1. What Have We Learned about COPD from Epidemiology A. Sonia Buist M.D. Oregon Health & Science University, Portland, Oregon, USA

2. Epidemiology Epidemiology is the study of the distribution and determinants of disease

3. Definition of COPD preventable and treatable COPD is a preventable and treatable disease with some significant extrapulmonary effects that my contribute to the severity in individual patients Its pulmonary component is characterized by airflow limitation that is not fully reversible The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases GOLD 2006

4. What is Epidemiology Telling Us? COPD is more common that previously estimated, and is becoming as common in women as men as smoking habits equalize The social and economic burden will increase worldwide as the demographics of the world’s populations changes COPD is costly for the patient and healthcare system We may need to change our focus from treatment to prevention

5. How is the Burden of COPD Estimated? Mortality Morbidity Prevalence Cost Quality of life

6. Percent Changes in Age-Adjusted Death Rates, US, 1965-1998 0 0 0.5 1.0 1.5 2.0 2.5 3.0 Proportion of 1965 Rate 1965 - 1998 –59% –64% –35% +163% –7% Coronary Heart Disease Coronary Heart Disease Stroke Other CVD COPD All Other Causes All Other Causes

7. Ford ES et al, NEJM 2007;356(23):2388-97 Explaining the Decrease in US Deaths from Coronary Disease, 1980-2000. Ford et al. NEJM 2007; 356: 2388 US Adults 25-84 yrs Age-adjusted deaths for CAD fell from 543.0 to 266.7 deaths/100K (M) and from 263.3 to 134.4 (W) 47% of decrease attributed to treatments, 44% to changing risk factors Increases on deaths as result of increased BMI & diabetes

8. World Health Statistics 2008, WHO

9. COPD Mortality in the US only one COPD is the only one of the top 6 leading causes of death in the US that is increasing

11. COPD Mortality by Gender, U.S., 1980-2000 Year Number Deaths x 1000

12. Age-Standardized Death rates from COPD in US, aged ≥18 years, by sex, 2000-2005

13. How is the Burden of COPD Estimated? Mortality Morbidity Prevalence Cost Quality of life

14. Morbidity in COPD Traditionally measured by: Physician visits Hospitalization Emergency visits

15. Morbidity in COPD May be affected by co-morbid chronic conditions that are not directly related to COPD but may have an impact on health status or may negatively interfere with COPD management Morbidity data are greatly affected by availability of hospital beds so should be interpreted with caution

16. Disability-Adjusted Life Years (DALYs) A metric used by WHO Combines premature death & disability A metric used by WHO Combines premature death & disability

17. Leading Causes Of Disability-adjusted Life-Years (DALYs) Lost Worldwide: 1990 and 2020 (projected) RANK RANK % total RANK RANK % total Disease or injury19902020 DALYs Disease or injury 19902020 DALYs Lower respiratory infections 1 6 3.1 Diarrheal diseases 2 9 2.7 Ischemic heart disease 5 1 5.9 Cerebrovascular disease 6 4 4.4 Tuberculosis 7 7 3.1 Road traffic accidents 9 3 5.0 COPD 12 5 4.1 Murray & Lopez, Lancet 1997

18. What Have We Learned from Epidemiology? Standardized methods allow comparison across countries Using BOLD & PLATINO standardized methods, prevalence of COPD is appreciably higher than previously reported Different criteria & definitions for “COPD” make a big difference to reported prevalances

19. What Else Have We Learned from Epidemiology? There is heterogeneity across countries/sites that is not completely explained by known risk factors Smoking and age are the most powerful risk factors Different criteria & definitions for “COPD” make a big difference to reported prevalances Irreversible airflow obstruction in never-smokers is still poorly understood

20. What Have We Learned from Epidemiology? Standardized methods allow comparison across countries Using BOLD & PLATINO standardized methods, prevalence of COPD is appreciably higher than previously reported Different criteria & definitions for “COPD” make a big difference to reported prevalances

21. Two Models of International Collaboration to Measure COPD Prevalence

22. Scientific Objectives of PLATINO & BOLD: Primary Measure the prevalence of COPD & its risk factors by age & sex Estimate the burden of COPD  quality of life & activity limitation  respiratory symptoms  use of health care services

23. Scientific Objectives: Secondary Compare different lung function criteria for the diagnosis of COPD Determine if variations in risk factors contribute to variations in COPD prevalence Characterize the clinical management of COPD in different countries

24. BOLD Entry Criteria  40 years Men & women Population-based e.g. random sample of population (non-institutionalized people) Recruitment: from well-defined target population that was approved by Operations Center

25. Methods (1) Questionnaires: all centers used the BOLD questionnaires but added supplementary local questionnaires if they wanted Translation: translation & back translation followed by reconciliation of any differences Spirometry: same spirometer, same software, same methods, same data transfer, same quality control measures used

26. Methods (2) Data Entry & Transfer: same methods for questionnaires & spirometry. Web-based, secure, auto error detect w/ site notification, online copies of protocol, Manual of Procedures, all data forms Participant safety: all centers obtained local ethical committee approval & observed confidentiality Quality Control: all methods the same & standardized, edited checks for data entry

27. What Data Are We Obtaining? Lung function Respiratory symptoms Risk factors (smoking, occupation, biomass) Respiratory medications Health status Health care utilization Burden of COPD/economic & social

28. How was COPD Defined? Post-bronchodilator FEV 1 /FVC <70% Severity staged using GOLD criteria For BOLD, GOLD Stage 2 & higher used to estimate burden of “clinically significant” COPD  Chronic cough, sputum, shortness of breath determined but not part of the definition of COPD

29. Classification by Severity Classification by Severity StageCharacteristics* Stage Characteristics* I: Mild FEV 1 /FVC 80% predicted II: Moderate FEV 1 /FVC < 70%; 50%<FEV 1 < 80% predicted III: SevereFEV 1 /FVC FEV 1 < 50% predicted IV: Very Severe FEV 1 /FVC < 70%; FEV 1 < 30% predicted or FEV 1 < 50% predicted plus chronic respiratory failure *Post-Bronchodilator GOLD 2006 GOLD 2006

30. Airflow Obstruction by Sex* 18% 11% 27% 23% 16% BrazilMexico UruguayChileVenezuela * Post-BD FEV1/FVC<70% Menezes et al Lancet 2005 Prevalence, % ≥ GOLD Stage 1

31. The BOLD Study: B B urden of O O bstructive L L ung D D isease Initiative

32. BOLD Sites FINISHED: Guangzhou (China);Adana (Turkey); Salzburg (Austria); Cape Town (South Africa); Reykjavik (Iceland); Krakow (Poland); Hannover (Germany); Bergen (Norway)l Vancouver (B.C., Canada); Lexington (Kentucky, USA); Manila (Philippines); Sydney (Australia); London (UK); Uppsala (Sweden); Mumbai (India) IN PROGRESS Lisbon (Portugal); Tartu (Estonia); Maastricht (The Netherlands); Pune (India); 4 additional sites in Canada & Australia; 1 additional site in Philippines PLANNING: Algeria, Tunisia, Morocco, Japan, Cambodia, Vietnam, Mongolia, 32

33. Prevalence of GOLD Stage II & III+ COPD in 12 Countries by Sex & Descending Prevalence of Smoking, BOLD Study Lancet,2007; 370: 741-50 11.8% (SE 7.9)8.5% (SE 5.8) Overall 10.1% (SE 4.8)

34. Odds Ratios of Stage II+ COPD for each 10 pack-year increments in smoking in ever smokers by sex & site, BOLD Study in 12 countries Lancet, 2007; 370: 741-50

35. Odds Ratios of Stage II+ COPD for each 10-year increment in age by sex and site, BOLD Study in 12 countries Lancet, 2007; 370: 741-50

36. Sydney, Australia Estimated Population Prevalence of Gold Stage II+ COPD* by pack years and sex *Post BD FEV 1 /FVC <70% and post BD FEV 1 <80% **For the 0-10 and 10-20 pack years cell size is <20

37. 37 The BOLD Study: Summary Findings for COPD stage II+ 1.Prevalence 10.1% overall 11.8% for men 8.5% for women 2.Odds ratio for 10-year age increment 1.94 overall/10-yr increment Same across sites for men & women 3.Odds ratio for 10 pack-year increment 1.28 in women, p=0.012 site specific variation 1.16 in men, p=0.743

38. 38 BOLD findings on COPD prevalence Heterogeneity in prevalence  Across sites (12 countries)  Between men & women within sites Partly explained by site & sex differences in prevalence of smoking & other risk factors Lancet, 2007, 370: 741-50

39. 39 BOLD findings on COPD prevalence Cape Town Highest prevalence of stage II+ COPD Had very high reported levels of prior TB & occupational exposure smoking rates Cape Town, Adana, Krakow, Lexington, Manila High prevalences of stage II+ in men Highest reported occupational exposures in men Lancet, 2007, 370: 741-50

40. How is the Burden of COPD Estimated? Mortality Morbidity Prevalence Cost Quality of life

41. Cost of COPD in US COPD is a very costly disease direct (diagnosis and management) indirect (cost of disability, missed work, premature mortality and family costs) Annual per capita expenditures for people with COPD nearly 2½x those without COPD ($8,482 vs $3,511 in 1992 study)

42. Direct Medical Costs of COPD in US

43. Halpin. Proc Am Thoracic Soc 2006;3(3): 227 Average UK societal costs of COPD according to severity.

44. Breakdown of Direct Costs of COPD care in the UK Halpin Proc Am Thoracic Soc 2006;3(3): 227

45. Why is the Burden of COPD Increasing Worldwide? Increase in exposure to risk factors (especially tobacco) in developing countries & in women

46. COPD is a classic gene-environment interaction disease

47. Risk Factors for COPD Nutrition Infections Socio-economic status Aging Populations GENES Smoking

48. Trends in Risk Factors Smoking Until 1940s, smoking prevalence in women much less than men worldwide Smoking increased in women in many countries in 1940s and gradually equaled rates in men

51. Mean Post-BD FEV 1 in Placebo Group Sustained Quitters Continuing Smokers Annual Visit Lung Health Studies I-III

52. Trends in Risk Factors Other Exposures Until World War2, men were much more likely than women to have heavy occupational exposures

54. Occupation as a Risk Factor Data from the US NHANES III Survey (1988-’94) used to estimate % of COPD attributable to occupation Fraction of COPD attributable to work estimated as 19.2% overall and 31.2% among never-smokers

55. Trends in Risk Factors Other Exposures Heavy exposures to indoor air pollution as a risk factor (especially in developing countries) were not recognized as important risk for COPD

57. Worldwide solid fuel use for cooking. Torres et al PATS, 2008; 5: 577-90

58. Indoor Concentrations of Pollutants from Typical Wood-Burning Stove Pollutant Emission (mg/m 3 ) Allowable standard (mg/m 3 ) Carbon Monoxide 15010 Particles 3.30.1 Benzene 0.80.002 1,3-Butadiene 0.150.0003 Formaldehyde 0.70.1 Source: Based on the UNDP/DESA/WEC World Energy Assessment

59. Regional Burden of Disease due to Indoor Air Pollution

60. Impact of Aging Populations Changing age structure of populations in developing countries (more are living into the COPD age range)

61. GOLD Stage 1+ ≥40 years in Salzburg, Austria, by Age & Sex (BOLD Study, 2006) Schirnhofer et al, Chest 2007; 131:29036 MaleFemale

62. Comparison of COPD Definitions, Austria Fixed ratio LLN FEV1/FVC GOLD IV GOLD III

63. Changing Demographics in China Total population: ~1.3 B Population growth rate: 0.6% ≥ age 65 in 2006: 100M ≥ age 65 in 2015: 200M ≥ age 65 in 2050: 430M By 2050, one quarter of the world’s population will be ≥60 years. 3 in 4 aged 80 years & over will be living in the developing world

64. Summary COPD is common, costly, and imposes a significant social and economic burden yet is mostly under- diagnosed and under-treated COPD has become as common in women as men as smoking habits have equalized COPD is common in smokers and ex-smokers but can also exist in nonsmokers The burden of COPD continues to rise steadily in all countries because of increasing life expectancy and decades of tobacco use

65. What Can We Do About the COPD “Epidemic”? Encourage tobacco-control legislation All health care professional should take tobacco control very seriously….for themselves and their patients and families There needs to be more research into risk factors and the natural history of COPD primary We need to focus on primary prevention of COPD

68. Key Messages to Physicians & Public Think COPD Do spirometry Reduce risk factors Manage actively “ COPD is preventable and treatable”