BACKGROUND:Real-world data on benralizumab in patients with severe eosinophilic asthma-while controlling for confounding factors-is currently lacking. AIM:This real-world controlled multicentre study evaluated asthma outcomes in patients who received benralizumab compared with a severe asthma cohort who did not receive biologic therapy. METHODS:Two years of data from patients with severe eosinophilic asthma in the Australian Benralizumab Registry (ABenRa) and the Australasian Severe Asthma Registry (ASAR) were included in the analysis. Asthma control questionnaire-5 (ACQ-5) scores, asthma-related quality of life (AQLQ) scores, maintenance oral corticosteroid (OCS) dose, annualised exacerbation rate and clinical remission (ACQ-5 ≤ 1, with no asthma attacks or OCS use for 12 months, assessed at the 24-month follow-up) rates were compared between the groups after adjusting for baseline imbalances. RESULTS:A total of 211 participants from ABenRa (64.5% female; mean age 57.4 ± 14.5 years) and 250 from ASAR (63.1% female; mean age 53.7 ± 14.8 years) were included. ACQ and AQLQ improved significantly in both groups. Participants in the ABenRa showed greater improvements in ACQ at 12- (β = -0.5, p = 0.002) and 24-months (β = -0.5, p = 0.003), as well as in AQLQ at 12- (β = 0.6, p < 0.001) and 24-months (β = 0.4, p = 0.019), compared with the ASAR group, with no difference in maintenance OCS dose or annualised exacerbation rates between groups. At 12- and 24-months, approximately 60% of participants in the ABenRa achieved controlled or partially controlled asthma as per the GINA guidelines. Notably, clinical benefit was evident within 14 days of initiating treatment. A higher proportion of participants in the ABenRa achieved clinical remission (30.9% vs. 20.4%; OR 2.1 (95% CI 1.1, 4.1), p = 0.037). CONCLUSION:Benralizumab was associated with significant improvement in asthma outcomes in patients with severe eosinophilic asthma. This benefit persisted when compared with patients who had severe eosinophilic asthma but did not receive any biologic therapy.

BACKGROUND:While clinical remission occurs in some patients receiving biologics for severe asthma after one year of treatment, sustaining remission and frequency of relapse are unclear. This study evaluated sustained clinical remission, relapse, and its predictors over two to four years among people with severe asthma receiving mepolizumab. METHODS:Data from 208 patients (median age 59.6 years [52.0, 68.9], 41.3% male) in the Australian Mepolizumab Registry, a real-world prospective severe asthma registry, were analysed. Clinical remission was defined as: mean Asthma Control Questionnaire-5 score ≤1.0, no exacerbations, and no oral corticosteroid use over a 12-month period. Remission and relapse were assessed from 12 to 48 months at 12-month intervals. RESULTS:Of 184 with data available at 24 months, 29.9% (n = 55) achieved remission. 20.1% (35 of 174 with data from baseline to 24 months) sustained remission showing certain degree of stability since treatment initiation, while 9.2% (16/174) relapsed during treatment. Older age, severe disease, obesity, and depression significantly reduced the odds of achieving remission at 24 months. When assessed longitudinally (n = 47 with data from baseline to 48 months), remission increased from 36.1% at 12 months to 48.9% at 48 months. However, 17% relapsed over four years. Patterns of persistent non-remission, stable, delayed and unstable remission were also observed. CONCLUSIONS:Although remission rates may be overestimated in a cohort skewed toward treatment-responsive patients, clinical remission is achievable and sustained in a subgroup of patients with asthma, while remaining transient in some patients who risk relapsing and transitioning between disease states during continued mepolizumab treatment.

Introduction: Respiratory oscillometry is a sensitive tool for assessing small airways dysfunction. However, limited evidence on cutoff values for interpretation remains a barrier to its clinical use. The aim of this study was to determine whether the presence and severity of abnormalities, defined by Z-scores for oscillometric parameters, are associated with asthma symptoms and exacerbation risk. Methods: We retrospectively reviewed the medical records of all patients with asthma managed in a severe asthma clinic between 2019 and 2022 who underwent routine oscillometry. Z-scores for oscillometric parameters were analyzed as continuous and categorical variables to assess their associations with asthma control and exacerbation risk. Results: When analyzed as categorical variables, Z-score-defined severity thresholds for resistance (R-5), reactance (X-5), and the area under the reactance curve (A(X)) were associated with levels of asthma control (as measured by the ACQ5). When analyzed as continuous variables, Z-scores were also correlated with worst asthma control (as assessed by both ACQ5 and the asthma control test) (P < 0.005). These correlations remained significant after adjustment for spirometric indices, FeNO, and treatment changes. Elevated Z-scores (>1.64) for R-5 were associated with a higher risk of exacerbations (OR 2.70, 95% CI 1.27-5.17, P = 0.009). The risk of exacerbation increased with the severity of airway obstruction. Similar trends were observed for A(X) and X-5; however, these associations did not reach statistical significance. Discussion: The presence and severity of airway obstruction, as defined by R-5 Z-scores, predict poorer asthma control and an increased risk of exacerbations. Similar associations with asthma control were also observed for X-5 and A(X) Z-scores. Clinicians should use Z-scores over other cutoffs to aid interpretation.

Background:Respiratory oscillometry measures the physiological effort and mechanics of moving air in and out of the lungs during normal breathing. It provides complementary information to spirometry. Uncertainty regarding the interpretation of oscillometry is a barrier to routine use. The aim of this study was to aid in oscillometry interpretation among adults with asthma or COPD by generating expert consensus statements. Methods:A Delphi method was used to develop consensus statements regarding the clinical use of oscillometry in adults to identify abnormal lung function, bronchodilator response and minimal clinically important differences. Initial statements were refined in the brainstorming round. Statements were assessed by 60 pulmonologists over three rounds, with consensus defined as ≥70% agreement. Results:Pulmonologists agreed that oscillometry is clinically useful to assess abnormal lung function and its severity, and to measure bronchodilator response. High consensus was reached for resistance at 5 Hz (R 5, 85%), reactance at 5 Hz (X 5, 79%) and area under the reactance curve (AX , 77%) based on z-scores, where >1.64 was considered abnormal for R 5 and AX and < -1.64 was considered abnormal for X 5. For measuring bronchodilator response, good agreement was based on using percentage change for R 5, X 5 and AX . Discussion:This international Delphi study combined evidence-based and expert opinion to inform clinicians in the interpretation of respiratory oscillometry. Focusing on a few key parameters of oscillometry will allow clinicians to become confident in its everyday use to assess abnormal lung function, grade severity of impairment, monitor progression over time and assess bronchodilator response.

BACKGROUND:The benefits of oral corticosteroid (OCS) stewardship approaches -including monoclonal antibody treatments for severe asthma- on reducing toxic OCS exposure and related comorbidities such as depression and anxiety require real-world evaluation. METHODS:This real-world observational study investigated OCS exposure and associated complications over 24 months in patients enrolled in the Australian Mepolizumab Registry (n = 412). RESULTS:Patients were median age 59 years, 58 % were female. The proportion of patients receiving OCS burst in the year prior to commencement was 95 % (44 % during second year of treatment, p < 0.001). In the year prior to baseline, 64 % received toxic level OCS exposure (≥1000 mg), with more disease burden and doctor diagnosed depression (27 % v 15 %, p = 0.020). Ongoing toxic level exposure was reduced to 25 % of patients in the second year of mepolizumab treatment (p < 0.001). At baseline, 42 % required maintenance OCS which reduced to 18 % after two years of treatment (p < 0.001). Hospital Anxiety and Depression Scale (HADS)-Depression score ≥8 was evident in 37 % of patients at baseline and reduced to 15 % after two years (p < 0.001). HADS-Anxiety score ≥8 was reduced from 44 % of patients to 25 % after two years (p < 0.001). Improvements in HADS scores correlated with improvement in Asthma Quality of Life Questionnaire score. CONCLUSION:Mepolizumab treatment reduces exposure to toxic levels of OCS in severe eosinophilic asthma, with reduction in associated complications, confirming the importance of OCS stewardship initiatives. Improvements in both asthma outcomes, and clinically relevant treatable traits including depression and anxiety, further highlights the role of biologics within the OCS stewardship framework.

BackgroundTo date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.AimTo elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.MethodsThis was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.ResultsOverall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE.ConclusionsThe ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.

BACKGROUND:Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS:Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS:5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS:Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

BACKGROUND:People with severe asthma remain at risk of toxicity from maintenance oral corticosteroid (OCS) use and/or frequent OCS burst therapy. Cumulative exposures above 500-1000 mg prednisolone are associated with adverse effects, and recently OCS stewardship principles were promulgated to guide OCS prescription. AIMS:To examine real-world registry data to quantify OCS burden, ascertain trends over time in prescription and assess whether opportunities to implement steroid-sparing strategies were utilised. METHODS:Participants were enrolled in the Australasian Severe Asthma Registry for the period 2013-2021. Assessments were taken at enrolment and then annual follow-up, which included asthma control and OCS use. Descriptive analyses were performed, and subgroups were compared at baseline and over time. RESULTS:Nine hundred and twenty-four participants were evaluated and 215/924 (23%) were taking maintenance OCS at baseline, with 44% and 32% of participants having exposure to ≥500 or 1000 mg of OCS respectively in the prior year. Twelve months later, an additional 10% and 9% of participants reached cumulative doses of 500 or 1000 mg. People exceeding thresholds had ongoing poor asthma control. At baseline, 240/924 (26%) people were treated with asthma biological therapy. An additional 83 (12%) participants were identified as potentially benefiting from this steroid-sparing medication. Of these patients, only 23% commenced a biologic agent in the next 12 months. CONCLUSIONS:A large national asthma registry identifies exposure to toxic cumulative doses of OCS in more than a third of participants, with further subsequent cumulative dose escalation over 2 years. Steroid-sparing strategies were often not employed, highlighting the need for implementation of OCS stewardship initiatives.

Disease of the peripheral (or small) airways is fundamental in asthma, being closely related to symptoms (or lack of control of them), airway hyperresponsiveness, spirometric abnormalities, risk of loss of control, or exacerbations and inflammation. Current technology now allows routine measurement of peripheral airway function. Having a working concept of peripheral airways disease in asthma is arguably very useful to clinicians and beneficial to patients because it allows a more comprehensive assessment of asthma severity (rather than just symptoms alone, which is the norm), tracking of progress or deterioration, and assessing response to treatment. Oscillometry is a sensitive way to monitor the peripheral airways, whereas multiple breath nitrogen washout parameters are excellent measures of future risk. In the longer term, physiologic measurements will be crucial in research to define causes and find new disease-modifying treatments.

Introduction: Small airways dysfunction contributes to asthma pathophysiology and clinical outcomes including exacerbations and asthma control. Respiratory oscillometry is a simple, non-invasive and effort independent lung function test that provides vital information about small airway function. However, interpretation and clinical utility of respiratory oscillometry has been in part limited by lack of agreed parameters and the respective cutoffs. The aim of this study was to determine the prevalence of small airways dysfunction based on published impulse oscillometry (IOS) definition in patients with asthma referred to a tertiary asthma clinic and the extent to which it correlates with asthma clinical outcomes. Methods: We retrospectively reviewed the medical records of all patients with asthma managed in the severe asthma clinic between January 2019 and December 2022 who underwent routine lung function tests with oscillometry and spirometry. Small airways dysfunction was determined from various published IOS parameter cutoffs, and the data were analysed to determine correlations between IOS parameters and asthma outcomes. Results: Amongst the 148 patients, the prevalence of small airways dysfunction ranged from 53% to 78% depending on the defining oscillometry parameter. All oscillometry parameters correlated with the severity of airflow obstruction (FEV1% predicted, p < 0.001). Several oscillometry parameters correlated with asthma symptom burden, the strongest correlation was seen for frequency dependent resistance (R-5-R-20) with scores of Asthma Control Questionnaire (ACQ6) (Spearman's rank coefficient 0.213, p = 0.028) and Asthma Control Test (ACT) (Spearman's rank coefficient -0.248, p = 0.012). R-5-R-20 was predictive of poor asthma control defined by ACQ6 >1.5 (OR 2.97, p = 0.022) or ACT <20 (OR 2.44, p = 0.055). Small airways dysfunction defined by R-5-R-20 and area under the reactance curve (AX) also significantly increases asthma exacerbation risk (OR 2.60, p = 0.02 and OR 2.31, p = 0.03 respectively). Conclusion: Respiratory oscillometry is a sensitive measure of small airways dysfunction that should complement spirometry in the routine assessment of asthma. Small airways dysfunction is highly prevalent in patients with asthma referred to a tertiary asthma clinic. R-5-R-20 was the metric most predictive in identifying patients at risk of asthma exacerbations and poor asthma control.

BACKGROUND:Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. METHODS:This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified. RESULTS:29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission. CONCLUSION:Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.

Background: Asthma remission is a potential treatment goal. Objective: To evaluate the efficacy of two biologics (mepolizumab/omalizumab) and azithromycin in achieving remission in severe asthma patients. Methods: 788 patients (41% male; mean age 56.9±14.5 years) from three severe asthma datasets (the Australian Mepolizumab Registry [AMR], the Australian Xolair Registry [AXR], and the AMAZES RCT) were included in the analysis. Each dataset was analysed separately. Three definitions of remission were explored: 1) symptom remission (no exacerbations and no OCS use during the previous six months plus ACQ-5≤1 at 12 months; 2) clinical remission (symptom remission plus FEV1≥80% at 12 months); and 3) complete remission (clinical remission plus blood eosinophil count≤300 cells/microliter at 12 months). The predictors of clinical remission were identified using logistic-regression analysis. Results: Among AMR patients, 29.3% achieved symptom remission and 8.9% achieved both clinical and complete remission. Among AXR patients, 22.8% achieved symptom and 5.2% achieved clinical remission. AMAZES patients had lower baseline disease severity, and 50.6%, 27.2% and 19.9% achieved symptom, clinical and complete remission, respectively. Better lung function, better asthma-related QoL and absence of OCS burst at baseline predicted the odds of achieving clinical remission. Conclusion: Twelve months treatment with add-on therapies, mepolizumab, omalizumab or azithromycin, induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target in severe asthma and future studies should consider remission as an outcome measure.

Introduction Asthma poses a significant burden for the Australian population. Understanding severe exacerbation rates, and steroid-related burden for adults diagnosed with asthma stands to offer insights into how this could be reduced. Methods Electronic medical records (EMR) and questionnaires from the Optimum Patient Care Research Database Australia (OPCRDA) were utilised retrospectively. OPCRDA is a real-world database with >800,000 medical records from Australian primary care practices. Outcomes were severe asthma exacerbations in Australian adults, over a 12-month period, stratified by Global Initiative for Asthma (GINA) treatment intensity steps, and steroid associated comorbidities. Results Of the 7868 adults treated for asthma, 19% experienced at least one severe exacerbation in the last 12-months. Severe exacerbation frequency increased with treatment intensity (≥1 severe exacerbation GINA 1 13%; GINA 4 23%; GINA 5a 33% and GINA 5b 28%). Questionnaire participants reported higher rates of severe exacerbations than suggested from their EMR (32% vs 23%) especially in steps 1, 4 and 5. Patients repeatedly exposed to steroids had an increased risk of osteoporosis (OR 1.95, 95% CI 1.43–2.66) and sleep apnoea (OR 1.78, 95% CI 1.30–2.46). Conclusion The Australian population living with GINA 1, 4, 5a and 5b asthma have high severe exacerbation rates and steroid-related burden, especially when compared to other first world countries, with these patients needing alternative strategies or possibly specialist assessment to better manage their condition.

Severe asthma imposes a significant burden on individuals, families and the healthcare system. Treatment is complex, due to disease heterogeneity, comorbidities and complexity in care pathways. New approaches and treatments improve health outcomes for people with severe asthma. However, emerging multidimensional and targeted treatment strategies require a reorganisation of asthma care. Consensus is required on how reorganisation should occur and what areas require further research. The Centre of Excellence in Severe Asthma convened three forums between 2015 and 2018, hosting experts from Australia, New Zealand and the UK. The forums were complemented by a survey of clinicians involved in the management of people with severe asthma. We sought to: (i) identify areas of consensus among experts; (ii) define activities and resources required for the implementation of findings into practice; and (iii) identify specific priority areas for future research. Discussions identified areas of unmet need including assessment and diagnosis of severe asthma, models of care and treatment pathways, add-on treatment approaches and patient perspectives. We recommend development of education and training activities, clinical resources and standards of care documents, increased stakeholder engagement and public awareness campaigns and improved access to infrastructure and funding. Further, we propose specific future research to inform clinical decision-making and develop novel therapies. A concerted effort is required from all stakeholders (including patients, healthcare professionals and organisations and government) to integrate new evidence-based practices into clinical care and to advance research to resolve questions relevant to improving outcomes for people with severe asthma.

Oral corticosteroids (OCS) are frequently used for asthma treatment. This medication is highly effective for both acute and chronic diseases, but evidence indicates that indiscriminate OCS use is common, posing a risk of serious side effects and irreversible harm. There is now an urgent need to introduce OCS stewardship approaches, akin to successful initiatives that optimized appropriate antibiotic usage. The aim of this TSANZ (Thoracic Society of Australia and New Zealand) position paper is to review current knowledge pertaining to OCS use in asthma and then delineate principles of OCS stewardship. Recent evidence indicates overuse and over-reliance on OCS for asthma and that doses >1000 mg prednisolone-equivalent cumulatively are likely to have serious side effects and adverse outcomes. Patient perspectives emphasize the detrimental impacts of OCS-related side effects such as weight gain, insomnia, mood disturbances and skin changes. Improvements in asthma control and prevention of exacerbations can be achieved by improved inhaler technique, adherence to therapy, asthma education, smoking cessation, multidisciplinary review, optimized medications and other strategies. Recently, add-on therapies including novel biological agents and macrolide antibiotics have demonstrated reductions in OCS requirements. Harm reduction may also be achieved through identification and mitigation of predictable adverse effects. OCS stewardship should entail greater awareness of appropriate indications for OCS prescription, risk-benefits of OCS medications, side effects, effective add-on therapies and multidisciplinary review. If implemented, OCS stewardship can ensure that clinicians and patients with asthma are aware that OCS should not be used lightly, while providing reassurance that asthma can be controlled in most people without frequent use of OCS.

Objective: To estimate the level of dispensing of oral corticosteroids (OCS) for managing asthma in Australia, with a particular focus on the cumulative dispensing of doses associated with long term toxicity (>= 1000 mg prednisolone-equivalent). Design: Retrospective cohort study; analysis of 10% random sample of Pharmaceutical Benefits Scheme (PBS) dispensing data. Participants, setting: People aged 12 years or more treated for asthma during 2014-2018, according to dispensing of controller inhaled corticosteroids (ICS). Main outcome measures: Number of people dispensed OCS for managing asthma during 2014-2018; proportion who were cumulatively dispensed at least 1000 mg prednisolone-equivalent. The secondary outcome was the number of people dispensed at least 1000 mg prednisolone-equivalent during 2018, stratified by inhaler controller dose and use. Results: 124 011 people had been dispensed at least two prescriptions of ICS during 2014-2018 and met the study definition for asthma, of whom 64 112 (51.7%) had also been dispensed OCS, including 34 580 (27.9% of the asthma group) cumulatively dispensed 1000 mg prednisolone-equivalent or more. Of 138 073 people dispensed OCS at this level, 68 077 (49%) were patients with airway diseases. Dispensing of diabetes and osteoporosis medications was more common for people cumulatively dispensed 1000 mg prednisolone-equivalent or more. During 2018, 4633 people with asthma using high dose ICS controllers were dispensed 1000 mg prednisolone-equivalent or more, for 2316 of whom (50%) controller use was inadequate. Conclusions: Cumulative exposure to OCS in Australia reaches levels associated with toxicity in one-quarter of patients with asthma using ICS. Cumulative dispensing of potentially toxic OCS amounts often accompanies inadequate inhaler controller dispensing. Better approaches are needed to improve adherence to controller therapy, improve outcomes for people with asthma, and to minimise the use and toxicity of OCS.

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population. The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia. Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL−1. Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%. Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29–0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33–0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline. Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting. In clinical practice, mepolizumab reduces the burden of severe eosinophilic asthma by reducing severe exacerbations and improving asthma control, quality of life and lung function. Super-responders have a T2 phenotype and few comorbidities. http://bit.ly/2UIio4x

OCS play an important role in the management of asthma. However, steroid-related AE are common and represent a leading cause of morbidity. Limited published studies suggest OCS usage varies across countries and recent registry data indicate that at least 25-60% of patients with severe asthma in developed countries may at some stage be prescribed OCS. Recent evidence indicate that many patients do not receive optimal therapy for asthma and are often prescribed maintenance OCS or repeated steroid bursts to treat exacerbations. Given the recent progress in adult severe asthma and new treatment options, judicious appraisal of steroid use is merited. A number of strategies and add-on therapies are now available to treat severe asthma. These include increasing specialist referral for multidisciplinary assessments and implementing OCS-sparing interventions, such as improving guideline adherence and add-on tiotropium and macrolides. Biologics have recently become available for severe asthma; these agents reduce asthma exacerbations and lower OCS exposure. Further research, collaboration and consensus are necessary to develop a structured stewardship approach including realistic OCS-weaning programmes for patients with severe asthma on regular OCS; education and public health campaigns to improve timely access to specialized severe asthma services for treatment optimization; and implementing targeted strategies to identify patients who warrant OCS use using objective biomarker-based strategies.