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Melissa H Roberts,1 David M Mannino,2,3 Douglas W Mapel,4 Orsolya Lunacsek,5 Shahla Amin,5 Eileen Farrelly,5 Norbert Feigler,6 Michael F Pollack6 1College of Pharmacy, University of New Mexico, Albuquerque, NM, USA; 2College of Medicine, University of Kentucky, Lexington, KY, USA; 3COPD Foundation, Miami, FL, USA; 4Northern Arizona Pulmonary Associates, Flagstaff, AZ, USA; 5Global Consulting, Cencora, Conshohocken, PA, USA; 6BioPharmaceuticals, US Medical, AstraZeneca, Wilmington, DE, USACorrespondence: Michael F Pollack, BioPharmaceuticals, Global Medical Evidence, AstraZeneca, Wilmington, DE, USA, Email michael.pollack1@astrazeneca.comPurpose: Chronic obstructive pulmonary disease (COPD) is a progressive disease associated with reduced life expectancy, increased morbidity, mortality, and cost. This study characterized the US COPD burden, including socioeconomic and health-related quality of life (HRQoL) outcomes.Study Design and Methods: In this retrospective, cross-sectional study using nationally representative estimates from Medical Expenditures Survey (MEPS) data (2016– 2019), adults (≥ 18 years) living with and without COPD were identified. Adults living without COPD (control cohort) and with COPD were matched 5:1 on age, sex, geographic region, and entry year. Demographics, clinical characteristics, socioeconomic, and generic HRQoL measures were examined to include a race-stratified analysis of people living with COPD.Results: A total of 4,135 people living with COPD were identified; the matched dataset represented a weighted non-institutionalized population of 11.3 million with and 54.2 million people without COPD. Among people living with COPD, 66.3% had ≥ 1 COPD-related condition; 62.7% had ≥ 1 cardiovascular condition, compared to 33.5% and 50.5% without COPD. More people living with COPD were unemployed (56.2% vs 45.3%), unable to work due to illness/disability (30.1% vs 12.1%), had problems paying bills (16.1% vs 8.8%), reported poorer perceived health (fair/poor: 36.2% vs 14.4%), missed more working days due to illness/injury per year (median, 2.5 days vs 0.0 days), and had limitations in physical functioning (40.1% vs 19.4%) (all P< 0.0001). In race-stratified analyses for people living with COPD, people self-reporting as Black had higher prevalence of cardiovascular-risk conditions, poorer socioeconomic and HRQoL outcomes, and higher healthcare expenses than White or Other races.Conclusion: Adults living with COPD had higher clinical disease burden, lower socioeconomic status, and reduced HRQoL than those without, with greater disparities among Black people living with COPD compared to White and other races. Understanding the characteristics of patients helps address care disparities and access challenges.Keywords: COPD, burden of illness, healthcare cost, race/ethnicity

Radmila Choate,1 Kristen E Holm,2,3 Robert A Sandhaus,2,3 David M Mannino,4 Charlie Strange3,5 1University of Kentucky College of Public Health, Lexington, Kentucky, USA; 2Department of Medicine, National Jewish Health, Denver, Colorado, USA; 3Alphanet, Inc., Coral Gables, Florida, USA; 4University of Kentucky College of Medicine, Lexington, Kentucky, USA; 5Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, South Carolina, USACorrespondence: Radmila Choate, University of Kentucky College of Public Health, Lexington, Kentucky, USA, Tel +1 859-218-2237, Email Radmila.choate@uky.eduBackground: Health-related quality of life (HRQoL) assessments such as St. George’s Respiratory Questionnaire (SGRQ) are often used as outcome measures to evaluate patient-perceived changes in health status among individuals with lung disease. Several factors have been linked to deterioration in SGRQ, including symptoms (dyspnea, wheezing) and exercise intolerance. Whether these findings apply to individuals with alpha-1 antitrypsin deficiency (AATD) remains incompletely studied. This longitudinal study examines the trajectory of SGRQ scores in a cohort of United States individuals with AATD-associated lung disease and defines factors associated with longitudinal change.Methods: Individuals with AATD-associated lung disease enrolled in AlphaNet, a disease management program, who had ≥ 3 SGRQ measurements collected between 2009 and 2019, and baseline data for clinically important variables were included in these analyses. Data collected after lung transplants were excluded. Mixed-effects model analyses were used to evaluate the changes in SGRQ total and subscale scores over time and by modified Medical Research Council (mMRC) Scale, use of oxygen, age, sex, productive cough, and exacerbation frequency at baseline. Sensitivity analyses were conducted to examine the potential effect of survivor bias.Results: Participants (n=2456, mean age 57.1± 9.9 years, 47% female) had a mean SGRQ total score of 44.7± 18.9 at baseline, 48% used oxygen regularly, and 55% had ≥ 2 exacerbations per year. The median length of follow-up was 6 (IQR 3– 9) years. The SGRQ total score and subscales remained stable throughout the observation period. Age, mMRC categories, presence or absence of productive cough, frequency of exacerbations, and use of oxygen at baseline were significantly associated with the rate of change of SGRQ total (p< 0.0001).Conclusion: We observed long-term stability in HRQoL and an association between the rate of change in SGRQ and baseline mMRC, exacerbation frequency, productive cough, and use of oxygen in this cohort of individuals with AATD-associated lung disease.Keywords: COPD, alpha-1 antitrypsin deficiency, quality of life

Muhammad Asad Faruqi,1 Malik M Khurram S Khan,1 David M Mannino1,2 1University of Kentucky College of Medicine, Lexington, KY, USA; 2COPD Foundation, Miami, FL, USACorrespondence: David M Mannino, Department of Medicine, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, 40536, USA, Email dmannino@uky.eduAbstract: Ensifentrine is a novel inhalational phosphodiesterase (PDE)3 and PDE4 inhibitor which improves bronchodilation and decreases inflammatory markers by acting locally on the bronchial tissue, with minimal systemic effects. Both preclinical and clinical trials have demonstrated benefits of this therapy, including improvement in lung function and reduction in exacerbations. This therapy is currently under review by the US Food and Drug Administration with a decision expected in 2024.Keywords: chronic obstructive pulmonary disease, therapy, phosphodiesterase inhibitor

Kimberly Daniels,1 Stephan Lanes,1 Arlene Tave,1 Michael F Pollack,2 David M Mannino,3 Gerard Criner,4 Amanda Neikirk,1 Kirsty Rhodes,5 Norbert Feigler,2 Clementine Nordon5 1Safety and Epidemiology, Carelon Research, Wilmington, DE, USA; 2Global Medical Affairs, AstraZeneca, Wilmington, DE, USA; 3College of Medicine, University of Kentucky, Lexington, KY, USA; 4Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; 5BioPharmaceuticals Medical, AstraZeneca, Cambridge, UKCorrespondence: Kimberly Daniels, Safety and Epidemiology, Carelon Research, 123 Justison Street, Suite 200, Wilmington, DE, 19801, USA, Tel +1 443-812-1731, Email Kimberly.Daniels@carelon.comPurpose: This study estimated the magnitude and duration of risk of cardiovascular events and mortality following acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and whether risks varied by number and severity of exacerbation in a commercially insured population in the United States.Methods: This was a retrospective cohort study of newly diagnosed COPD patients ≥ 40 years old in the Healthcare Integrated Research Database from 2012 to 2019. Patients experiencing exacerbations comprised the “exacerbation cohort”. Moderate exacerbations were outpatient visits with contemporaneous antibiotic or glucocorticoid administration; severe exacerbations were emergency department visits or hospitalizations for AECOPD. Follow-up started on the exacerbation date. Distribution of time between diagnosis and first exacerbation was used to assign index dates to the “unexposed” cohort. Cox proportional hazards models estimated risks of a cardiovascular event or death following an exacerbation adjusted for medical and prescription history and stratified by follow-up time, type of cardiovascular event, exacerbation severity, and rank of exacerbation (first, second, or third).Results: Among 435,925 patients, 170,236 experienced ≥ 1 exacerbation. Risk of death was increased for 2 years following an exacerbation and was highest during the first 30 days (any exacerbation hazard ratio (HR)=1.79, 95% CI=1.58— 2.04; moderate HR=1.22, 95% CI=1.04— 1.43; severe HR=5.09, 95% CI=4.30— 6.03). Risks of cardiovascular events were increased for 1 year following an AECOPD and highest in the first 30-days (any exacerbation HR=1.34, 95% CI=1.23— 1.46; moderate HR=1.23 (95% CI 1.12— 1.35); severe HR=1.93 (95% CI=1.67— 2.22)). Each subsequent AECOPD was associated with incrementally higher rates of both death and cardiovascular events.Conclusion: Risk of death and cardiovascular events was greatest in the first 30 days and rose with subsequent exacerbations. Risks were elevated for 1– 2 years following moderate and severe exacerbations, highlighting a sustained increased cardiopulmonary risk associated with exacerbations.Keywords: COPD, cardiopulmonary, cardiac events, epidemiology, longitudinal studies

David Mannino,1 James Siddall,2 Mark Small,2 Adam Haq,2 Marjorie Stiegler,3 Michael Bogart3 1Department of Medicine, University of Kentucky, Lexington, KY, USA; 2Respiratory DSP Franchise, Adelphi Real World, Bollington, UK; 3US Value Evidence and Outcomes, GlaxoSmithKline plc, Durham, NC, USACorrespondence: Michael Bogart, US Value Evidence and Outcomes, GlaxoSmithKline plc, 5 Moore Dr, Research Triangle Park, Durham, NC, USA, Tel +19198897413, Email michael.r.bogart@gsk.comPurpose: There is a high prevalence of chronic obstructive pulmonary disease (COPD) in the United States (US). Although guidelines are available for the treatment of COPD, evidence suggests that management of COPD in clinical practice is not always aligned with this guidance. This study aimed to further understand the current use of COPD maintenance medication in the US.Patients and Methods: This study was an analysis of data from the Adelphi Respiratory Disease Specific Programme (DSP™) 2019. Point-in-time data were collected from participating US physicians and their COPD patients. Physicians were either primary care physicians (PCPs) or pulmonologists, with a minimum workload of ≥ 3 COPD patients per month. Patients were aged ≥ 18 years with a physician-confirmed diagnosis of COPD.Results: In total, 171 physicians completed the survey (92 PCPs and 79 pulmonologists). Mean patient age was 66.4 years, 45% were female, with moderate COPD in 49.4% of patients and severe/very severe in 19.3%. Pulmonologists more frequently prescribed dual bronchodilation and triple therapy than PCPs, whereas inhaled corticosteroid/long-acting β2-agonist was more frequently prescribed by PCPs than pulmonologists. For both physician types, the most common reason for prescribing their patients’ current treatment was 24-hour symptom relief. The majority of PCPs (70.1%) and pulmonologists (71.9%) reported referring to COPD guidelines when making treatment decisions.Conclusion: Prescribing patterns for COPD patients were found to differ between PCPs and pulmonologists. Improved physician understanding of how to tailor treatment for each patient, based on current symptoms and exacerbation risk, could help optimize patient care in COPD.Keywords: COPD, inhaled corticosteroids, long-acting β2-agonist, long-acting muscarinic antagonist, maintenance therapy, survey

David Mannino,1 Michael Bogart,2 Guillaume Germain,3 Shirley P Huang,2 Afisi S Ismaila,4,5 François Laliberté,3 Young Jung,3 Sean D MacKnight,3 Marjorie A Stiegler,6,7 Mei Sheng Duh8 1Department of Medicine, University of Kentucky, Lexington, KY, USA; 2GlaxoSmithKline, Value Evidence and Outcomes, Research Triangle Park, NC, USA; 3Groupe d’analyse, Ltée, Montréal, QC, Canada; 4GlaxoSmithKline, Value Evidence and Outcomes, Collegeville, PA, USA; 5Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; 6GlaxoSmithKline, Medical Affairs, Research Triangle Park, NC, USA; 7Department of Anesthesiology and Critical Care, University of North Carolina, Chapel Hill, NC, USA; 8Analysis Group, Boston, MA, USACorrespondence: Michael Bogart, GlaxoSmithKline, Value Evidence and Outcomes, 5 Moore Drive, PO Box 13398, Research Triangle Park, NC, 27709-3398, USA, Tel +1919-889-7413, Email michael.r.bogart@gsk.comPurpose: Triple therapy (TT; inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β2-agonist) is recommended for patients with chronic obstructive pulmonary disease (COPD) at risk of exacerbation, although the optimum timing of TT initiation remains unclear. This study evaluated the impact of prompt versus delayed initiation of single-inhaler TT (fluticasone furoate, umeclidinium, and vilanterol [FF/UMEC/VI]) following a COPD exacerbation.Patients and Methods: This retrospective cohort study used data from the IQVIA PharMetrics® Plus database. Patients initiating FF/UMEC/VI following a COPD exacerbation between September 18, 2017 and September 30, 2019 (exacerbation = index date) were categorized as prompt (within 30 days of index) or delayed (31– 180 days after index) FF/UMEC/VI initiators. Patients were aged ≥ 40 years at index, had ≥ 12 months’ continuous health insurance coverage before index (baseline), and ≥ 6 months’ coverage after index (follow-up). Patients with a COPD exacerbation or claim for FF/UMEC/VI during baseline were excluded. Inverse probability weighting was used to adjust for differences in baseline characteristics between cohorts. Exacerbations (overall, moderate, and severe), healthcare costs, and readmissions were evaluated during follow-up.Results: A total of 1904 patients (prompt: 529; delayed: 1375) were included. After weighting, baseline characteristics were well balanced between cohorts. Patients in the prompt cohort had significantly lower rates per person-year (PPY) of overall (0.98 vs 1.23; rate ratio [RR] [95% CI] = 0.79 [0.65– 0.94], p = 0.004), moderate (0.86 vs 1.03; RR [95% CI] = 0.84 [0.69– 0.99], p = 0.038), and severe (0.11 vs 0.20; RR [95% CI] = 0.57 [0.37– 0.79], p = 0.002) exacerbations, compared with delayed initiators. Mean all-cause and COPD-related healthcare costs were significantly lower among prompt initiators (all-cause: $26,107 vs $32,400 PPY, p = 0.014; COPD-related: $12,694 vs $17,640 PPY, p = 0.002).Conclusion: Prompt initiation of FF/UMEC/VI following a moderate or severe COPD exacerbation was associated with significant reductions in exacerbations and healthcare costs relative to delayed initiation.Keywords: chronic obstructive pulmonary disease, exacerbation, healthcare cost, single-inhaler triple therapy

Barbara P Yawn,1 Barry Make,2 David Mannino,3 Fernando J Martinez,4 Meilan K Han5 1Department of Family and Community Health, University of Minnesota, Minneapolis, MN, USA; 2Pulmonary Sciences and Critical Care Medicine, National Jewish Health, Denver, CO, USA; 3College of Public Health, Department of Preventive Medicine and Environmental Health, University of Kentucky, Lexington, KY, USA; 4Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA; 5Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USACorrespondence: Barbara P Yawn Email byawn47@gmail.com View the original paper by Dr Tamaki and colleagues

Nancy K Leidy,1 Fernando J Martinez,2 Karen G Malley,1 David M Mannino,3 MeiLan K Han,4 Elizabeth D Bacci,5 Randall W Brown,6 Julia F Houfek,7 Wassim W Labaki,4 Barry J Make,8 Catherine A Meldrum,4 Wilson Quezada,9 Stephen Rennard,10 Byron Thomashow,9 Barbara P Yawn11 1Evidera, Patient-Centered Research, Bethesda, MD, USA; 2Weill Cornell Medicine, Joan & Sanford Weill Department of Medicine, New York, NY, USA; 3University of Kentucky, Preventive Medicine & Environmental Health, Lexington, KY, USA; 4University of Michigan, Division of Pulmonary & Critical Care Medicine, Ann Arbor, MI, USA; 5Evidera, Patient-Centered Research, Seattle, WA, USA; 6University of Michigan, Department of Health Behavior & Health Education, School of Public Health, Ann Arbor, MI, USA; 7University of Nebraska Medical Center College of Nursing, Omaha, NE, USA; 8National Jewish Health, Department of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, Denver, CO, USA; 9Columbia University Medical Center, Division of Pulmonary, Allergy, & Critical Care, New York, NY, USA; 10AstraZeneca, IMED Biotech Unit, Cambridge, UK & University of Nebraska Medical Center, Department of Medicine, Omaha, NE, USA; 11University of Minnesota, Department of Family & Community Health, Minneapolis, MN & COPD Foundation, Miami, FL, USA Background: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) 2: 37% vs 5%, p10: 86% vs 57%, p

David M Mannino,1 Emmanuelle M Clerisme-Beaty,2 Joanne Franceschina,2 Naitee Ting,2 Nancy K Leidy3 1Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington, KY, USA; 2Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 3Evidera, Bethesda, MD, USA Background: Little is known about the recovery patterns from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in newly diagnosed or maintenance treatment-naïve patients with COPD. This study describes the course of AECOPD in these patients at the time of treatment for the symptoms of acute respiratory tract infection (RTI). Methods: This study was a secondary analysis of data from a 12-week, randomized clinical trial (TICARI 1) testing the efficacy and safety of once-daily tiotropium 18 µg maintenance therapy versus placebo in newly diagnosed or maintenance treatment-naïve COPD patients with acute RTI symptoms for ≤7 days. Patients received standard care for AECOPD and RTI. Due to under-recruitment, the trial ended early and hence was underpowered to detect treatment differences. Data were pooled and exacerbation recovery patterns examined by using the EXAcerbation of Chronic Pulmonary Disease Tool (EXACT), forced expiratory volume in 1 second, rescue medication use, COPD Assessment Test™, Functional Assessment of Chronic Illness Therapy–Short Form, and Work Productivity and Activity Impairment Questionnaire: Respiratory Symptoms. Results: Of 140 patients, 73.6% had a prior COPD diagnosis without maintenance therapy; 80.0% had moderate-to-severe airflow obstruction. In addition to study drug, 40.0% were prescribed pharmacologic therapy (corticosteroids [34.3%], antibiotics [16.4%], and short-acting β2-adrenergic agonists [5.0%]) within ±7 days of randomization. Over 12 weeks, 78.6% exhibited symptomatic recovery (EXACT score) in a median of 5.0 days. Across all patients, 49.3% recovered without relapse, 29.3% recovered and then relapsed, and 21.4% had persistent symptoms (recovery criteria unmet). Conclusion: A substantial portion of newly diagnosed or maintenance treatment-naïve patients with COPD experience relapse or persistent symptoms following a clinic visit for AECOPD with symptoms of RTI. Whether initiating maintenance therapy could improve outcomes and reduce exacerbation risk requires further study. Keywords: acute respiratory tract infection symptoms, acute exacerbation of chronic obstructive pulmonary disease, AECOPD, COPD Assessment Test™, EXACT, maintenance therapy, pulmonary function, tiotropium

Neil A Accortt,1 James B Chung,2 Machaon Bonafede,3 Brendan L Limone,3 David M Mannino4 1Amgen, Inc., Center for Observational Research, Thousand Oaks, CA, 2Amgen, Inc., US Medical Organization, Thousand Oaks, CA, 3Truven Health Analytics, an IBM Company, Outcomes Research, Cambridge, MA, 4University of Kentucky College of Public Health, Lexington, KY, USA Background: Limited information exists on the impact of tumor necrosis factor inhibition on COPD exacerbations. This retrospective study characterized this impact among COPD patients with underlying autoimmune conditions, exposed to tumor necrosis factor inhibitors (TNFi) and/or non-biologic disease-modifying antirheumatic drugs (DMARDs).Patients and methods: Adult COPD patients with ≥1 diagnosis for rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) before or within 6 months following the index COPD diagnosis were identified from the Truven Health MarketScan® databases. Patients were required to have a second claim for RA, PsO, PsA, AS, or DMARD use (biologic or non-biologic) prior to or up to 6 months following the index date. Incidence of COPD-related hospitalizations and emergency room (ER) visits was evaluated in relation to treatment with TNFi and/or DMARDs and other potential risk factors.Results: The study cohort included 40,687 patients (untreated, 37.7%; non-biologic DMARD, 35.4%; TNFi + non-biologic DMARD, 18%; TNFi, 8.8%). The proportion of patients with a COPD-related hospitalization and the incidence of COPD-related hospitalization (per 100 person-years) were lowest in the TNFi cohort (8.6%; 3.54, 95% confidence interval [CI]: 3.16–3.95) and the TNFi + non-biologic DMARD cohort (8.4%; 2.85, 95% CI: 2.63–3.08). In multivariate models, treatment with TNFi + non-biologic DMARD reduced the risk of COPD-related hospitalization or ER visits by 32% relative to non-biologic DMARDs (hazard ratio: 0.68; 95% CI: 0.61–0.75).Conclusion: In real-world settings, TNFi monotherapy confers similar risk for COPD-related hospitalization or ER visits as a non-biologic DMARD. Decreased risk was found among those treated with both TNFi and a non-biologic DMARD. Keywords: COPD, TNF inhibitor, exacerbation, incidence, biologic DMARD

Roy A Pleasants,1–3 Isaretta L Riley,1–3 David M Mannino4 1Duke Asthma, Allergy, and Airways Center, 2Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, 3Durham VA Medical Center, Durham, NC, 4Division of Pulmonary, Critical Care, and Sleep Medicine, Pulmonary Epidemiology Research Laboratory, University of Kentucky, Lexington, KY, USA Abstract: The global burden of chronic obstructive pulmonary disease (COPD) continues to grow in part due to better outcomes in other major diseases and in part because a substantial portion of the worldwide population continues to be exposed to inhalant toxins. However, a disproportionate burden of COPD occurs in people of low socioeconomic status (SES) due to differences in health behaviors, sociopolitical factors, and social and structural environmental exposures. Tobacco use, occupations with exposure to inhalant toxins, and indoor biomass fuel (BF) exposure are more common in low SES populations. Not only does SES affect the risk of developing COPD and etiologies, it is also associated with worsened COPD health outcomes. Effective interventions in these people are needed to decrease these disparities. Efforts that may help lessen these health inequities in low SES include 1) better surveillance targeting diagnosed and undiagnosed COPD in disadvantaged people, 2) educating the public and those involved in health care provision about the disease, 3) improving access to cost-effective and affordable health care, and 4) markedly increasing the efforts to prevent disease through smoking cessation, minimizing use and exposure to BF, and decreasing occupational exposures. COPD is considered to be one the most preventable major causes of death from a chronic disease in the world; therefore, effective interventions could have a major impact on reducing the global burden of the disease, especially in socioeconomically disadvantaged populations. Keywords: health disparities, COPD, interventions, prevention, management, international, socioeconomic status

Xuehua Ke,1 Jessica Marvel,2 Tzy-Chyi Yu,2 Debra Wertz,1 Caroline Geremakis,1 Liya Wang,1 Judith J Stephenson,1 David M Mannino3 1HealthCore Inc., Wilmington, DE, 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, 3University of Kentucky, Lexington, KY, USA Objective: To evaluate the impact of lung function, measured as forced expiratory volume in 1 second (FEV1) % predicted, on health care resource utilization and costs among patients with COPD in a real-world US managed-care population.Methods: This observational retrospective cohort study utilized administrative claim data augmented with medical record data. The study population consisted of patients with one or more medical claims for pre- and postbronchodilator spirometry during the intake period (July 1, 2012 to June 30, 2013). The index date was the date of the earliest medical claim for pre- and postbronchodilator spirometry. Spirometry results were abstracted from patients’ medical records. Patients were divided into two groups (low FEV1% predicted [

Hana Müllerová,1 Sarah H Landis,1 Zaurbek Aisanov,2 Kourtney J Davis,3 Masakazu Ichinose,4 David M Mannino,5 Joe Maskell,1 Ana M Menezes,6 Thys van der Molen,7 Yeon-Mok Oh,8 Maggie Tabberer,9 MeiLan K Han10 1GSK, Worldwide Epidemiology, Uxbridge, UK; 2Pulmonology Research Institute, Moscow, Russia; 3GSK, Worldwide Epidemiology, Upper Providence, PA, USA; 4Tohoku University Graduate School of Medicine, Sendai, Japan; 5University of Kentucky College of Public Health, Lexington, KY, USA; 6Federal University of Pelotas, Pelotas, Brazil; 7University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 8University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; 9GSK, Value Evidence Outcomes, Uxbridge, UK; 10Division of Pulmonary and Critical Care, University of Michigan, Ann Arbor, MI, USA Background and aims: We used data from the Continuing to Confront COPD International Patient Survey to test the hypothesis that patients with COPD who report less engagement with their disease management are also more likely to report greater impact of the disease. Methods: This was a population-based, cross-sectional survey of 4,343 subjects aged ≥40 years from 12 countries, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. The impact of COPD was measured with COPD Assessment Test, modified Medical Research Council Dyspnea Scale, and hospital admissions and emergency department visits for COPD in the prior year. The 13-item Patient Activation Measure (PAM-13) instrument and the 8-item Morisky Medication Adherence Scale (MMAS-8) were used to measure patient disease engagement and medication adherence, respectively. Results: Twenty-eight percent of subjects reported being either disengaged or struggling with their disease (low engagement: PAM-13 levels 1 and 2), and 35% reported poor adherence (MMAS-8

Sei Won Lee,1 Hyun Kuk Kim,2 Seunghee Baek,3 Ji-Ye Jung,4 Young Sam Kim,4 Jae Seung Lee,1 Sang-Do Lee,1 David M Mannino,5 Yeon-Mok Oh1 1Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 2Department of Pulmonary and Critical Care Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, 3Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 4Division of Pulmonary, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 5Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington, KY, USA Background and objective: Spirometry values may be expressed as T-scores in standard deviation units relative to a reference in a young, normal population as an analogy to the T-score for bone mineral density. This study was performed to develop the spirometry T-score. Methods: T-scores were calculated from lambda-mu-sigma-derived Z-scores using a young, normal age reference. Three outcomes of all-cause death, respiratory death, and COPD death were evaluated in 9,101 US subjects followed for 10 years; an outcome of COPD-related health care utilization (COPD utilization) was evaluated in 1,894 Korean subjects followed for 4 years. Results: The probability of all-cause death appeared to remain nearly zero until -1 of forced expiratory volume in 1 second (FEV1) T-score but increased steeply where FEV1 T-score reached below -2.5. Survival curves for all-cause death, respiratory death, COPD death, and COPD utilization differed significantly among the groups when stratified by FEV1 T-score (P

Yong Liu,1 Roy A Pleasants,2 Janet B Croft,1 Anne G Wheaton,1 Khosrow Heidari,3 Ann M Malarcher,4 Jill A Ohar,5 Monica Kraft,6 David M Mannino,7 Charlie Strange8 1Division of Population Health, Centers for Disease Control and Prevention, Atlanta, GA, 2Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, NC, 3Chronic Disease Epidemiology Office, Department of Health and Environmental Control, South Carolina, SC, 4Office of Smoking and Health, Centers for Disease Control and Prevention, Atlanta, GA, 5Section on Pulmonary, Critical Care, Allergy and Immunologic Disease, Wake Forest University, Winston Salem, NC, 6Department of Medicine, University of Arizona, Phoenix, AZ, 7Division of Pulmonary, Critical Care, and Sleep Medicine, Pulmonary Epidemiology Research Laboratory, University of Kentucky, Lexington, KY, 8Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, SC, USA Background: The purpose of this study was to assess the relationship of smoking duration with respiratory symptoms and history of chronic obstructive pulmonary disease (COPD) in the South Carolina Behavioral Risk Factor Surveillance System survey in 2012.Methods: Data from 4,135 adults aged ≥45 years with a smoking history were analyzed using multivariable logistic regression that accounted for sex, age, race/ethnicity, education, and current smoking status, as well as the complex sampling design.Results: The distribution of smoking duration ranged from 19.2% (1–9 years) to 36.2% (≥30 years). Among 1,454 respondents who had smoked for ≥30 years, 58.3% were current smokers, 25.0% had frequent productive cough, 11.2% had frequent shortness of breath, 16.7% strongly agreed that shortness of breath affected physical activity, and 25.6% had been diagnosed with COPD. Prevalence of COPD and each respiratory symptom was lower among former smokers who quit ≥10 years earlier compared with current smokers. Smoking duration had a linear relationship with COPD (P

Ana M Menezes,1 Sarah H Landis,2 MeiLan K Han,3 Hana Muellerova,2 Zaurbek Aisanov,4 Thys van der Molen,5 Yeon-Mok Oh,6 Masakazu Ichinose,7 David M Mannino,8 Kourtney J Davis9 1Federal University of Pelotas, Pelotas, Brazil; 2Worldwide Epidemiology, GlaxoSmithKline, Uxbridge, UK; 3Division of Pulmonary and Critical Care, University of Michigan, Ann Arbor, MI, USA; 4Pulmonology Research Institute, Moscow, Russia; 5University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 6University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; 7Tohoku University Graduate School of Medicine, Sendai, Japan; 8University of Kentucky College of Public Health, Lexington, KY, USA; 9Worldwide Epidemiology, GlaxoSmithKline, Wavre, Belgium Purpose: Using data from the Continuing to Confront COPD International Physician and Patient Surveys, this paper describes physicians’ attitudes and beliefs regarding chronic obstructive pulmonary disease (COPD) prognosis, and compares physician and patient perceptions with respect to COPD. Methods: In 12 countries worldwide, 4,343 patients with COPD were identified through systematic screening of population samples, and 1,307 physicians who regularly saw patients with COPD were sampled from in-country professional databases. Both patients and physicians completed surveys about their COPD knowledge, beliefs, and perceptions; physicians answered further questions about diagnostic methods and treatment choices for COPD. Results: Most physicians (79%) responded that the long-term health outlook for patients with COPD has improved over the past decade, largely attributed to the introduction of better medications. However, patient access to medication remains an issue in many countries, and some physicians (39%) and patients (46%) agreed/strongly agreed with the statement “there are no truly effective treatments for COPD”. There was strong concordance between physicians and patients regarding COPD management practices, including the use of spirometry (86% of physicians and 76% of patients reporting they used/had undergone a spirometry test) and smoking cessation counseling (76% of physicians reported they counseled their smoking patients at every clinic visit, and 71% of smoking patients stated that they had received counseling in the past year). However, the groups differed in their perception about the role of smoking in COPD, with 78% of physicians versus 38% of patients strongly agreeing with the statement “smoking is the cause of most cases of COPD”. Conclusion: The Continuing to Confront COPD International Surveys demonstrate that while physicians and patients largely agreed about COPD management practices and the need for more effective treatments for COPD, a gap exists about the causal role of smoking in COPD. Keywords: chronic obstructive pulmonary disease, physician survey, patient survey, beliefs, perceptions

Kourtney J Davis,1 Sarah H Landis,2 Yeon-Mok Oh,3 David M Mannino,4 MeiLan K Han,5 Thys van der Molen,6 Zaurbek Aisanov,7 Ana M Menezes,8 Masakazu Ichinose,9 Hana Muellerova11Worldwide Epidemiology, GlaxoSmithKline, Wavre, Belgium; 2Worldwide Epidemiology, GlaxoSmithKline, Uxbridge, UK; 3University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; 4University of Kentucky College of Public Health, Lexington, KY, USA; 5Division of Pulmonary and Critical Care, University of Michigan, Ann Arbor, MI, USA; 6University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 7Pulmonology Research Institute, Moscow, Russia; 8Federal University of Pelotas, Pelotas, Brazil; 9Tohoku University Graduate School of Medicine, Sendai, JapanAim: Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.Materials and methods: Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face. Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.Results: Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P

Shambhu Aryal,1 Enrique Diaz-Guzman,2 David M Mannino3 1Division of Pulmonary, Allergy and Critical Care Medicine, Duke University, Durham, NC, 2Division of Pulmonary, Allergy and Critical Care, University of Alabama, Birmingham, AL, 3Department of Preventive Medicine and Environmental Health, University of Kentucky, Lexington, KY, USA Abstract: Chronic obstructive pulmonary disease (COPD), one of the most common chronic diseases and a leading cause of death, has historically been considered a disease of men. However, there has been a rapid increase in the prevalence, morbidity, and mortality of COPD in women over the last two decades. This has largely been attributed to historical increases in tobacco consumption among women. But the influence of sex on COPD is complex and involves several other factors, including differential susceptibility to the effects of tobacco, anatomic, hormonal, and behavioral differences, and differential response to therapy. Interestingly, nonsmokers with COPD are more likely to be women. In addition, women with COPD are more likely to have a chronic bronchitis phenotype, suffer from less cardiovascular comorbidity, have more concomitant depression and osteoporosis, and have a better outcome with acute exacerbations. Women historically have had lower mortality with COPD, but this is changing as well. There are also differences in how men and women respond to different therapies. Despite the changing face of COPD, care providers continue to harbor a sex bias, leading to underdiagnosis and delayed diagnosis of COPD in women. In this review, we present the current knowledge on the influence of sex on COPD risk factors, epidemiology, diagnosis, comorbidities, treatment, and outcomes, and how this knowledge may be applied to improve clinical practices and advance research. Keywords: chronic obstructive lung disease, sex, smoking, comorbidity, sex bias

Sarah H Landis,1 Hana Muellerova,1 David M Mannino,2 Ana M Menezes,3 MeiLan K Han,4 Thys van der Molen,5 Masakazu Ichinose,6 Zaurbek Aisanov,7 Yeon-Mok Oh,8 Kourtney J Davis,9 1Worldwide Epidemiology, GlaxoSmithKline, Uxbridge, UK; 2University of Kentucky College of Public Health, Lexington, KY, USA; 3Federal University of Pelotas, Pelotas, Brazil; 4Division of Pulmonary and Critical Care, University of Michigan, Ann Arbor, MI, USA; 5University Medical Center Groningen, Groningen, Netherlands; 6Tohoku University Graduate School of Medicine, Sendai, Japan; 7Pulmonology Research Institute, Moscow, Russia; 8University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; 9Worldwide Epidemiology, GlaxoSmithKline, Wavre, Belgium Purpose: The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999–2000. Materials and methods: Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples. Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments. Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis. The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale. Results: Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey. COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%–9%. In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%–14%) than among women (range 5%–11%). A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries. Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment. Conclusion: This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey. A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. Keywords: chronic obstructive pulmonary disease, patient perspective, prevalence, patient-reported outcomes

Deepa Valvi1, David M Mannino1,2, Hana Müllerova3, Ruth Tal-Singer41Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington, KY, USA; 2Department of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky College of Medicine, Lexington, KY, USA; 3GlaxoSmithKline Research and Development, Worldwide Epidemiology, Stockley Park, Middlesex, UK; 4GlaxoSmithKline Research and Development, Respiratory Therapy Area Unit, King of Prussia, PA, USABackground: Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD).Methods: We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations.Results: Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period. The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels >393.0 mg/dL. Subjects with Stage 3 or 4 COPD were more likely to have a fibrinogen level >393.0 mg/dL (odds ratio 2.28, 95% confidence interval [CI]: 1.79–2.95). In the longitudinal adjusted models, fibrinogen levels >393 mg/dL predicted mortality (hazards ratio 1.54, 95% CI: 1.39–1.70), COPD-related hospitalization (hazards ratio 1.45, 95% CI: 1.27–1.67), and incident Stage 2 COPD (odds ratio 1.36, 95% CI: 1.07–1.74). Similar findings were seen with continuous fibrinogen levels.Conclusion: In the Atherosclerosis Risk in Communities/Cardiovascular Health Studies cohort data, higher fibrinogen levels are predictors of mortality, COPD-related hospitalizations, and incident Stage 2 COPD.Keywords: COPD, fibrinogen, epidemiology, mortality, hospitalization

Müllerová H, Landis SH, Aisanov Z, et al. Int J Chron Obstruct Pulmon Dis. 2016;11:881–890.On page 882, right column, second paragraph, the sentence “The primary hypotheses were addressed using the PAM-13,2 and Morisky Medication Adherence Scale (MMAS)-8.18 should have read “The primary hypotheses were addressed using the PAM-13,2 and Morisky Medication Adherence Scale (MMAS)-8.18,40,41On page 882, right column, last paragraph, the sentence “Adherence is classified as low (score 1–5), medium (score 6–7), or high (score 8) according to the overall score.” should read “Adherence is classified as low (score ,6), medium (score 6 to ,8), or high (score 8) according to the overall score.”On page 886, Table 3, the copyright statement “Use of the ©MMAS is protected by US copyright laws. Permission for use is required. A license agreement is available from: Donald E Morisky, ScD, ScM, MSPH, Professor, Department of Community Health Sciences, UCLA School of Public Health, 650 Charles E. Young Drive South, Los Angeles, CA 90095-1772.18,40,41” was not included in the Note section.Read the original article

Barbara P Yawn1, Douglas W Mapel2, David M Mannino3, Fernando J Martinez4, James F Donohue5, Nicola A Hanania6, Mark Kosinski7, Regina Rendas-Baum7, Matthew Mintz8, Steven Samuels9, Anand A Dalal10, On behalf of the Lung Function Questionnaire Working Group*1Olmsted Medical Center, Department of Research, Rochester, MN, USA; 2Lovelace Clinic Foundation, Albuquerque, NM, USA; 3University of Kentucky School of Medicine, Lexington, KT, USA; 4University of Michigan Health System, Ann Arbor, MI, USA; 5University of North Carolina School of Medicine, Chapel Hill, NC, USA; 6Baylor College of Medicine, Houston, TX, USA; 7QualityMetric, Inc., Lincoln, RI, USA; 8George Washington University School of Medicine, Washington, DC, USA; 9Indiana Internal Medicine Consultants, Greenwood, IN, USA; 10GlaxosmithKline, Research Triangle Park, NC, USA; *The Lung Function Questionnaire Working Group includes Barbara P Yawn, Douglas W Mapel, David M Mannino, Fernando Martinez, James Donohue, Nicola Hanania, Matthew Mintz, and Steven SamuelsObjective: To describe the item-selection and item-reduction for the Lung Function Questionnaire (LFQ), being developed to help clinicians identify patients appropriate for diagnostic evaluation for chronic obstructive pulmonary disease (COPD) using spirometry.Methods: Item selection and reduction were based on information from 387 ≥40-year-old respondents to the third National Health and Nutrition Examination Survey who had self-reported chronic bronchitis. Item reduction involved stepwise logistic regression. The accuracy of the final subset of items for identifying individuals with airflow obstruction (forced expiratory volume in one second/forced vital capacity

Robert M Shavelle1, David R Paculdo1, Scott J Kush1, David M Mannino2, David J Strauss11Life Expectancy Project, San Francisco, CA, USA; 2Pulmonary Epidemiology Research Laboratory, University of Kentucky School of Medicine, Division of Pulmonary and Critical Care Medicine, Lexington, KY, USARationale: Previous studies have demonstrated that chronic obstructive pulmonary disease (COPD) causes increased mortality in the general population. But life expectancy and the years of life lost have not been reported.Objectives: To quantify mortality, examine how it varies with age, sex, and other risk factors, and determine how life expectancy is affected.Methods: We constructed mortality models using the Third National Health and Nutrition Examination Survey, adjusting for age, sex, race, and major medical conditions. We used these to compute life expectancy and the years of life lost. Measurements and main results: Pulmonary function testing classifi ed patients as having Global Initiative on Obstructive Lung Disease (GOLD) stage 0, 1, 2, 3 or 4 COPD or restriction. COPD is associated with only a modest reduction in life expectancy for never smokers, but with a very large reduction for current and former smokers. At age 65, the reductions in male life expectancy for stage 1, stage 2, and stages 3 or 4 disease in current smokers are 0.3 years, 2.2 years, and 5.8 years. These are in addition to the 3.5 years lost due to smoking. In former smokers the reductions are 1.4 years and 5.6 years for stage 2 and stages 3 or 4 disease, and in never smokers they are 0.7 and 1.3 years.Conclusions: Persons with COPD have an increased risk of mortality compared to those who do not, with consequent reduction in life expectancy. The effect is most marked in current smokers, and this is further reason for smokers to quit.Keywords: survival, mortality, longevity, COPD