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Tham T Le,1 David B Price,2– 4 Clement Erhard,5 Bill Cook,6 Anna Quinton,7 Rohit Katial,8 George C Christoff,9 Luis Perez-de-Llano,10 Alan Altraja,11,12 Celine Bergeron,13 Arnaud Bourdin,14 Mariko Siyue Koh,15,16 Lauri Lehtimäki,17,18 Bassam Mahboub,19 Nikolaos G Papadopoulos,20,21 Paul Pfeffer,22,23 Chin Kook Rhee,24 Victoria Carter,2,3 Neil Martin,25,26 Trung N Tran1 On behalf of the EVEREST Study Working Group1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Observational and Pragmatic Research Institute, Singapore; 3Optimum Patient Care Global, Cambridge, UK; 4Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 5BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 6Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 7BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK; 8Global Medical Respiratory, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 9Faculty of Public Health, Medical University Sofia, Sofia, Bulgaria; 10Department of Respiratory Medicine, University Hospital Lucus Augusti, Lugo, Spain; 11Department of Pulmonology, University of Tartu, Tartu, Estonia; 12Lung Clinic, Tartu University Hospital, Tartu, Estonia; 13Centre for Lung Health, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada; 14PhyMedExp, University of Montpellier, CNRS, INSERM, University Hospital of Montpellier, Montpellier, France; 15Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore; 16Duke-NUS Medical School, Singapore; 17Allergy Centre, Tampere University Hospital, Tampere, Finland; 18Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 19Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 20Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK; 21Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 22Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 23Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 24Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 25Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 26University of Leicester, Leicester, UKCorrespondence: Trung N Tran, BioPharmaceuticals Medical, Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA, Email trung.tran1@astrazeneca.comIntroduction: Patients with severe asthma may be prescribed biologic therapies to improve disease control. The EVEREST study aimed to characterize the global disease burden of patients with severe asthma without access to biologics and those who have access but do not receive biologics, as well as the remaining unmet need despite use of these therapies.Methods: This was a historical cohort study of patients with severe asthma (aged ≥ 18 years) in the International Severe Asthma Registry receiving Global Initiative for Asthma (GINA) 2018 step 5 treatment, or with uncontrolled disease at GINA step 4. Prospective data on patient clinical characteristics, healthcare resource utilization, and medication use over a 12-month period between December 2017 and May 2022 were assessed for the following five groups: biologics accessible (omalizumab, mepolizumab, reslizumab, benralizumab, or dupilumab); biologics inaccessible; biologics accessible but not received; biologics accessible and received; and biologic recipients whose asthma remained suboptimally controlled.Results: Overall, 9587 patients from 21 countries were included. Among patients in the biologics accessible (n=5073), biologics inaccessible (n=3041), and biologics accessible but not received (n=382) groups, 41.4%, 18.7%, and 49.6% experienced at least two exacerbations, 11.5%, 10.5%, and 6.2% required at least one hospitalization, 47.9%, 54.6%, and 71.2% had uncontrolled asthma, and 23.9%, 8.6%, and 11.0% received long-term oral corticosteroids (LTOCS), respectively. Following biologic therapy, among patients who received biologics overall (n=2666) and among those whose asthma remained suboptimally controlled (n=1780), 19.1% and 23.0% experienced at least two exacerbations, 2.7% and 2.9% required at least one hospitalization, and 16.7% and 22.0% received LTOCS, respectively.Conclusion: There is a substantial disease burden in both patients without access to biologics and those with access who do not receive these therapies, although specific outcomes may vary between these groups. There also remains a high unmet need among biologic recipients, many of whom have a suboptimal response to treatment.Keywords: biologic, disease burden, healthcare resource utilization, severe asthma

Trung N Tran,1 Heath Heatley,2 Arnaud Bourdin,3 Andrew Menzies-Gow,4,5 David J Jackson,6 Ekaterina Maslova,5 Jatin Chapaneri,5 William Henley,2,7 Victoria Carter,2 Jeffrey Shi Kai Chan,2 Cono Ariti,2 John Haughney,8,9 David Price2,9 1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Observational and Pragmatic Research Institute, Singapore; 3Department of Respiratory Diseases, PhyMedExp, University of Montpellier, Montpellier, France; 4Royal Brompton & Harefield Hospitals and School of Immunology & Microbial Sciences, King’s College London, London, UK; 5BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 6Guy’s Severe Asthma Centre, Guy’s and St Thomas’ Hospitals, School of Immunology & Microbial Sciences, King’s College London, London, UK; 7Department of Health and Community Sciences University of Exeter Medical School, Exeter, UK; 8NHS Clinical Research Facilities, Glasgow, UK; 9Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgPurpose: Oral corticosteroid (OCS) use for asthma is associated with considerable healthcare resource utilization (HCRU) and costs. However, no study has investigated this in relation to patterns of intermittent OCS prescription.Methods: This historical UK cohort study used primary care medical records, linked to Hospital Episode Statistics, from 2008 to 2019, of patients (≥ 4 years old) with asthma prescribed intermittent OCS. Patients were categorized by OCS prescribing pattern (one-off [single], less frequent [≥ 90-day gap] and frequent [< 90-day gap]) and matched 1:1 (by sex, age and index date) with people never prescribed OCS with/without asthma. HCRU (reported as episodes, except for length of hospital stay [days] and any prescription [records]) and associated costs were compared between intermittent OCS and non-OCS cohorts, and among intermittent OCS prescribing patterns.Results: Of 149,191 eligible patients, 50.3% had one-off, 27.4% less frequent, and 22.3% frequent intermittent OCS prescribing patterns. Annualized non-respiratory HCRU rates were greater in the intermittent OCS versus non-OCS cohorts for GP visits (5.93 vs 4.70 episodes, p < 0.0001), hospital admissions (0.24 vs 0.16 episodes, p < 0.0001), and length of stay (1.87 vs 1.58 days, p < 0.0001). In the intermittent OCS cohort, rates were highest in the frequent prescribing group for GP visits (7.49 episodes; p < 0.0001 vs one-off), length of stay (2.15 days; p < 0.0001) and any prescription including OCS (25.22 prescriptions; p < 0.0001). Mean per-patient non-respiratory related and all-cause HCRU-related costs were higher with intermittent OCS than no OCS (£ 3902 vs £ 2722 and £ 8623 vs £ 4929, respectively), as were mean annualized costs (£ 565 vs £ 313 and £ 1526 vs £ 634, respectively). A dose–response relationship existed; HCRU-related costs were highest in the frequent prescribing cohort (p < 0.0001).Conclusion: Intermittent OCS use and more frequent intermittent OCS prescription patterns were associated with increased HCRU and associated costs. Improved asthma management is needed to reduce reliance on intermittent OCS in primary care.Keywords: asthma, costs, healthcare resource utilization, intermittent, oral corticosteroids

Hana Müllerová,1 Jeffrey Shi Kai Chan,2 Heath Heatley,2 Victoria Carter,2 John Townend,2 Derek Skinner,2 Stefan Franzén,3 Jonathan Marshall,4 David Price2,5 1Medical Evidence Strategy, Biopharmaceuticals R&I Medical, AstraZeneca, Cambridge, UK; 2Observational and Pragmatic Research Institute, Singapore, Singapore; 3BPM Evidence Statistics, Biopharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden; 4Global Medical Affairs, Biopharmaceuticals R&I Medical, AstraZeneca, Cambridge, UK; 5Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06 Midview City, Singapore, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgPurpose: Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the frequency of medication success among patients with COPD who initiated BGF using real-world data.Patients and Methods: Patients with a recorded diagnostic COPD code who started BGF with ≥ 2 prescriptions within 90-days were identified in the UK Optimum Patient Care Research Database and followed from first prescription until censoring at the end of follow-up (180-days), death, leaving database or end of data at 24/10/2022. The primary outcome was medication success at 90-days post-BGF initiation, defined as no major cardiac or respiratory event (ie no complicated COPD exacerbation, hospitalization for any respiratory event, myocardial infarction, new/hospitalized heart failure, and death) and no incidence of pneumonia. Medication success was also assessed at 180-days post-BGF initiation. Overall real-life medication success was claimed if the lower 95% confidence interval (CI) for the proportion of patients meeting the primary outcome was ≥ 70% (defined a priori).Results: Two hundred eighty-five patients were included. Prior to BGF initiation, these patients often had severe airflow obstruction (mean ppFEV1: 54.5%), were highly symptomatic (mMRC ≥ 2: 77.9% (n = 205/263); mean CAT score: 21.7 (SD 7.8)), with evidence of short-acting β2-agonist (SABA) over-use (≥ 3 inhalers/year: 62.1%, n=179/285), repeat OCS prescriptions (≥ 2 courses/year: 33.0%, n = 95/285) and multiple primary care consultations (≥ 2 visits/year: 61.1%, n = 174/285). Overall, 39.6% of patients (n = 113/285) switched from previous triple therapies. Real-life medication success was achieved by 96.5% of patients (n = 275/285 [95% CI: 93.6, 98.3]) during 90-days treatment with BGF and by 91.8% (n = 169/184 [95% CI: 86.9, 95.4]) of patients at 180-days. The prescribed daily dose of SABA remained stable over the study period.Conclusion: The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events. These benefits were apparent after 90-days of treatment and sustained over 180-days.Keywords: death, exacerbation, heart failure, myocardial infarction, pneumonia

David Price,1,2 William Henley,1,3 José Eduardo Delfini Cançado,4 Leonardo M Fabbri,5 Huib AM Kerstjens,6 Alberto Papi,7 Nicolas Roche,8 Elif &Scedil;en,9 Dave Singh,10 Claus F Vogelmeier,11 Elena Nudo,12 Victoria Carter,1 Derek Skinner,1 Rebecca Vella,1 Joan B Soriano,13 Maxim Kots,12 George Georges14 1Observational and Pragmatic Research Institute, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Health Statistics Group, Department of Health and Community Sciences, University of Exeter Medical School, Exeter, UK; 4Santa Casa de São Paulo Medical School, São Paulo, Brazil; 5Respiratory Medicine, Department of Translational Medicine and for Romagna, University of Ferrara, Ferrara, Italy; 6Department of Pulmonary Diseases, University of Groningen and University Medical Centre Groningen, and Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands; 7Respiratory Medicine, University of Ferrara, Ferrara, Italy; 8Department of Respiratory Medicine, APHP-Centre University of Paris, Cochin Hospital and Institute (UMR1016), Paris, France; 9Department of Pulmonary Medicine, Ankara University School of Medicine, Ankara, Turkey; 10Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 11Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 12Global Medical Affairs, Chiesi Farmaceutici, S.p.A, Parma, Italy; 13Respiratory Department, Hospital Universitario de La Princesa and Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; 14Global Clinical Development, Chiesi Farmaceutici, S.p.A, Parma, ItalyCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgBackground: Combined ICS and long-acting bronchodilators (LABD) more effectively reduce COPD exacerbations than LABD therapy alone. Corticosteroid-related adverse effects, including pneumonia, limit ICS use. Previous data suggest this risk is lower for extrafine beclometasone (ef-BDP). We compared pneumonia risk among new users of fixed dose ICS/LABD formulations containing ef-BDP, versus patients initiating LABD without any ICS.Methods: A propensity-matched historical cohort study design used data from OPCRD. COPD patients with ≥ 1 year of continuous data who initiated LABD or ICS/LABD formulations containing ef-BDP were matched. Primary outcome was time to pneumonia event, as treated, using either sensitive (physician diagnosed) or specific (physician diagnosed and x-ray or hospital admission confirmed) definitions, with non-inferiority boundary of 15%.Results: 23,898 COPD patients were matched, who were 68± 11 years, 54.3% male and 56% current-smokers, while 43% were former-smokers. Initiation of ef-BDP/LABD was not associated with an increased risk of pneumonia versus LABD, for either a sensitive 0.89 (0.78– 1.02), P = 0.08 or a specific 0.91 (0.78– 1.05), P = 0.18 definition of pneumonia. The probability of remaining pneumonia free 1-year after ef-BDP/LABD was 98.4%, which was comparable to LABD at 97.7%, and was sustained up to 6 years of observation; non-inferiority criterion was met for both definitions. Initiation of ef-BDP/LABD was also associated with a reduced risk of developing LRTIs in the propensity matched cohort.Conclusion: Risk of pneumonia when using ICS for the management of COPD reported in several randomised controlled trials may not be relevant with ef-BDP in a diverse real-world clinical population.Keywords: inhaled corticosteroids, pneumonia, COPD, extrafine beclometasone, long-acting bronchodilators

Gary Tse,1,2 Benjamin Emmanuel,3 Cono Ariti,1 Mona Bafadhel,4 Alberto Papi,5 Victoria Carter,1 Jiandong Zhou,1 Derek Skinner,1 Xiao Xu,3 Hana Müllerová,6 David Price1,7 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, People’s Republic of China; 3AstraZeneca, Gaithersburg, MD, USA; 4Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 5Respiratory Medicine, Department of Translational Medicine, University of Ferrara, Ferrara, Italy; 6AstraZeneca, Cambridge, UK; 7Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgBackground: Oral corticosteroids (OCS) are often prescribed for chronic obstructive pulmonary disease (COPD) exacerbations.Methods: This observational, individually matched historical cohort study used electronic medical records (1987– 2019) from the UK Clinical Practice Research Datalink linked to English Hospital Episode Statistics (HES) to evaluate adverse outcomes in patients with COPD who used OCS (OCS cohort) and those not exposed to OCS (non-OCS cohort). Risk of 17 adverse outcomes was estimated using proportional hazard regression.Results: Of 323,722 patients, 106,775 (33.0%) had COPD-related OCS prescriptions. Of the 106,775 patients in the overall cohort, 58,955 had HES linkage and were eligible for inclusion in the OCS cohort. The individual matching process identified 53,299 pairs of patients to form the OCS and non-OCS cohorts. Median follow-up post-index was 6.9 years (OCS cohort) and 5.4 years (non-OCS cohort). Adjusted risk of multiple adverse outcomes was higher for the OCS cohort versus the non-OCS cohort, including osteoporosis with/without fractures (adjusted hazard ratio [aHR] 1.80; 95% confidence interval [CI] 1.70– 1.92), type 2 diabetes mellitus (aHR 1.44; 95% CI 1.37– 1.51), cardiovascular/cerebrovascular disease (aHR 1.26; 95% CI 1.21– 1.30), and all-cause mortality (aHR 1.04; 95% CI 1.02– 1.07). In the OCS cohort, risk of most adverse outcomes increased with increasing categorized cumulative OCS dose. For example, risk of cardiovascular/cerebrovascular disease was 34% higher in the 1.0–< 2.5 g group versus the < 0.5 g group (HR 1.34; 95% CI 1.26– 1.42).Conclusion: Any OCS use was associated with higher risk of adverse outcomes in patients with COPD, with risk generally increasing with greater cumulative OCS dose.Plain Language Summary: Many patients with chronic obstructive pulmonary disease (COPD) have occasions when their symptoms suddenly worsen, called flare-ups or exacerbations. To treat flare-ups, doctors might prescribe a course of steroid tablets (oral corticosteroids or OCS for short). Doctors might also prescribe “rescue packs” containing OCS and antibiotics, to keep at home and start taking when needed.While OCS may speed up recovery from flare-ups, repeated use may have negative health effects. We studied effects of OCS use in patients with COPD, using anonymized electronic patient medical records in England. These databases are made available following a high-quality research proposal to research and ethics committees.Of 323,722 patients with COPD, around one-third received OCS for flare-ups. We studied 17 outcomes including important medical diagnoses and death. We grouped patients into 53,299 pairs so that every patient who used OCS matched a similar patient (eg, the same age and sex) who never used OCS. The patients were followed for an average of 6.9 years (used OCS) and 5.4 years (never used OCS).Most diagnoses, including diabetes, osteoporosis, cardiovascular/cerebrovascular disease, and death, were more likely in patients who used OCS than those who never used OCS. Patients using larger amounts of OCS over time were generally more likely to experience diagnoses or die.These results show risks of using OCS, even occasionally, in patients with COPD. Flare-up prevention is important, for example with appropriate daily “maintenance” medication, vaccinations for infections, and quitting smoking, thereby reducing health effects from OCS use for flare-ups. Keywords: chronic obstructive pulmonary disease, cohort study, COPD, corticosteroids, observational, primary care

Anita Lynam,1 Charlotte Curtis,1 Brooklyn Stanley,2,3 Heath Heatley,3 Chloe Worthington,2,3 Emma-Jane Roberts,2,3 Christopher Price,2,3 Victoria Carter,2,3 John Dennis,1 Andrew McGovern,1 David Price2,3 1Momentum Data, Pendragon House, St. Albans, Hertfordshire, UK; 2Optimum Patient Care, Cambridge, UK; 3Observational and Pragmatic Research Institute, SingaporeCorrespondence: Andrew McGovern, Momentum Data, Pendragon House, St. Albans, Hertfordshire, UK, Email andy.mcgovern@momentumdata.co.ukIntroduction: Electronic medical records (EMRs) maintained in primary care in the UK and collected and stored in EMR databases offer a world-leading resource for observational clinical research. We aimed to profile one such database: the Optimum Patient Care Research Database (OPCRD).Methods and Participants: The OPCRD, incepted in 2010, is a growing primary care EMR database collecting data from 992 general practices within the UK. It covers over 16.6 million patients across all four countries within the UK, and is broadly representative of the UK population in terms of age, sex, ethnicity and socio-economic status. Patients have a mean duration of 11.7 years’ follow-up (SD 17.50), with a majority having key summary data from birth to last data entry. Data for the OPCRD are collected incrementally monthly and extracted from all of the major clinical software systems used within the UK and across all four coding systems (Read version 2, Read CTV3, SNOMED DM+D and SNOMED CT codes). Via quality-improvement programmes provided to GP surgeries, the OPCRD also includes patient-reported outcomes from a range of disease-specific validated questionnaires, with over 66,000 patient responses on asthma, COPD, and COVID-19. Further, bespoke data collection is possible by working with GPs to collect new research via patient-reported questionnaires.Findings to Date: The OPCRD has contributed to over 96 peer-reviewed research publications since its inception encompassing a broad range of medical conditions, including COVID-19.Conclusion: The OPCRD represents a unique resource with great potential to support epidemiological research, from retrospective observational studies through to embedded cluster-randomised trials. Advantages of the OPCRD over other EMR databases are its large size, UK-wide geographical coverage, the availability of up-to-date patient data from all major GP software systems, and the unique collection of patient-reported information on respiratory health.Keywords: primary care, electronic health records, medical records, datasets, demography, health outcomes

Wenjia Chen,1 Mohsen Sadatsafavi,2 Trung N Tran,3 Ruth B Murray,4 Chong Boon Nigel Wong,1 Nasloon Ali,4,5 Cono Ariti,4,5 Esther Garcia Gil,6 Anthony Newell,5,7 Marianna Alacqua,8 Mona Al-Ahmad,9 Alan Altraja,10 Riyad Al-Lehebi,11,12 Mohit Bhutani,13 Leif Bjermer,14 Anne Sofie Bjerrum,15 Arnaud Bourdin,16 Lakmini Bulathsinhala,4,5 Anna von Bülow,17 John Busby,18 Giorgio Walter Canonica,19,20 Victoria Carter,4,5 George C Christoff,21 Borja G Cosio,22 Richard W Costello,23 J Mark FitzGerald,24 João A Fonseca,25 Kwang Ha Yoo,26 Liam G Heaney,27 Enrico Heffler,19,20 Mark Hew,28,29 Ole Hilberg,30 Flavia Hoyte,31,32 Takashi Iwanaga,33 David J Jackson,34,35 Rupert C Jones,36 Mariko Siyue Koh,37,38 Piotr Kuna,39 Désirée Larenas-Linnemann,40 Sverre Lehmann,41 Lauri A Lehtimäki,42,43 Juntao Lyu,5,7 Bassam Mahboub,44,45 Jorge Maspero,46,47 Andrew N Menzies-Gow,48 Concetta Sirena,49 Nikolaos Papadopoulos,50,51 Andriana I Papaioannou,52 Luis Pérez de Llano,53,54 Diahn-Warng Perng,55,56 Matthew Peters,57 Paul E Pfeffer,58,59 Celeste M Porsbjerg,17 Todor A Popov,60 Chin Kook Rhee,61 Sundeep Salvi,62 Camille Taillé,63 Christian Taube,64 Carlos A Torres-Duque,65 Charlotte S Ulrik,66 Seung Won Ra,67 Eileen Wang,31,32 Michael E Wechsler,68 David B Price4,5,69 1Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; 2Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 3AstraZeneca, Gaithersburg, MD, USA; 4Optimum Patient Care, Cambridge, UK; 5Observational and Pragmatic Research Institute, Singapore, Singapore; 6AstraZeneca, Barcelona, Spain; 7Optimum Patient Care, Queensland, VIC, Australia; 8AstraZeneca, Cambridge, UK; 9Microbiology Department, Faculty of Medicine, Kuwait University, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 10Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 11Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia; 12College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 13Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Western Canada, AB, Canada; 14Department of Clinical Sciences, Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden; 15Department of Respiratory Medicine and Allergy, Aarhus University Hospital, Jutland, Aarhus, Denmark; 16PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 17Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 18Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland; 19Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Milan, Italy; 20Department of Biomedical Sciences, Humanitas University, Milan, Italy; 21Medical University-Sofia, Faculty of Public Health, Sofia, Bulgaria; 22Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 23Department of Respiratory Medicine, Clinical Research Centre, Smurfit Building Beaumont Hospital, RCSI, Dublin, Ireland; 24Department of Medicine, the University of British Columbia, Vancouver, BC, Canada; 25Comunity Health, Information and Decision Sciences Department (MEDCIDS) & Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine of University of Porto, Porto, Portugal; 26KonKuk University School of Medicine in Seoul, Seoul, Korea; 27Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland; 28Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, VIC, Australia; 29Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 30Medical Department, Vejle University Hospital, Jutland, Vejle, Denmark; 31Department of Medicine, Division of Allergy and Clinical Immunology, National Jewish Health, Denver, CO, USA; 32Department of Internal Medicine, Division of Allergy & Clinical Immunology, University of Colorado School of Medicine, Aurora, CO, USA; 33Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan; 34UK Severe Asthma Network and National Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 35School of Immunology & Microbial Sciences, King’s College London, London, UK; 36Research and Knowledge Exchange, Plymouth Marjon University, Plymouth, UK; 37Respiratory & Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 38SingHealth Duke-NUS Lung Centre, Singapore, Singapore; 39Division of Internal Medicine, Asthma and Allergy Medical University of &Lstrok;ód&zacute;, &Lstrok;ód&zacute;, Poland; 40Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 41Section of Thoracic Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway; 42Allergy Centre, Tampere University Hospital, Tampere, Finland; 43Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 44College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 45Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 46Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 47University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 48Royal Brompton & Harefield Hospitals, London, UK; 49Severe Asthma Network in Italy (SANI), Milano, Italy; 50Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 51Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 52 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece; 53Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Lugo, Spain; 54Biodiscovery Research Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain; 55Division of Clinical Respiratory Physiology Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan; 56COPD Assembly of the Asian Pacific Society of Respirology Hongo, Bunkyo-ku, Tokyo, Japan; 57Department of Thoracic Medicine, Concord Hospital, Sydney, NSW, Australia; 58Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 59Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 60University Hospital ”sv. Ivan Rilski”, Sofia, Bulgaria; 61Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 62Pulmocare Research and Education Foundation, Pune, India; 63Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université de Paris, Paris, France; 64Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 65CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 66Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark; 67Department of Internal Medicine, Division of Pulmonology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea; 68Department of Medicine, NJH Cohen Family Asthma Institute, National Jewish Health, Denver, CO, USA; 69Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06 Midview City, Singapore, Singapore, 573969, Tel +65 3105 1489, Email dprice@opri.sgBackground: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics.Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥ 4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson’s chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons.Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/μL, p=0.003), serious infections (49.0% vs 13.3%, p< 0.001), nasal polyps (35.2% vs 23.6%, p< 0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147).Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.Keywords: severe asthma, biologics, real-world, treatment pattern, patient characteristics

Stephanie Chen,1 Marc Miravitlles,2 Chin Kook Rhee,3 Ian D Pavord,4 Rupert Jones,5 Victoria Carter,6 Benjamin Emmanuel,1 Marianna Alacqua,7 David B Price6,8 1BioPharmaceuticals Medical, Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, USA; 2Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 3College of Medicine, Seoul St Mary’s Hospital, the Catholic University of Korea, Seoul, South Korea; 4Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 5Faculty of Health, University of Plymouth, Plymouth, UK; 6Observational and Pragmatic Research Institute, Singapore, Singapore; 7BioPharmaceuticals Medical, Respiratory & Immunology, AstraZeneca, Cambridge, UK; 8Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, #06-76, Midview City, Singapore, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgBackground: Some patients with chronic obstructive pulmonary disease (COPD) experience frequent exacerbations despite maximal inhaled therapy (“triple therapy”), possibly leading to high health care resource utilization (HCRU).Aim: Describe characteristics, future HCRU, and mortality of patients with COPD who experience frequent exacerbations despite triple therapy; characterize individuals who may be candidates for biologic therapies.Methods: This descriptive observational study used primary care data of patients aged ≥ 40 years in the United Kingdom receiving maintenance therapy for COPD who had ≥ 1 year of data prior to index date and ≥ 1 year of follow-up data. We described these patients’ clinical and demographic characteristics, including blood eosinophil counts (BEC), pattern of exacerbations, hospitalizations, and corticosteroid exposure, as well as future exacerbations, hospitalizations, and death.Results: Of 43,753 patients with maintenance-treated COPD, 6480 experienced exacerbations despite ≥ 3 months of triple therapy. Of these, 5669 had available BEC: 1287 (22.7%) had BEC ≥ 250 cells/μL and ≥ 3 exacerbations in the year prior to the index date; 471 (36.6%) received ≥ 4 acute courses of oral corticosteroids. Patients with a pattern of high disease burden continued to have high disease burden: 51.1% experienced ≥ 3 exacerbations and 2.6% experienced ≥ 3 hospitalizations. Patients who experienced exacerbations despite triple therapy had a significantly higher risk of COPD-related death than other maintenance-treated patients (5.8% vs 2.1%).Conclusion: Nearly one-quarter of patients receiving triple therapy for COPD who experienced frequent exacerbations had elevated BEC and ≥ 3 exacerbations, suggesting a potential mechanism of persistent eosinophilic inflammation that could be a target for eosinophil-depleting biologic therapy.Keywords: chronic obstructive pulmonary disease, disease burden, eosinophils, exacerbations, health care resource utilization

David B Price,1,2 William Henley,1,3 José Eduardo Delfini Cançado,4 Leonardo M Fabbri,5 Huib AM Kerstjens,6 Alberto Papi,7 Nicolas Roche,8 Elif &Scedil;en,9 Dave Singh,10 Claus F Vogelmeier,11 Sara Barille,12 Elena Nudo,12 Victoria Carter,1 Derek Skinner,1 Rebecca Vella,1 George Georges13 1Observational and Pragmatic Research Institute, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Health Statistics Group, Institute of Health Research, University of Exeter Medical School, Exeter, UK; 4Santa Casa de São Paulo Medical School, São Paulo, Brazil; 5Respiratory Medicine, Department of Translational Medicine, University of Ferrara, Ferrara, Italy; 6Department of Pulmonary Diseases, University of Groningen and University Medical Centre Groningen, and Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands; 7Respiratory Medicine, University of Ferrara, Ferrara, Italy; 8Department of Respiratory Medicine, APHP-Centre University of Paris, Cochin Institute, Paris, France; 9Department of Pulmonary Medicine, Ankara University School of Medicine, Ankara, Turkey; 10Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 11Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 12Global Medical Affairs, Chiesi Farmaceutici, S.p.A., Parma, Italy; 13Global Clinical Development, Chiesi Farmaceutici, S.p.A., Parma, ItalyCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, #06-76, Midview City, 573969, Singapore, Email dprice@opri.sgBackground: Inhaled corticosteroids (ICS) afford therapeutic benefits in some COPD patients, but their widespread use is cautioned due to an increased risk of developing pneumonia. Subclass variations exist, and the risk profile differs for individual ICS. Formulation particle size has been identified as a potential effect modifier. The present study compared the risk of pneumonia among new COPD users of fixed-dose combination inhalers containing fine-particle fluticasone (fp-FDC-F) versus extrafine particle beclometasone (ef-FDC-BDP).Methods: A propensity matched historical cohort study was conducted using data from the Optimum Patient Care Research Database. COPD patients aged ≥ 40 years with ≥ 1 year of continuous medical data who initiated fp-FDC-F or ef-FDC-BDP were compared. The primary outcome was time to pneumonia event, as treated, using either sensitive (physician diagnosed) or specific (physician diagnosed and x-ray or hospital admission confirmed) definitions.Results: A total of 13,316 patients were matched. Initiation of fp-FDC-F (mean dosage furoate 99 μg; propionate 710 μg) was associated with an increased risk of pneumonia versus ef-FDC-BDP (mean beclometasone dose 395 μg), irrespective of definition (sensitive HR 1.38 95% CI 1.14– 1.68; specific HR 1.31 95% CI 1.05– 1.62).Conclusion: In the current investigation, we found that in comparison to extrafine beclomethasone, commencing a formulation containing fluticasone is associated with an increased risk of developing pneumonia. These observations support the idea that not all ICS are equal in their adverse effects and subclass variations exist and should be carefully considered in the treatment choice.Keywords: inhaled corticosteroids, pneumonia, COPD, extrafine beclomethasone, fluticasone

Luis Alves,1 Rachel Pullen,2 John R Hurst,3 Marc Miravitlles,4 Victoria Carter,5 Rongchang Chen,6 Amy Couper,2 Mark Dransfield,7 Alexander Evans,5 Antony Hardjojo,2 David Jones,5 Rupert Jones,8 Margee Kerr,5 Konstantinos Kostikas,9 Jonathan Marshall,10 Fernando Martinez,11 Marije van Melle,5 Ruth Murray,5 Shigeo Muro,12 Clementine Nordon,10 Michael Pollack,13 Chris Price,5 Anita Sharma,14 Dave Singh,15 Tonya Winders,16 David B Price2 1EPIUnit - Epidemiology Research Unit, ITR - Laboratory for Integrative and Translational Research in Population Health, Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal; 2Observational and Pragmatic Research Institute, Singapore, Singapore; 3UCL Respiratory, University College London, London, UK; 4Pneumology Dept, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 5Optimum Patient Care, Cambridge, UK; 6Key Laboratory of Respiratory Disease of Shenzhen, Shenzhen Institute of Respiratory Disease, Shenzhen People’s Hospital (Second Affiliated Hospital of Jinan University, First Affiliated Hospital of South University of Science and Technology of China), Shenzhen, Guangdong, People’s Republic of China; 7Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, USA; 8Research and Knowledge Exchange, Plymouth Marjon University, Plymouth, UK; 9Respiratory Medicine Department, University of Ioannina School of Medicine, Ioannina, Greece; 10BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 11New York-Presbyterian Weill Cornell Medical Center, New York, NY, USA; 12Department of Respiratory Medicine, Nara Medical University, Nara, Japan; 13BioPharmaceuticals Medical, AstraZeneca, Wilmington, DE, USA; 14Platinum Medical Centre, Chermside, QLD, Australia; 15Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 16USA & Global Allergy & Airways Patient Platform, Vienna, AustriaCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, #06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgAbstract: The COllaboration on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST) aims to improve the quality of COPD care in primary care. The CONQUEST target population includes patients diagnosed with COPD, and those undiagnosed but with COPD-like exacerbations, who are at high but modifiable risk of COPD exacerbations, increased morbidity, and mortality. Timely diagnosis and optimized management to reduce these risks is vital. There is a need for a quality improvement program (QIP) that enables long-term improvement of patient clinical outcomes via integration of the program into routine clinical care. Core to the CONQUEST program is the adoption of four specifically designed, globally applicable, and expert-agreed quality standards (QS) for modifiable high-risk COPD patients. Translation of the QS into clinical practice, and implementation of the QIP, is guided by the CONQUEST global operational protocol provided to sites meeting the minimum healthcare system requirements. Initial analyses of current practices are conducted to generate baseline assessments of need within healthcare systems and sites looking to implement the QIP. Implementation is supported by the provision of CONQUEST resources and tools, such as clinical decision support, that promote prompt identification and treatment of patients. Utilization of electronic medical record (EMR) and patient-reported data are integral components of the QIP. Regular, automated collection and analysis of data, combined with a cyclical review of the implementation process, will be conducted for long-term, continuous improvement and health impact evaluation. The CONQUEST QIP will be an important resource in the identification and management of patients with modifiable high-risk COPD. Embedding the CONQUEST QS into routine clinical practice with regular evaluation and feedback will result in long-term quality of care improvement.Keywords: patient-reported outcome, patient-reported information, clinical decision support, primary care, quality standards, integrated care

David Price,1,2 Andrew Menzies-Gow,3 Claus Bachert,4 Giorgio Walter Canonica,5 Janwillem Kocks,1 Asif H Khan,6 Fen Ye,7 Paul J Rowe,7 Yufang Lu,8 Siddhesh Kamat,8 Victoria Carter,1 Jaco Voorham1,9 1Observational and Pragmatic Research Institute (OPRI), Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland; 3Royal Brompton Hospital, London, England; 4Upper Airways Research Laboratory, Ghent University, Ghent, Belgium; 5Personalized Medicine Asthma and Allergy Center, Humanitas University and Research Hospital, IRCCS, Milan, Italy; 6Sanofi, Chilly-Mazarin, Paris, France; 7Sanofi, Bridgewater, NJ, USA; 8Regeneron Pharmaceuticals Inc., Westchester County, NY, USA; 9Data to Insights Research Solutions, Lisbon, PortugalCorrespondence: David PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, ScotlandTel +65 6802 9724Email dprice@opri.sgBackground: Although prevalence of co-existing type 2 inflammatory diseases (cT2) in asthma patients has been reported, limited data exist regarding their impact on asthma outcomes.Objective: To assess the impact of cT2 burden on asthma outcomes and to evaluate patterns of clustering of cT2 in a real-world setting.Methods: From medical records of 4.5 million enrollees in 650 primary care practices in the UK (January 2010–December 2017), patients with ≥ 1 diagnosis code for asthma at any time pre-index date (date of most recent asthma-related medical encounter) and ≥ 2 asthma-related prescriptions during the year before index date were categorized into the Global Initiative of Asthma (GINA) guideline severity steps. A cT2 burden score (range 0– 9) was assigned based on the total number of co-existing conditions (allergic conjunctivitis, allergic rhinitis, anaphylaxis, eczema/atopic dermatitis, chronic rhinosinusitis, eosinophilic esophagitis, food allergy, nasal polyps, or urticaria) for which patients received a medical diagnosis. Multivariate regression models evaluated associations between cT2 burden score and asthma exacerbations and asthma control. Factor analysis was performed to assess which cT2 comorbidities were correlated and exhibited patterns of clustering.Results: Overall, 245,893 patients with asthma were included (mean [SD] age 44.8 [22.1] years; 43.8% male). Between 55% (GINA step 1) and 60% (GINA step 5) of asthma patients had a medical diagnosis for ≥ 1 other type2dx. Patients with increased cT2 burden were significantly more likely to experience asthma exacerbations and less likely to achieve asthma control.Conclusion: Asthma patients with a higher cumulative cT2 burden score were more likely to experience worse asthma outcomes than those without any cT2 (burden score of 0).Keywords: type 2 inflammation, asthma, exacerbations, control, comorbidities, burden

Rachel Pullen, 1, 2 Marc Miravitlles, 3 Anita Sharma, 4 Dave Singh, 5 Fernando Martinez, 6 John R Hurst, 7 Luis Alves, 8, 9 Mark Dransfield, 10 Rongchang Chen, 11 Shigeo Muro, 12 Tonya Winders, 13 Christopher Blango, 14 Hana Muellerova, 15 Frank Trudo, 16 Paul Dorinsky, 17 Marianna Alacqua, 15, 18 Tamsin Morris, 19 Victoria Carter, 1, 2 Amy Couper, 1, 2 Rupert Jones, 20 Konstantinos Kostikas, 1, 21 Ruth Murray, 1 David B Price 1, 2, 22 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Optimum Patient Care, Cambridge, UK; 3Pneumology Dept, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 4Platinum Medical Centre, Chermside, QLD, Australia; 5Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 6New York-Presbyterian Weill Cornell Medical Center, New York, NY, USA; 7UCL Respiratory, University College London, London, UK; 8EPI Unit, Institute of Public Health, University of Porto, Porto, Portugal; 9Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, Portugal; 10Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, USA; 11Key Laboratory of Respiratory Disease of Shenzhen, Shenzhen Institute of Respiratory Disease, Shenzhen People’s Hospital (Second Affiliated Hospital of Jinan University, First Affiliated Hospital of South University of Science and Technology of China), Shenzhen, People’s Republic of China; 12Department of Respiratory Medicine, Nara Medical University, Nara, Japan; 13USA & Global Allergy & Airways Patient Platform, Vienna, Austria; 14Janssen Pharmaceutical Companies of Johnson & Johnson, Philadelphia, PA, USA; 15AstraZeneca, Cambridge, UK; 16AstraZeneca, Wilmington, DE, USA; 17AstraZeneca, Durham, NC, USA; 18CSL Behring SpA, Milan, Italy; 19AstraZeneca, Luton, UK; 20Research and Knowledge Exchange, Plymouth Marjon University, Plymouth, UK; 21Respiratory Medicine Department, University of Ioannina School of Medicine, Ioannina, Greece; 22Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UKTel +65 3105 1489Email dprice@opri.sgBackground: Chronic obstructive pulmonary disease (COPD) are managed predominantly in primary care. However, key opportunities to optimize treatment are often not realized due to unrecognized disease and delayed implementation of appropriate interventions for both diagnosed and undiagnosed individuals. The COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST) is the first-of-its-kind, collaborative, interventional COPD registry. It comprises an integrated quality improvement program focusing on patients (diagnosed and undiagnosed) at a modifiable and higher risk of COPD exacerbations. The first step in CONQUEST was the development of quality standards (QS). The QS will be imbedded in routine primary and secondary care, and are designed to drive patient-centered, targeted, risk-based assessment and management optimization. Our aim is to provide an overview of the CONQUEST QS, including how they were developed, as well as the rationale for, and evidence to support, their inclusion in healthcare systems.Methods: The QS were developed (between November 2019 and December 2020) by the CONQUEST Global Steering Committee, including 11 internationally recognized experts with a specialty and research focus in COPD. The process included an extensive literature review, generation of QS draft wording, three iterative rounds of review, and consensus.Results: Four QS were developed: 1) identification of COPD target population, 2) assessment of disease and quantification of future risk, 3) non-pharmacological and pharmacological intervention, and 4) appropriate follow-up. Each QS is followed by a rationale statement and a summary of current guidelines and research evidence relating to the standard and its components.Conclusion: The CONQUEST QS represent an important step in our aim to improve care for patients with COPD in primary and secondary care. They will help to transform the patient journey, by encouraging early intervention to identify, assess, optimally manage and followup COPD patients with modifiable high risk of future exacerbations.Keywords: identification, assessment, intervention, follow-up

Trung N Tran,1 Marjan Kerkhof,2 Victoria Carter,3,4 David B Price3– 5 1Global Medicine Development, AstraZeneca, Gaithersburg, MD, USA; 2Mescio Research, Blauwestad, the Netherlands; 3Observational and Pragmatic Research Institute, Singapore; 4Optimum Patient Care, Cambridge, UK; 5Division of Applied Health Sciences, Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UKCorrespondence: Trung N TranGlobal Medicine Development, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USATel +1-301-398-5406Email trung.tran1@astrazeneca.comPurpose: Eosinophil count elevations are predictive of adverse outcomes in patients with asthma, yet little is known regarding longitudinal eosinophil patterns and their association with clinical outcomes. The goal of this study was to assess associations between longitudinal persistence of eosinophil elevations and both clinical outcomes and health care resource utilization (HCRU).Methods: Data were extracted from 2 databases in the United Kingdom. Patients included were aged ≥ 13 years, had active asthma, and had ≥ 3 blood eosinophil count (BEC) recordings. Patients were categorized by BEC as: never high (all BEC ≤ 300 cells/μL), intermittently high (≥ 1 BEC > 300 cells/μL but < 75% of BEC > 300 cells/μL), or persistently high (≥ 75% of BEC > 300 cells/μL). Asthma exacerbations, asthma control (risk domain, overall, and full), and HCRU were evaluated for 12 months after the last BEC.Results: The study population comprised 148,021 patients. Persistently high, intermittently high, and never high eosinophil patterns were detected in 13.6%, 40.5%, and 45.9% of patients, respectively. Patients with ≥ 1 elevated BEC were at greater risk for severe asthma exacerbations, regardless of whether the elevation was persistent (rate ratio [RR]: 1.28 [95% CI 1.24– 1.33]; P < 0.001) or intermittent (RR: 1.24 [95% CI 1.21– 1.27]; P < 0.001), compared with patients with no eosinophil elevations. Full asthma control was achieved by < 25% of patients across eosinophil pattern groups, and HCRU did not appreciably differ, although patients with persistently high BEC had the shortest hospital stay duration among the groups.Conclusion: These data suggest that elevated blood eosinophils, regardless of persistency, signify increased risk of severe asthma exacerbations.Keywords: asthma control, asthma exacerbation, biomarker, eosinophilia, phenotype, type 2 inflammation

Simon Wan Yau Ming,1 John Haughney,2 Dermot Ryan,3 Iain Small,4 Federico Lavorini,5 Alberto Papi,6 Dave Singh,7 David MG Halpin,8 John R Hurst,9 Shishir Patel,10 Matthias Ochel,10 Janwillem Kocks,1,11,12 Victoria Carter,1 Antony Hardjojo,1 David B Price1,2 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Optimum Patient Care, Cambridge, UK; 4Peterhead Health Centre, Aberdeen, UK; 5Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy; 6University of Ferrara, Ferrara, Italy; 7University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 8Royal Devon and Exeter Hospital, Exeter, UK; 9UCL Respiratory, University College London, London, UK; 10Chiesi Limited, Manchester, UK; 11General Practitioners Research Institute, Groningen, the Netherlands; 12University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the NetherlandsCorrespondence: David B PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UKTel +65 6802 9724Email dprice@opri.sgIntroduction: The Fostair® 100/6 (BDP/FF) pressurized metered-dose inhaler, delivering an extrafine formulation, is licensed for asthma and COPD in the UK. However, its real-life effectiveness for COPD has not been evaluated. This study compared the clinical effectiveness of BDP/FF against other licensed ICS/LABA combination inhalers: the Seretide® Accuhaler® (FP/SAL) and the Symbicort® Turbohaler® (BUD/FF).Methods: A matched historical cohort study was conducted using records of patients with diagnostic codes for COPD from the Optimum Patient Care Research Database (OPCRD). Patients who had received BDP/FF as their first ICS/LABA were matched 1:1 with patients who had received FP/SAL or BUD/FF, resulting in two matched comparisons. Additional analysis was conducted on patients who had never had diagnostic codes for asthma. Noninferiority in terms of the proportion of patients with moderate/severe COPD exacerbations on the different inhalers in the following year was assessed. Noninferiority was achieved if the upper CI limit were ≤ 1.2.Results: This study included 537 and 540 patient pairs in the BDP/FF vs FP/SAL cohort and the BDP/FF vs BUD/FF cohort, respectively. The proportion of patients with COPD exacerbations in the BDP/FF group was not significantly different from either the FP/SAL (68.7% vs 70.2%, AOR 0.89, 95% CI 0.67– 1.19) or BUD/FF group (68.5% vs 69.4%, AOR 0.79, 95% CI 0.58– 1.08). Noninferiority of BDP/FF in preventing COPD exacerbations was fulfilled in both comparisons. In patients without asthma, BDP/FF was also noninferior to BUD/FF (proportion with COPD exacerbations, 67.8% vs 64.7%, AOR 0.79, 95% CI 0.51– 1.1997). Additionally, a significantly lower proportion of patients prescribed BDP/FF had COPD exacerbations than FP/SAL (64.8% vs 73.7%, AOR 0.64 95% CI 0.43– 0.96).Conclusion: Initiating ICS/LABA treatment of COPD with extrafine-formulation BDP/FF was noninferior in preventing moderate/severe exacerbations compared to FP/SAL and BUD/FF.Keywords: metered-dose inhaler, dry-powder inhaler, chronic obstructive pulmonary disease, treatment efficacy, cost-effectiveness

Vicky Kritikos,1,2 David Price,3– 5 Alberto Papi,6 Antonio Infantino,7 Björn Ställberg,8 Dermot Ryan,3,9 Federico Lavorini,10 Henry Chrystyn,11 John Haughney,12 Karin Lisspers,8 Kevin Gruffydd-Jones,13 Miguel Román Rodríguez,14 Svein Høegh Henrichsen,15 Thys van der Molen,16 Victoria Carter,3,4 Sinthia Bosnic-Anticevich1,17,18 1Quality Use of Respiratory Medicines Group, Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia; 2Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 3Optimum Patient Care, Cambridge, UK; 4Observational and Pragmatic Research Institute, Singapore, Singapore; 5Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 6Respiratory Medicine, University of Ferrara, Ferrara, Italy; 7Special Interest Respiratory Area, Italian Interdisciplinary Society for Primary Care, Bari, Italy; 8Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 9Usher Institute, University of Edinburgh, Edinburgh, UK; 10Department Experimental and Clinical Medicine, University of Florence, Florence, Italy; 11Inhalation Consultancy Ltd, Leeds, UK; 12NHS Greater Glasgow & Clyde R&D, Glasgow, UK; 13Box Surgery, Box, UK; 14Primary Care Respiratory Research Unit Instituto De Investigación Sanitaria De Baleares (IdISBa), Palma, Spain; 15Department of Primary Health Care Services, Norwegian Directorate of Health, Oslo, Norway; 16Department of Primary Care, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands; 17Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; 18Central Sydney Local Area Health District, Sydney, NSW, AustraliaCorrespondence: Vicky KritikosWoolcock Institute of Medical Research, Glebe, Sydney, NSW, AustraliaTel +61 4 0299 5125Fax +61 2 9114 0014Email vicky.kritikos@sydney.edu.auPurpose: There is a dearth of research regarding the prevalence and nature of patient-reported rhinitis and its relationship with risk of asthma exacerbations. The aim of this study was to (i) determine the prevalence, severity and treatment of self-reported rhinitis symptoms among adults aged ≥ 18 years with asthma treated at Global Initiative for Asthma (GINA) Step 3 and above and (ii) compare the demographics, clinical characteristics, medication use, side-effects and healthcare practitioner review between patients who report rhinitis symptoms and those who do not and (iii) determine whether patient-reported rhinitis is associated with risk of asthma exacerbations in the total patient sample.Patients and Methods: This analysis used data from the iHARP (Initiative Helping Asthma in Real-life Patients) asthma review service – a cross-sectional observational study (2011 and 2014) in seven countries that captured data on patient demographics, rhinitis symptoms, asthma symptoms, indicators of exacerbations, medication use, oropharyngeal effects and side-effects, using practitioner- and patient-reported questionnaires. Comparisons between patients with and without rhinitis were tested. Univariate logistic regression was used to identify variables associated with risk of exacerbations for entry into multivariable logistic regression.Results: This report contains data from 4274 patients: 67.4% (2881/4274) reported rhinitis symptoms and of which 65.7% (1894/2881) had not received a doctor diagnosis; 36.5% (1052/2881) had moderate-severe rhinitis, 12.4% (358/2881) had used intranasal corticosteroids and 19.8% (569/2881) oral antihistamines. Patients with coexisting moderate-severe rhinitis were more likely to have GINA-defined uncontrolled asthma than those with mild rhinitis or no rhinitis. Moderate-severe rhinitis was associated with 40% increased risk of asthma exacerbations (OR=1.40, 95% CI: 1.02– 1.90).Conclusion: This study identified a major gap in the diagnosis and management of rhinitis in a cohort of people with asthma treated at GINA Step 3 and above who are managed in general practice. It highlights the need for practitioners to identify, evaluate and optimally treat rhinitis in adults with asthma, which is a significant factor associated with exacerbation risk.Keywords: asthma symptom control, comorbidities, oral steroids, preventer, reliever, side-effects

Marjan Kerkhof,1 Jaco Voorham,1 Paul Dorinsky,2 Claudia Cabrera,3,4 Patrick Darken,5 Janwillem WH Kocks,1,6 Mohsen Sadatsafavi,7,8 Don D Sin,7,8 Victoria Carter,1 David B Price1,9 1Observational & Pragmatic Research Institute Pte Ltd, Singapore, Singapore; 2AstraZeneca, Durham, NC, USA; 3AstraZeneca, Mölndal, Sweden; 4Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; 5AstraZeneca, Morristown, NJ, USA; 6General Practitioners Research Institute, Groningen, The Netherlands; 7Respiratory Evaluation Sciences Program, Collaboration for Outcomes Research and Evaluation, University of British Columbia, Vancouver, BC, Canada; 8Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC, Canada; 9Academic Primary Care, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UKTel +65 6962 3627Email dprice@opri.sgIntroduction: Early identification of preventable risk factors of COPD progression is important. Whether exacerbations have a negative impact on disease progression is largely unknown. We investigated whether the long-term occurrence of exacerbations is associated with lung function decline at early stages of COPD.Methods: Patients diagnosed with mild/moderate COPD (obstruction and FEV1% predicted 50– 90%), aged ≥ 35 years, and a smoking history, who had ≥ 6 years of UK electronic medical records after initiation of maintenance therapy were studied. Multilevel mixed-effect linear regression was performed to determine the association between the count of any year in which the patient had ≥ 1 exacerbation over a 6-year period and FEV1 decline, adjusted for sex, age, anthropometrics and smoking habits. Exacerbations were defined as any prescription for an acute oral corticosteroid course and/or lower respiratory-related antibiotics and/or any COPD-related emergency or inpatient hospitalization.Results: Of 11,337 patients included (mean age 65 years; 49% female) 31.6%, 23.3%, 16.6%, 11.6%, 8.1%, 5.3% and 3.4% had 0, 1, 2, 3, 4, 5 and 6 years with ≥ 1 exacerbation. The mean annual FEV1 decline accelerated by 1.50 mL/year (95% Confidence Interval 1.02; 1.98) with every additional year with ≥ 1 exacerbation from 31.0 mL/year in subjects without any exacerbation to 40.0 mL/year in patients experiencing ≥ 1 exacerbation every year. Patients with more years with ≥ 1 exacerbation had a lower mean FEV1 at first diagnosis: 14.7 mL (11.7; 17.8) lower with every additional year with exacerbations. When counting years with ≥ 2 exacerbations, greater effects were observed (2.19 [1.50; 2.88] mL/year excess decline per year with ≥ 2 exacerbations; 16.5 mL [12.1; 20.8] lower FEV1 at diagnosis).Conclusion: Patients who experienced a greater exacerbation burden after initiation of maintenance therapy had worse lung function at diagnosis and a more rapid lung function decline thereafter, which emphasizes the need for better treatment strategies.Keywords: COPD, exacerbations, spirometry, inhalation therapy, observational study

Kyu Yean Kim,1 Marc Miravitlles,2,3 Pawel Sliwinski,4 Richard Costello,5 Victoria Carter,6,7 Jessica Tan,8 Therese Sophie Lapperre,8,9 Bernardino Alcazar,10 Caroline Gouder,11 Cristina Esquinas,2,12 Juan Luis García-Rivero,13 Anu Kemppinen,6 Augustine Tee,14 Miguel Roman-Rodríguez,15 Juan José Soler-Cataluña,3,16 David Price,6–7,17 Chin Kook Rhee11Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Pneumology Department, University Hospital Vall d’Hebron/Vall d’Hebron Research Institute (VHIR), Barcelona, Spain; 3CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain; 42nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland; 5Department of Respiratory Medicine, Royal College of Surgeons, Dublin, Ireland; 6Optimum Patient Care, Cambridge, UK; 7Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UK; 8Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen, Denmark; 9Singhealth Duke-NUS Medical Academic Clinical Programme, Duke-NUS Medical School, Singapore; 10Respiratory Department, Hospital de Alta Resolución de Loja, Madrid, Spain; 11Department of Respiratory Medicine, Mater Dei Hospital, L-Imsida, Malta; 12Public Health, Mental, Maternal and Child Health Nursing Department, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; 13Hospital Comarcal de Laredo, Cantabria, Spain; 14Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore; 15Primary Health-care Center Son Pisà, IB-Salut, Palma, Spain; 16Pneumology Department, Hospital Arnau de Vilanova, Valencia, Spain; 17Observational and Pragmatic Research Institute, SingaporeAbstract: We aimed to compare clinical characteristics between Asian and Western chronic obstructive pulmonary disease (COPD) patients. This was a sub-analysis of an international, multicenter, prospective cohort study. Asian patients were enrolled in Singapore and South Korea. Western patients were enrolled in Spain, Poland, Ireland, the United Kingdom, and Malta. A total of 349 patients were analyzed. Among them, 110 (32%) patients were Asian and 239 (68%) Western. Male sex was more predominant in Asian than in Western (95% versus 63%, respectively; P

David B Price,1,2 Sen Yang,1 Simon Wan Yau Ming,1 Antony Hardjojo,1 Claudia Cabrera,3,4 Andriana I Papaioannou,5 Stelios Loukides,5 Vicky Kritikos,6 Sinthia Z Bosnic-Anticevich,6 Victoria Carter,7 Paul M Dorinsky8 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Global Medical Affairs, AstraZeneca R and D, Mölndal, Sweden; 4Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; 52nd Respiratory Medicine Department, Medical School, National and Kapodistrian University of Athens, Attikon General Hospital, Athens, Greece; 6Woolcock Institute of Medical Research, Quality Use of Respiratory Medicines Group, School of Medical Sciences, University of Sydney, Glebe, Australia; 7Optimum Patient Care, Cambridge, UK; 8Pearl – a member of the AstraZeneca Group, Durham, NC, USABackground: Peak inspiratory flow (PIF) as generated through the resistance of a dry powder inhaler (DPI) device is a critical patient-dependent maneuver impacting the success of DPI medication delivery. Despite its importance, it is not routinely measured in clinical practice. Little is currently known about the relationship, if any, between PIF through DPI devices, routine spirometry and disease outcomes.Aim: The aim of this study was to identify potential predictors of PIF for different DPIs from spirometric parameters and patient characteristics and explore the association between PIF and follow-up events.Patients and methods: A retrospective observational study at discharge among patients hospitalized for a COPD exacerbation at Attikon hospital, Athens, Greece. Spirometry was performed using an Easy on-PC™ spirometer. PIF was measured through four DPI resistances using the In-Check™ DIAL. Regression analyses were used to investigate the association between PIF through resistances and spirometric parameters obtained at discharge, comorbidities and demographic parameters.Results: Forty-seven COPD patients (mean [±SD], age 71 [±9] years, 72% males, 51% current smokers) were included in this study. Overall, 85% and 15% were classified as GOLD (2017) groups D and C, respectively. Most prevalent comorbidities were hypertension (70%) and cardiovascular disease (53%). In the final regression model, higher PIF was significantly associated with the following: higher FEV1 and % predicted peak expiratory flow (PEF) for Turbohaler® (R-squared value 0.374); higher FEV1 and diagnosis of gastroesophageal reflux disease (GERD) for Aerolizer® (R-squared value 0.209) and higher FEV1, younger age and diagnosis of ischemic heart disease (IHD) for Diskus® (R-squared value 0.350). However, R-squared values for all three devices were weak (

Pete Smith,1 David Price,2,3 Richard Harvey,4,5 Andrew Simon Carney,6 Vicky Kritikos,7 Sinthia Z Bosnic-Anticevich,7,8 Louise Christian,9 Derek Skinner,10 Victoria Carter,10 Alice Marie Sybille Durieux3 1Clinical Medicine, Griffith University, Southport, QLD, Australia; 2Observational and Pragmatic Research Institute, Singapore; 3Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UK; 4Applied Medical Research Center, University of New South Wales, Sydney, NSW, Australia; 5Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia; 6Department of Otolaryngology – Head and Neck Surgery, Flinders University, Adelaide, SA, Australia; 7Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia; 8Central Sydney Area Health Service, Sydney, NSW, Australia; 9NostraData, Kew, VIC, Australia; 10Optimum Patient Care, Cambridge, UK Purpose: There is a relative paucity of research regarding medication expenditure associated with multiple-therapy use for rhinitis in Australia. To describe 1) the nature and extent of multiple-therapy use for rhinitis in Australia using data on therapies purchased with prescription or over-the-counter (OTC) and 2) additional costs incurred by multiple-therapy use compared with intranasal corticosteroid (INCS) therapy alone. Patients and methods: A retrospective observational study was carried out using a database containing anonymous pharmacy transaction data available from 20% of pharmacies in Australia that links doctor prescriptions and OTC purchase information. Pharmacy purchases of at least one prescription or OTC rhinitis treatment, with or without additional asthma/chronic obstructive pulmonary disease (COPD) therapy, by patients during 2013 and 2014 were assessed. Results: In total, 4,247,193 prescription and OTC rhinitis treatments were purchased from 909 pharmacies over 24 months. The majority of rhinitis therapy transactions were single-therapy purchases without additional asthma/COPD therapy. Of the single therapies purchased, 73% were oral antihistamines (OAHs) and 15% were INCS therapy. Dual-therapy purchases of INCSs and OAHs accounted for 40% of multiple-therapy purchases. Patients frequently purchased OAHs, nonsteroidal nasal sprays, and eye drops for allergic conjunctivitis alongside INCSs, resulting in higher financial costs (up to AU$21 per treatment episode) compared with INCS monotherapy. Conclusion: This study highlighted the significant burden posed on community pharmacy to address the needs of people with rhinitis symptoms, and the failure to translate the evidence that INCSs are the most effective monotherapy for moderate to severe and/or persistent rhinitis into clinical practice in light of the lack of evidence supporting combination of INCS and OAH therapy. Health care professional engagement, especially at the pharmacy level, will be extremely important if we wish to ensure that the purchase of rhinitis treatment is in accordance with guidelines and that their use is optimal. Keywords: community pharmacy, intranasal corticosteroids, oral antihistamines, over-the-counter, prescription, rhinitis, therapy

Environmental justice advocates often argue that environmental hazards and their health effects vary by neighborhood, income, and race. To assess these patterns and advance preventive policy, their colleagues in the research world often use complex and methodologically sophisticated statistical and geospatial techniques. One way to bridge the gap between the technical work and the expert knowledge of local residents is through community-based participatory research strategies. We document how an environmental justice screening method was coupled with "ground-truthing"-a project in which community members worked with researchers to collect data across six Los Angeles neighborhoods-which demonstrated the clustering of potentially hazardous facilities, high levels of air pollution, and elevated health risks. We discuss recommendations and implications for future research and collaborations between researchers and community-based organizations. © 2013 Society for Public Health Education.

Andrew N Menzies-Gow,1,2 Trung N Tran,3 Brooklyn Stanley,4 Victoria Ann Carter,4 Josef S Smolen,5 Arnaud Bourdin,6 J Mark Fitzgerald7 ,† Tim Raine,8 Jatin Chapaneri,2 Benjamin Emmanuel,3 David J Jackson,9,10 David B Price4,11 1Royal Brompton and Harefield Hospitals, Guys & St Thomas’ NHS Foundation Trust, London, UK; 2AstraZeneca, Cambridge, UK; 3AstraZeneca, Gaithersburg, MD, USA; 4Observational and Pragmatic Research Institute, Singapore; 5Medical University of Vienna, Vienna, Austria; 6Université de Montpellier, CHU Montpellier, PhyMedExp, INSERM, CNRS, Montpellier, France; 7The University of British Columbia, Vancouver, British Columbia, Canada; 8Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, UK; 9Guy’s Severe Asthma Centre, Guy’s & St Thomas’ NHS Trust, London, UK; 10School of Immunology & Microbial Sciences, King’s College London, London, UK; 11Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK†J. Mark Fitzgerald passed away on January 18, 2022Correspondence: David B Price, Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building-Foresterhill, Aberdeen, AB25 2ZD, UK, Tel +65 3105 1489, Email dprice@opri.sgPurpose: Associations between systemic glucocorticoid (SGC) exposure and risk for adverse outcomes have spurred a move toward steroid-sparing treatment strategies. Real-world changes in SGC exposure over time, after the introduction of steroid-sparing treatment strategies, reveal areas of successful risk mitigation as well as unmet needs.Patients and Methods: A population-based ecological study was performed from the Optimum Patient Care Research Database to describe SGC prescribing trends of steroid-sparing treatment strategies in primary care practices before and after licensure of biologics in the United Kingdom from 1990 to 2019. Each analysis year included patients aged ≥ 5 years who were registered for ≥ 1 year with a participating primary care practice. The primary analysis was SGC exposure, defined as total cumulative SGC dose per patient per year, for asthma, severe asthma, chronic obstructive pulmonary disease (COPD), nasal polyps, Crohn’s disease, rheumatoid arthritis, ulcerative colitis, and systemic lupus erythematosus. Secondary outcomes were percentages of patients prescribed SGCs and number of SGC prescriptions per patient per year.Results: The number of patients who met study inclusion criteria ranged from 219,862 (1990) to 1,261,550 (2019). At the population level, patients with asthma or COPD accounted for 67.7% to 73.2% of patients per year with an SGC prescription. Over three decades, decreases in SGC total yearly dose ≥ 1000 mg have been achieved in multiple conditions. Patients with COPD prescribed SGCs increased from 5.8% (1990) to 34.8% (2017). SGC prescribing trends for severe asthma, Crohn’s disease, and ulcerative colitis show decreased prescribing trends after the introduction of biologics.Conclusion: Decreases in total yearly SGC doses have been shown in multiple conditions; however, for conditions such as severe asthma and COPD, an unmet need remains for increased awareness of SGC burden and the adoption or development of SGC-sparing alternatives to reduce overuse.Keywords: glucocorticoids, practice patterns, drug prescriptions, biological products, drug utilization