are added at Steps 3-4. Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.

Global Initiative for Asthma Strategy 2021. Executive Summary and Rationale for Key Changes

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes.GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting β2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS–formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA.Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS–formoterol as the reliever at all steps: as needed only in Steps 1–2 (mild asthma), and with daily maintenance ICS–formoterol (maintenance-and-reliever therapy, “MART”) in Steps 3–5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS–long-acting β2-agonist (Steps 3–5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6–11 years, new treatment options are added at Steps 3–4.Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.

Novelties in the Treatment of Asthma

Novelties in the Treatment of Asthma Abstract. For general practitioners there have been important novelties in the treatment of asthma due to recent modifications of the international guidelines from Global Initiative for Asthma (GINA). Step 1 no longer recommends the use of short-acting β2-agonists (SABA) without concomitant inhaled corticosteroids (ICS) as a controller because of the lack of efficacy and for safety reasons. Instead, low dose ICS-formoterol as needed is recommended. GINA step 5 recommends targeted biologic therapies like interleukin antibodies in patients with severe uncontrolled asthma. Asthma patients presenting simultaneously with symptoms of chronic obstructive pulmonary disease (COPD) should receive treatment containing ICS. Independent of the current corona pandemic, GINA recommendations stay in place. Recent data on prescriptions of SABA and oral corticosteroids (OCS) in Switzerland indicate that they still play an important role in asthma management and that GINA recommendations have not yet been sufficiently implemented into practice.

Albuterol/budesonide for the treatment of exercise-induced bronchoconstriction in patients with asthma: The TYREE study

BackgroundPT027 is a fixed-dose combination of albuterol (salbutamol) and budesonide in a single pressurized metered-dose inhaler. ObjectiveTo evaluate the efficacy and safety of albuterol/budesonide compared with placebo in patients with asthma and exercise-induced bronchoconstriction (EIB). MethodsIn this randomized, double-blind, 2-period, single-dose crossover study, adolescents and adults with asthma and EIB (defined by ≥20% decrease from pre-exercise challenge forced expiratory volume in 1 second [FEV1]) were randomized to albuterol/budesonide (180/160 µg) followed by placebo (n = 29) or the reverse sequence (n = 31). Subjects were stratified by background therapy (as-needed short-acting β2-agonist alone or low-to-medium dose inhaled corticosteroid plus as-needed short-acting β2-agonist). FEV1 was measured 5 minutes pre-dose, 30 minutes postdose (5 minutes pre-exercise challenge [baseline]), and 5, 10, 15, 30, and 60 minutes postexercise. The primary end point was maximum percentage fall from baseline in FEV1 up to 60 minutes postexercise challenge. ResultsLeast squares mean maximum percentage fall in FEV1 up to 60 minutes postexercise challenge was 5.45% with albuterol/budesonide vs 18.97% with placebo (difference, −13.51% [95% confidence interval, −16.94% to −10.09%]; P < .001). More subjects were fully protected (maximum percentage fall in FEV1 post-exercise challenge < 10%) with albuterol/budesonide than with placebo (78.3% vs 28.3%; P < .001). The treatment effect was consistent irrespective of background inhaled corticosteroid therapy, and albuterol/budesonide was well tolerated. ConclusionIn adolescents and adults with asthma and EIB, a single dose of albuterol/budesonide 180/160 µg taken approximately 30 minutes before exercise was significantly more effective than placebo in preventing EIB. Trial RegistrationClinicalTrials.gov Identifier: NCT04234464

Budesonide/formoterol versus salmeterol/fluticasonefor asthmain children: an effectiveness and safety analysis.

Background: The efficacy of budesonide+formoterol therapy compared with high-dose salmeterol+fluticasone therapy plus short-acting β-agonist (SABA) has not beenevaluated specifically in children. Objectives: To evaluate the efficacy and safety of budesonide+formoterolcombination therapy two times a day plus as needed compared with salmeterol+fluticasone two times a dayplusSABA (as needed) in children in China. Methods: This prospective cohort study included 164 children with persistent asthma (aged 12-17years) who had experienced a minimum of one asthma exacerbation in12months prior to the study. The primary outcome was the time to the first severe exacerbation. Results: Eighty-twochildren were assigned to each of twogroups. The exacerbation rate per 100 patients per year was notfound to besignificantly different. The number of patients with hospitalization/emergency room therapy was lower inbudesonide+formoterol group, but the risk difference was not statistically significant. Asthma control measures showed comparable effects. Bothtreatments were well-tolerated. Conclusion: No significant differences were observed in the outcome measures between the groups. Budesonide+formoterol therapy is a favorable approach in terms of a low load of ICS, steroid exposure, need for multiple inhalers and cost.

Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes.GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting β2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS–formoterol reduces severe exacerbations by ⩾60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA.Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS–formoterol as the reliever at all steps: as needed only in Steps 1–2 (mild asthma), and with daily maintenance ICS–formoterol (maintenance-and-reliever therapy, “MART”) in Steps 3–5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS–long-acting β2-agonist (Steps 3–5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6–11 years, new treatment options are added at Steps 3–4.Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.

The cost-effectiveness of as-needed budesonide-formoterol versus low-dose inhaled corticosteroid maintenance therapy in patients with mild asthma in Canada

BackgroundThe Global Initiative for Asthma recommends the use of as-needed low-dose inhaled corticosteroid (ICS)-formoterol as a preferred controller therapy for patients with mild asthma. These recommendations were based, in part, on evidence from the SYGMA 1 and 2 studies of as-needed budesonide-formoterol. This analysis aimed to compare the cost-effectiveness of as-needed budesonide-formoterol to low-dose maintenance ICS plus as-needed short-acting β2-agonist (SABA) in patients with mild asthma.MethodsA Markov cohort model was designed that included three possible health states (non-exacerbation, severe exacerbation, and death) to compare as-needed budesonide-formoterol 200–6 μg to twice-daily budesonide 200 μg maintenance therapy (low-dose ICS) plus as-needed terbutaline 0.5 mg (SABA). The deterministic base-case analysis used severe exacerbation, adverse event (AE), and healthcare resource use data from SYGMA 2, and was conducted from a Canadian public payer perspective with a 50-year time horizon, and a discount rate of 1.5% per annum. Moderate exacerbation was modelled on data from SYGMA 1 in sensitivity analyses. Utility values were derived from SYGMA 2 quality of life data. All-cause- and asthma-related mortality rates and costs (reported in 2019 Canadian dollars) were based on published data, using Canada-specific values where available. One-way deterministic sensitivity, probabilistic sensitivity, and eight scenario analyses were conducted to examine the robustness of the results.ResultsAs-needed budesonide-formoterol was the dominant treatment option in the base-case analysis, providing incremental cost savings of $9882 per patient and quality-adjusted life year (QALY) gains of 0.002 versus low-dose maintenance ICS plus as-needed SABA over a 50-year time horizon. Using a willingness-to-pay threshold of $50,000/QALY ($100,000/QALY), as-needed budesonide-formoterol had a 94% (95%) probability of being cost-effective compared with maintenance ICS plus as-needed SABA. Cost-saving was mostly driven by lower overall medication and AE-related costs. As-needed budesonide-formoterol remained the dominant treatment in sensitivity and scenario analyses.ConclusionsAs-needed budesonide-formoterol is a cost-saving option for the treatment of mild asthma from the perspective of the Canadian public payer compared with low-dose maintenance ICS plus as-needed SABA.

Short-acting β2-agonist prescriptions are associated with poor clinical outcomes of asthma: the multi-country, cross-sectional SABINA III study.

BackgroundTo gain a global perspective on short-acting β2-agonist (SABA) prescriptions and associated asthma-related clinical outcomes in patients with asthma, we assessed primary health data across 24 countries in five continents.MethodsSABINA III was a cross-sectional study that employed electronic case report forms at a study visit (in primary or specialist care) to record prescribed medication(s), over-the-counter (OTC) SABA purchases and clinical outcomes in asthma patients (≥12 years old) during the past 12 months. In patients with ≥1 SABA prescriptions, associations of SABA with asthma symptom control and severe exacerbations were analysed using multivariable regression models.ResultsOf 8351 patients recruited (n=6872, specialists; n=1440, primary care), 76.5% had moderate-to-severe asthma and 45.4% experienced ≥1 severe exacerbations in the past 12 months. 38% of patients were prescribed ≥3 SABA canisters; 18.0% purchased OTC SABA, of whom 76.8% also received SABA prescriptions. Prescriptions of 3–5, 6–9, 10–12 and ≥13 SABA canisters (versus 1–2) were associated with increasingly lower odds of controlled or partly controlled asthma (adjusted OR 0.64 (95% CI 0.53–0.78), 0.49 (95% CI 0.39–0.61), 0.42 (95% CI 0.34–0.51) and 0.33 (95% CI 0.25–0.45), respectively; n=4597) and higher severe exacerbation rates (adjusted incidence rate ratio 1.40 (95% CI 1.24–1.58), 1.52 (95% CI 1.33–1.74), 1.78 (95% CI 1.57–2.02) and 1.92 (95% CI 1.61–2.29), respectively; n=4612).ConclusionsThis study indicates an association between high SABA prescriptions and poor clinical outcomes across a broad range of countries, healthcare settings and asthma severities, providing support for initiatives to improve asthma morbidity by reducing SABA overreliance.

Cost-utility of as-needed combination low-dose budesonide-formoterol in adolescents mild asthma.

Previously evidence has demonstrated that as-needed combination low-dose budesonide-formoterol reduced the risk of severe exacerbations compared with short-acting β2-agonist (SABA) reliever therapy in an adolescent with mild asthma. Concerns as if the extra benefit offered by this drug outweighs the additional cost. This study aimed to evaluate the cost-effectiveness of as-needed combination low-dose budesonide-formoterol compared with short-acting β2-agonist (SABA) reliever therapy in adolescents with mild asthma in Colombia. A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with mild asthma in Colombia. Total costs and QALYs of low-dose budesonide-formoterol compared with short-acting β2-agonist (SABA) were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000. The model suggests a potential gain of 0.03 QALYs and per patient per year on low-dose budesonide-formoterol. The cost difference per person was US$-4 per patient per year in favor of budesonide- formoterol. The position of dominance negates the need to calculate an incremental cost-effectiveness ratio. In the one-way and probabilistic sensitivity analyses, our base-case results were robust to variations of all assumptions and parameters. In conclusion, low-dose budesonide-formoterol as a reliever was found to be cost-effective when added to usual care in adolescents with mild asthma. This evidence should promote economic evaluations in developed and developing countries for the inclusion of new drugs in health insurance plans.

The use of ipratropium bromide for treating moderate to severe asthma exacerbations in pediatric patients in an emergency setting: A cost-effectiveness analysis.

Although the efficacy of the addition of ipratropium bromide (IB) to short-acting β2-agonists (SABAs) for treating children with moderate to severe asthma exacerbations has been demonstrated, evidence of its cost-effectiveness is scarce. The aim of the present study was to evaluate the cost-effectiveness of treatment with a combination of SABAs and IB compared with SABAs alone for the treatment of children with moderate to severe asthma exacerbations. To achieve the objectives of the study, a decision-analysis model was adapted. Effectiveness parameters were obtained from a systematic review of the literature with meta-analysis. Cost data were obtained from hospital bills and from the national manual of drug prices in Colombia. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome of the model was avoidance of hospital admission. In children with moderate to severe asthma exacerbations, the base-case analysis showed that compared to SABAs alone, treatment with a combination of SABAs and IB was associated with lower overall treatment costs (US$126.24 vs. US$170.69 mean cost per patient) and a higher probability of hospital admission avoided (0.7999 vs. 0.7100), thus leading to dominance. For children with severe asthma exacerbations, these values were US$132.99 versus US$170.69 and 0.7883 versus 0.7100, respectively. In Colombia, when compared to therapy with SABAs alone, therapy with a combination of SABAs and IB for treating pediatric patients with moderate to severe asthma exacerbations involves a lower probability of hospital admission at lower treatment costs.

The controversial role of as-needed short-acting β2-agonist monotherapy in mild asthma: Short review of current guidelines

The controversy surrounding short-acting β2-agonist (SABA) monotherapy for very mild and mild asthma continues in guidelines despite increasing evidence in favor of combined inhaled corticosteroid/reliever therapy. We herein briefly review the findings from two high-quality randomized controlled trials and other safety data to conclude that the efficacy and safety of SABA monotherapy have been overstated, especially in type-2 high or allergic disease.

Is respiratory care carbon conscious? Rationale and future implications for the CARBON respiratory program

BACKGROUND AND AIM: Healthcare systems need to substantially reduce greenhouse gas (GHG) emissions as societies decarbonize their economies. In respiratory medicine, contributions from healthcare resource utilization (HCRU) and short-acting β₂-agonist (SABA) relievers, which provide rapid relief from asthma symptoms, are significant. SABA relievers contribute to the majority of inhaler usage and total carbon footprint of inhaler devices across Europe. In asthma, high SABA use is common and associated with poor disease control and increased exacerbation risk.¹ In chronic obstructive pulmonary disease (COPD), exacerbation history is linked with increased rate of future exacerbations;² both SABA use and exacerbations increase HCRU requirements. Here, we provide an overview of the healthCARe-Based carbON cost of treatment (CARBON) sustainability program, which evaluates the carbon footprint associated with poorly and well-managed care of common respiratory diseases. METHODS: CARBON is the first program to quantify the carbon footprint of HCRU and medications in respiratory healthcare by using a combination of certified published studies and methodologies. RESULTS:Patients with well-managed asthma and COPD are likely to have a lower carbon impact through reduced requirements for SABA medication use and HCRU. This CARBON group of studies is evaluating the overall carbon footprint associated with SABA use, exacerbations, and HCRU in over 1.5 million patients with asthma or COPD in over 30 European and North American countries. CONCLUSIONS:Understanding what comprises the carbon footprint of respiratory healthcare and how it is impacted by poor disease control or disease progression is the first step in understanding how innovative treatments and guideline implementation can drive carbon reduction without risking improvements in patient outcomes. The principle of evidence-led care improvement as a means to achieve greater sustainability will have multiple benefits for patients and society.

Innovations of the GINA 2020 for Children and the Effects of COVID-19 on Children with Asthma

Die Global Initiative for Asthma (GINA) hat in den Jahren 2019–2021 einige substanzielle Änderungen für das Management von Patienten mit Asthma empfohlen, die auch Schulkinder und Jugendliche betreffen. Eine sehr wesentliche neue Empfehlung ist, dass kurzwirksame Betamimetika (SABA) aus Sicherheitsgründen nur mehr in Kombination mit inhalativen Steroiden (ICS) gegeben werden sollten. Bei Jugendlichen werden GINA-Stufe 1 und 2 zusammengezogen und bei Asthmaproblemen eine Bedarfsinhalation mit niedrig dosierter ICS-Formoterol-Kombination empfohlen. Als Alternative wird die Trennung in Stufe 1 mit Inhalation von SABA und einem ICS bei Bedarf und in Stufe 2 wie bisher die tägliche Inhalation eines ICS und SABA bei Bedarf empfohlen. Dieser Weg wird auch als der bevorzugte bei Kindern von 6 bis 11 Jahren vorgeschlagen. Diese neuen GINA-Empfehlungen wurden jedoch nicht von allen nationalen oder internationalen Leitlinien übernommen, da vor allem für Kinder die Evidenz dafür gering ist. Tiotropium, Mepolizumab und Dupilumab wurden in die Therapie des schweren Asthmas aufgenommen.Kinder mit Asthma erkranken nicht häufiger oder schwerer an COVID-19 als Kinder ohne Asthma. Verschiedene Mechanismen wie ein möglich protektiver Effekt der Typ-2-Inflammation, die antivirale und immunmodulierende Wirkung von ICS und die Niederregulierung von ACE2-Rezeptoren durch die allergische Sensibilisierung könnten dafür verantwortlich sein.