BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. METHODS: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. MAIN OUTCOMES: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. FINDINGS: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. CONCLUSIONS: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed.

2nd Department of Internal Medicine Nara Medical University Nara Japan

Academic Respiratory Unit University of Bristol North Bristol Lung Centre Southmead Hospital Bristol United Kingdom

Academic Unit of Sleep and Ventilation National Heart and Lung Institute Imperial College London NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton United Kingdom; Harefield NHS Foundation Trust and Imperial College London United Kingdom

Adelphi Real World Bollington United Kingdom

Arbeitsbereich Ambulante Pneumologie Charité Universitätsmedizin Berlin Berlin Germany

Australian Respiratory and Sleep Medicine Institute Flinders Medical Center Adelaide Australia

Biomax Informatics AG Planegg Germany

Center for Exercise and Rehabilitation Science NIHR Leicester Respiratory Biomedical Research Unit University Hospitals of Leicester NHS Trust Leicester United Kingdom

Central Surgery Surbiton Health Centre Surbiton Surrey United Kingdom

Department of Chest Diseases Faculty of Medicine Selcuk University Konya Turkey

Department of Medicine McMaster University Hamilton Ontario Canada

Department of Medicine Queen's University and Kingston General Hospital Kingston ON Canada

Department of Pneumology Faculty of Medicine in Hradec Kralove Charles University Prague and University Hospital Hradec Kralove Hradec Kralove Czech Republic

Department of Primary Care Groningen Research Institute for Asthma and COPD GRIAC University Medical Centre Groningen University of Groningen Groningen The Netherlands

Department of Primary Care Groningen Research Institute for Asthma and COPD GRIAC University Medical Centre Groningen University of Groningen Groningen The Netherlands; Agia Barbara Health Care Center Heraklion Crete Greece

Department of Psychology TOBB University of Economics and Technology Ankara Turkey

Department of Pulmonary and Critical Care Medicine Clinical Research Center for Chronic Obstructive Airway Diseases Asan Medical Center University of Ulsan College of Medicine Seoul South Korea

Department of Pulmonology Yokohama City University Graduate School of Medicine Yokohama Japan

Department of Research and Education CIRO Horn The Netherlands

Department of Research and Education CIRO Horn The Netherlands; Department of Respiratory Medicine Maastricht University Medical Center Maastricht The Netherlands

Department of Research and Education CIRO Horn The Netherlands; REVAL Rehabilitation Research Center BIOMED Biomedical Research Institute Faculty of Medicine and Life Sciences Hasselt University Diepenbeek Belgium; Department of Respiratory Medicine Maastricht University Medical Centre NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht The Netherlands

Department of Respiratory Medicine Hospital Son Espases IdISPa CIBERES Islas Baleares Spain

Department of Respiratory Medicine Hvidovre Hospital University of Copenhagen Denmark

Department of Respiratory Medicine Osaka Police Hospital Osaka Japan

Department of Respiratory Medicine Osaka Police Hospital Osaka Japan; Department of Respiratory Medicine Allergy and Rheumatic Diseases Osaka University Graduate School of Medicine Suita Osaka Japan

Department of Respiratory Medicine Shanghai General Hospital Shanghai Jiao Tong University School of Medicine China

Department of Thoracic Medicine University Hospital of Heraklion Medical School University of Crete Crete Greece

Division of Pulmonary Critical Care and Allergy Department of Internal Medicine Faculty of Medicine Chiang Mai University Chiang Mai Thailand

Division of Pulmonology Department of Internal Medicine Chonnam National University Hospital Donggu Gwangju South Korea

Federal University of Ceará Brazil Fortaleza Brazil

GlaxoSmithKline King of Prussia PA

Hospital Clínico Universidad de Chile Región Metropolitana Chile

Hospital General Universitario Gregorio Marañón Madrid Pulmonary Department Madrid Spain

Hospital General Universitario Gregorio Marañon Pulmonary Department Madrid Spain

Hospital Universitario Miguel Servet IISAragon CIBER Enfermedades Respiratorias Zaragoza Spain

Institute and Output Clinic for Occupational and Environmental Medicine Munich Germany

Institute for Biostatistics Hannover Medical School Hannover Germany

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno Czech Republic

Institute of Pneumology Marius Nasta Bucharest Romania

Instituto de Investigación Hospital Universitario de la Princesa IISP Universidad Autónoma de Madrid Madrid Spain

Intensive Care Unit G Gennimats General Hospital Thessaloniki Greece; Respiratory Failure Unit Aristotle University of Thessaloniki Greece

Internal Medicine Department Medical Faculty Kurdistan University of Medical Sciences Sanandaj Iran

King's College London Florence Nightingale Faculty of Nursing and Midwifery London United Kingdom

NIHR Respiratory Biomedical Research Unit at Royal Brompton and Harefield NHS Foundation Trust Imperial College London London United Kingdom

NIHR Respiratory Biomedical Research Unit Royal Brompton and Harefield NHS Foundation Trust and Imperial College United Kingdom

Observational and Pragmatic Research Institute Singapore; University of Aberdeen Aberdeen United Kingdom

Pneumology Department Hospital Universitari Vall d'Hebron CIBER de Enfermedades Respiratorias Barcelona Spain

Pneumology Service Instituto Nacional de Silicosis Hospital Universitario Central de Asturias Oviedo Spain

Pulmonary Department and Research Unit Hospital Universitario NS La Candelaria Santa Cruz de Tenerife Spain

Pulmonary Department Clinica Universidad de Navarra Pamplona Spain

Pulmonary Research Institute at Lung Clinic Grosshansdorf German Center for Lung Research Grosshansdorf Germany

Pulmonology Department of Centro Hospitalar Vila Nova de Gaia Espinho EPE Portugal

Respiratory Franchise Medical GlaxoSmithKline London United Kingdom

Respiratory Institute Hospital Clinic University of Barcelona and CIBERES Spain

Servicio de Neumología Instituto de Investigación Biomédica de Vigo IBIV Complexo Hospitalario de Vigo Vigo Pontevedra España

The Hillingdon Hospital NHS Foundation Trust United Kingdom; NIHR Respiratory Biomedical Research Unit Royal Brompton and Harefield NHS Foundation Trust and Imperial College United Kingdom

Unidad Médico Quirúrgica de Enfermedades Respiratorias Instituto de Biomedicina de Sevilla IBiS Hospital Universitario Virgen del Rocio Universidad de Sevilla Sevilla Spain; CIBER de Enfermedades Respiratorias CIBERES Instituto de Salud Carlos 3 Madrid Spain

University Clinic of Medicine Cantonal Hospital Baselland Liestal Switzerland

University Hospital Osijek; Department of Internal Medicine; Faculty of Medicine University J J Strossmayer Osijek Osijek Croatia

University of Fortaleza UNIFOR Fortaleza Brazil

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