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To describe clinical outcomes in patients with severe asthma (SA) by common sociodemographic determinants of health: sex, race, ethnicity, and age. CHRONICLE is an observational study of subspecialist-treated, United States adults with SA receiving biologic therapy, maintenance systemic corticosteroids, or uncontrolled by high-dosage inhaled corticosteroids with additional controllers. For patients enrolled between February 2018 and February 2020, clinical characteristics and asthma outcomes were assessed by sex, race, ethnicity, age at enrollment, and age at diagnosis. Treating subspecialists reported exacerbations, exacerbation-related emergency department visits, and asthma hospitalizations from 12 months before enrollment through the latest data collection. Patients completed the St. George’s Respiratory Questionnaire and the Asthma Control Test at enrollment. Among 1884 enrolled patients, the majority were female (69%), reported White race (75%), non-Hispanic ethnicity (69%), and were diagnosed with asthma as adults (60%). Female, Black, Hispanic, and younger patients experienced higher annualized rates of exacerbations that were statistically significant compared with male, White, non-Hispanic, and older patients, respectively. Black, Hispanic, and younger patients also experienced higher rates of asthma hospitalizations. Female and Black patients exhibited poorer symptom control and poorer health-related quality of life. In this contemporary, real-world cohort of subspecialist-treated adults with SA, female sex, Black race, Hispanic ethnicity, and younger age were important determinants of health, potentially attributable to physiologic and social factors. Knowledge of these disparities in SA disease burden among subspecialist-treated patients may help optimize care for all patients. Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Gary T Ferguson,1 Tor Skärby,2 Lars H Nordenmark,2 Rosa Lamarca,3 Audrone Aksomaityte,4 Dan Lythgoe,4 Ileen Gilbert,5 Frank Trudo5 1Department of Medicine, Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA; 2BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; 3BioPharmaceuticals R&D, AstraZeneca, Barcelona, Spain; 4Statistics Department, Phastar, London, UK; 5BioPharmaceuticals Medical – US, AstraZeneca LP, Wilmington, DE, USACorrespondence: Gary T FergusonMD, Pulmonary Research Institute of Southeast Michigan, 29255 West 10 Mile Road, Suite A, Farmington Hills, MI 48336, USATel +1 248 478 6561Email garytferguson@msn.comPurpose: Moderate and severe COPD exacerbations are a significant health-care burden, but patients also experience “mild” exacerbations, or COPD symptom-related attacks, which often go unreported. We aimed to define and then determine the incidence of COPD symptom-related attacks and their impact on future risk of moderate/severe exacerbations, health-related quality of life (HRQoL), and lung function. The effect of COPD maintenance therapy on the attack definition was then evaluated by comparing budesonide/formoterol with formoterol alone.Patients and Methods: This post hoc analysis of the RISE study defined COPD symptom-related attacks as ≥ 2 consecutive days of both worsening symptoms and increased daily rescue medication use based upon thresholds of > 2 and > 4 short-acting β2-agonist (SABA) inhalations/day above baseline. The impact of these events on subsequent moderate/severe exacerbation risk was estimated using a time-varying Cox proportional hazards model. The effects of COPD symptom-related attacks on St George’s Respiratory Questionnaire (SGRQ) total score and pre-bronchodilator forced expiratory volume in 1 second (FEV1) were evaluated as average changes from baseline to first post-attack measurement. Rates of attacks were compared between treatment groups using negative binomial regression models.Results: COPD symptom-related attacks elevated the risk of subsequent moderate/severe exacerbations at both > 2 and > 4 inhalations/day above baseline (HR 1.86 and 2.21, respectively; p< 0.0001), with a cumulative increase in risk with increasing attacks. HRQoL and lung function were reduced for patients with ≥ 1 versus no COPD symptom-related attacks at both rescue medication thresholds. There were fewer COPD symptom-related attacks with budesonide/formoterol versus formoterol alone, with no increased risk of pneumonia and lower respiratory tract infections.Conclusion: COPD symptom-related attacks are common and typically unreported. Importantly, these attacks can account for considerable morbidity and should not be regarded as “mild”. Detection of such exacerbations may be valuable in identifying patients at greater risk and guiding preventive therapeutic interventions.Keywords: COPD, exacerbation, symptoms, rescue inhaler, mild COPD exacerbations

Matthew J Hegewald,1,2 Benjamin D Horne,3,4 Frank Trudo,5 James L Kreindler,5 Yen Chung,5 Susan Rea,6 Denitza P Blagev1,2 1Pulmonary and Critical Care Medicine Division, Intermountain Medical Center, Murray, UT, USA; 2Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, UT, USA; 3Intermountain Heart Institute at Intermountain Healthcare, Salt Lake City, UT, USA; 4Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; 5Health Economics Outcomes Research, AstraZeneca, Wilmington, DE, USA; 6Enterprise Analytics, Intermountain Healthcare, Salt Lake City, UT, USACorrespondence: Matthew J HegewaldPulmonary and Critical Care Medicine Division, Intermountain Medical Center, 5121 S Cottonwood Street, Murray, UT 84107, USATel +1-801-507-4870Fax +1-801-507-4792Email matt.hegewald@imail.orgPurpose: This retrospective, observational cohort study investigated the association of blood eosinophil counts within 1 week of hospitalization for acute exacerbation of COPD (AECOPD) with subsequent risk of all-cause and COPD-related readmission from a large integrated health system.Patients and Methods: Electronic medical records were extracted for index hospitalization for AECOPD at all Intermountain Healthcare hospitals. The primary outcome was the relationship of blood eosinophil count to 30-day all-cause readmission; secondary outcomes were 60-day, 90-day, and 12-month all-cause readmission, COPD-related readmission, and empiric derivation of the eosinophil count with the highest area under the curve (AUC) for predicting 30-day all-cause readmission.Results: Of 2445 included patients, 1935 (79%) had a blood eosinophil count < 300 cells/μL and 510 (21%) had a count ≥ 300 cells/μL. Using a 300-cells/μL threshold, there was no significant difference between high and low eosinophil groups in 30-day (odds ratio [OR]=1.05, 95% confidence interval [CI]=0.75– 1.47) or 60-day (OR=1.15, 95% CI=0.88– 1.51) all-cause readmissions. However, patients with greater (versus lesser) eosinophil counts had increased 90-day and 12-month all-cause readmissions (OR=1.35, 95% CI=1.06– 1.72, and OR=1.32, 95% CI=1.07– 1.62). COPD-related readmission rates were significantly greater for patients with greater (versus lesser) eosinophil counts at 30, 60, and 90 days and 12 months (OR range=1.52– 1.97). A total of 70 cells/μL had the most discriminatory power to predict 30-day all-cause readmission (highest AUC).Conclusion: Eosinophil counts in patients with COPD were not associated with a difference in 30-day all-cause readmissions. However, greater eosinophil counts were associated with increased risk of all-cause readmission at 90 days and 12 months and COPD-related readmission at 30, 60, and 90 days and 12 months. Patients with eosinophils < 70 cells/μL had the lowest risk for 30-day all-cause readmission. Blood eosinophils in patients hospitalized with AECOPD may be a useful biomarker for the risk of hospital readmission.Keywords: AECOPD, phenotype, biomarkers, eosinophils, electronic medical records

Christopher S Ambrose,1 Bradley E Chipps,2 Wendy C Moore,3 Weily Soong,4 Jennifer Trevor,5 Dennis K Ledford,6 Warner W Carr,7 Njira Lugogo,8 Frank Trudo,9 Trung N Tran,10 Reynold A Panettieri Jr11 1US Medical Affairs, AstraZeneca, Gaithersburg, MD, USA; 2Capital Allergy & Respiratory Disease Center, Sacramento, CA, USA; 3Pulmonary, Critical Care, Allergy, and Immunologic Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Alabama Allergy & Asthma Center, Birmingham, AL, USA; 5Pulmonary, Allergy, & Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 6Division of Allergy and Immunology, University of South Florida, Tampa, FL, USA; 7Allergy & Asthma Associates of Southern California, Mission Viejo, CA, USA; 8Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA; 9US Medical Affairs, AstraZeneca, Wilmington, DE, USA; 10Biopharmaceuticals Medical, Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA; 11Institute for Translational Medicine and Science, Rutgers, The State University of New Jersey, New Brunswick, NJ, USACorrespondence: Christopher S Ambrose Tel +1 (301) 398-4454Fax +1 301-398-9454Email chris.ambrose@astrazeneca.comBackground: Approximately 5– 10% of patients with asthma have severe disease. High-quality real-world studies are needed to identify areas for improved management.Objective: Aligned with the International Severe Asthma Registry, the CHRONICLE study (ClinicalTrials.gov: NCT03373045) was developed to address this need in the US.Study Design: Learnings from prior studies were applied to develop a real-world, prospective, noninterventional study of US patients with confirmed severe asthma who are treated by subspecialist physicians and require biologic or maintenance systemic immunosuppressant therapy or who are uncontrolled by high-dosage inhaled corticosteroids and additional controllers. Target enrollment is 4000 patients, with patient observation for ≥ 3 years. A geographically diverse sample of allergist/immunologist and pulmonologist sites approach all eligible patients under their care and report patient characteristics, treatment, and health outcomes every 6 months. Patients complete online surveys every 1– 6 months.Initial Results: From February 2018 to February 2019, 102 sites screened 1428 eligible patients; 936 patients enrolled. Study sites (40% allergist/immunologist, 42% pulmonologist, 18% both) were similar to other US asthma subspecialist samples. Enrolled patients were 67% female with median ages at enrollment and diagnosis of 55 (range: 18– 89) and 26 (0– 80) years, respectively. Median body mass index was 31 kg/m2; 3% and 29% were current or former smokers, respectively, and > 60% reported ≥ 1 exacerbation in the prior year and suboptimal symptom control.Conclusion: CHRONICLE will provide high-quality provider- and patient-reported data from a large, real-world cohort of US adults with subspecialist-treated severe asthma.Keywords: asthma exacerbations, longitudinal studies, allergists, pulmonologists, biologic therapy

Frank Trudo,1 Lee Kallenbach,2 Joseph Vasey,2 Yen Chung,1 Alan Wilk,2 Lukas Slipski,2 Dan O’Brien,2 Charlie Strange3 1Respiratory and Inflammation Therapeutic Area, AstraZeneca, Wilmington, DE, USA; 2Life Sciences, Practice Fusion, San Francisco, CA, USA; 3Department of Medicine, Medical University of South Carolina, Charleston, SC, USACorrespondence: Frank TrudoAstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE 19897, USAEmail Frank.Trudo@astrazeneca.comPurpose: We sought to describe clinical and economic outcomes for COPD patients by blood eosinophil (EOS) count.Methods: This retrospective cohort study of COPD patients used data from the Practice Fusion electronic medical records (EMR) database linked to Symphony Health Solutions transactional pharmacy, medical, outpatient, and inpatient claims data to evaluate COPD-related and all-cause health care resource utilization and cost in the 12-month period following the date of each patient’s greatest recorded blood eosinophil count during the 27-month period from January 2014 to March 2016. A post-index moderate exacerbation was defined as an outpatient or emergency care visit for COPD and a prescription for oral corticosteroid and/or antibiotics within 10 days of the visit. Severe exacerbation was defined as an inpatient hospitalization with COPD as primary diagnosis.Results: Of 48,090 EMR patients, 39,939 (83.1%) had a charge in the claims data both pre- and post-index (mean age 67.2 years, 58.3% female), 17,397 (43.6%) had EOS ≥220 cells/μL. Moderate and severe exacerbations were more frequent for patients with EOS≥220 cells/μL compared with those with EOS Conclusion: COPD patients with EOS counts ≥220 cells/μL were more likely to have had moderate or severe exacerbations and greater cost of care than those with EOS Keywords: clinical phenotypes, electronic medical records, exacerbations, health care resource utilization, eosinophils