1.Global Initiative for ChronicObstructiveCOPYL ungRIGHD isease TEDMATERIAL ,DONOTALTER OR RE PROD CEU .GLOBAL STRATEGY FOR THE DIAGNOSIS,MANAGEMENT, AND PREVENTION OFCHRONIC OBSTRUCTIVE PULMONARY DISEASE UPDATED 2008

2. GLOBAL INITIATIVE FOR CO CHRONIC OBSTRUCTIVE LUNG DISEASE PY GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, ANDRIPREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASEGH (UPDATED 2008) TED MA TE RI AL,DO NO TA LT ER OR RE PROD U CE . 2008 Medical Communications Resources, Inc i 3. Global Strategy for the Diagnosis, Management, and Prevention ofChronic Obstructive Pulmonary Disease (UPDATED 2007)GOLD EXECUTIVE COMMITTEE*Observers: Alvaro Cruz, MDRoberto Rodriguez Roisin, MD, Chair(Representing World Health Organization)University of BarcelonaGeneva, SwitzerlandBarcelona, SpainCO Mark Woodhead, MDKlaus F. Rabe MD, PhD, Vice-Chair(Representing European Respiratory Society)PYLeiden University Medical Center Manchester Royal InfirmaryLeiden, The NetherlandsManchester England, UK RIAntonio Anzueto, MDGOLD SCIENCE COMMITTEE* GH(Representing American Thoracic Society)University of Texas Health Science CenterPeter Calverley, MD, ChairTESan Antonio, Texas, USAUniversity Hospital Aintree Liverpool, England, UK DJean Bourbeau, MDMcGill University Health CentreA. G. Agusti, MDMAMontreal, Quebec, Canada Hospital University Son Dureta Palma de Mallorca, SpainTEPeter Calverley, MDUniversity Hospital AintreeAntonio Anzueto, MDRILiverpool, England, UK University of Texas Health Science CenterAL San Antonio, Texas, USAAlejandro Casas, MD ,(Representing Latin American Thoracic Society) Peter J. Barnes, MD DOFundacin Neumolgica Colombiana National Heart and Lung InstituteBogot, Colombia SALondon, England, UKNOTeresita S. deGuia, MD Marc Decramer, MDPhilippine Heart CenterUniversity HospitalsTAQuezon City, Philippines Leuven, BelgiumYoshinosuke Fukuchi, MDYoshinosuke Fukuchi, MDLT(Representing Asian Pacific Society for Respirology) Tokyo, JapanERTokyo, Japan Paul Jones, MDDavid S.C. Hui, MD St Georges Hospital Medical School ORThe Chinese University of Hong London, England, UKHong Kong, ROC Fernando Martinez, MDREChristine Jenkins, MDUniversity of Michigan School of MedicineWoolcock Institute of Medical Research Ann Arbor, Michigan, USAPRSydney NSW, Australia Klaus F. Rabe MD, PhD, Vice-Chair ODAli Kocabas, MDLeiden University Medical CenterCukurova University School of Medicine Leiden, The NetherlandsUAdana, Turkey Roberto Rodriguez Roisin, MD CEFernando Martinez, MDUniversity of BarcelonaUniversity of Michigan School of MedicineBarcelona, Spain .Ann Arbor, Michigan, USA Jorgen Vestbo, MDChris van Weel, MD Hvidovre University Hospital(Representing the World Organization of Family Doctors)Hvidore, DenmarkUniversity of NijmegenNijmegen, The NetherlandsJan Zielinski, MD Institute of TB and Lung DiseasesJorgen Vestbo, MDWarsaw, PolandHvidovre University HospitalHvidore, Denmark*Disclosure forms for GOLD Committees are posted on the GOLD Website, www.goldcopd.orgii 4. PREFACEChronic Obstructive Pulmonary Disease (COPD) remains In spite of the achievements since the GOLD report wasa major public health problem. It is the fourth leadingoriginally published, considerable additional work isCOcause of chronic morbidity and mortality in the United ahead of all of us if we are to control this major publicStates, and is projected to rank fifth in 2020 in burden health problem. The GOLD initiative will continue toPYof disease caused worldwide, according to a studybring COPD to the attention of governments, publicpublished by the World Bank/World Health Organization. health officials, health care workers, and the generalRIFurthermore, although COPD has received increasing public, but a concerted effort by all involved in healthGHattention from the medical community in recent years, it care will be necessary.is still relatively unknown or ignored by the public as well TEas public health and government officials. I would like to acknowledge the work of the members ofD the GOLD Science Committee who prepared this revisedIn 1998, in an effort to bring more attention to COPD, its report. We look forward to our continued work withMAmanagement, and its prevention, a committed group of interested organizations and the GOLD National Leadersscientists encouraged the US National Heart, Lung, andTE to meet the goals of this initiative.Blood Institute and the World Health Organization to formRIthe Global Initiative for Chronic Obstructive Lung Disease We are most appreciative of the unrestricted educationalAL(GOLD). Among the important objectives of GOLD are togrants from Almirall, AstraZeneca, Boehringer Ingelheim,increase awareness of COPD and to help the millions of Chiesi, Dey, Forest Laboratories, GlaxoSmithKline, ,people who suffer from this disease and die prematurelyMitsubishi Tanabe Pharma, Novartis, Nycomed, Pfizer,DOfrom it or its complications.and Schering-Plough that enabled development of this report.NOThe first step in the GOLD program was to prepare aconsensus report, Global Strategy for the Diagnosis,TAManagement, and Prevention of COPD, which waspublished in 2001. The report was written by an ExpertLTPanel, which was chaired by Professor Romain PauwelsERof Belgium and included a distinguished group of healthRoberto Rodriguez Roisin, MDprofessionals from the fields of respiratory medicine, Chair, GOLD Executive Committee, 2007 - 2008ORepidemiology, socioeconomics, public health, and healthProfessor of Medicineeducation. The Expert Panel reviewed existing COPD Hospital Clnic, Universitat de BarcelonaREguidelines and new information on pathogenic mechanismsVillarroel, Barcelona, Spainof COPD, bringing all of this material together in thePRconsensus document. The present, newly revised documentfollows the same format as the original consensus report, ODbut has been updated to reflect the many publications onCOPD that have appeared since 2001.UCESince the original consensus report was published in .2001, a network of international experts known as GOLDNational Leaders has been formed to implement thereports recommendations. Many of these experts haveinitiated investigations of the causes and prevalence ofCOPD in their countries, and developed innovativeapproaches for the dissemination and implementationof COPD management guidelines. We appreciate theenormous amount of work the GOLD National Leadershave done on behalf of their patients with COPD. iii 5. TABLE OF CONTENTSMethodology and Summary of New 4. Pathology, Pathogenesis, and Pathophysiology . .23Recommendations: 2007 Update . . . . . . . . . . . . . . . .viiKey Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xiiIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24CO Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .241. Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25PYKey Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 Inflammatory Cells . . . . . . . . . . . . . . . . . . . . . . . . . .25 RIDefinition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 Inflammatory Mediators . . . . . . . . . . . . . . . . . . . . . .25Oxidative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . .25 GH Airflow limitation in COPD . . . . . . . . . . . . . . . . . . . . . .2 COPD and Comorbidities . . . . . . . . . . . . . . . . . . . . . .3Protease-Antiprotease Imbalance . . . . . . . . . . . . . .26TENatural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3Differences in Inflammation Between COPD Spirometric Classification of Severity . . . . . . . . . . . . .3 and Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26 D Stages of COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4 Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26MAScope of the Report . . . . . . . . . . . . . . . . . . . . . . . . . . . .5Airflow Limitation and Air Trapping . . . . . . . . . . . . . .26 Asthma and COPD . . . . . . . . . . . . . . . . . . . . . . . . . . .5 Gas Exchange Abnormalities . . . . . . . . . . . . . . . . . .26TE Pulmonary Tuberculosis and COPD . . . . . . . . . . . . . .5 Mucus Hypersecretion . . . . . . . . . . . . . . . . . . . . . . .26RIReferences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5 Pulmonary Hypertension . . . . . . . . . . . . . . . . . . . . .28Systemic Features . . . . . . . . . . . . . . . . . . . . . . . . . .28AL2. Burden of COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . .7 Exacerbations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28 ,Key Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28DOIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .85. Management of COPD . . . . . . . . . . . . . . . . . . . . . .31NOPrevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .32 Morbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9TA Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10 Component 1: Assess and Monitor Disease . . . . . .33 Key Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33LTEconomic and Social Burden of COPD . . . . . . . . . . . .11 Economic Burden . . . . . . . . . . . . . . . . . . . . . . . . . . .11 Initial Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33ER Social Burden . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12Assessment of Symptoms . . . . . . . . . . . . . . . . . . . .33References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12 Dyspnea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .34OR Cough . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .343. Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15Sputum production . . . . . . . . . . . . . . . . . . . . . . . .34REKey Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16 Wheezing and chest tightness . . . . . . . . . . . . . . .34Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16 Additional features in severe disease . . . . . . . . . .35PRRisk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16 Medical History . . . . . . . . . . . . . . . . . . . . . . . . . . . . .35 OD Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16 Physical Examination . . . . . . . . . . . . . . . . . . . . . . . .35 Inhalational Exposures . . . . . . . . . . . . . . . . . . . . . . .17Inspection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .35U Tobacco smoke . . . . . . . . . . . . . . . . . . . . . . . . . . .17 Palpation and percussion . . . . . . . . . . . . . . . . . . .35CE Occupational dusts and chemicals . . . . . . . . . . . .17Auscultation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .35 Indoor air pollution . . . . . . . . . . . . . . . . . . . . . . . . .17Measurement of Airflow Limitation . . . . . . . . . . . . . .36. Outdoor air pollution . . . . . . . . . . . . . . . . . . . . . . .18Assessment of COPD Severity . . . . . . . . . . . . . . . . .37 Lung Growth and Development . . . . . . . . . . . . . . . .18Additional Investigations . . . . . . . . . . . . . . . . . . . . . .37 Oxidative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . .18Bronchodilator reversibility testing . . . . . . . . . . . . .37 Gender . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18Chest X-ray . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38 Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18Arterial blood gas measurement . . . . . . . . . . . . . .38 Socioeconomic Status . . . . . . . . . . . . . . . . . . . . . . .18Alpha-1 antitrypsin deficiency screening . . . . . . . .38 Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18 Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . .38 Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19Ongoing Monitoring and Assessment . . . . . . . . . . . . . .39References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19iv 6. Monitor Disease Progression and Pharmacologic Therapy by Disease Severity . . . . . .54Development of Complications . . . . . . . . . . . . . . . .40 Other Pharmacologic Treatments . . . . . . . . . . . . . . .55 Pulmonary function . . . . . . . . . . . . . . . . . . . . . .40 Vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55 Arterial blood gas measurement . . . . . . . . . . . .40Alpha-1 antitrypsin augmentation therapy . . . .55 Assessment of pulmonary hemodynamics . . . .40Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55Diagnosis of right heart failure or cor pulmonale . .40 Mucolytic agents . . . . . . . . . . . . . . . . . . . . . . . .55 CT and ventilation-perfusion scanning . . . . . . .40 Antioxidant agents . . . . . . . . . . . . . . . . . . . . . . .55 CO Hematocrit . . . . . . . . . . . . . . . . . . . . . . . . . . . . .40 Immunoregulators . . . . . . . . . . . . . . . . . . . . . . .55 Respiratory muscle function . . . . . . . . . . . . . . .40 Antitussives . . . . . . . . . . . . . . . . . . . . . . . . . . . .55 PY Sleep studies . . . . . . . . . . . . . . . . . . . . . . . . . .40Vasodilators . . . . . . . . . . . . . . . . . . . . . . . . . . . .55RI Exercise testing . . . . . . . . . . . . . . . . . . . . . . . . .40 Narcotics (morphine) . . . . . . . . . . . . . . . . . . . . .55 Monitor Pharmacotherapy andOthers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .56GH Other Medical Treatment . . . . . . . . . . . . . . . . . . .40 Non-Pharmacologic Treatment . . . . . . . . . . . . . . . . . . .56 TE Monitor Exacerbation History . . . . . . . . . . . . . . . . .41Rehabilitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .56 Monitor Comorbidities . . . . . . . . . . . . . . . . . . . . . . .41Patient selection and program design . . . . . . .56DComponents of pulmonary rehabilitation MAComponent 2: Reduce Risk Factors . . . . . . . . . . . . .42programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . .57Key Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42 Assessment and follow-up . . . . . . . . . . . . . . . .58 TEIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42Economic cost of rehabilitation programs . . . . .58 RITobacco Smoke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42Oxygen Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . .58 Smoking Prevention . . . . . . . . . . . . . . . . . . . . . . . . .42 Cost considerations . . . . . . . . . . . . . . . . . . . . .59 AL Smoking Cessation . . . . . . . . . . . . . . . . . . . . . . . . . .43Oxygen use in air travel . . . . . . . . . . . . . . . . . .59, The role of health care providers inVentilatory Support . . . . . . . . . . . . . . . . . . . . . . . . . .60DO smoking cessation . . . . . . . . . . . . . . . . . . . . .43 Surgical Treatments . . . . . . . . . . . . . . . . . . . . . . . . .60 Counseling . . . . . . . . . . . . . . . . . . . . . . . . . . . .44 Bullectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . .60NO Pharmacotherapy . . . . . . . . . . . . . . . . . . . . . . .45Lung volume reduction surgery . . . . . . . . . . . .60Occupational Exposures . . . . . . . . . . . . . . . . . . . . . . . .45Lung transplantation . . . . . . . . . . . . . . . . . . . . .60TAIndoor/Outdoor Air Pollution . . . . . . . . . . . . . . . . . . . . .46 Special Considerations . . . . . . . . . . . . . . . . . . . . . . .61 Regulation of Air Quality . . . . . . . . . . . . . . . . . . . . . .46Surgery in COPD . . . . . . . . . . . . . . . . . . . . . . .61LT Steps for Health Care Providers/Patients . . . . . . . . .46ER Component 4: Manage Exacerbations . . . . . . . . . . .62Component 3: Manage Stable COPD . . . . . . . . . . . .47Key Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .62 ORKey Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .62Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47 Diagnosis and Assessment of Severity . . . . . . . . . . . . .62REEducation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47 Medical History . . . . . . . . . . . . . . . . . . . . . . . . . . . . .62 Goals and Educational Strategies . . . . . . . . . . . . . .48 Assessment of Severity . . . . . . . . . . . . . . . . . . . . . .63PR Components of an Education Program . . . . . . . . . .48 Spirometry and PEF . . . . . . . . . . . . . . . . . . . . .63 OD Cost Effectiveness of EducationPulse oximetry/Arterial blood gases . . . . . . . . .63Programs for COPD Patients . . . . . . . . . . . . . . .49Chest X-ray and ECG . . . . . . . . . . . . . . . . . . . .63UPharmacologic Treatment . . . . . . . . . . . . . . . . . . . . . . .49 Other laboratory tests . . . . . . . . . . . . . . . . . . . .63CE Overview of the Medications . . . . . . . . . . . . . . . . . .49 Differential Diagnoses . . . . . . . . . . . . . . . . . . . . . . .63 Bronchodilators . . . . . . . . . . . . . . . . . . . . . . . . . . . . .50 Home Management . . . . . . . . . . . . . . . . . . . . . . . . . . . .64. 2-agonists . . . . . . . . . . . . . . . . . . . . . . . . . . . .51Bronchodilator Therapy . . . . . . . . . . . . . . . . . . . . . .64 Anticholinergics . . . . . . . . . . . . . . . . . . . . . . . . .52 Glucocorticosteroids . . . . . . . . . . . . . . . . . . . . . . . . .64 Methylxanthines . . . . . . . . . . . . . . . . . . . . . . . .52Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .64 Combination bronchodilator therapy . . . . . . . . .53Hospital Management . . . . . . . . . . . . . . . . . . . . . . . . . .64 Glucocorticosteroids . . . . . . . . . . . . . . . . . . . . . . . . .53 Emergency Department or Hospital . . . . . . . . . . . . .65 Oral glucocorticosteroids: short-term . . . . . . . .53Controlled oxygen therapy . . . . . . . . . . . . . . . .65 Oral glucocorticosteroids: long-term . . . . . . . . .53 Bronchodilator therapy . . . . . . . . . . . . . . . . . . .65 Inhaled glucocorticosteroids . . . . . . . . . . . . . . .53 Glucocorticosteroids . . . . . . . . . . . . . . . . . . . . .66 v 7. Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . .66 Respiratory Stimulants . . . . . . . . . . . . . . . . . . .67 Ventilatory support . . . . . . . . . . . . . . . . . . . . . .67 Other measures . . . . . . . . . . . . . . . . . . . . . . . .69Hospital Discharge and Follow-Up . . . . . . . . . . . . . .69References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .69 CO6. Translating Guideline Recommendations to the Context of (Primary) Care . . . . . . . . . . . . . . . . . . .85 PYKey Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86RIIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86GH Respiratory Symptoms . . . . . . . . . . . . . . . . . . . . . . .86 TE Spirometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86Comorbidities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .87DReducing Exposure to Risk Factors . . . . . . . . . . . . . . .87 MAImplementation of COPD Guidelines . . . . . . . . . . . . . .87References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .88 TE RI AL, DONOTALTERORREPR ODCEU. vi 8. METHODOLOGY AND SUMMARY OF NEW RECOMMENDATIONS GLOBAL STRATEGY FORDIAGNOSIS, MANAGEMENT AND PREVENTION OFCOPD: 2008 UPDATE CO PYRIWhen the Global Initiative for Chronic Obstructive Lungoffered the opportunity to provide an opinion on anyDisease (GOLD) program was initiated in 1998, a goal abstract. Members evaluated the abstract or, up toGHwas to produce recommendations for management of her/his judgment, the full publication, by answering spe- TECOPD based on the best scientific information available. cific written questions from a short questionnaire, and toThe first report, Global Strategy for Diagnosis, indicate if the scientific data presented impacted on rec-DManagement and Prevention of COPD was issued inommendations in the GOLD report. If so, the member MA2001 and in 2006 a complete revision was preparedwas asked to specifically identify modifications thatbased on research published through June, 2006. Theseshould be made. The entire GOLD Science Committee TEreports, and their companion documents, have beenmet on a regular basis to discuss each individual publica-widely distributed and translated into many languagestion that was indicated to have an impact on COPD man- RIand can be found on the GOLD website agement and prevention by at least 1 member of the AL(www.goldcopd.org).Committee, and to reach a consensus on the changes in the report. Disagreements were decided by vote.,The GOLD Science Committee was established in 2002 DOto review published research on COPD management andSummary of Recommendations in the 2008 Update: Between July 1, 2007 and June 30, 2008, 226 articlesNOprevention, to evaluate the impact of this research onrecommendations in the GOLD documents related to met the search criteria. Of the 138 reviewed, 27 papersTAmanagement and prevention, and to post yearly updateswere identified to have an impact on the GOLD reporton the GOLD website. The first update of the 2006 report that was posted on the website in December 2008 eitherLTincluded the impact of publications from July 1, 2006by: 1) confirming, that is, adding or replacing an existingthrough June 30, 2007; this second update includes the reference, or 2) modifying, that is, changing the text orERimpact of publications from July 1, 2007 through June 30,introducing a concept requiring a new recommendation to2008.the report. The summary (below) is reported in threeOR segments: A) Modifications in the text; B) ReferencesMethods: The process to produce this 2008 update that provided confirmation or an update of previous rec-REincluded a Pub Med search using search fields estab- ommendations; and C) Changes to the text for clarifica-lished by the Committee: 1) COPD OR chronic bronchitis tion or to correct errors.PROR emphysema, All Fields, All Adult: 19+ years, only Evidence Reviews: In preparation of GOLD reports, ODitems with abstracts, Clinical Trial, Human; and 2) COPDOR chronic bronchitis OR emphysema AND systematic, including this 2008 update, grading of evidence has beenUAll Fields, only items with abstracts, human. Publications completed using four categories as described on page xi. CEin peer review journals not captured by Pub Med couldHowever, new GRADE technology has been described1be submitted to individual members of the Committeeand is being widely adopted. Thus, during the 2008 peri- .providing an abstract and the full paper were submitted in od, GOLD has been developing a system to make a tran-(or translated into) English.sition to the GRADE technology to identify key recom- mendations that require more in-depth evaluation, and toAll members of the Committee received a summary of implement the creation and evaluation of evidencecitations and all abstracts. Each abstract was assigned to tables. The 2009 update will begin to reflect this work.two Committee members, although all members were (See section D.)*The Global Strategy for Diagnosis, Management and Prevention of COPD (updated 2008), the Executive Summary (updated 2008), the Pocket Guide(updated 2008) and the complete list of references examined by the Committee are available on the GOLD website www.goldcopd.org.Members (2007-2008): P. Calverley, Chair; A. Agusti, A. Anzueto, P. Barnes, M. Decramer, Y. Fukuchi, P. Jones, K. Rabe, R. Rodriguez-Roisin, J.Vestbo, J. Zielinski. vii 9. A. Modifications in the text:INSPIRE Investigators. The prevention of chronic obstructive pulmonary disease exacerbations by salme-Page 16, Figure 3-1, insert (after Respiratory infections):terol/fluticasone propionate or tiotropium bromide. Am JPrevious tuberculosisRespir Crit Care Med. 2008 Jan 1;177(1):19-26. Epub 2007 Oct 4.Page 18, right column, insert line 11: "In patients withsevere COPD, women, relative to men, exhibit anatomi-Page 55, right column at end of paragraph 1, insert:COcally smaller airway lumens with disproportionately thick- "There is some evidence, however, that in COPD patientser airway walls, and emphysema that is less extensivewho have not been treated with inhaled glucocorticos-PYand characterized by smaller hole size and less peripher-teroids, treatment with mucolytics such as carbocisteineal involvement62." may reduce exacerbations426." RIReference 62: Martinez FJ, Curtis JL, Sciurba F, Reference 426: Zheng JP, Kang J, Huang SG, Chen P, GHMumford J, Giardino ND, Weinmann G, Kazerooni E, Yao WZ, Yang L, Bai CX, Wang CZ, Wang C, Chen BY,Murray S, Criner GJ, Sin DD, Hogg J, Ries AL, Han M, Shi Y, Liu CT, Chen P, Li Q, Wang ZS, Huang YJ, Luo ZY,TEFishman AP, Make B, Hoffman EA, Mohsenifar Z, Wise Chen FP, Yuan JZ, Yuan BT, Qian HP, Zhi RC, ZhongR; National Emphysema Treatment Trial Research NS. Effect of carbocisteine on acute exacerbation of DGroup. Sex differences in severe pulmonary emphyse-chronic obstructive pulmonary disease (PEACE Study): a MAma. Am J Respir Crit Care Med 2007 Aug 1;176(3):243- randomised placebo-controlled study. Lancet. 2008 Jun52. Epub 2007 Apr 12.14;371(9629):2013-8. TE RIPage 18, right column, insert line 28: "A history of tuber-Page 57, right column, line 14, delete "or use of pursedculosis has been found to be associated with airflow lip breathing." At end of sentence add: "There is some ALobstruction in adults older than 40 years63."evidence to suggest that pursed lip breathing may pro-,Reference 63: Menezes AM, Hallal PC, Perez-Padilla R,vide sustained improvement in exertional dyspnea and DOJardim JR, Muio A, Lopez MV, Valdivia G, Montes dephysical function427."Oca M, Talamo C, Pertuze J, Victora CG; Latin American Reference 427: Nield MA, Soo Hoo GW, Roper JM, NOProject for the Investigation of Obstructive Lung DiseaseSantiago S. Efficacy of pursed-lips breathing: a breath-(PLATINO) Team. Tuberculosis and airflow obstruction:ing pattern retraining strategy for dyspnea reduction. J TAevidence from the PLATINO study in Latin America. EurCardiopulm Rehabil Prev. 2007 Jul-Aug;27(4):237-44.Respir J 2007 Dec;30(6):1180-5. Epub 2007 Sep 5. LT Page 57, right column, line 35, modify to read: "..of ERPage 52, left column, insert line 25: "Meaningful increas- respiratory muscle weakness242. In contrast, inspiratoryes in lung function can be achieved following administra-muscle training appears to provide additional benefitstion of inhaled anticholinergic plus sympathomimetic when used as part of a comprehensive pulmonary reha-ORbronchodilators even in patients with moderate to severe bilitation program243, 428, 429COPD423. Treatment with long-acting anticholinergic drug Reference 428: Magadle R, McConnell AK, BeckermanREimproves the effectiveness of pulmonary rehabilitation424."M, Weiner P. Inspiratory muscle training in pulmonaryPRReference 423: Tashkin DP, Celli B, Decramer M, Liurehabilitation program in COPD patients. Respir Med.D, Burkhart D, Cassino C, Kesten S. Bronchodilator 2007 Jul;101(7):1500-5. Epub 2007 Feb 27. ODresponsiveness in patients with COPD. Eur Respir J.Reference 429: OBrien K, Geddes EL, Reid WD, Brooks2008 Apr;31(4):742-50. Epub 2008 Feb 6.D, Crowe J. Inspiratory muscle training compared withUReference 424: Kesten S, Casaburi R, Kukafka D,other rehabilitation interventions in chronic obstructive CECooper CB. Improvement in self-reported exercise partic- pulmonary disease: a systematic review update. Jipation with the combination of tiotropium and rehabilita- Cardiopulm Rehabil Prev. 2008 Mar-Apr;28(2):128-41. .tive exercise training in COPD patients. Int J ChronObstruct Pulmon Dis. 2008;3(1):127-36. Page 60, left column, first paragraph, modify last two lines to read: "...strength, or quality of life in COPDPage 53, left column, insert at end of paragraph 1: "In apatients with chronic respiratory failure282, 430."large study, combination therapy compared to tiotropiumReference 430: Kolodziej MA, Jensen L, Rowe B, Sinshowed no difference in exacerbation rate although moreD. Systematic review of noninvasive positive pressurepatients randomized to combination treatment completed ventilation in severe stable COPD. Eur Respir J. 2007the study425." Aug;30(2):293-306. Epub 2007 Apr 25.Reference 425: Wedzicha JA, Calverley PM,Seemungal TA, Hagan G, Ansari Z, Stockley RA;viii 10. Page 60, right column, line 20, delete "In addition" andpractitioners with practice nurses in one model had amodify line 22 to read: " quality of life293, and surgerypositive effect on patient compliance12. An integratedreduced the frequency of COPD exacerbations and care intervention including education, coordinationincreased the time to first exacerbation431." among levels of care, and improved accessibility,Reference 431: Washko GR, Fan VS, Ramsey SD,reduced hospital readmissions in chronic obstructive pul-Mohsenifar Z, Martinez F, Make BJ, Sciurba FC, Criner monary disease (COPD) after 1 year13."GJ, Minai O, Decamp MM, Reilly JJ; for the National Reference 12: Meulepas MA, Jacobs JE, Smeenk FW,COEmphysema Treatment Trial Research Group. The effectSmeele I, Lucas AE, Bottema BJ, Grol RP. Effect of anof lung volume reduction surgery on chronic obstructive integrated primary care model on the management ofPYpulmonary disease exacerbations. Am J Respir Crit middle-aged and old patients with obstructive lungCare Med. 2008 Jan 15;177(2):164-9. Epub 2007 Oct 25. diseases. Scand J Prim Health Care. 2007RISep;25(3):186-92.GHPage 64, right column, add after references 346, 349, Reference 13: Garcia-Aymerich J, Hernandez C,350. "Therapy with oral prednisolone is preferable432." Alonso A, Casas A, Rodriguez-Roisin R, Anto JM, Roca TEReference 432: de Jong YP, Uil SM, Grotjohan HP,J. Effects of an integrated care intervention on risk fac-Postma DS, Kerstjens HA, van den Berg JW. Oral or IVtors of COPD readmission. Respir Med 2007Dprednisolone in the treatment of COPD exacerbations: aJul;101(7):1462-9. Epub 2007 Mar 6. MArandomized, controlled, double-blind study. Chest. 2007Dec;132(6):1741-7. Epub 2007 Jul 23.B. References that provided confirmation or update of TEprevious recommendations. RIPage 68, left column, last paragraph after reference 324add: "Despite this, there is evidence that patients who Pg 3: Reference 25. Fan VS, Ramsey SD, Giardino ALmight otherwise survive may be denied admission toND, Make BJ, Emery CF, Diaz PT, Benditt JO, Mosenifar,intensive care for intubation because of unwarrantedZ, McKenna R Jr, Curtis JL, Fishman AP, Martinez FJ;DOprognostic pessimism434." National Emphysema Treatment Trial (NETT) ResearchReference 434: Wildman MJ, Sanderson C, Groves J, Group. Sex, depression, and risk of hospitalization andNOReeves BC, Ayres J, Harrison D, Young D, Rowan K. mortality in chronic obstructive pulmonary disease. ArchImplications of prognostic pessimism in patients with Intern Med. 2007 Nov 26;167(21):2345-53.TAchronic obstructive pulmonary disease (COPD) or asth-ma admitted to intensive care in the UK within the COPD Pg 46: Reference 421: Harber P, Tashkin DP, SimmonsLTand asthma outcome study (CAOS): multicentre observa- M, Crawford L, Hnizdo E, Connett J; Lung Health StudyERtional cohort study. BMJ 2007 Dec 1;335(7630):1132. Group. Effect of occupational exposures on decline ofEpub 2007 Nov 1.lung function in early chronic obstructive pulmonary dis- ORease. Am J Respir Crit Care Med 2007 NovPage 69, left column, third paragraph, after spirometric15;176(10):994-1000. Epub 2007 Jul 12.paramaters 355 add: "Prior hospital admission, oral gluco- REcorticosteroids, use of long term oxygen therapy, poorPage 51: Reference 422: Al-Showair RA, Tarsin WY, PRhealth related quality of life, and lack of routine physicalAssi KH, Pearson SB, Chrystyn H. Can all patients withactivity have been found to be predictive of readmis- COPD use the correct inhalation flow with all inhalersODsion435." and does training help? Respir Med. 2007Reference 435: Bahadori K, FitzGerald JM. Risk factorsNov;101(11):2395-401. Epub 2007 Jul 12. Uof hospitalization and readmission of patients with COPDCEexacerbation--systematic review. Int J Chron Obstruct Page 66: Reference 433: Murphy TF, Brauer AL,Pulmon Dis 2007;2(3):241-51.Eschberger K, Lobbins P, Grove L, Cai X, Sethi S..Pseudomonas aeruginosa in chronic obstructive pul-Page 88, move last paragraph from page 88 to page 87monary disease. Am J Respir Crit Care Med 2008 Aprand insert (before section on implementation of COPD15;177(8):853-60. Epub 2008 Jan 17.Guidelines): "Integrative Care in the Management ofCOPD. Evidence is increasing that a chronic diseasemanagement program for COPD patients that incorpo-rates a variety of interventions, includes pulmonary reha-bilitation, and is implemented by primary care reducehospital admissions and bed days11. Combining general ix 11. C. The committee recommended changes to text:Page 50, Figure 5.3-4: Modification in entry for leval-buterol to include MDI formulation.Page 51, Figure 5.3-5: To clarify the "one or more long-acting bronchodilators" statement in Figure 5.3-7, modify COthe last statement in Figure 5.3-5 to read: "Combiningbronchodilators of different pharmacological classes may PYimprove efficacy and decrease the risk of side effectscompared to increasing the dose of a single bronchodila-RItor."GHPage 58: Line 38: After references 261 and 262, add TEEvidence ADD. Grading Evidence: The GOLD document GlobalMAStrategy for Diagnosis, Management and Prevention ofCOPD will continue to include background informationTEand will eventually include a series of specific recommen-RIdations based on evidence tables1 (included as anALappendix to the volume and/or on the GOLD website.)The GOLD Science Committee will develop a system to ,identify recommendations that are relatively controversial DOand have a less robust evidence base, to assemble andanalyze the evidence, and to routinely update the evi- NOdence. Three questions that have been identified tobegin the work include: TA1. Should glucocorticosteroid and long-acting beta-ago- LTnist in one inhaler vs inhaled long-acting beta-agonist ERalone be used in patients with moderate or severe chron-ic obstructive pulmonary disease? OR2. Should glucocorticosteroid and long-acting beta-ago-nist in one inhaler vs no treatment be used for moderate REand severe chronic obstructive pulmonary disease?3. Should glucocorticosteroid and long-acting beta-ago- PRnist in one inhaler vs inhaled steroids alone be used inpatients with moderate and severe chronic obstructiveODpulmonary disease? UThe analysis of the data from these questions is under CEreview and will be available in the 2009 update. .REFERENCES1. Guyatt GH, Oxman AD, Kunz R, et al. Going from evi-dence to recommendations. BMJ 2008;336:1049-51. x 12. GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF COPD One strategy to help achieve the objectives of GOLD isINTRODUCTION to provide health care workers, health care authorities, and the general public with state-of-the-art informationCOChronic Obstructive Pulmonary Disease (COPD) is amajor cause of chronic morbidity and mortality throughoutabout COPD and specific recommendations on the most appropriate management and prevention strategies.PYthe world. Many people suffer from this disease for yearsand die prematurely from it or its complications. COPD isThe GOLD report, Global Strategy for the Diagnosis, RIthe fourth leading cause of death in the world1, and further Management, and Prevention of COPD, is based on the best-validated current concepts of COPD pathogenesis GHincreases in its prevalence and mortality can be predictedin the coming decades2.and the available evidence on the most appropriateTE management and prevention strategies. The report,The goals of the Global Initiative for Chronic Obstructive developed by individuals with expertise in COPD research DLung Disease (GOLD) are to increase awareness of and patient care and reviewed by many additional experts, MACOPD and decrease morbidity and mortality from the provides state-of-the-art information about COPD fordisease. GOLD aims to improve prevention and manage- pulmonary specialists and other interested physicians. TEment of COPD through a concerted worldwide effort of The document serves as a source for the production of various communications for other audiences, including RIpeople involved in all facets of health care and health carepolicy, and to encourage an expanded level of research an Executive Summary, a Pocket Guide for Health Care ALinterest in this highly prevalent disease. A nihilisticProfessionals, and a Patient Guide2.,attitude toward COPD continues among some healthDOcare providers, due to the relatively limited success of The GOLD report is not intended to be a comprehensiveprimary and secondary prevention (i.e., avoidance of textbook on COPD, but rather to summarize the current state of the field. Each chapter starts with Key PointsNOfactors that cause COPD or its progression), the prevailingnotion that COPD is largely a self-inflicted disease, andthat crystallize current knowledge. The chapters on theTAdisappointment with available treatment options. Another Burden of COPD and Risk Factors demonstrate the globalimportant goal of the GOLD initiative is to work towardimportance of COPD and the various causal factorsLTcombating this nihilistic attitude by disseminating informationinvolved. The chapter on Pathology, Pathogenesis, and Pathophysiology documents the current understandingERabout available treatments (both pharmacologic andnonpharmacologic), and by working with a network ofof, and remaining questions about, the mechanism(s) that lead to COPD, as well as the structural and functionalORexpertsthe GOLD National Leadersto implementeffective COPD management programs developed inabnormalities of the lung that are characteristic ofaccordance with local health care practices. the disease.RE A major part of the GOLD report is devoted to the clinicalPRTobacco smoking continues to be a major cause ofCOPD, as well as of many other diseases. A worldwide Management of COPD and presents a management plan with four components: (1) Assess and Monitor Disease; ODdecline in tobacco smoking would result in substantialhealth benefits and a decrease in the prevalence of(2) Reduce Risk Factors; (3) Manage Stable COPD; (4)UCOPD and other smoking-related diseases. There is an Manage Exacerbations.CEurgent need for improved strategies to decrease tobaccoconsumption. However, tobacco smoking is not the onlyManagement recommendations are presented according.cause of COPD, and it may not even be the major causeto the severity of the disease, using a simple classificationin some parts of the world. Furthermore, not all smokers of severity to facilitate the practical implementation ofdevelop clinically significant COPD, which suggeststhe available management options. Where appropriate,that additional factors are involved in determining each information about health education for patients is includ-individuals susceptibility. Thus, investigations of COPDed. A new chapter at the end of the document will assistrisk factors, ways to reduce exposure to these factors,readers in Translating Guideline Recommendations to theand the molecular and cellular mechanisms involved inContext of (Primary) Care.COPD pathogenesis continue to be important areas ofresearch to develop more effective treatments that slowor halt the course of the disease.xi 13. A large segment of the worlds population lives in areasAll members of the committee received a summary ofwith inadequate medical facilities and meager financialcitations and all abstracts. Each abstract was assignedresources, and fixed international guidelines and rigidto two committee members (members were not assignedscientific protocols will not work in many locations. Thus,papers they had authored), although any member wasthe recommendations found in this report must be adapted offered the opportunity to provide an opinion on anyto fit local practices and the availability of health care abstract. Each member evaluated the assigned abstractsresources. As the individuals who participate in the or, where s/he judged necessary, the full publication, by COGOLD program expand their work, every effort will be answering specific written questions from a shortmade to interact with patient and physician groups atquestionnaire, and indicating whether the scientific data PYnational, district, and local levels, and in multiple health presented affected recommendations in the GOLD report.care settings, to continuously examine new and innovativeIf so, the member was asked to specifically identify RIapproaches that will ensure the delivery of the best caremodifications that should be made. The GOLD Science GHpossible to COPD patients, and the initiation of programsCommittee met on a regular basis to discuss eachfor early detection and prevention of this disease. GOLD individual publication indicated by at least one member ofTEis a partner organization in a program launched in March the committee to have an impact on COPD management,2006 by the World Health Organization, the Globaland to reach a consensus on the changes needed in the DAlliance Against Chronic Respiratory Diseases (GARD).report. Disagreements were decided by vote.MAThrough the work of the GOLD committees, and incooperation with GARD initiatives, progress toward betterThe publications that met the search criteria for eachTEcare for all patients with COPD should be substantial in yearly update (between 100 and 200 articles per year)RIthe next decade. mainly affected Chapter 5, Management of COPD. ListsAL of the publications considered by the Science CommitteeMETHODOLOGYeach year, along with the yearly updated reports, are , posted on the GOLD Website, www.goldcopd.org. DOA. Preparation of yearly updates: Immediately followingthe release of the first GOLD report in 2001, the GOLD B. Preparation of the New 2006 Report: In January NOExecutive Committee appointed a Science Committee, 2005, the GOLD Science Committee initiated its work oncharged with keeping the GOLD documents up-to-date a comprehensively updated version of the GOLD report. TAby reviewing published research, evaluating the impact During a two-day meeting, the committee established thatof this research on the management recommendations the report structure should remain the same as in the LTin the GOLD documents, and posting yearly updates of 2001 document, but that each chapter would be carefully ERthese documents on the GOLD Website. The first updatereviewed and modified in accordance with new publishedto the GOLD report was posted in July 2003, based on literature. The committee met in May and Septemberpublications from January 2001 through December 2002. OR 2005 to evaluate progress and to reach consensus on theA second update appeared in July 2004, and a third inmessages to be provided in each chapter. Throughout itsJuly 2005, each including the impact of publications fromwork, the committee made a commitment to develop a REJanuary through December of the previous year. document that would reach a global audience, be based PR on the most current scientific literature, and be as conciseProducing the yearly updates began with a PubMed as possible, while at the same time recognizing that oneOD(http://www.nlm.nih.gov) search using search fieldsof the values of the GOLD report has been to provideestablished by the Science Committee: 1) COPD OR background information on COPD management and the Uchronic bronchitis OR emphysema, All Fields, All Adult,scientific principles on which management recommendations CE19+ years, only items with abstracts, Clinical Trial,are based.Human, sorted by Author; and 2) COPD OR chronic .bronchitis OR emphysema AND systematic, All Fields,In January 2006, the Science Committee met with theAll Adult, 19+ years, only items with abstracts, Human,Executive Committee for a two-day session during whichsorted by Author. In addition, publications in peer- another in-depth evaluation of each chapter was conducted.reviewed journals not captured by PubMed could be sub- At this meeting, members reviewed the literature thatmitted to individual members of the Science Committee, appeared in 2005using the same criteria developedprovided that an abstract and the full paper were submittedfor the update process. The list of 2005 publications thatin (or translated into) English. were considered is posted on the GOLD website. At the January meeting, it was clear that work remaining would xii 14. permit the report to be finished during the summer ofproduction, normal spirometry) necessarily progress on to2006, and the Science Committee requested that, as Stage I. Nevertheless, the importance of the publicpublications appeared throughout early 2006, they be health message that chronic cough and sputum are notreviewed carefully for their impact on the recommenda- normal is unchanged.tions. At the committees next meeting, in May 2006,publications meeting the search criteria were considered 4. The spirometric classification of severity continues toand incorporated into the current drafts of the chapters recommend use of the fixed ratio, postbronchodilator COwhere appropriate. A final meeting of the committee wasFEV1/FVC < 0.7, to define airflow limitation. Using theheld in September 2006, at which time publications thatfixed ratio (FEV1/FVC) is particularly problematic in PYappeared prior to July 31, 2006 were considered for theirmilder patients who are elderly as the normal process ofimpact on the document.aging affects lung volumes. Postbronchodilator reference RI values in this population are urgently needed to avoid GHPeriodically throughout the preparation of this report potential overdiagnosis.(May and September 2005, May and September 2006),TErepresentatives from the GOLD Science Committee met5. Chapter 2, Burden of COPD, provides references towith the GOLD National Leaders to discuss COPD man-published data from prevalence surveys carried out in a Dagement and issues specific to each of the chapters. number of countries, using standardized methods andMAThe GOLD National Leaders include representatives from including spirometry, to estimate that about 15 to 25%over 50 countries and many participated in these interim of adults aged 40 years and older may have airflowTEdiscussions. In addition, GOLD National Leaders were limitation classified as Stage I: Mild COPD or higher.RIinvited to submit comments on a DRAFT document and Evidence is also provided that the prevalence of COPDtheir comments were considered by the committee. (Stage I: Mild COPD and higher) is appreciably higher inALWhen the committee completed its work, several other smokers and ex-smokers than in nonsmokers, in those ,individuals were invited to submit comments on the over 40 years than those under 40, and higher in menDOdocument as reviewers. The names of reviewers andthan in women. The chapter also provides new data onGOLD National Leaders who submitted comments are COPD morbidity and mortality.NOin the front material. 6. Throughout it is emphasized that cigarette smoke isTANEW ISSUES PRESENTED IN THIS REPORTthe most commonly encountered risk factor for COPD and elimination of this risk factor is an important stepLT1. Throughout the document, emphasis has been made toward prevention and control of COPD. However, otherERthat COPD is characterized by chronic airflow limitation risk factors for COPD should be taken into account whereand a range of pathological changes in the lung, somepossible. These include occupational dusts andORsignificant extrapulmonary effects, and importantchemicals, and indoor air pollution from biomass cookingcomorbidities that may contribute to the severity of the and heating in poorly ventilated dwellingsthe latterdisease in individual patients.especially among women in developing countries.REPR2. In the definition of COPD, the phrase preventable7. Chapter 4, Pathology, Pathogenesis, andand treatable has been incorporated following the Pathophysiology, continues with the theme that inhaled ODATS/ERS recommendations to recognize the need to cigarette smoke and other noxious particles cause lungpresent a positive outlook for patients, to encourage theinflammation, a normal response which appears to beUhealth care community to take a more active role inamplified in patients who develop COPD. The chapter CEdeveloping programs for COPD prevention, and tohas been considerably updated and revised.stimulate effective management programs to treat those .with the disease.8. Management of COPD continues to be presented in four components: (1) Assess and Monitor Disease; (2)3. The spirometric classification of severity of COPDReduce Risk Factors; (3) Manage Stable COPD; (4)now includes four stagesStage I: Mild; Stage II:Manage Exacerbations. All components have beenModerate; Stage III: Severe; Stage IV: Very Severe. Aupdated based on recently published literature. Throughoutfifth category - Stage 0: At Risk, - that appeared in thethe document, it is emphasized that the overall approach2001 report is no longer included as a stage of COPD,to managing stable COPD should be individualized toas there is incomplete evidence that the individuals who address symptoms and improve quality of life.meet the definition of At Risk (chronic cough and sputumxiii 15. 9. In Component 4, Manage Exacerbations, a COPDLEVELS OF EVIDENCEexacerbation is defined as: an event in the naturalcourse of the disease characterized by a change in the Levels of evidence are assigned to managementpatients baseline dyspnea, cough, and/or sputum that isrecommendations where appropriate in Chapter 5,beyond normal day-to-day variations, is acute in onset,Management of COPD. Evidence levels are indicated inand may warrant a change in regular medication in aboldface type enclosed in parentheses after the relevantpatient with underlying COPD.statemente.g., (Evidence A). The methodological CO issues concerning the use of evidence from meta-analy-10. It is widely recognized that a wide spectrum of health ses were carefully considered3. PYcare providers are required to assure that COPD isdiagnosed accurately, and that individuals who haveThis evidence level scheme (Figure A) has been used inRICOPD are treated effectively. The identification of effectiveprevious GOLD reports, and was in use throughout theGHhealth care teams will depend on the local health care preparation of this document. The GOLD Sciencesystem, and much work remains to identify how best toCommittee was recently introduced to a new approach to TEbuild these health care teams. A chapter on COPD evidence levels4 and plans to review and consider theimplementation programs and issues for clinical practice possible introduction of this approach in future reports.Dhas been included but it remains a field that requiresMAconsiderable attention.TEFigure A. Description of Levels of EvidenceRI EvidenceAL Sources of EvidenceDefinition Category ,ARandomized controlledEvidence is from endpoints of well-designed RCTs that provide a consistent DO trials (RCTs). Rich body of data.pattern of findings in the population for which the recommendation is made.Category A requires substantial numbers of studies involving substantialnumbers of participants. NOBRandomized controlled trials Evidence is from endpoints of intervention studies that include only a limited TA (RCTs). Limited body of data.number of patients, posthoc or subgroup analysis of RCTs, or meta-analysisof RCTs. In general, Category B pertains when few randomized trials exist, LTthey are small in size, they were undertaken in a population that differs fromthe target population of the recommendation, or the results are somewhat ERinconsistent.CNonrandomized trials.Evidence is from outcomes of uncontrolled or nonrandomized trials or from OR Observational studies. observational studies.DPanel Consensus Judgment.This category is used only in cases where the provision of some guidanceREwas deemed valuable but the clinical literature addressing the subject wasdeemed insufficient to justify placement in one of the other categories. ThePRPanel Consensus is based on clinical experience or knowledge that does notmeet the above-listed criteria. ODREFERENCESU CE1.World Health Report. Geneva: World Health Organization. Available from URL: http://www.who.int/whr/2000/en/statistics.htm; 2000..2.Lopez AD, Shibuya K, Rao C, Mathers CD, Hansell AL, Held LS, et al. Chronic obstructive pulmonary disease: current burden andfuture projections. Eur Respir J 2006;27(2):397-412.3.Jadad AR, Moher M, Browman GP, Booker L, Sigouin C, Fuentes M, et al. Systematic reviews and meta-analyses on treatment ofasthma: critical evaluation. BMJ 2000;320(7234):537-40.4.Guyatt G, Vist G, Falck-Ytter Y, Kunz R, Magrini N, Schunemann H. An emerging consensus on grading recommendations? ACP JClub 2006;144(1):A8-9. Available from URL: http://www.evidence-basedmedicine.com. xiv 16. DEFINITION CHAPTER . U CE 1OD PR REOR ER LT TA NO, DO AL RI TE MA DTE GH RIPYCO 17. CHAPTER 1: DEFINITION Based on current knowledge, a working definition is: KEY POINTS: Chronic Obstructive Pulmonary Disease (COPD) Chronic Obstructive Pulmonary Disease (COPD) is ais a preventable and treatable disease with some preventable and treatable disease with some significant COsignificant extrapulmonary effects that mayextrapulmonary effects that may contribute to thecontribute to the severity in individual patients. severity in individual patients. Its pulmonary component PYIts pulmonary component is characterized byis characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive RIairflow limitation that is not fully reversible.The airflow limitation is usually progressive andand associated with an abnormal inflammatory response GHassociated with an abnormal inflammatory responseof the lung to noxious particles or gases.of the lung to noxious particles or gases.TE Worldwide, cigarette smoking is the most commonly encountered risk factor for COPD, although in many D The chronic airflow limitation characteristic of countries, air pollution resulting from the burning of woodMACOPD is caused by a mixture of small airwayand other biomass fuels has also been identified as a COPD risk factor.TEdisease (obstructive bronchiolitis) and parenchymaldestruction (emphysema), the relative contributionsRIof which vary from person to person. Airflow Limitation in COPDAL The chronic airflow limitation characteristic of COPD is , COPD has a variable natural history and not allcaused by a mixture of small airway disease (obstructiveDOindividuals follow the same course. However, bronchiolitis) and parenchymal destruction (emphysema),COPD is generally a progressive disease, the relative contributions of which vary from person toNOespecially if a patients exposure to noxiousperson (Figure 1-1). Chronic inflammation causesagents continues.structural changes and narrowing of the small airways.TA Destruction of the lung parenchyma, also by inflammatory processes, leads to the loss of alveolar attachments toLT The impact of COPD on an individual patientthe small airways and decreases lung elastic recoil; inERdepends on the severity of symptoms (especiallyturn, these changes diminish the ability of the airways tobreathlessness and decreased exercise capacity), remain open during expiration. Airflow limitation is bestORsystemic effects, and any comorbidities themeasured by spirometry, as this is the most widelypatient may havenot just on the degree of available, reproducible test of lung function.airflow limitation.REPRFigure 1-1. Mechanisms Underlying AirflowDEFINITIONLimitation in COPD ODChronic obstructive pulmonary disease (COPD) is INFLAMMATIONUcharacterized by chronic airflow limitation and a range CEof pathological changes in the lung, some significantextra-pulmonary effects, and important comorbidities .which may contribute to the severity of the disease inindividual patients. Thus, COPD should be regarded asSmall airway disease Parenchymal destructiona pulmonary disease, but these significant comorbiditiesAirway inflammationLoss of alveolar attachments Airway remodelingDecrease of elastic recallmust be taken into account in a comprehensivediagnostic assessment of severity and in determiningappropriate treatment.AIRFLOW LIMITATION2 DEFINITION 18. Many previous definitions of COPD have emphasizedslow or even halt progression of the disease. However,the terms emphysema and chronic bronchitis, whichonce developed, COPD and its comorbidities cannot beare not included in the definition used in this and earliercured and thus must be treated continuously. COPDGOLD reports. Emphysema, or destruction of the gas-treatment can reduce symptoms, improve quality of life,exchanging surfaces of the lung (alveoli), is a pathological reduce exacerbations, and possibly reduce mortality.term that is often (but incorrectly) used clinically anddescribes only one of several structural abnormalities Spirometric Classification of Severity COpresent in patients with COPD. Chronic bronchitis, or thepresence of cough and sputum production for at least For educational reasons, a simple spirometric classification PY3 months in each of two consecutive years, remains a of disease severity into four stages is recommendedclinically and epidemiologically useful term. However, (Figure 1-2). Spirometry is essential for diagnosis andRIit does not reflect the major impact of airflow limitation provides a useful description of the severity of pathologicalGHon morbidity and mortality in COPD patients. It is alsochanges in COPD. Specific spirometric cut-points (e.g.,important to recognize that cough and sputum productionpost-bronchodilator FEV1/FVC ratio < 0.70 or FEV1 < 80, TEmay precede the development of airflow limitation; 50, or 30% predicted) are used for purposes of simplicity:conversely, some patients develop significant airflowthese cut-points have not been clinically validated.Dlimitation without chronic cough and sputum production.A study in a random population sample found that the MA post-bronchodilator FEV1/FVC exceeded 0.70 in all ageCOPD and Comorbidities groups, supporting the use of this fixed ratio9. TEBecause COPD often develops in long-time smokers in RImiddle age, patients often have a variety of other diseases Figure 1-2. Spirometric Classification of COPD ALrelated to either smoking or aging1. COPD itself also hasSeverity Based on Post-Bronchodilator FEV1,significant extrapulmonary (systemic) effects that lead toDOcomorbid conditions2. Data from the Netherlands showStage I: MildFEV1/FVC < 0.70that up to 25% of the population 65 years and older suffer FEV1 80% predictedNOfrom two comorbid conditions and up to 17% have three3.Weight loss, nutritional abnormalities and skeletal muscleStage II: Moderate FEV1/FVC < 0.70 50% FEV < 80% predictedTAdysfunction are well-recognized extrapulmonary effects of 1COPD and patients are at increased risk for myocardialStage III: SevereFEV1/FVC < 0.70LTinfarction, angina, osteoporosis, respiratory infection, 30% FEV < 50% predicted1bone fractures, depression24, 25, diabetes, sleep-disorders,ERanemia, and glaucoma4. The existence of COPD mayStage IV: Very SevereFEV1/FVC < 0.70actually increase the risk for other diseases; this is FEV1 < 30% predicted or FEV1 < 50% ORparticularly striking for COPD and lung cancer5-8. predicted plus chronic respiratoryWhether this association is due to common risk factors failureRE(e.g., smoking), involvement of susceptibility genes, or FEV1: forced expiratory volume in one second; FVC: forced vital capacity; respiratoryimpaired clearance of carcinogens is not clear.PR failure: arterial partial pressure of oxygen (PaO2) less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of CO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) while breathing air at sea level.Thus, COPD should be managed with careful attention ODalso paid to comorbidities and their effect on the patientsUquality of life. A careful differential diagnosis andHowever, because the process of aging does affect CEcomprehensive assessment of severity of comorbid lung volumes, the use of this fixed ratio may result inconditions should be performed in every patient with over diagnosis of COPD in the elderly, especially of mild .chronic airflow limitation.disease. Using the lower limit of normal (LLN) values for FEV1/FVC, that are based on the normal distributionNATURAL HISTORYand classify the bottom 5% of the healthy population as abnormal, is one way to minimize the potential misclassi-COPD has a variable natural history and not all individuals fication. In principle, all programmable spirometers couldfollow the same course. However, COPD is generally a do this calculation if reference equations for the LLN ofprogressive disease, especially if a patients exposure to the ratio were available. However, reference equationsnoxious agents continues. Stopping exposure to these using post-bronchodilator FEV1 and longitudinal studiesagents, even when significant airflow limitation is present, to validate the use of the LLN are urgently needed.may result in some improvement in lung function and DEFINITION 3 19. Spirometry should be performed after the administration Conversely, significant airflow limitation may developof an adequate dose of an inhaled bronchodilator (e.g., without chronic cough and sputum production. Although400 g salbutamol)10 in order to minimize variability. In a COPD is defined on the basis of airflow limitation, inrandom population study to determine spirometry reference practice the decision to seek medical help (and so permitvalues, post-bronchodilator values differed markedlythe diagnosis to be made) is normally determined by thefrom pre-bronchodilator values9. Furthermore, post- impact of a particular symptom on a patients lifestyle.bronchodilator lung function testing in a community setting Thus, COPD may be diagnosed at any stage of the illness.has been demonstrated to be an effective method to COidentify individuals with COPD11. Stage I: Mild COPD - Characterized by mild airflow PYlimitation (FEV1/FVC < 0.70; FEV1 80 % predicted).While post-bronchodilator FEV1/FVC and FEV1 measure-Symptoms of chronic cough and sputum production may RIments are recommended for the diagnosis and assessmentbe present, but not always. At this stage, the individual isof severity of COPD, the degree of reversibility of airflow usually unaware that his or her lung function is abnormal. GHlimitation (e.g., FEV1 after bronchodilator or gluco-corticosteroids) is no longer recommended for diagnosis,TEStage II: Moderate COPD - Characterized by worseningdifferential diagnosis with asthma, or predicting the airflow limitation (FEV1/FVC < 0.70; 50% FEV1 < 80% Dresponse to long-term treatment with bronchodilatorspredicted), with shortness of breath typically developingor glucocorticosteroids. MAon exertion and cough and sputum production sometimesalso present. This is the stage at which patients typically TEStages of COPDseek medical attention because of chronic respiratorysymptoms or an exacerbation of their disease. RIThe impact of COPD on an individual patient depends ALnot just on the degree of airflow limitation, but also on Stage III: Severe COPD - Characterized by further wors-the severity of symptoms (especially breathlessness and ening of airflow limitation (FEV1/FVC < 0.70; 30% FEV 1,decreased exercise capacity). There is only an imperfect< 50% predicted), greater shortness of breath, reducedDOrelationship between the degree of airflow limitation exercise capacity, fatigue, and repeated exacerbations thatand the presence of symptoms. Spirometric staging,almost always have an impact on patients quality of life. NOtherefore, is a pragmatic approach aimed at practicalimplementation and should only be regarded as anStage IV: Very Severe COPD - Characterized by severe TAeducational tool and a general indication to the initialairflow limitation (FEV1/FVC < 0.70; FEV1 < 30% predictedapproach to management. or FEV1 < 50% predicted plus the presence of chronic LTrespiratory failure). Respiratory failure is defined as anThe characteristic symptoms of COPD are chronic and ERarterial partial pressure of O2 (PaO2) less than 8.0 kPaprogressive dyspnea, cough, and sputum production.(60 mm Hg), with or without arterial partial pressure ofChronic cough and sputum production may precede the ORCO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) whiledevelopment of airflow limitation by many years. This breathing air at sea level. Respiratory failure may alsopattern offers a unique opportunity to identify smokers lead to effects on the heart such as cor pulmonale (right REand others at risk for COPD (Figure 1-3), and intervene heart failure). Clinical signs of cor pulmonale includewhen the disease is not yet a major health problem. elevation of the jugular venous pressure and pitting ankle PRedema. Patients may have Stage IV: Very Severe COPDODFigure 1-3. At Risk for COPDeven if the FEV1 is > 30% predicted, whenever thesecomplications are present. At this stage, quality of life UA major objective of GOLD is to increase awareness amongis very appreciably impaired and exacerbations may beCEhealth care providers and the general public of the significance of life threatening.COPD symptoms. The classification of severity of COPD now.includes four stages classified by spirometryStage I: Mild The common statement that only 15-20% of smokersCOPD; Stage II: Moderate COPD; Stage III: Severe COPD;develop clinically significant COPD is misleading12. AStage IV: Very Severe COPD. A fifth category - Stage 0: At much higher proportion may develop abnormal lungRisk, that appeared in the 2001 report is no longer included function at some point if they continue to smoke13. Not allas a stage of COPD, as there is incomplete evidence that theindividuals with COPD follow the classical linear courseindividuals who meet the definition of At Risk (chronic cough as outlined in the Fletcher and Peto diagram, which isand sputum production, normal spirometry) necessarily actually the mean of many individual courses14. Causesprogress on to Stage I. Mild COPD. Nevertheless, theof death in patients with COPD are mainly cardiovascularimportance of the public health message that chronic coughdiseases, lung cancer, and, in those with advancedand sputum are not normal is unchanged and their presenceCOPD, respiratory failure15.should trigger a search for underlying cause(s).4 DEFINITION 20. Pulmonary Tuberculosis and COPDSCOPE OF THE REPORT In many developing countries both pulmonary tuberculosisIt is not the scope of this report to provide a comprehensive and COPD are common21. In countries where tuberculosisdiscussion of the natural history of comorbidities is very common, respiratory abnormalities may be tooassociated with COPD but to focus primarily on chronic readily attributed to this disease22. Conversely, whereairflow limitation caused by inhaled particles and gases, the rate of tuberculosis is greatly diminished, the possiblethe most common of which worldwide is cigarette smoke. CO diagnosis of this disease is sometimes overlooked.However, chronic airflow limitation may develop also in Therefore, in all subjects with symptoms of COPD, anonsmokers who present with similar symptoms and PY possible diagnosis of tuberculosis should be considered,may be associated with other diseases, e.g., asthma, especially in areas where this disease is known to beRIcongestive heart failure, lung carcinoma, bronchiectasis, prevalent23.pulmonary tuberculosis, bronchiolitis obliterans, andGHinterstitial lung diseases. Poorly reversible airflow limitationassociated with these conditions is not addressed except TE REFERENCESinsofar as these conditions overlap with COPD.D 1.Soriano JB, Visick GT, Muellerova H, Payvandi N, Hansell AL.MAAsthma and COPDPatterns of comorbidities in newly diagnosed COPD and asthma in primary care. Chest 2005;128(4):2099-107.TECOPD can coexist with asthma, the other major chronic 2.Agusti AG. Systemic effects of chronic obstructive pulmonaryobstructive airway disease characterized by an underlyingRI disease. Proc Am Thorac Soc 2005;2(4):367-70.airway inflammation. The underlying chronic airwayALinflammation is very different in these two diseases 3.van Weel C. Chronic diseases in general practice: the(Figure 1-4). However, individuals with asthma who are longitudinal dimension. Eur J Gen Pract 1996;2:17-21. , DOexposed to noxious agents, particularly cigarette smoke16, 4.van Weel C, Schellevis FG. Comorbidity and guidelines:may also develop fixed airflow limitation and a mixture of conflicting interests. Lancet 2006;367(9510):550-1.asthma-like and COPD-like inflammation. Furthermore,NOthere is epidemiologic evidence that longstanding asthma 5.Stavem K, Aaser E, Sandvik L, Bjornholt JV, Erikssen G, Thaulow E, et al. Lung function, smoking and mortality in aTAon its own can lead to fixed airflow limitation17. Other 26-year follow-up of healthy middle-aged males. Eur Respir Jpatients with COPD may have features of asthma such as 2005;25(4):618-25.LTa mixed inflammatory pattern with increased eosinophils18.Thus, while asthma can usually be distinguished from 6.Skillrud DM, Offord KP, Miller RD. Higher risk of lung cancerERCOPD, in some individuals with chronic respiratory in chronic obstructive pulmonary disease. A prospective, matched, controlled study. Ann Intern Med 1986;105(4):503-7.symptoms and fixed airflow limitation it remains difficultORto differentiate the two diseases. Population-based7.Tockman MS, Anthonisen NR, Wright EC, Donithan MG.surveys19,20 have documented that chronic airflow limitation Airways obstruction and the risk for lung cancer. Ann Intern REmay occur in up to 10% of lifetime nonsmokers 40 years Med 1987;106(4):512-8.and older; the causes of airflow limitation in nonsmokers PR 8.Lange P, Nyboe J, Appleyard M, Jensen G, Schnohr P.needs further investigation. Ventilatory function and chronic mucus hypersecretion asOD predictors of death from lung cancer. Am Rev Respir Dis 1990;141(3):613-7. Figure 1-4. Asthma and COPD U 9.Johannessen A, Lehmann S, Omenaas ER, Eide GE, Bakke CE PS, Gulsvik A. Post-bronchodilator spirometry reference values in adults and implications for disease management. . Am J Respir Crit Care Med 2006;173(12):1316-25. 10. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J 2005;26(5):948-68. 11. Johannessen A, Omenaas ER, Bakke PS, Gulsvik A. Implications of reversibility testing on prevalence and risk factors for chronic obstructive pulmonary disease: a community study. Thorax 2005;60(10):842-7. DEFINITION 5 21. 12. Rennard S, Vestbo J. COPD: the dangerous underestimateof 15%. Lancet 2006;367:1216-9.13. Lokke A, Lange P, Scharling H, Fabricius P, Vestbo J.Developing COPD - a 25 years follow-up study of the generalpopulation. Thorax 2006;61:935-9.14. Fletcher C, Peto R. The natural history of chronic airflowobstruction. BMJ 1977;1(6077):1645-8.CO15. Mannino DM, Doherty DE, Sonia Buist A. Global Initiative onPYObstructive Lung Disease (GOLD) classification of lungdisease and mortality: findings from the Atherosclerosis Risk inRICommunities (ARIC) study. Respir Med 2006;100(1):115-22.GH16. Thomson NC, Chaudhuri R, Livingston E. Asthma and cigarettesmoking. Eur Respir J 2004;24(5):822-33. TE17. Lange P, Parner J, Vestbo J, Schnohr P, Jensen G. A 15-yearDfollow-up study of ventilatory function in adults with asthma.MAN Engl J Med 1998;339(17):1194-200.18. Chanez P, Vignola AM, OShaugnessy T, Enander I, Li D,TEJeffery PK, et al. Corticosteroid reversibility in COPD isrelated to features of asthma. Am J Respir Crit Care MedRI1997;155(5):1529-34.AL19. Menezes AM, Perez-Padilla R, Jardim JR, Muino A, Lopez MV, ,Valdivia G, et al. Chronic obstructive pulmonary disease in fiveDOLatin American cities (the PLATINO study): a prevalencestudy. Lancet 2005;366(9500):1875-81. NO20. Centers for Disease Control and Prevention. SurveillanceSummaries. MMWR 2002:51(No. SS-6). TA21. Fairall LR, Zwarenstein M, Bateman ED, Bachmann M, LTLombard C, Majara BP, et al. Effect of educational outreachto nurses on tuberculosis case detection and primary care of ERrespiratory illness: pragmatic cluster randomised controlledtrial. BMJ 2005;331(7519):750-4. OR22. de Valliere S, Barker RD. Residual lung damage aftercompletion of treatment for multidrug-resistant tuberculosis. REInt J Tuberc Lung Dis 2004;8(6):767-71. PR23. Bateman ED, Feldman C, OBrien J, Plit M, Joubert JR.Guideline for the management of chronic obstructiveODpulmonary disease (COPD): 2004 revision. S Afr Med J2004;94(7 Pt 2):559-75. U24. Ng TP, Niti M, Tan WC, Cao Z, Ong KC, Eng P. Depressive CEsymptoms and chronic obstructive pulmonary disease: effecton mortality, hospital readmission, symptom burden, functional .status, and quality of life. Arch Intern Med 2007 Jan8;167(1):60-7.25. Fan VS, Ramsey SD, Giardino ND, Make BJ, Emery CF, DiazPT, Benditt JO, Mosenifar Z, McKenna R Jr, Curtis JL,Fishman AP, Martinez FJ; National Emphysema TreatmentTrial (NETT) Research Group. Sex, depression, and risk ofhospitalization and mortality in chronic obstructive pulmonarydisease. Arch Intern Med. 2007 Nov 26;167(21):2345-53.6 DEFINITION 22. BURDEN OF COPD CHAPTER . U CEOD 2 PR REOR ER LT TA NO, DO AL RI TE MA DTE GH RIPYCO 23. CHAPTER 2: BURDEN OF COPD underdiagnosis of COPD lead to significant underreporting. KEY POINTS: The extent of the underreporting varies across countries and depends on the level of awareness and understanding COPD is a leading cause of morbidity and mortality of COPD among health professionals, the organization ofCOworldwide and results in an economic and social health care services to cope with chronic diseases, andburden that is both substantial and increasing. the availability of medications for the treatment of COPD1.PY COPD prevalence, morbidity, and mortality vary RI There are several sources of information on the burdenacross countries and across different groups of COPD: publications such as the 2003 European GHwithin countries but, in general, are directly related Lung White Book2, international Websites such as theto the prevalence of tobacco smoking, althoughTE World Health Organization (http://www.who.int) and thein many countries, air pollution resulting from the World Bank/WHO Global Burden of Disease Studyburning of wood and other biomass fuels has D (http://www.who.int/topics/global_burden_of_disease), andalso been identified as a COPD risk factor.MA country-specific Websites such as the US Centers for Disease Control and Prevention (http://www.cdc.gov) and The prevalence and burden of COPD are projectedTE the UK Health Survey for England (http://www.doh.gov.uk).to increase in the coming decades due to continuedRIexposure to COPD risk factors and the changing Prevalenceage structure of the worlds population.AL Existing COPD prevalence data show remarkable variation , COPD is a costly disease with both direct costsDO(value of health care resources devoted to due to differences in survey methods, diagnostic criteria,diagnosis and medical management) and indirect and analytic approaches3,4. Survey methods can include:NOcosts (monetary consequences of disability,missed work, premature mortality, and caregiver Self-report of a doctor diagnosis of COPD or equivalentTAor family costs resulting from the illness). condition Spirometry with or without a bronchodilatorLT Questionnaires that ask about the presence of respiratory symptomsERINTRODUCTION The lowest estimates of prevalence are usually thoseORCOPD is a leading cause of morbidity and mortality based on self-reporting of a doctor diagnosis of COPDworldwide and results in an economic and social burden or equivalent condition. For example, most national dataREthat is both substantial and increasing. COPD prevalence,show that less than 6% of the population has been toldmorbidity, and mortality vary across countries and acrossthat they have COPD3. This likely reflects the wide-PRdifferent groups within countries but, in general, are spread underrecognition and underdiagnosis of COPD5directly related to the prevalence of tobacco smokingas well as the fact that those with Stage I: Mild COPD ODalthough in many countries, air pollution resulting from may have no symptoms, or else symptoms (such asthe burning of wood and other biomass fuels has alsoU chronic cough and sputum) that are not perceived bybeen identified as a COPD risk factor. The prevalenceCE individuals or their health care providers as abnormaland burden of COPD are projected to increase in theand possibly indicative of early COPD5. These estimates.coming decades due to continued exposure to COPD may have value, however, since they may most accuratelyrisk factors and the changing age structure of the worldsreflect the burden of clinically significant disease that is ofpopulation (with more people living longer, and thus sufficient severity to require health services, and thereforereaching the age at which COPD normally develops). is likely to generate significant direct and indirect costs.EPIDEMIOLOGY By contrast, data from prevalence surveys carried out in a number of countries, using standardized methods andIn the past, imprecise and variable definitions of COPDincluding spirometry, estimate that up to about one-quarterhave made it difficult to quantify prevalence, morbidity of adults aged 40 years and older may have airflowand mortality. Furthermore, the underrecognition and limitation classified as Stage I: Mild COPD or higher6-9.8 BURDEN OF COPD 24. Because of the large gap between the prevalence of The Latin American Project for the Investigation ofCOPD as defined by the presence of airflow limitationObstructive Lung Disease (PLATINO) examined theand the prevalence of COPD as defined by clinicallyprevalence of post-bronchodilator airflow limitationsignificant disease, the debate continues as to which of (Stage I: Mild COPD and higher) among persons overthese it is better to use in estimating the burden ofage 40 in five major Latin American cities each in aCOPD. Early diagnosis and intervention may help to different country Brazil, Chile, Mexico, Uruguay, andidentify the number of individuals who progress to a Venezuela. In each country, the prevalence of Stage I:COclinically significant stage of disease, but there isMild COPD and higher increased steeply with ageinsufficient evidence at this time to recommend(Figure 2-1), with the highest prevalence among thosePYcommunity-based spirometric screening for COPD10.over 60 years, ranging from a low of 18.4% in Mexico City, Mexico to a high of 32.1% in Mentevideo, Uruguay.RIDifferent diagnostic criteria also give widely different In all cities/countries the prevalence was appreciablyGHestimates and there is little consensus regarding thehigher in men than in women. The reasons for themost appropriate criteria for different settings (e.g.,differences in prevalence across the five Latin American TEepidemiologic surveys, clinical diagnosis), or the strengths cities are still under investigation6.and weaknesses of the different criteria. It is recognizedDthat defining irreversible airflow obstruction as a post-In 12 Asia-Pacific countries and regions a study based MAbronchodilator FEV1/FVC ratio less than 0.70 leads toon a prevalence estimation model indicated a meanthe potential for significant misclassification, withprevalence rate for moderate to severe COPD among TEunderdiagnosis (false negatives) in younger adults and individuals 30 years and older of 6.3% for the region. RIover-diagnosis (false positives) over age 50 years11-13. The rates varied twofold across the 12 Asian countriesThis has led to the recommendation that the use of the and ranged from a minimum of 3.5% (Hong Kong and ALlower limit of normal (LLN) of the post-bronchodilator Singapore) to a maximum of 6.7% (Vietnam)18.,FEV1/FVC ratio rather than the fixed ratio be used toDOdefine irreversible airflow obstruction14,15. However, moreFigure 2-1. COPD Prevalence by Age in Fiveinformation is needed from population-based longitudinalLatin American Cities6NOstudies to determine the outcome of individuals classifiedusing either definition.TAMany additional sources of variation can affect estimatesLTof COPD prevalence, including sampling methods,ERresponse rates, quality control of spirometry, and whetherspirometry is performed pre- or post-bronchodilator.ORSamples that are not population-based and poor responserates may give biased estimates of prevalence, with thedirection of bias sometimes hard to determine. InadequateREemptying of the lungs during the spirometric maneuverPRis common and leads to an artificially high ratio ofFEV1/FVC and therefore to an underestimate of the ODprevalence of COPD. Failure to use post-bronchodilatorvalue instead of pre-bronchodilator values leads to anUoverdiagnosis of irreversible airflow limitation In futureCEprevalence surveys, post-bronchodilator spirometry Prevalence = postbronchodilator FEV1 /FVC < 0.70 (Stage I: Mild COPD and higher)should be used to confirm the diagnosis of COPD16.. MorbidityDespite these complexities, data are emerging thatenable some conclusions to be drawn regarding COPD Morbidity measures traditionally include physician visits,prevalence. A systematic review and meta-analysis of emergency department visits, and hospitalizations.studies carried out in 28 countries between 1990 and Although COPD databases for these outcome parameters20043, and an additional study from Japan17, provide are less readily available and usually less reliable thanevidence that the prevalence of COPD (Stage I: Mildmortality databases, the limited data available indicateCOPD and higher) is appreciably higher in smokers andthat morbidity due to COPD increases with age and isex-smokers than in nonsmokers, in those over 40 yearsgreater in men than in women19-21. In these data sets,than those under 40, and in men than in women. however, COPD in its early stages (Stage I: Mild COPD BURDEN OF COPD 9 25. and Stage 2: Moderate COPD) is usually not recognized,Revisions of the ICD, in which deaths from COPD ordiagnosed, or treated, and therefore may not be includedchronic airways obstruction are included in the broadas a diagnosis in a patients medical record.category of COPD and allied conditions (ICD-9 codes490-496 and ICD-10 codes J42-46).Morbidity from COPD may be affected by other comorbidchronic conditions22 (e.g., musculoskeletal disease,Thus, the problem of labeling has been partly solved, butdiabetes mellitus) that are not directly related to COPDunderrecognition and underdiagnosis of COPD still affectCObut nevertheless may have an impact on the patients the accuracy of mortality data. Although COPD is often ahealth status, or may negatively interfere with COPDprimary cause of death, it is more likely to be listed as aPYmanagement. In patients with more advanced diseasecontributory cause of death or omitted from the death(Stage III: Severe COPD and Stage IV: Very Severe certificate entirely, and the death attributed to anotherRICOPD), morbidity from COPD may be misattributed tocondition such as cardiovascular disease.GHanother comorbid condition.Despite the problems with the accuracy of the COPD TEMorbidity data are greatly affected by the availability ofmortality data, it is clear that COPD is one of the mostresources (e.g,, hospitalization rates are highly dependent important causes of death in most countries. The GlobalDon the availability of hospital beds) and thus have to be Burden of Disease Study8,24,25 has projected that COPD, MAinterpreted cautiously and with a clear understanding ofwhich ranked sixth as the cause of death in 1990, willthe possible biases inherent in the dataset. Despite thebecome the third leading cause of death worldwide by TElimitations in the data for COPD, the European White2020. This increased mortality is driven by the expanding RIBook provides good data on the mean number of epidemic of smoking and the changing demographics inconsultations for major respiratory diseases across most countries, with more of the population living longer. AL19 countries of the European Economic Community2. Of these two forces, demographics is the stronger driver,In most countries, consultations for COPD greatly out-of the trend.DOnumbered consultations for asthma, pneumonia, lungand tracheal cancer, and tuberculosis. In the UnitedTrends in mortality rates over time provide further importantNOStates in 2000, there were 8 million physician office/information but, again, these statistics are greatly affectedhospital outpatient visits for COPD, 1.5 million emergencyby terminology, awareness of the disease, and potentialTAdepartment visits, and 673,000 hospitalizations23.gender bias in its diagnosis. COPD mortality trendsgenerally track several decades behind smoking trends.LTAnother way of estimating the morbidity burden of disease Trends in age-standardized death rates for the six leadingERis to calculate years of living with disability (YLD). Thecauses of death in the United States from 1970 throughGlobal Burden of Disease Study estimates that COPD200226 indicates that while mortality from several of theseresults in 1.68 YLD per 1,000 population, representingchronic conditions declined over that period, COPD OR1.8% of all YLDs, with a greater burden in men than inmortality increased (Figure 2-2). Death rates for COPDwomen (1.93% vs. 1.42%)8,24,25. in Canada, in both men and women, have also been REincreasing since 1997. In Europe, however, the trends PRMortality are different, with decreasing mortality from COPDalready being seen in many countries7. There is noODThe World Health Organization publishes mortality obvious reason for the difference between trends in Northstatistics for selected causes of death annually for allAmerica and Europe, although presumably factors such UWHO regions; additional information is available from as awareness, changing terminology, and diagnostic bias CEthe WHO Evidence for Health Policy Department contribute to these differences.(http://www.who.int/evidence). Data must be interpreted .cautiously, however, because of inconsistent use ofterminology for COPD. Prior to about 1968 and theEighth Revision of the International Classification ofDiseases (ICD), the terms chronic bronchitis andemphysema were used extensively. During the 1970s,the term COPD increasingly replaced those terms insome but not all countries, making COPD mortalitycomparisons in different countries very difficult. However,the situation has improved with the Ninth and Tenth10 BURDEN OF COPD 26. Figure 2-2. Trends in Age-standardized Death RatesECONOMIC AND SOCIAL BURDEN OF COPD for the 6 Leading Causes of Death in the United States,1970-200226 Economic BurdenCOPD is a costly disease with both direct costs (valueof health care resources devoted to diagnosis andmedical management) and indirect costs (monetaryCOconsequences of disability, missed work, prematuremortality, and caregiver or family costs resulting from thePYillness)2. In developed countries, exacerbations of COPDaccount for the greatest burden on the health care system.RIIn the European Union, the total direct costs of respiratoryGHdisease are estimated to be about 6% of the total healthcare budget, with COPD accounting for 56% (38.6 billion TEEuros) of this cost of respiratory disease2. In the UnitedStates in 2002, the direct costs of COPD were $18 billionDand the indirect costs totaled $14.1 billion28. Costs perMApatient will vary across countries since these costsdepend on how health care is provided and paid7.TERINot surprisingly, there is a striking direct relationshipbetween the severity of COPD and the cost of care29,ALand the distribution of costs changes as the disease ,progresses. For example, hospitalization and ambulatoryDOoxygen costs soar as COPD severity increases, asillustrated by data from Sweden shown in Figure 2-3. NO TA Figure 2-3. Distribution of Direct Costs of COPD by Severity29 LTReprinted from Jemal A, Ward E, Hao Y, Thun M. Trends in the leading causesof death in the United States, 1970-2002. JAMA 2005;294(10):1255-9. with ERpermission from JAMA ORThe mortality trends for COPD have been particularlystriking for women. In Canada, the death rate from COPD REamong women accelerated in the 1990s and is expectedto soon ov