Global Initiative For Asthma Step Research Articles

Predictors of exacerbation in Japanese patients with severe asthma: Analysis of the severe asthma research program (Okayama-SARP) cohort

BackgroundBecause exacerbation of severe asthma decreases patients’ quality of life, this study aimed to identify predictive factors for asthma exacerbation. MethodsJapanese patients with severe asthma requiring treatment according to the Global Initiative for Asthma (GINA) guidelines ≥ Step 4 between January 2018 and August 2021 were prospectively enrolled and followed up for one year at facilities participating in the Okayama Respiratory Disease Study Group (Okayama Severe Asthma Research Program). ResultsA total of 85 patients (29 men and 56 women) were included. The median age was 64 (interquartile range [IQR], 51–72) years. Treatment according to GINA Steps 4 and 5 was required in 29 and 56 patients, respectively, and 44 patients (51.8%) were treated with biologics. The median peripheral-blood eosinophil count, fractional exhaled nitric oxide, IgE level, and percent predicted FEV1 (%FEV1) at enrollment were 204 (IQR, 49–436)/μL, 28 (IQR, 15–43) ppb, 172 (IQR, 56–473) IU/mL, and 80.0 (IQR, 61.1–96.1) %, respectively. Exacerbation during the previous year, asthma control test (ACT) score <20, %FEV1 <60%, and serum IL-10 level >6.7 pg/mL were associated with exacerbation during the observation period. ConclusionsExacerbation during the previous year, low ACT score, and low %FEV1 were predictive factors of future exacerbation, even in a cohort with >50% of patients treated with biologics. Furthermore, high serum IL-10 levels might be a new predictive factor.

Safety and efficacy of bronchial thermoplasty in refractory asthma with severe obstructive respiratory dysfunction.

Bronchial thermoplasty (BT) is a recently developed non-pharmacological therapy for refractory bronchial asthma. Although increasing evidence has suggested that BT is effective for various phenotypes of severe asthma, its safety and efficacy in patients with severe irreversible impaired lung function are unclear. To assess the efficacy and safety of BT in patients with refractory asthma, including patients with a severely impaired forced expiratory volume in 1 second (FEV1). This was a single-center, retrospective, observational cohort study. We retrospectively reviewed the medical records of 15 patients with refractory asthma (Global Initiative for Asthma step 4 or 5), including patients with severely impaired airflow limitation (% predicted pre-bronchodilator FEV1 <60%), who had undergone BT between June 2016 and January 2022. We analyzed the efficacy (change in asthma symptoms, exacerbation rate, pulmonary function, asthma medication, and serum inflammatory chemokine/cytokines before and after BT) and complications in all patients. We compared these data between patients with severe obstructive lung dysfunction [group 1(G1)] and patients with FEV1 ⩾ 60% [group 2 (G2)]. Six patients were in G1 and nine were in G2. Clinical characteristics, T2 inflammation, and concurrent treatment were equivalent in both groups. BT significantly improved asthma-related symptoms (measured using the Asthma Control Test and Asthma Quality of Life Questionnaire scores) in both groups. FEV1 was significantly improved in G1 but not in G2. Four patients in G2, but none in G1, experienced asthma exacerbation requiring additional systemic corticosteroids (including two requiring prolonged hospitalization) after BT. Long-term responders (patients who reduced systemic or inhaled corticosteroid without newly adding biologics in a follow-up > 2 years) of BT were identified in G1 and G2 (n = 2, 33.3% and n = 4, 44.4%, respectively). BT in patients with refractory asthma and severe airflow limitation is equally safe and efficacious as that in patients with moderate airflow limitation.

Incremental cost burden among patients with severe uncontrolled asthma in the United States.

BACKGROUND: The economic burden of severe asthma and severe uncontrolled asthma (SUA) is significant. Updated assessments of health care resource utilization (HCRU) and cost are needed given the increase in treatment options and updates to guidelines in recent years. OBJECTIVE: To describe all-cause and asthma-related HCRU and costs among patients with SUA vs patients with nonsevere asthma in the United States using real-world data. METHODS: MarketScan administrative claims databases were used to select adults with persistent asthma for this retrospective analysis between January 1, 2013, and December 31, 2019. Asthma severity status was defined using the Global Initiative for Asthma step 4/5 criteria (index is the earliest date qualifying patients as severe or randomly assigned for nonsevere patients). Patients with SUA were a subset of the severe cohort meeting the following criteria: those who were hospitalized with asthma as the primary diagnosis or had at least 2 emergency department or outpatient visits with an asthma diagnosis and a steroid burst within 7 days. HCRU, costs (allcause and asthma-related defined as medical claims with an asthma diagnosis and pharmacy claims for asthma treatment), work loss, and indirect costs due to absenteeism and short-term disability (STD) were compared between patients with SUA, severe, and nonsevere asthma. Outcomes were reported during a fixed 12-month post-index period using chi-square and t-tests where appropriate. RESULTS: 533,172 patients with persistent asthma were identified (41.9% [223,610]) severe and 58.1% [309,562] nonsevere). Of the severe patients, 17.6% (39,380) had SUA. The mean (SD) all-cause total health care costs were significantly higher in patients with SUA ($23,353 [$40,817]) and severe asthma ($18,554 [$36,147]) compared with those with nonsevere asthma ($16,177 [$37,897], P < 0.001 vs nonsevere asthma). The results were consistent for asthma-related costs. In addition, although patients with severe asthma made up 41.9% of the total study population, they contributed disproportionately higher costs (60.5%) to the total asthma-related direct costs, with the effect more evident among patients with SUA (7.4% of study population contributed 17.7% of the total asthma-related costs). For the subset of patients with asthma with workplace absenteeism, patients with SUA lost more time from work (259.3 vs 236.2 hours lost, P = 0.002; 7.8 vs 5.3 STD days, P < 0.001), and had higher corresponding indirect costs ($5,944 vs $5,415, P = 0.002 for absenteeism related; $856 vs $582, P < 0.001 for STD related) compared with patients with nonsevere asthma. CONCLUSIONS: Patients with SUA have significantly higher asthma-related economic burden compared with patients with nonsevere asthma and contribute a disproportionally higher percentage of asthma-related costs. DISCLOSURES: This study was funded by Amgen and AstraZeneca. The design and analysis for this study was conducted primarily by Merative. Amgen and AstraZeneca provided funding to support protocol development, data analysis, and manuscript development activities associated with this study. Dr Burnette is on the advisory board and a consultant for GSK, a consultant and member of the advisory boards and speakers' bureaus of Sanofi, Genzyme, Regeneron, AstraZeneca, and Amgen Inc. Dr Wang, Dr Rane, Dr Lindsley, and Dr Llanos are employees and shareholders of Amgen Inc. Dr Chung and Dr Ambrose are employees and shareholders of AstraZeneca. Ms Princic and Ms Park are employees of Merative, which received funding from Amgen to conduct this study.

Patterns of rescue and maintenance therapy claims surrounding a clinical encounter for an asthma exacerbation

BackgroundA “window of opportunity” has been proposed where anti-inflammatory therapy administration in response to symptoms could prevent exacerbation. ObjectiveTo evaluate rescue and maintenance therapy claims surrounding a severe asthma exacerbation serious enough to require a face-to-face clinical encounter. MethodsMerative MarketScan research databases (US administrative claims 2011 to 2017) were analyzed for patients aged ≥4 years, with an asthma diagnosis code, who filled short-acting β2-agonist (SABA) and Global Initiative for Asthma Steps 3 to 5 maintenance therapies. Patients were indexed on a random SABA claim and had 12 months’ continuous health plan eligibility pre- and post-index. Serious exacerbations were severe exacerbations requiring systemic corticosteroids prescribed from an outpatient clinic, urgent care or emergency department, or hospitalization for asthma. SABA and maintenance claims 30 days pre- and post-event were analyzed. ResultsOf 319,342 patients (30% children 4 to 11 years; 70% adults or adolescents ≥12 years), 27.2% of children and 16.8% of adolescents or adults experienced ≥ 1 serious exacerbation (unadjusted odds ratio [OR], 1.85 [95% confidence interval, 1.81–1.88]). In the 30 days pre-event, 42.6% filled ≥1 SABA (children: 44.3%; adolescents or adults: 41.5%; OR, 1.12 [1.09–1.16]) and 57.4% filled maintenance (children: 59.0%; adolescents or adults: 56.3%; OR, 1.12 [1.08–1.15]). In the 30 days post-event, 61.4% filled SABA (children: 69.7%; adolescents or adults: 55.6%; OR, 1.84 [1.78–1.90]) and 94.8% filled maintenance (children: 98.6%; adolescents or adults: 92.2%; OR, 6.09 [5.45–6.81]). ConclusionMany patients treated as having moderate-to-severe asthma escalate SABA claims before a serious exacerbation, but approximately 40% have no anti-inflammatory maintenance fill, highlighting a “window of opportunity” to prevent exacerbations using inhaled corticosteroids concomitantly with SABA as rescue.

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy.

The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. For non-OCS-dependent patients, 53.3% (n= 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n= 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n= 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n= 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n= 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n= 50 of 99) eliminated OCS and 74.7% (n= 74 of 99) achieved dosages of 5 mg or lower at EOT. These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction.

Asthma control among treated US asthma patients in Practice Fusion’s electronic medical record research database

This study investigated burden of ‘not well-controlled’ asthma, overall and by Global Initiative for Asthma (GINA) Step, among treated asthma patients in Practice Fusion’s research database. Asthma control (Asthma Control Test [ACT]) was stratified by GINA Step; prevalence ratios were estimated using Poisson regression with robust variance controlled for confounders. ACT scores ≤19 reflect not well-controlled; >19 reflect ‘well-controlled’ asthma. Of 15,579 patients, 30% had not well-controlled asthma at index date. The proportion of patients with not well-controlled asthma increased from GINA Step 1 (29%) to Step 5 (45%). Compared with Step 1, the proportion of patients with not well-controlled asthma was 0.87-times lower in Step 2, 1.10-times greater in Step 4, and 1.37-times greater in Step 5. Results suggest that despite available treatments, patients remain symptomatic across GINA Steps in real-world primary care and specialist outpatient practices, with incremental disease burden and unmet medical need in these populations.

Clinical features of asthma with connective tissue diseases.

The clinical features of asthma with connective tissue diseases (CTDs) are not well-known. This study therefore aimed to investigate the clinical characteristics of asthma with CTDs. We retrospectively examined the records of adults (≥18 years old) with asthma followed up between January 2010 and December 2019. We then compared the clinical features of asthma with and without CTDs. Among 568 subjects with asthma, 42 subjects (7.4%) had CTDs. The most frequent concomitant CTD was rheumatoid arthritis (n = 23, 54.8%), followed by systemic lupus erythematosus (n = 6, 14.3%). The proportion of women (with vs. without CTDs, 85.7% vs. 56.5%, p < 0.001) and Global Initiative for Asthma step were higher (Step 4 or 5, with vs. without CTDs, 81.0% vs. 62.0%, p = 0.01) in asthma with CTDs, whereas frequency of allergic rhinitis was higher in asthma without CTDs (with vs. without CTDs, 7.1% vs. 26.1%, p = 0.005). Eosinophil ratio (with vs. without CTDs, 2.1% vs. 3.5%, p = 0.009) and total immunoglobulin E level (with vs. without CTDs, 43 IU/mL vs. 237 IU/mL, p = 0.002) were lower in asthma with CTDs. In terms of lung function, percentage predicted forced vital capacity (with vs. without CTDs, 86.7% vs. 99.7%, p = 0.008) and percentage predicted forced expiratory volume in 1s (%FEV1) (with vs. without CTDs, 77.2% vs. 88.4%, p = 0.02) were all lower in asthma with CTDs. With multivariable analysis, CTDs (odds ratio [OR] 2.8, 95%CI 1.3-6.0; p = 0.008), chronic obstructive pulmonary disease (OR 3.8, 95%CI 2.1-6.7; p < 0.001) and asthma onset at <20 years old (OR 1.8, 95%CI 1.1-3.2; p = 0.03) were associated with low FEV1 (defined as %FEV1 < 80%) in asthma. Asthma with CTDs was related to lower lung function and low-T2 inflammation asthma.

Adverse perception of cough in patients with severe asthma: a discrete choice experiment.

Asthma symptoms adversely impact quality of life in particular in those with poor disease control. Commonly used patient-reported measures for asthma used to assess asthma control often inadequately capture the impact of cough, despite evidence that cough is one of the most bothersome symptoms for patients with asthma. This study aims to improve our understanding of how patients with asthma perceive cough to better understand its clinical impact. A discrete choice experiment (DCE) was performed in two distinct adult asthma populations; those with severe asthma as defined by Global Initiative for Asthma (GINA) step 4/5 classification and those with moderate asthma (a GINA steps 2 or 3 classification of asthma severity). Choices were highly dominated by the cough attribute in the symptoms complexes; 48.4% of patients with severe asthma and 31.3% with moderate asthma consistently chose the alternative with the lowest level of cough. Furthermore, cough predominance was found to be significantly associated with severity of asthma (p=0.047). Patients with moderate asthma were not willing to accept any additional symptoms to reduce cough from severe to mild. However, these patients were willing to accept mild breathlessness, mild sleep disturbance, severe chest tightness and severe wheezing to remove coughing altogether. Patients with asthma prefer to have less cough and are willing to accept greater levels of other symptoms to achieve this. Additionally, asthma severity may influence an individual's perception of their symptoms; cough is a more important symptom for patients with severe asthma than those with a milder disease.

Assessment of Real-World Escalation to Biologics in US Patients With Asthma

Previous studies indicate that suboptimal medication adherence may contribute to uncontrolled asthma. Global Initiative for Asthma (GINA) guidelines recommend treatment escalation to biologics for patients with uncontrolled asthma despite adherence to high-dose maintenance medication and who have eosinophilic/allergic biomarkers or require maintenance oral corticosteroids. This study aimed to describe the clinical status of patients with asthma escalated to biologic therapy. This retrospective claims database analysis enrolled US patients with asthma who were escalated to biologics between January 2016 and June 2020. Exacerbations, control status, GINA step, and maintenance medication adherence during the 12 months before biologic therapy initiation were analyzed. Asthma control was assessed using both the European Respiratory Society/American Thoracic Society (ERS/ATS) and Stempel criteria. Adherence was defined as the proportion of days covered (PDC) by maintenance medication claims. Of 1786 patients escalated to biologics, 506 were included for analysis. During the 12 months before escalation, 346 patients had confirmed exacerbations. Uncontrolled asthma status was estimated in 55% and 70% of patients (ERS/ATS and Stempel criteria, respectively). GINA step was inferred for 395 patients: 154 were at step 2, 11 at step 3, 104 at step 4, and 126 at step 5. Of 403 patients with maintenance medication claims, 63% had suboptimal maintenance medication adherence (PDC <80%). In this study, most patients initiating biologic therapy had mild-to-moderate asthma or suboptimal maintenance medication adherence, possibly indicating inappropriate escalation. Incorporating objective medication adherence monitoring into existing guidelines may reduce inappropriate escalation to biologics.

The use of short-acting bronchodilators and cost burden of asthma across Global Initiative for Asthma-based severity levels: Insights from a large US commercial and managed Medicaid population.

BACKGROUND: Despite the availability of effective treatments, patients with asthma, regardless of severity, remain at risk of severe exacerbations resulting in significant burden to patients, the health care system, and insurance providers. OBJECTIVE: To examine severe exacerbations, treatment patterns, health care resource utilization (HCRU), and costs across all asthma severities. METHODS: In this retrospective study, patients aged 4 years and older filling 1 short-acting (β2-agonist (SABA) and at least 1 maintenance fill or at least 2 SABAs with or without maintenance fills were identified from administrative claims data from the IBM MarketScan Commercial and IBM MarketScan Multistate Medicaid Research databases (January 2010 to December 2017). Patients were indexed on a random SABA fill (2011-2016) and had 12 months of continuous eligibility pre-index and post-index. Patients were classified into Global Initiative for Asthma (GINA) 2018 severity steps and by asthma control, as measured by SABA fill use in the 12 months pre-index: low (1 SABA fill per year), medium (2-3 SABA fills per year), and high (≥ 4 SABA fills per year); well controlled, not well controlled, and very poorly controlled, respectively. Severe asthma exacerbation events, health care costs, and asthma-related HCRU and costs were assessed relative to asthma severity and asthma control post-index. RESULTS: Of 1,005,522 patients, 50.3% filled GINA Step 1; 19.7% GINA Step 2; 10.9% GINA Step 3; and 19.1% GINA Steps 4-5 treatments. Overall, 953,337 severe exacerbation events occurred (approximately 0.95 events per patient), equating to 0.96, 0.67, 0.83, and 1.28 events per patient for patients filling GINA Step 1 through Steps 4-5, respectively. GINA Step 1 had the highest proportion of patients experiencing at least 1 event (57.0%), followed by GINA Steps 4-5 (55.2%), GINA Step 3 (45.0%), and GINA Step 2 (41.9%) treatments (P < 0.05). For GINA Step 1, 64.4% of well-controlled patients experienced at least 1 exacerbation event vs 50.4% of not well-controlled and 53.0% of very poorly controlled patients (P < 0.05). For patients filling GINA Step 2-5 treatments, a greater proportion of very poorly controlled patients experienced at least 1 exacerbation event vs well-controlled patients (P < 0.05). The average total annual health care cost per patient was $7,148 and total annual asthma-related costs were $1,741. Each additional SABA fill was associated with a 26.0%, 10.8%, and 34.6% increase in incidence of total exacerbations, all-cause costs, and asthma-related costs, respectively (P < 0.05). CONCLUSIONS: In this real-world database study, increased SABA fills and occurrence of exacerbations were correlated and associated with higher all-cause and asthma-related costs across all severities. New treatment paradigms, particularly for rescue therapies, are warranted to improve clinical and cost outcomes in these patients. DISCLOSURES: This analysis was funded by AstraZeneca. Michael Pollack, Hitesh Gandhi, and Ileen Gilbert are employees and stockholders of AstraZeneca and contributed to the design and conduct of the study. AstraZeneca was given an opportunity to review the final version of the manuscript. At the time of the study, Joseph Tkacz was an employee of IBM Watson Health, which received funding from AstraZeneca to conduct this study. Miguel Lanz has received research funding from AstraZeneca, Optinose, and Regeneron and consulting fees and honoraria from ALK, Amgen, AstraZeneca, Novartis, Sanofi, and Regeneron. Njira Lugogo received consulting fees for advisory board participation from Amgen, AstraZeneca, Genentech, GlaxoSmith-Kline, Novartis, Regeneron, Sanofi, and Teva; honoraria for nonspeaker's bureau presentations from GlaxoSmithKline and AstraZeneca; and travel support from AstraZeneca. Her institution received research support from Amgen, AstraZeneca, Avillion, Gossamer Bio, Genentech, GlaxoSmithKline, Regeneron, Sanofi, and Teva.

Classifications of moderate to severe asthma phenotypes in Japan and analysis of serum biomarkers: A Nationwide Cohort Study in Japan (NHOM Asthma Study)

BackgroundAsthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. MethodsAdult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1–3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal–Wallis, and chi-square tests were used to compare cluster differences. ResultsThe following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. ConclusionsFive distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.)

SABA prescriptions and asthma management practices in patients treated by specialists in Taiwan: Results from the SABINA III study

Limited data exist on asthma medication patterns in Taiwan. The objectives of the SABINA III cross-sectional study in Taiwan were thus, to describe patient demographics and clinical features and estimate short-acting β2-agonist (SABA) and inhaled corticosteroids (ICS) prescriptions per patient. Patients (≥18 years) with asthma were classified by investigator-defined asthma severity per the 2017 Global Initiative for Asthma (GINA) recommendations. Data on asthma symptom control (per GINA 2017 recommendations), severe exacerbation history, and prescribed treatments in the 12 months before study visit were collected using electronic case-report forms. Analyses were descriptive. Overall, all 294 analyzed patients (mean [SD] age, 57.9 [15.6] years; female, 69%) were enrolled by specialists and had fully reimbursed healthcare. Most patients were classified with moderate-to-severe asthma (93.2%; GINA steps 3-5), were obese (53.4%) and nonsmokers (79.6%), reported high school or university and/or postgraduate education (61.9%), and had ≤2 comorbidities (89.1%). Mean (SD) asthma duration was 8.3 (10.0) years, with 37.8% of patients experiencing ≥1 severe exacerbation 12 months before the study visit. Overall, 62.2%, 26.2%, and 11.6% of patients had well-controlled, partly controlled, and uncontrolled asthma, respectively. Crucially, 19.3% of patients were prescribed ≥3 SABA canisters in the preceding 12 months (overprescription). ICS, ICS+long-acting β2-agonist fixed-dose combination, and oral corticosteroid bursts were prescribed to 6.5%, 97.3%, and 31.6% of patients, respectively. Despite treatment by specialists and fully reimbursed healthcare, findings indicate room for improvement in asthma control and SABA prescription practices in Taiwan, emphasizing the need to adhere to latest evidence-based guidelines.

Regional variation in intensity of inhaled asthma medication and oral corticosteroid use in Denmark, Finland, and Sweden

ABSTRACT Oral corticosteroids (OCS) are often prescribed to patients with asthma that remains uncontrolled with maintenance therapy. We performed a real-world analysis to describe the geographic distributions of patients with asthma and OCS dispensed in Nordic countries. This observational, retrospective study examined patient-level data from nationally prescribed drug registries from January to December 2018 for individuals aged ≥12 years in Denmark, Finland, and Sweden. Using an algorithm based on asthma treatment combinations defined by the Global Initiative for Asthma (GINA), we identified patients with asthma, those on GINA Step 4–5 treatments, and those being dispensed ≥2 courses of OCS and determined volumes of OCS dispensed to these patients over the 1-year analysis period. Data were plotted geographically within each country using colour-coded heat maps. The overall asthma prevalence rates were 7.4% in Denmark, 11.6% in Finland, and 8.1% in Sweden. In Denmark, Finland, and Sweden, respectively, the frequencies of patients on GINA Step 4–5 treatments were 19%, 15%, and 16%; among whom 10%, 23%, and 5% received ≥2 courses of OCS. The rates of patients on GINA Step 4–5 treatments who were dispensed OCS in each country were 23%, 30%, and 46%, of which 22%, 17%, and 10% were dispensed doses averaging ≥5 mg/day over the year. Heat maps revealed considerable heterogeneity in geographic densities of patients with asthma and OCS claims within each country. Taken together, these results demonstrate regional variations in estimated asthma severity, control, and OCS dispensed within and between countries. Patterns of medication use suggest that a high proportion of patients in Denmark, Finland, and Sweden are on GINA Step 4–5 treatments, many of whom are dispensed OCS; this poses a considerable corticosteroid burden to these patients. Geographic differences in medication use within and between Nordic countries may reflect variations in population characteristics and/or treatment approaches.

Evaluation of Budesonide-Formoterol for Maintenance and Reliever Therapy Among Patients With Poorly Controlled Asthma

The Global Initiative for Asthma (GINA) recommends 2 alternative treatments for patients receiving treatment at steps 3 to 5: single inhaler combination inhaled corticosteroid-formoterol as both maintenance and reliever (SMART) or inhaled corticosteroid-long-acting β2-agonist as maintenance plus short-acting β2-agonist as reliever. To assess whether switching to SMART is associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever among patients with poorly controlled asthma. For this systematic review and meta-analysis, the literature, internal study databases at AstraZeneca and the Medical Research Institute of New Zealand, and references from a previous systematic review and meta-analysis on SMART were searched to identify randomized clinical trials published from January 1990 to February 2018, that compared budesonide-formoterol by SMART with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever. Trials of at least 24 weeks' duration were included if they reported baseline data on GINA treatment step, asthma control status, and efficacy measures of severe exacerbations. Included patients were adults and adolescents with asthma and baseline Asthma Control Questionnaire 5-item version scores of 1.5 or higher. Patient-level data were identified by independent extraction, and analyses were performed using a fixed-effect model. Data analysis was performed from August 2018 to November 2021. The primary outcome was time to first severe asthma exacerbation associated with each treatment, analyzed by Cox proportional hazards regression. Overall, 4863 patients were included (3034 [62.4%] female; mean [SD] age, 39.8 [16.3] years). Switching patients with uncontrolled asthma at GINA step 3 (n = 1950) to SMART at either step 3 or 4 was associated with a prolonged time to first severe asthma exacerbation, with a 29% reduced risk compared with stepping up to step 4 inhaled corticosteroid-long-acting β2-agonist maintenance plus short-acting β2-agonist reliever (hazard ratio, 0.71; 95% CI, 0.52-0.97). For patients with uncontrolled asthma at step 3 and step 4 (n = 2913), switching to SMART was associated with a prolonged time to first severe asthma exacerbation and a 30% reduced risk compared with remaining at the same treatment step (hazard ratio, 0.70; 95% CI, 0.58-0.85). In this systematic review and meta-analysis, for patients with poorly controlled asthma, SMART was associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever. These findings suggest that if an adult or adolescent receiving treatment at GINA step 3 or 4 has poorly controlled asthma, it is preferable to switch to the SMART regimen rather than to step up or continue the GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever therapy.

Pathways of Escalation to Asthma Biologics in Real-world Clinical Practice: an Analysis of US Claims Data

Current Global Initiative for Asthma (GINA) guidelines recommend a stepwise approach to asthma treatment. Patients recommended for step-up to biologics include those whose asthma is uncontrolled by high-dose inhaled corticosteroids/long-acting beta-agonists. We examined prior GINA step (GS), exacerbations, and asthma control among patients escalated to biologics during the 12-months prior to escalation.

Short-acting β2-agonist Prescription Patterns in Patients with Asthma in the Philippines: Results from SABINA III

Objectives. As asthma is a chronic inflammatory disease of the airways, anti‑inflammatory treatment should bepositioned at the forefront of guideline-directed asthma care. However, patients tend to rely on short-acting β2-agonists (SABAs) for rapid-onset symptom relief. The impact of SABA overuse and associated clinical outcomeshave been investigated extensively in Europe and North America. Limited data are available from countries in Asia, Africa, Latin America, and the Middle East. The SABA use IN Asthma (SABINA) III program, a large multicountry, observational study, was undertaken to describe the global extent of SABA use and its potential contribution to suboptimal disease control. As part of the SABINA III study, we aimed to characterize SABA prescription collection and asthma-related clinical outcomes among patients in the Philippines.Methods. This nationwide, observational, cross-sectional, SABINA III study included patients (aged ≥12 years) with a documented asthma diagnosis recruited between May 2019 and January 2020 from 10 sites in the Philippines. Demographics, disease characteristics and prescribed asthma treatments, including SABA and inhaled corticosteroids (ICS) in the 12 months preceding study start, were recorded during a single visit, and transcribed onto an electronic case report form (eCRF). Patients were classified by investigator‑defined asthma severity, guided by the 2017 Global Initiative for Asthma (GINA) report and practice type, either primary or pulmonary medicine specialist care.Results. Of 245 patients analyzed, 63.3% were classified as having moderate-to-severe asthma (GINA steps 3−5), and most patients (63.3%) were enrolled by pulmonary medicine specialists. Overall, 33.1% (n=81) of patients had experienced ≥1 severe exacerbation in the previous 12 months and 18.4% (n=45) of patients had uncontrolled asthma. With respect to asthma treatments, a total of 6.5% (n=16), 40.4% (n=99), and 2.4% (n=6) of patients were prescribed SABA monotherapy, SABA in addition to maintenance therapy, and ICS, respectively, in the 12 months prior to their study visit. Most patients (n=156 [63.7%]) received prescriptions of fixed‑dose combinations of ICS and long-acting β2-agonists. SABA over-prescription, defined as ≥3 SABA canister prescriptions per year, was observed in 10.6% (n=21) of patients. Additionally, 25.6% (n=23) ofpatients classified as having mild asthma were prescribed either nebulized SABA (n=17) or oral SABA (n=6). Nearly one-third of patients (n=75 [30.6%]) had purchased over-the-counter (OTC) SABA, and 46.9% (n=115) were prescribed antibiotics.Conclusions. In this SABINA III Philippines study cohort, more than 10% of patients were over-prescribed SABAcanisters. Additionally, prescriptions for oral or nebulized SABA, the purchase of non-prescription (OTC) SABA,and the high percentage of prescriptions for antibiotics warrant country-wide improvements in asthma care and management.

Obstructive sleep apnea in patients with severe asthma: Prevalence and association between severity and asthma control

INTRODUCTION:Asthma and obstructive sleep apnea (OSA) are common respiratory disorders that can coexist and cause sleep disturbances. The strength of this association and the impact of OSA on asthma severity and control remain unclear. The study aims to estimate the prevalence of OSA in patients with severe asthma in Oman and to examine whether the severity of OSA contributed to the level of asthma control.METHODS:Adult patients with confirmed diagnosis of severe asthma who attended the respiratory clinic in a tertiary hospital in Oman over a period of 19 months were enrolled in the study. Eligible participants were screened by asthma control test (ACT) and Berlin questionnaire (BQ). Patients with high risk for OSA were subjected further to level 3 sleep study. The prevalence of OSA in patients with severe asthma and the associations between the severity of OSA and asthma control were calculated.RESULTS:We identified 312 adult asthma patients on Global Initiative for Asthma step 4 or 5 management out of 550 who were screened. The mean age of the study population was 56.59 ± 12.40 years and the mean body mass index (BMI) 40.30 ± 12.24 kg/m2. The prevalence of OSA in asthma patients with severe asthma was found to be 32.4%. Out of the 138 well-controlled asthma patients (ACT ≥20), 35 had high risk of OSA based on BQ, and 32 were confirmed to have OSA (23%). Of the 174 uncontrolled patients, 80 patients had high risk of OSA and 69 patients were confirmed to have OSA (39.65%). Severe OSA was seen in 63.8% and 9.4% in uncontrolled and controlled asthma patients, respectively (P = 0.002). The median respiratory event index in the uncontrolled group was 43, and it was significantly higher than 12.5 in the controlled group (P < 0.001).CONCLUSIONS:The prevalence of OSA was high (32.37%) in patients with severe asthma. Uncontrolled severe asthma was significantly associated with severe OSA.

Biologics for Asthma and Allergic Skin Diseases in Children.

An estimated 7 million children in the United States have asthma, which causes a significant health care burden and affects quality of life. The minority of these children have asthma that does not respond to Global Initiative for Asthma steps 4 and 5 care, and biological medications are recommended at this level in the 2019 Global Initiative for Asthma recommendations. In addition, biologics have been introduced into the care of children with allergic skin diseases. Omalizumab and mepolizumab are approved for children as young as 6 years, and benralizumab and dupilumab are approved for people aged ≥12 years. Reslizumab is approved only for people aged ≥18 years. These monoclonal antibodies may be added for appropriate patients when asthma or allergic skin diseases are not well controlled. Pediatricians and pediatric subspecialists should work together and be aware of the benefits and risks of these medications for their patients, as well as the practical implications of providing these options for their patients. This clinical report serves as an evaluation of the current literature on these types of medications in the treatment of children with asthma and allergic skin disease.

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.

Self-reported asthma prevalence and management in adults in France in 2018: ASTHMAPOP survey

BackgroundThere is a paucity of epidemiological data on asthma classified by disease severity in France. The ASTHMAPOP cross-sectional study aimed to review the prevalence and current management of asthma in people aged ≥18 years in France. MethodsA self-administered questionnaire was mailed to 19 676 people representative of the French population in age, gender, region, and socio-economic status. Asthma was classified by treatment steps per the 2017 Global Initiative for Asthma (GINA) report, according to prescribed treatments. Analyses were mostly descriptive. ResultsThe questionnaire return rate was 81.7% (n = 16 083), and 15 587 questionnaires were analyzed. The prevalence of lifetime asthma was 12.8% (95% confidence interval (CI):12.3−13.3%; n = 1 989) in 2018. The prevalence of current asthma (i.e., 12 months before the survey) was 6.4% (95% CI: 6.0−6.8%; n = 993); most of these respondents (95.3% [n = 946]) were receiving asthma treatment, and 49.4% (n = 491) were treated for mild asthma (GINA step 1 or 2). Of people with current asthma, 47.6% reported ≥1 asthma exacerbation in the past 12 months—defined as episodes (several days) during which symptoms (cough, sputum, and dyspnea) were worse than usual; 14.3% had ≥1 emergency visit, and 3.1% had ≥1 hospitalization due to asthma. Of those taking continuous asthma controller medications who answered all Morisky Medication Adherence Scale questions (n = 501), 46.4% were adherent (score=4) to their treatment regimen. Based on the 6-item Asthma Control Questionnaire scores, asthma was partially controlled or uncontrolled in 47.7% of 969 people. ConclusionsThe prevalence of asthma in France has remained stable since 2006, but levels of asthma control and treatment adherence continue to be relatively poor. Asthma management in France requires improvement.