The Association Between Short-Acting ß2-Agonist Over-Prescription, and Patient-Reported Acquisition and Use on Asthma Control and Exacerbations: Data from Australia.

INTRODUCTION: In Australia, short-acting ß2-agonists (SABA) are available both over the counter (OTC) and on prescription. This ease of access may impact SABA use in the Australian population. Our aim was to assess patterns and outcome associations of prescribed, acquired OTC and reported use of SABA by Australians with asthma. METHODS: This was a cross-sectional study, using data derived from primary care electronic medical records (EMRs) and patient completed questionnaires within Optimum Patient Care Research Database Australia (OPCRDA). A total of 720 individuals aged ≥ 12 years with an asthma diagnosis in their EMRs and receiving asthma therapy were included. The annual number of SABA inhalers authorised on prescription, acquired OTC and reported, and the association with self-reported exacerbations and asthma control were investigated. RESULTS: 92.9% (n = 380/409) of individuals issued with SABA prescription were authorised ≥ 3 inhalers annually, although this differed from self-reported usage. Of individuals reporting SABA use (n = 546) in the last 12 months, 37.0% reported using ≥ 3 inhalers. These patients who reported SABA overuse experienced 2.52 (95% confidence interval [CI] 1.73-3.70) times more severe exacerbations and were 4.51 times (95% CI 3.13-6.55) more likely to have poor asthma control than those who reported using 1-2 SABA inhalers. Patients who did not receive SABA on prescription (43.2%; n = 311/720) also experienced 2.71 (95% CI 1.07-7.26) times more severe exacerbations than those prescribed 1-2 inhalers. Of these patients, 38.9% reported using OTC SABA and other prescription medications, 26.4% reported using SABA OTC as their only asthma medication, 13.2% were prescribed other therapies but not SABA OTC and 14.5% were not using any medication. CONCLUSION: Both self-reported SABA overuse and zero SABA prescriptions were associated with poor asthma outcomes. The disconnect between prescribing authorisation, OTC availability and actual use, make it difficult for clinicians to quantify SABA use.

Genetic and T2 biomarkers linked to the efficacy of HDM sublingual immunotherapy in asthma.

BACKGROUND: Hypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT). OBJECTIVE: To investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT. METHODS: MITRA (NCT01433523) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort. RESULTS: An increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p=0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p=0.006) for subjects with a higher number of elevated T2 biomarkers. CONCLUSIONS: HDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype. TRIAL REGISTRATION NUMBER: NCT01433523.

Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update.

The Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and the US National Heart Lung and Blood Institute to improve asthma awareness, prevention and management worldwide. GINA develops and publishes evidence-based, annually updated resources for clinicians. GINA guidance is adopted by national asthma guidelines in many countries, adapted to fit local healthcare systems, practices, and resource availability. GINA is independent of industry, funded by the sale and licensing of its materials. This review summarizes key practical guidance for primary care from the 2022 GINA strategy report. It provides guidance on confirming the diagnosis of asthma using spirometry or peak expiratory flow. GINA recommends that all adults, adolescents and most children with asthma should receive inhaled corticosteroid (ICS)-containing therapy to reduce the risk of severe exacerbations, either taken regularly, or (for adults and adolescents with "mild" asthma) as combination ICS-formoterol taken as needed for symptom relief. For patients with moderate-severe asthma, the preferred regimen is maintenance-and-reliever therapy (MART) with ICS-formoterol. Asthma treatment is not "one size fits all"; GINA recommends individualized assessment, adjustment, and review of treatment. As many patients with difficult-to-treat or severe asthma are not referred early for specialist review, we provide updated guidance for primary care on diagnosis, further investigation, optimization and treatment of severe asthma across secondary and tertiary care. While the GINA strategy has global relevance, we recognize that there are special considerations for its adoption in low- and middle-income countries, particularly the current poor access to inhaled medications.

Efficacy of dupilumab in patients with moderate-to-severe asthma and persistent airflow obstruction.

BACKGROUND: The 52-week, phase 3 LIBERTY ASTHMA QUEST study (NCT02414854) in patients aged above or equal to 12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilumab 200 mg and 300 mg every 2 weeks vs matched placebo. OBJECTIVE: To assess whether dupilumab improves clinical outcomes in QUEST patients with persistent airflow obstruction (PAO) defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio less than 0.7 at baseline. METHODS: End points were annualized rate of severe exacerbations, pre and post-bronchodilator forced expiratory volume in 1 second over time, proportion achieving reversal of PAO, and quality of life. Efficacy was evaluated in patients with or without PAO at baseline in subpopulations with eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 25 ppb or eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb. RESULTS: Of 1902 patients enrolled in QUEST, 1039 (55%) had PAO at baseline. Dupilumab vs placebo rapidly and significantly improved lung function in patients with PAO and elevated type 2 inflammatory biomarkers at baseline. Dupilumab improved probability of reversing airflow obstruction (hazard ratio vs placebo 1.616 [95% confidence interval, 1.272-2.052] and 1.813 [1.291-2.546]; both P < .001) and significantly reduced severe exacerbations by 69% (relative risk, 0.411; 95% confidence interval [0.327-0.516]; P < .0001) and by 75% (0.252 [0.178-0.356]; P < .0001) in patients with PAO with eosinophils ≥ 150 cells/µL or FeNO ≥ 25 ppb and eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb, respectively. Similar results were observed in patient subgroups without PAO. CONCLUSION: In patients with uncontrolled moderate-to-severe asthma, treatment with dupilumab facilitates reversal of PAO status and improves clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02414854.

Dupilumab Is Effective in Patients With Moderate-to-Severe Uncontrolled GINA-Defined Type 2 Asthma Irrespective of an Allergic Asthma Phenotype.

BACKGROUND: The Global Initiative for Asthma report recommends consideration of add-on biologics for patients with type 2 inflammation (blood eosinophils ≥150 cells/µL, fractional exhaled nitric oxide [Feno] ≥20 parts per billion or allergic asthma) whose asthma cannot be controlled by high-dose inhaled corticosteroids. In QUEST (NCT02414854), add-on dupilumab versus placebo was efficacious in patients with uncontrolled, moderate to severe asthma, including those with eosinophils greater than or equal to 150 cells/µL and/or Feno greater than or equal to 25 parts per billion. OBJECTIVE: To assess dupilumab efficacy in patients with a type 2 phenotype in the presence or absence of allergic asthma phenotype. METHODS: Patients aged 12 years or older received add-on dupilumab 200/300 mg versus matched placebo every 2 weeks for 52 weeks. Allergic asthma phenotype was defined as baseline serum total IgE greater than or equal to 30 IU/mL and 1 or more perennial aeroallergen-specific IgE level greater than or equal to 0.35 kU/L. Annualized rate of severe asthma exacerbations and changes from study baseline in prebronchodilator and postbronchodilator FEV1 were evaluated in patients with allergic and nonallergic phenotype with baseline blood eosinophils greater than or equal to 150 cells/µL and/or Feno greater than or equal to 20 parts per billion. RESULTS: Of 1902 patients in QUEST, 83.3% had eosinophils and/or Feno above Global Initiative for Asthma thresholds; 56.9% had evidence for allergic asthma. Dupilumab significantly reduced the rate of severe asthma exacerbations in patients with (48.8%) and without (64.0%) evidence of allergic asthma and improved prebronchodilator and postbronchodilator FEV1 in patients with elevated type 2 biomarkers, irrespective of whether they showed evidence of an allergic asthma phenotype. CONCLUSIONS: In patients with type 2 biomarkers over Global Initiative for Asthma thresholds, dupilumab significantly reduced exacerbations and improved lung function. Efficacy was not impacted by allergic status.

Practical approach lung health-global alliance against chronic respiratory diseases (PAL-GARD) initiative in Brazil.

Background: To evaluate the impact of training primary care physicians (PCPs) in the use of the practical approach lung health-global alliance against chronic respiratory diseases (PAL-GARD) upon their diagnostic skills. Methods: In this real-life three-phase study, PCPs were allocated to a PAL-GARD training or control group. Patients who sought a primary care health facility due to cough, dyspnea and/or wheezing were eligible. The clinical diagnoses made by PCPs during the baseline and post-intervention phase were audited by a panel of pulmonologists. Kappa inter-rater statistics was used to compare agreement between PCPs and pulmonologists. Results: Thirty PCPs evaluated 536 patients, 358 in the intervention and 178 in the control group. According to Kappa, there was an increase in the agreement in the diagnosis of asthma (from 0.546 to 0.638), tuberculosis (from 0.393 to 0.655) and acute respiratory infections (ARI) (from 0.577 to 0.584) was observed in the PAL-GARD group, but there was a reduction in chronic obstructive pulmonary disease (COPD) (from 0.430 to 0.284). Conclusions: In this setting, PAL-GARD-based guide and training improved the clinical diagnosis of common respiratory diseases with the exception of COPD.

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 ß2-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 ß2-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.

Asthma management in low and middle income countries: case for change.

Asthma is the most common noncommunicable disease in children, and among the most common in adults. The great majority of people with asthma live in low and middle income countries (LMICs), which have disproportionately high asthma-related morbidity and mortality. Essential inhaled medications, particularly those containing inhaled corticosteroids (ICS), are often unavailable or unaffordable, and this explains much of the global burden of preventable asthma morbidity and mortality. Guidelines developed for LMICs are generally based on the outdated assumption that patients with asthma symptoms <1-3 times per week do not need (or benefit from) ICS. Even when ICS are prescribed, many patients manage their asthma with oral or inhaled short-acting ß2-agonists (SABA) alone, owing to issues of availability and affordability. A single ICS-formoterol inhaler-based approach to asthma management for all severities of asthma, from mild to severe, starting at diagnosis, might overcome SABA overuse/over-reliance and reduce the burden of symptoms and severe exacerbations. However, ICS-formoterol inhalers are currently very poorly available or unaffordable in LMICs. There is a pressing need for pragmatic clinical trial evidence of the feasibility and cost-effectiveness of this and other strategies to improve asthma care in these countries. The global health inequality in asthma care that deprives so many children, adolescents and adults of healthy lives and puts them at increased risk of death, despite the availability of highly effective therapeutic approaches, is unacceptable. A World Health Assembly Resolution on universal access to affordable and effective asthma care is needed to focus attention and investment on addressing this need.

Pairwise indirect treatment comparison of dupilumab versus other biologics in patients with uncontrolled persistent asthma.

BACKGROUND: Currently, five biologic treatment options are available for use in patients with uncontrolled persistent asthma: three interleukin (IL)-5 antagonists, which either bind to the anti-IL-5 ligand (mepolizumab, reslizumab) or to the IL-5 receptor (benralizumab); one anti-immunoglobulin E (anti-IgE) therapy (omalizumab); and one anti-IL-4/IL-13 therapy (dupilumab). To date, no comparative data from head-to-head clinical trials are available for these biologics. OBJECTIVE: An indirect treatment comparison (ITC) of dupilumab versus each of the anti-IL-5 and anti-IgE therapies using the endpoints of annualized severe asthma exacerbation rates and change in pre-bronchodilator forced expiratory volume in 1 s (FEV1). METHODS: Embase®, MEDLINE®, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for studies published between January 1, 1980 and March 25, 2019. Eligible articles included randomized controlled trials (RCTs) in patients aged ≥ 12 years with persistent/uncontrolled asthma using at least medium-to-high dose inhaled corticosteroid plus long-acting ß2-agonist with add-on biologic therapy. Bucher ITCs were performed to compare subgroups of dupilumab patients with the anti-IL-5s and anti-IgE trial populations. RESULTS: Fourteen RCTs were included in the analyses. The matched dupilumab subgroups were associated with greater reductions in annualized severe exacerbation rates compared with benralizumab, mepolizumab, reslizumab, and omalizumab (54%, 28%, 38%, and 26% greater reduction, respectively). A greater improvement in FEV1 was also observed for dupilumab at week 12 and/or week 24/52 than for the other biologics (0.06-0.14 L). CONCLUSION: In this ITC, dupilumab was associated with lower severe asthma exacerbation rates and greater improvements in lung function than anti-IL-5s and omalizumab.

Estrategia Global para el Manejo del Asma 2021. Resumen ejecutivo y razones de los cambios clave / 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. Keywords: Asthma Asthma diagnosis Asthma management Asthma prevention

El Informe sobre la Estrategia Global para el Manejo y la Prevención del Asma (GINA) proporciona a los clínicos una estrategia basada en la evidencia que se actualiza anualmente para el manejo y la prevención del asma, la cual puede adaptarse a las circunstancias locales (por ejemplo, en cuanto a acceso a medicamentos). Este artículo resume las recomendaciones clave de la GINA 2021 y la evidencia que apoya los cambios recientes. La GINA recomienda que el asma en adultos y adolescentes no se trate con agonistas β2 de acción corta (SABA) en monoterapia, debido a los riesgos que acompañan a la monoterapia con SABA y a su uso excesivo, y a la evidencia que demuestra los beneficios del uso de corticosteroides inhalados (ICS). Diversos ensayos clínicos de gran tamaño muestran que la combinación de ICS-formoterol a demanda reduce el número de exacerbaciones graves en el asma leve en ≥ 60% en comparación con los SABA en monoterapia, presentando también resultados similares en las exacerbaciones, síntomas, función pulmonar y efectos antiinflamatorios que el uso diario de ICS más SABA a demanda. Los cambios clave en la GINA 2021 incluyen la división del algoritmo de tratamiento para adultos y adolescentes en dos vías. La vía 1 (la preferencial) cuenta con ICS–formoterol a dosis bajas como tratamiento de rescate en todos los escalones: a demanda solo en los escalones 1–2 (asma leve), y como tratamiento de mantenimiento diario (control y rescate, MART) en los pasos 3–5. La vía 2 (la alternativa) cuenta con SABA a demanda en todos los escalones, más tratamiento regular con ICS (paso 2) o ICS-Agonista β2 de acción prolongada en los escalones 3–5. Para los adultos con asma moderada a grave, la GINA realiza recomendaciones adicionales en el escalón 5, con el agregado de agonistas muscarínicos de larga duración y azitromicina y de tratamientos biológicos en el asma grave. Para los niños entre seis y 11 años, se han añadido opciones nuevas de tratamiento en los escalones 3 y 4. En todos los grupos de edad y gravedad, sigue siendo esencial una valoración personalizada regular, el tratamiento de los factores de riesgo modificables, la educación para el autocontrol de síntomas, técnicas y habilidades del paciente, el ajuste apropiado de la medicación y las revisiones para optimizar la evolución del asma. Palabras clave: Asma Diagnóstico del asma Gestión del asma Prevención del asma

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 ß2-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 ß2-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 ß2-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 ß2-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.

A Practical Guide to Implementing SMART in Asthma Management.

The use of a single inhaler containing the combination of an inhaled corticosteroid (ICS) and formoterol, a specific long-acting bronchodilator, for both maintenance and quick relief therapy (single maintenance and reliever therapy [SMART or MART]) is recommended by both the Global Initiative for Asthma and the National Asthma Education and Prevention Program Coordinating Committee in steps 3 and 4 of asthma management. This article provides practical advice about implementing SMART in clinical practice based on evidence and clinical experience. Fundamental to SMART is that ICS-formoterol provides quick relief of asthma symptoms similar to that of short-acting ß2-agonists such as albuterol, while reducing the risk for severe asthma exacerbations and at an overall lower ICS exposure. Most SMART clinical trials were in adults and adolescents (aged ≥12 years), using budesonide-formoterol 160/4.5 µg (delivered dose), one inhalation once or twice daily (step 3) and two inhalations twice daily (step 4). For both steps 3 and 4, patients take additional inhalations of budesonide-formoterol 160/4.5 µg, one inhalation whenever needed for symptom relief, up to a maximum for adults and adolescents of 12 total inhalations in any single day (delivering 54 µg formoterol). The efficacy and safety of SMART with budesonide-formoterol and beclometasone-formoterol have been confirmed, but other ICS-long-acting bronchodilator combinations have not been studied. The SMART regimen should be introduced with a careful explanation of its role in self-management, preferably with a customized written asthma action plan. The cost to patients and the availability of SMART treatment will depend on the prescribed dose and national or local payer agreements.

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 ß2 -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 ß2 -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.

Short-acting ß2-agonist prescriptions are associated with poor clinical outcomes of asthma: the multi-country, cross-sectional SABINA III study.

BACKGROUND: To gain a global perspective on short-acting ß2-agonist (SABA) prescriptions and associated asthma-related clinical outcomes in patients with asthma, we assessed primary health data across 24 countries in five continents. METHODS: SABINA 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. RESULTS: Of 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). CONCLUSIONS: This 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.