Impact of sex on severe asthma: a cross-sectional retrospective analysis of UK primary and specialist care.

INTRODUCTION: After puberty, females are more likely to develop asthma and in a more severe form than males. The associations between asthma and sex are complex with multiple intrinsic and external factors. AIM: To evaluate the sex differences in the characteristics and treatment of patients with severe asthma (SA) in a real-world setting. METHODS: Demographic, clinical and treatment characteristics for patients with SA in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD) were retrospectively analysed by sex using univariable and multivariable logistic regression analyses adjusted for year, age and hospital/practice. RESULTS: 3679 (60.9% female) patients from UKSAR and 18 369 patients (67.9% female) from OPCRD with SA were included. Females were more likely to be symptomatic with increased Asthma Control Questionnaire-6 (UKSAR adjusted OR (aOR) 1.14, 95% CI 1.09 to 1.18) and Royal College of Physicians-3 Question scores (OPCRD aOR 1.29, 95% CI 1.13 to 1.47). However, they had a higher forced expiratory volume in 1 second per cent (FEV1%) predicted (UKSAR 68.7% vs 64.8%, p<0.001) with no significant difference in peak expiratory flow. Type 2 biomarkers IgE (UKSAR 129 IU/mL vs 208 IU/mL, p<0.001) and FeNO (UKSAR 36ppb vs 46ppb, p<0.001) were lower in females with no significant difference in blood eosinophils or biological therapy. Females were less likely to be on maintenance oral corticosteroids (UKSAR aOR 0.86, 95% CI 0.75 to 0.99) but more likely to be obese (UKSAR aOR 1.67, 95% CI 145 to 1.93; OPCRD SA aOR 1.46, 95% CI 1.34 to 1.58). CONCLUSIONS: Females had increased symptoms and were more likely to be obese despite higher FEV1% predicted and lower type 2 biomarkers with consistent and clinically important differences across both datasets.

Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma.

BACKGROUND: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. OBJECTIVE: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. METHODS: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV1]: <50% to ≥80%). RESULTS: Percentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV1. The proportion of patients having improvement post-biologic tended to be greater for anti-IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. CONCLUSION: Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies. TRIAL REGISTRATION: The ISAR database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization studies (ENCEPP/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220).

Observational UK cohort study to describe intermittent oral corticosteroid prescribing patterns and their association with adverse outcomes in asthma.

INTRODUCTION: Oral corticosteroids (OCS) for asthma are associated with increased risks of developing adverse outcomes (adverse outcomes); no previous study has focused exclusively on intermittent OCS use. METHODS: This historical (2008-2019) UK cohort study using primary care medical records from two anonymised, real-life databases (OPCRD and CPRD) included patients aged≥4 years with asthma receiving only intermittent OCS. Patients were indexed on their first recorded intermittent OCS prescription for asthma and categorised by OCS prescribing patterns: one-off (single), less frequent (≥90 day gap) and frequent (<90 day gap). Non-OCS patients matched 1:1 on gender, age and index date served as controls. The association of OCS prescribing patterns with OCS-related AO risk was studied, stratified by age, Global Initiative for Asthma (GINA) 2020 treatment step, and pre index inhaled corticosteroid (ICS) and short-acting ß2-agonist (SABA) prescriptions using a multivariable Cox-proportional hazard model. FINDINGS: Of 476 167 eligible patients, 41.7%, 26.8% and 31.6% had one-off, less frequent and frequent intermittent OCS prescribing patterns, respectively. Risk of any AO increased with increasingly frequent patterns of intermittent OCS versus non-OCS (HR; 95% CI: one-off 1.19 (1.18 to 1.20), less frequent 1.35 (1.34 to 1.36), frequent 1.42 (1.42 to 1.43)), and was consistent across age, GINA treatment step and ICS and SABA subgroups. The highest risks of individual OCS-related adverse outcomes with increasingly frequent OCS were for pneumonia and sleep apnoea. CONCLUSION: A considerable proportion of patients with asthma receiving intermittent OCS experienced a frequent prescribing pattern. Increasingly frequent OCS prescribing patterns were associated with higher risk of OCS-related adverse outcomes. Mitigation strategies are needed to minimise intermittent OCS prescription in primary care.

Asthma exacerbations are associated with a decline in lung function: a longitudinal population-based study.

RATIONALE: Progressive lung function (LF) decline in patients with asthma contributes to worse outcomes. Asthma exacerbations are thought to contribute to this decline; however, evidence is limited with mixed results. METHODS: This historical cohort study of a broad asthma patient population in the Optimum Patient Care Research Database, examined asthma patients with 3+eligible post-18th birthday peak expiratory flow rate (PEF) records (primary analysis) or records of forced expiratory flow in 1 s (FEV1) (sensitivity analysis). Adjusted linear growth models tested the association between mean annual exacerbation rate (AER) and LF trajectory. RESULTS: We studied 1 09 182 patients with follow-up ranging from 5 to 50 years, of which 75 280 had data for all variables included in the adjusted analyses. For each additional exacerbation, an estimated additional -1.34 L/min PEF per year (95% CI -1.23 to -1.50) were lost. Patients with AERs >2/year and aged 18-24 years at baseline lost an additional -5.95 L/min PEF/year (95% CI -8.63 to -3.28) compared with those with AER 0. These differences in the rate of LF decline between AER groups became progressively smaller as age at baseline increased. The results using FEV1 were consistent with the above. CONCLUSION: To our knowledge, this study is the largest nationwide cohort of its kind and demonstrates that asthma exacerbations are associated with faster LF decline. This was more prominent in younger patients but was evident in older patients when it was related to lower starting LF, suggesting a persistent deteriorating phenotype that develops in adulthood over time. Earlier intervention with appropriate management in younger patients with asthma could be of value to prevent excessive LF decline.

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.

COPD Population in US Primary Care: Data From the Optimum Patient Care DARTNet Research Database and the Advancing the Patient Experience in COPD Registry.

PURPOSE: To describe demographic and clinical characteristics of chronic obstructive pulmonary disease patients managed in US primary care. METHODS: This was an observational registry study using data from the Chronic Obstructive Pulmonary Disease (COPD) Optimum Patient Care DARTNet Research Database from which the Advancing the Patient Experience COPD registry is derived. Registry patients were aged ≥35 years at diagnosis. Electronic health record data were collected from both registries, supplemented with patient-reported information/outcomes from the Advancing the Patient Experience registry from 5 primary care groups in Texas, Ohio, Colorado, New York, and North Carolina (June 2019 through November 2020). RESULTS: Of 17,192 patients included, 1,354 were also in the Advancing the Patient Experience registry. Patients were predominantly female (56%; 9,689/17,192), White (64%; 9,732/15,225), current/ex-smokers (80%; 13,784/17,192), and overweight/obese (69%; 11,628/16,849). The most commonly prescribed maintenance treatments were inhaled corticosteroid with a long-acting ß2-agonist (30%) and inhaled corticosteroid with a long-acting muscarinic antagonist (27%). Although 3% (565/17,192) of patitents were untreated, 9% (1,587/17,192) were on short-acting bronchodilator monotherapy, and 4% (756/17,192) were on inhaled corticosteroid monotherapy. Despite treatment, 38% (6,579/17,192) of patients experienced 1 or more exacerbations in the last 12 months. These findings were mirrored in the Advancing Patient Experience registry with many patients reporting high or very high impact of disease on their health (43%; 580/1,322), a breathlessness score 2 or more (45%; 588/1,315), and 1 or more exacerbation in the last 12 months (50%; 646/1,294). CONCLUSIONS: Our findings highlight the high exacerbation, symptom, and treatment burdens experienced by COPD patients managed in US primary care, and the need for more real-life effectiveness trials to support decision making at the primary care level.

Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study.

BACKGROUND: Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma. METHODS: We used the Optimum Patient Care Research Database, a population-based, longitudinal, anonymised primary care database in the UK, to construct a 17-year (1 January 2000-31 December 2016) retrospective cohort of reproductive-age (16-45 years, n=83 084) women with asthma. Using Read codes, we defined use, subtypes and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendations of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition. RESULTS: The 17-year follow-up resulted in 456 803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen) and 9% progestogen-only contraceptives. Previous (incidence rate ratio (IRR) 0.94, 95% CI 0.92 to 0.97) and current (IRR 0.96, 95% CI 0.94 to 0.98) use of any, previous (IRR 0.92, 95% CI 0.87 to 0.97) and current use of combined (IRR 0.93, 95% CI 0.91 to 0.96) and longer duration of use (3-4 years: IRR 0.94, 95% CI 0.92 to 0.97; 5+ years: IRR 0.91, 95% CI 0.89 to 0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared with non-use. CONCLUSIONS: Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for the influence of hormonal contraceptives on clinical outcomes of asthma in women are required. PROTOCOL REGISTRATION NUMBER: European Union electronic Register of Post-Authorisation Studies (EUPAS22967).

Identifying patients at risk of poor asthma outcomes associated with making inhaler technique errors.

OBJECTIVES: Correct inhaler technique is essential to optimal clinical outcomes in asthma patients. The study aim was to use real-life data from the iHARP database to determine patient factors associated with the performance of inhaler technique errors associated with poor asthma outcomes (as identified in the Critikal study) in patients with asthma prescribed the Turbuhaler (TH), Metered Dose Inhaler (MDI), and Accuhaler (AH) device. METHODS: This was a retrospective cross-sectional study using the iHARP database, a multinational initiative including questionnaires and technique review. Identification of inhaler technique errors specifically associated with poor asthma outcomes was performed by reference to the Critikal study. Multivariable logistic regression was used to identify demographic and clinical factors associated with ≥ 1 of these errors. RESULTS: Factors significantly associated with ≥ 1 inhaler technique error and worsening asthma outcomes for the TH cohort include female gender, very poor to average self-assessment of inhaler technique; for the MDI cohort, female gender, secondary education, and current smoking status; and, in the AH cohort, lack of inhaler technique review by a trained healthcare professional in the previous twelve months and very poor to average self-assessment of inhaler technique. CONCLUSIONS: Numerous specific patient demographic and clinical factors associated with the performance of these errors have been identified, differing according to device. Inhaler technique error associated with poor asthma outcomes is further widespread across devices. Knowledge of these factors and the frequency of their occurence may assist in optimizing device selection and training.

Reducing the hidden burden of severe asthma: recognition and referrals from primary practice.

Since their introduction many decades ago, systemic corticosteroids have become a mainstay treatment for asthma. Despite being a highly effective therapy, corticosteroids can cause significant adverse effects in patients. This results in a "double hit" for some patients as they suffer the burden of disease as well as the burden of treatment-induced morbidity.This article aims to raise awareness of the potential, harmful side effects of prolonged or repeated exposure to systemic corticosteroids in asthma. It also highlights the importance of referral of the appropriate patients with asthma from primary care for specialist assessment once other considerations such as adherence, inhaler technique and co-morbidity have been evaluated. We propose a simple decision step that may help busy primary care physicians and general practitioners to identify patients who could benefit from specialist assessment.Our decision step suggests that a patient with asthma should be reviewed at least once by an asthma specialist if he/she (i) has received ≥2 courses of oral corticosteroids in the previous year; asthma remains uncontrolled despite good adherence and inhaler technique; or (ii) has attended an emergency department or was hospitalized for asthma care.Such referral could facilitate wider access to diagnostic tools, in-depth assessment of confounding comorbidities, and non-corticosteroid-based therapies as needed, which may be unavailable in primary practice.

Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management.

Systemic corticosteroid use to manage uncontrolled asthma and its associated healthcare burden may account for important health-related adverse effects. We conducted a systematic literature review to investigate the real-world extent and burden of systemic corticosteroid use in asthma. We searched MEDLINE and Embase databases to identify English-language articles published in 2010-2017, using search terms for asthma with keywords for oral corticosteroids and systemic corticosteroids. Observational studies, prescription database analyses, economic analyses, and surveys on oral/systemic corticosteroid use in children (>5 yr old), adolescents (12-17 yr old), and adults with asthma were included. We identified and reviewed 387 full-text articles, and our review included data from 139 studies. The included studies were conducted in Europe, North America, and Asia. Overall, oral/systemic corticosteroids were commonly used for asthma management and were more frequently used in patients with severe asthma than in those with milder disease. Long-term oral/systemic corticosteroid use was, in general, less frequent than short-term use. Compared with no use, long-term and repeated short-term oral/systemic corticosteroid use were associated with an increased risk of acute and chronic adverse events, even when doses were comparatively low. Greater oral/systemic corticosteroid exposure was also associated with increased costs and healthcare resource use. This review provides a comprehensive overview of oral/systemic corticosteroid use and associated adverse events for patients with all degrees of asthma severity and exposure duration. We report that oral/systemic corticosteroid use is prevalent in asthma management, and the risks of acute and chronic complications increase with the cumulative oral corticosteroid dosage.

Association between COPD exacerbations and lung function decline during maintenance therapy.

BACKGROUND: Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study. METHODS: The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline. Effect modification by blood eosinophils was studied through interaction terms. RESULTS: Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4 mL/year (95% CI 12.0 to 26.7, p<0.0001). This excess decline was reduced by 15.1 mL/year (6.6 to 23.6) to 4.3 mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS. CONCLUSION: Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.

International severe asthma registry (ISAR): protocol for a global registry.

BACKGROUND: Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour. METHODS: ISAR is a multi-disciplinary initiative benefitting from the combined experience of the ISAR Steering Committee (ISC; comprising 47 clinicians and researchers across 29 countries, who have a special interest and/or experience in severe asthma management or establishment and maintenance of severe asthma registries) in collaboration with scientists and experts in database management and communication. Patients (≥18 years old) receiving treatment according to the 2018 definitions of the Global Initiative for Asthma (GINA) Step 5 or uncontrolled on GINA Step 4 treatment will be included. Data will be collected on a core set of 95 variables identified using the Delphi method. Participating registries will agree to provide access to and share standardised anonymous patient-level data with ISAR. ISAR is a registered data source on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. ISAR's collaborators include Optimum Patient Care, the Respiratory Effectiveness Group (REG) and AstraZeneca. ISAR is overseen by the ISC, REG, the Anonymised Data Ethics & Protocol Transparency Committee and the ISAR operational committee, ensuring the conduct of ethical, clinically relevant research that brings value to all key stakeholders. CONCLUSIONS: ISAR aims to offer a rich source of real-life data for scientific research to understand and improve disease burden, treatment patterns and patient outcomes in severe asthma. Furthermore, the registry will provide an international platform for research collaboration in respiratory medicine, with the overarching aim of improving primary and secondary care of adults with severe asthma globally.

Predictive value of control of COPD for risk of exacerbations: An international, prospective study.

BACKGROUND AND OBJECTIVE: The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. METHODS: This international, multicentre, prospective study aimed to validate the concept of control in COPD. Patients with COPD were classified as controlled/uncontrolled by clinical criteria or CAT scores at baseline and followed up for 18 months. The main outcome was the difference in rate of a composite endpoint of moderate and severe exacerbations or death over the 18-month follow-up period. RESULTS: A total of 307 patients were analysed (mean age = 68.6 years and mean FEV1 % = 52.5%). Up to 65% and 37.9% of patients were classified as controlled by clinical criteria or CAT, respectively. Controlled patients had significantly less exacerbations during follow-up (by clinical criteria: 1.1 vs 2.6, P < 0.001; by CAT: 1.1 vs 1.9, P = 0.014). Time to first exacerbation was significantly prolonged for patients controlled by clinical criteria only (median: 93 days, IQR: 63; 242 vs 274 days, IQR: 221; 497 days; P < 0.001). Control status by clinical criteria was a better predictor of exacerbations compared to CAT criteria (AUC: 0.67 vs 0.57). CONCLUSION: Control status, defined by easy-to-obtain clinical criteria, is predictive of future exacerbation risk and time to the next exacerbation. The concept of control can be used in clinical practice at each clinical visit as a complement to the current recommendations of initial treatment proposed by guidelines.

Healthcare resource utilization and costs associated with incremental systemic corticosteroid exposure in asthma.

BACKGROUND: Although systemic corticosteroid (SCS) treatment, irrespective of duration or dosage, is associated with adverse outcomes for patients with asthma, the longitudinal effects of this treatment on adverse outcomes, healthcare resource utilization (HCRU), and healthcare costs are unknown. METHODS: We identified patients initiating intermittent or long-term SCS who were diagnosed with active asthma from UK general practice with linked secondary care data. Control (non-SCS) patients were matched by sex and index date with those initiating SCS. Minimum baseline period was 1 year prior to index date; minimum follow-up duration was 2 years post-index date. Cumulative incidence of SCS-associated adverse outcomes and associated HCRU and costs were compared between SCS and non-SCS patient groups and among average SCS daily exposure categories. Associations between exposure and annualized HCRU and costs were assessed, adjusted for confounders. RESULTS: Analyses included 9413 matched pairs. Median (interquartile range) follow up was as follows: SCS group: 7.1 (4.1-11.8) years; control group: 6.4 (3.8-10.0) years. Greater SCS dosages were correlated with greater cumulative incidence. For example, patients with type 2 diabetes receiving an average daily dosage of ≥7.5 mg had a 15-year cumulative incidence (37.5%) that was 1.5-5 times greater than those receiving lower dosages. HCRU and costs increased annually for SCS patients but not for non-SCS patients. Increases in all-cause adverse outcome (excluding asthma)-associated HCRU and costs were dose-dependent. CONCLUSIONS: Over the long term, adverse outcomes associated with SCS initiation were relatively frequent and costly, with a positive dosage-response relationship with SCS exposure.

Pediatric asthma: An unmet need for more effective, focused treatments.

BACKGROUND: Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. METHODS: A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. RESULTS: These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. CONCLUSIONS: There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real-world evidence studies assessing anti-immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti-IgE and non-steroid-based alternative therapies may delay disease progression, leading to improved clinical outcomes.

Real-life effectiveness of inhaler device switch from dry powder inhalers to pressurized metred-dose inhalers in patients with asthma treated with ICS/LABA.

BACKGROUND AND OBJECTIVE: Mixed inhaler device use for asthma is associated with worse inhaler technique and outcomes. Given that relievers are commonly prescribed as pressurized metred-dose inhalers (pMDI), changing preventers from dry powder inhalers (DPI) to pMDI may improve asthma outcomes. This study aimed to assess the persistence and effectiveness of switching from DPI to pMDI for inhaled corticosteroid and long-acting ß2 -agonist combination therapy (ICS/LABA). METHODS: This was a historical cohort study using Ajou University Hospital (Korea) patient records. Persistence of switch was defined as receiving ≥1 pMDI and no DPI after the switch. Effectiveness of switch was assessed as the proportion without severe asthma exacerbation and the proportion achieving risk domain asthma control (RDAC; no asthma-related hospitalization, antibiotics without upper respiratory diagnosis or acute course of oral corticosteroids) and overall asthma control (OAC; RDAC and ≤ 200 µg salbutamol/≤500 µg terbutaline average daily dose) comparing 1 year after and before the switch. RESULTS: Within 85 patients who switched from DPI to pMDI and persisted for a year, higher proportion were free from asthma exacerbation after the switch (mean difference in proportion = 0.129, 95% CI: 0.038-0.220). Switching to pMDI was also associated with better RDAC (75.3% vs 57.7%, P = 0.001) and OAC (57.7% vs 45.9%, P = 0.021). From the entire 117 patients who switched to fixed-dose combination (FDC)/ICS LABA pMDI, 76.1% (95% CI: 69.0-100.0%) patients persisted in the following 6 months. CONCLUSION: Switching to and persisting with pMDI was associated with decreased asthma exacerbations and improved asthma control. The majority of patients persisted with the switch to pMDI for ICS/LABA treatment.

Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population.

BACKGROUND: Little is known about the prevalence of severe, uncontrolled eosinophilic asthma (SUEA) and associated costs. AIMS: We sought to determine the prevalence of SUEA and compare asthma-related healthcare resource use (HCRU) and associated costs with overall means for a general asthma population. METHODS: This cohort study evaluated anonymised medical record data (December 1989 through June 2015) from the Clinical Practice Research Datalink and the Optimum Patient Care Research Database to study UK patients with active asthma (diagnostic code and one or more drug prescriptions in the baseline year), aged 5 years and older, without concomitant COPD, and with recorded eosinophil count. SUEA was defined as two or more asthma attacks during 1 baseline year preceding a high blood eosinophil count (≥0.3×109/L) for patients prescribed long-acting ß2-agonist (LABA) and high-dosage inhaled corticosteroids (ICS) during baseline plus 1 follow-up year. We compared asthma-related HCRU and associated direct costs (2015 pounds sterling, £) during the follow-up year for SUEA versus the general asthma population. RESULTS: Of 363 558 patients with active asthma and recorded eosinophil count, 64% were women, mean (SD) age was 49 (21) years; 43% had high eosinophil counts, 7% had two or more attacks in the baseline year and 10% were prescribed high-dosage ICS/LABA for 2 study years. Overall, 2940 (0.81%; 95% CI 0.78% to 0.84%) patients had SUEA. Total mean per-patient HCRU and associated costs were four times greater for SUEA versus all patients (HCRU and cost ratios 3.9; 95% CI 3.7 to 4.1). CONCLUSIONS: Less than 1% of patients in a general asthma population had SUEA. These patients accounted for substantially greater asthma-related HCRU and costs than average patients with asthma.

Inhaler technique mastery and maintenance in healthcare professionals trained on different devices.

OBJECTIVE: Healthcare professionals (HCPs) are required to assess and train patients in the correct use of inhalers but are often unable to demonstrate correct technique themselves. We sought to assess the level of training required for HCPs to master and maintain device mastery when using two different dry powder inhalers (DPIs). METHODS: We conducted a randomized, un-blinded, crossover study in undergraduate HCPs who undertook a six-step training procedure (intuitive use, patient information leaflet, instructional video, individual tuition from expert, then two repeats of individual tuition) for the use of Turbuhaler® (an established device) and Spiromax® (a newer device, reportedly easier to use). Device mastery (absence of errors) was evaluated by expert assessors at each training step. Maintenance of mastery was assessed 4 ± 1 week (visit 2) and 8 ± 2 weeks (visit 3) after initial training (visit 1). RESULTS: Of 516 eligible participants, 113 (22%) demonstrated device mastery prior to training on Spiromax® compared with 20 (4%) on Turbuhaler® (p < 0.001). The median number of training steps required to achieve mastery was 2 (interquartile range [IQR] 2-4) for Spiromax® and 3 (IQR 2-4) for Turbuhaler® (p < 0.001). A higher number of participants maintained mastery with Spiromax® compared with Turbuhaler®, at visits 2 and 3 (64% vs 41% and 79% vs 65%, respectively; p < 0.001). CONCLUSIONS: There are significant differences in the nature and extent of training required to achieve and maintain mastery for Spiromax® and Turbuhaler® devices. The implications on clinical practice, device education delivery, and patient outcomes require further evaluation.

Evaluation of inhaler technique and achievement and maintenance of mastery of budesonide/formoterol Spiromax® compared with budesonide/formoterol Turbuhaler® in adult patients with asthma: the Easy Low Instruction Over Time (ELIOT) study.

BACKGROUND: Incorrect inhaler technique is a common cause of poor asthma control. This two-phase pragmatic study evaluated inhaler technique mastery and maintenance of mastery with DuoResp® (budesonide-formoterol [BF]) Spiromax® compared with Symbicort® (BF) Turbuhaler® in patients with asthma who were receiving inhaled corticosteroids/long-acting ß2-agonists. METHODS: In the initial cross-sectional phase, patients were randomized to a 6-step training protocol with empty Spiromax and Turbuhaler devices. Patients initially demonstrating ≥1 error with their current device, and then achieving mastery with both Spiromax and Turbuhaler (absence of healthcare professional [HCP]-observed errors), were eligible for the longitudinal phase. In the longitudinal phase, patients were randomized to BF Spiromax or BF Turbuhaler. Co-primary endpoints were the proportions of patients achieving device mastery after three training steps and maintaining device mastery (defined as the absence of HCP-observed errors after 12 weeks of use). Secondary endpoints included device preference, handling error frequency, asthma control, and safety. Exploratory endpoints included assessment of device mastery by an independent external expert reviewing video recordings of a subset of patients. RESULTS: Four hundred ninety-three patients participated in the cross-sectional phase, and 395 patients in the longitudinal phase. In the cross-sectional phase, more patients achieved device mastery after three training steps with Spiromax (94%) versus Turbuhaler (87%) (odds ratio [OR] 3.77 [95% confidence interval (CI) 2.05-6.95], p < 0.001). Longitudinal phase data indicated that the odds of maintaining inhaler mastery at 12 weeks were not statistically significantly different (OR 1.26 [95% CI 0.80-1.98], p = 0.316). Asthma control improved in both groups with no significant difference between groups (OR 0.11 [95% CI -0.09-0.30]). An exploratory analysis indicated that the odds of maintaining independent expert-verified device mastery were significantly higher for patients using Spiromax versus Turbuhaler (OR 2.11 [95% CI 1.25-3.54]). CONCLUSIONS: In the cross-sectional phase, a significantly greater proportion of patients using Spiromax versus Turbuhaler achieved device mastery; in the longitudinal phase, the proportion of patients maintaining device mastery with Spiromax versus Turbuhaler was similar. An exploratory independent expert-verified analysis found Spiromax was associated with higher levels of device mastery after 12 weeks. Asthma control was improved by treatment with both BF Spiromax and BF Turbuhaler. TRIAL REGISTRATION: EudraCT 2013-004630-14 (registration date 23 January 2014); NCT02570425 .