Goals. Occupational COPD and Chronic Bronchitis. Case History. Smoking History. Patient presents at age 68. Active cigarette smoker, age 14-30

Transcription

1 Occupational COPD and Chronic Bronchitis Occupational and Environmental Respiratory Disease UCSF March 2016 Paul D. Blanc MD MSPH University of California San Francisco Division of Occupational and Environmental Medicine Goals Define COPD and chronic bronchitis (CB) epidemiologically and clinically Cover key points in the 2003 ATS statement on COPD and occupation (data through 1999) Present data from several UCSF COPD studies Summarize data from other recent studies Address policy and clinical implications Case History Patient presents at age 68 Progressive dyspnea over 5 years Now short of breath one flight of stairs or with carrying groceries up hill No dyspnea at rest; no paroxysmal symptoms Occasional wheezing, chest colds; no cough Smoking History Active cigarette smoker, age Maximum of 1½ packs per day Quit 40 years previously Under 25 pack years total 1

2 Occupational History Extremely dusty work (concrete dust) Grinding large concrete display tanks as an exhibit preparatory in an aquarium Also exposed to epoxies and fiberglass Did 6-8 tanks per year x 7 years ( ) Less exposure , then retired Physical Exam Thin, but not cachectic Prolonged expiratory phase No wheezes or rhonchi No pulmonic component to S2 No clubbing Initial Spirometry Obstruction without reversibility DLco 59% predicted DLco/VA 69% predicted Follow-up PFTs s/p 40mg prednisone/14 days no improved airflow 2

3 Serial PFTS - Because work was dusty work, PFTs done at his job 9 serial measurements/11 years Gap/6 years 12 f/u measurements/9 years New measurements include DLco Volume in Liters (FEV 1, FVC) While at work: 99mls loss FEV 1 /yr [p<0.01]; After exposure cessation: FEV 1 NS While at work: FVC NS; After exposure cessation 109 mls loss FVC/yr [p<0.01] FVC FEV FEF Flow in Liters Second -1 (FEF ) 6 DLco/VA Other Data 5 Serum alpha1anti-trypsin (AIAT) assay 4 3 DLco/VA Electrophoresis with agarose immunofixation 2 1 ZZ phenotype 0 2/1/2005 6/1/ /1/2005 2/1/2006 6/1/ /1/2006 2/1/2007 6/1/ /1/2007 2/1/2008 6/1/ /1/2008 2/1/2009 6/1/ /1/2009 2/1/2010 6/1/ /1/2010 2/1/2011 6/1/ /1/2011 2/1/2012 6/1/ /1/2012 2/1/2013 6/1/ /1/2013 2/1/2014 6/1/2014 Quantified value: 24 units (normal 90). 3

4 What Diagnosis Does He Have? A. Smoking-Related COPD B. Alpha-1 Anti-Trypsin Deficiency C. Occupationally-Related COPD D. Emphysema E. All of the Above Defining Chronic Obstructive Pulmonary Disease [COPD] This is a modern construct It subsumes 3 main disease labels: COPD, Emphysema, Chronic Bronchitis Each label is based on different criteria COPD - Diagnosis Based on lung function defined by: Deficit, amount breathed out in 1 second [FEV 1 ] And/or its ratio to the total breath [FEV 1 /FVC] Cut-points use to define COPD vary: FEV 1 /FVC < 0.70 [GOLD Stage I] FEV 1 /FVC < FEV 1 <80% pred [Gold II] FEV 1 /FVC < 0.60 [some older studies] FEV 1 /FVC <90 th %tile Lower Limit Normal Role of Cigarette Smoking Leading risk factor established for COPD Accounts for 80% of all cases of disease 80%= Population Attributable Risk [PAR%] [also=population Attributable Fraction, PAF] PAF=disease stopped if risk eliminated 4

5 Impact of Smoking Role Primary focus of prevention efforts; minimizing attention to other factors PAF allows overlapping risks [can be >100%] Eliminating any risk factor can reduce disease Diagnostic impacts Reluctance to diagnose COPD in nonsmokers Reluctance to diagnose asthma in smokers Going Beyond Direct Smoking If direct cigarette smoking doesn t account for all COPD cases, what else matters? What is the role of workplace exposures? Is there a strong and plausible effect, consistent in multiple studies? ATS Statement Drafted in 2002, published in 2003; data through 1999 Reviewed occupational links to asthma and to COPD Concentrated on population attributable risk (PAR) % / pop attributable fraction (PAF) Work hazard defined broadly - typically: exposure to vapors, gas, dust, and fumes 5

6 ATS Statement: Chronic Bronchitis 8 epidemiological studies reviewed including > 38,000 subjects U.S. (1987), France (1988), Poland (1990), Italy (1991), Norway (1991), China (1993), Holland (1994), Spain (1998) PAF for occupational dust/fume: Range = 4-24%, Median = 15% ATS Statement: COPD Breathlessness (Effort Dyspnea) 6 epidemiological studies reviewed including > 25,000 subjects U.S. (1987), France (1988), Italy (1991), Norway (1991), China (1993), New Zealand (1997) PAF for occupational dust/fume: Range = 6-30%, Median = 13% ATS Statement: COPD Airflow Obstruction (PFT Deficit) 6 epidemiological studies reviewed including > 12,000 subjects U.S. (1977,1987), Italy (1991), Norway (1991), Spain (1998), New Zealand (1997) PAF for occupational dust/fume: Range = 12-55%, Median = 18% ATS Statement: Conclusion occupational exposures account for a substantial proportion (i.e., from 10-20%) of either symptoms or functional impairment consistent with COPD a value of 15% is a reasonable estimate of the occupational contribution to the population of the burden of COPD. 6

7 UCSF COPD Study Trupin, Earnest, San Pedro, Balmes, Eisner, Yelin, Katz, Blanc Eur Respir J :462-9 Study designed to estimate occupational risk for COPD Recruit subjects across a wide range of industries and occupations Define exposure broadly to capture PAR% Focus on older age groups at greatest risk Methods Data from a population-based random digit dial telephone sample, adults aged National USA (48 contiguous states) Over-sampling in regions with higher COPD-related mortality Supplemental recruitment of subjectreported MD diagnosis of asthma/copd Exposure Definitions Focus on exposure from longest-held job Defined by reported exposure to vapors, gas, dust, or fumes [VGDF] 16 specific exposures elicited: combustion byproducts; inorganic, organic dust-fumes Also defined by job exposure matrix (JEM) of low, moderate, high likelihood exposure Outcomes Definitions Diagnosis: reported physician diagnosis of COPD, emphysema, chronic bronchitis Diagnosis of asthma also elicited COPD = COPD or emphysema or chronic bronchitis (+/- asthma) All analyses adjust for cigarette smoking 7

8 Figure 1. Telephone Area Codes Corresponding to Hot Spot Health Service Areas with Highest Age-Adjusted COPD Mortality Rates, Figure 2. Recruitment of Study Participants in Three Cohorts National Random Sample Hot Spots Random Sample Hot Spots Condition Sample North Minnesota Washington Montana Dakota Maine South Wisconsin 207 Dakota VT Oregon Wyoming 802 NH Idaho New MI York MA Iowa 530 Nebraska 814 CT Ohio Pennsylvania Nevada Utah Colorado Illinois IN MD NJ RI 209 WV Kansas Missouri DE Kentucky Virginia North Oklahoma Tennessee Arizona Arkansas Carolina New Mexico South 909 Carolina MS Alabama Texas Georgia 17,442 Total contacts 2,081 Potential participants 16,042 Total contacts 1,850 Potential participants 7,583 Total contacts 155 Potential participants (with airway condition) Louisiana Florida 1,001 (48%) 1,002 (54%) 110 (71%) Interview completed Interview completed Interview completed VGDF v. 16 Specific Exposures Specific exposures ranged from >40% [indoor engines and diesel exhaust] to < 10% [grain dust and cotton dust] The frequency of exposures not captured by VGDF item ranged from 1% to 5% No single item accounted for substantial added exposure detection % reporting 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Irritant gas Combustion Oil Figure 3. Specific and Global VGDF Coal dust Silica or sand Indoor motors Diesel exhaust global exp Specific VGDF Exposure Grain dust Animal feed Cotton dust Wood dust Cadmium Other metal Welding Fiberglass Explosives no global exp 8

9 Diagnosis By Exposure Status Risk of COPD by Exposure All COPD and COPD without Chronic Bronchitis Smoking-VGDF Interactions UCSF COPD Study: Principal Conclusions Between 9-20% (JEM vs. VGDF) of COPD is attributable to occupational exposures Excluding chronic bronchitis alone, the PAR% to 14% (JEM) or 31% (VGDF) There is potential interaction with cigarette smoking exposure 9

10 Occupational Factors as Predictors of COPD Outcomes Blanc et al. Occup Envrion Med 2004; 61: month follow-up, airways disease cohort 517 at baseline 352 (69%) re-interviewed 267 of 352 (76%) with COPD 242 with any work history/ 234 complete data Risk of Health Utilization for Respiratory Disease Adjusted for Smoking, Age, Sex, Race Occupational Risk Factor 1 ED visit OR (95% CI) Hospitalization OR (95% CI) Vapors, gas, dust, fume on longest held job 0.9 ( ) 2.1 ( ) Prior job change due to breathing 1.2 ( ) 6.3 ( ) Both risk factors 3.9 ( ) 7.6 ( ) UCSF COPD Follow-up Study: Principal Conclusions Prior working factors are related to future ED visits and hospitalization The risk of past respiratory work disability past work exposure may be additive or interactive Occupation in chronic obstructive lung disease and chronic bronchitis: an update Blanc & Torén, Int J Tuberc Lung Dis (IJTLD) 2007; 11: Systematic review of the literature Medline search with cross check of citations Studies published since the ATS review Focus on population attributable risk, as published or calculated from the data 10

11 COPD Post-ATS Review Airflow Obstruction (PFT Deficit) 6 studies including > 18,000 subjects; 1 mortality study >300,000 subjects Sweden (2), USA (2), Spain, Australia, International (13 countries); PAF for occupational exposure: Range = 0-37%, Median = 15% PAF for Non-smokers (4 estimates) 26, 30, 42, 53%, Median = 36% Chronic Bronchitis Post-ATS Review 8 studies including > 88,000 subjects; (1 study contributed 50,000 subjects) Denmark (2), Sweden (1), Netherlands, Spain, Singapore, International (2 analyses: 14 countries and 13 countries); PAF for occupational exposure: Range = 0-34%, Median = 15.5% PAF for Non-smokers (1 estimate) 12% Emphysema [COPD findings included in previous slide] (Matheson et al. Thorax 2005; 60: ) Australia. Community based study n=1213; emphysema based on DLco + dyspnea. OR adj age, pack years, smoking status, sex. Biological dust by JEM: OR 3.2 ( ) [PAR% >45%] Mineral dust by JEM: OR 1.07 ( ) [PAR% 2%] Gases and fumes by JEM: 1.3 ( ) [PAR% 13%] Three Additional UCSF Studies COPD risk in a well-defined cohort sampled from a large HMO COPD risk in an additional random population sample with PFT data COPD risk in an ecological analysis of 3 large international data sets 11

12 UCSF COPD FLOW Study: Occupational exposures and the risk of COPD: dusty trades revisited Blanc et al. Thorax 2009; 64:6-12 Closed-panel HMO patients aged mi. radius of research clinic Health utilization for COPD by IC-9 code & prescribed a COPD medication Structured telephone interview Direct exam, including spirometry FLOW Study Subject Pool 2,198 valid interviews of COPD valid cases 1,202 of these also completed clinic visits 302 age-gender matched referents with no clinical history or PFT evidence of COPD Exposure to Vapors Gas Dusts of Fume on Longest Held Job Multiple logistic regression adjusted for smoking age, race, sex Exposure by Job Exposure Matrix (JEM) on Longest Held Job Multiple logistic regression adjusted for smoking, age, race, sex Exposure Exposure to VGDF [GOLD 2] Exposure to VGDF COPD n=1202 Controls n=302 OR (95% CI) PAR% 58% 39% 1.9 ( ) 27% [n=742] 60% [n=302] 39% 1.9 ( ) 27% JEM Exposure Intermediate Exposure High Exposure COPD n=1202 Controls n=302 OR (95% CI) PAR% 9% 7% 1.3 ( ) 2% 23% 11% 2.1 ( ) 13% 12

13 Cigarette/ Work VGDF Exposure Smoking-Occupation Effects All COPD vs. Controls Subject n Probability COPD Excess Prob. Adjusted OR Never/No (REF) Never/Yes ( ) Ever/No ( ) Ever/Yes (9.3-21) Further Exploration of the Links Between Occupational Exposure and COPD Blanc et al. J Occup Environ Med : Analysis of new population-based sample of self-report of MD diagnosed COPD Comparison to previous referent sample Spirometry in COPD cases at home visits Analysis of step-up in risk with combine smoking and exposure Risk of COPD (cases v. referent) by exposure group and smoking status Risk of COPD by Spirometry (FEV 1 /FVC <0.70) among 98 cases and 1652 Referents Risk Group OR (95% CI) No smoking up to 10 pack-years 1.0 (Referent) and no occupational exposure No or minimal smoking; 2.0 ( ) occupational exposure Smoking>10 pack years; No 3.7 ( ) occupational exposure Smoking and occupational 5.9 ( ) exposure Occupational Exposures and COPD: An Ecological Analysis of International Data Blanc et al. Eur Respir J. 2009; 33: Study Cohort (n) Nations Study Study Subject Number per Site Included Sites Men Women N n Median (Range) Median (Range) BOLD ( ) 343 ( ) (8775) ECRHS II (30-179) 78.5 (35-79) (4648) PLATINO ( ) 632 ( ) (5671) All (19094) (65-324) 108 (72-334) 13

14 BOLD COPD cohort grouped data by site: Spearman correlation r=0.48 (p=0.02) ECHRS II COPD cohort grouped data by site: Spearman correlation r=0.26 (p=0.06) PLATINO COPD cohort grouped data by site: Spearman correlation r=0.63 (p=0.05) COPD prevalence in BOLD, ECHRS II, PLATINO: Mixed model including mean age, pack-years per stratum; study cohort as random effect variable; weighted by study site n Independent Variables COPD Gold II p value per 10% EXP All study sites/strata (n=90) % Ever Held Dusty/Dirty Jobs 0.8% ( %) % Ever Smokers 1.3 ( %) <0.001 Men only (n=45 sites) % Ever Held Dusty/Dirty Jobs 0.8% ( %) % Ever Smokers 0.9% ( %) 0.04 Women only (n=45 sites) % Ever Held Dusty/Dirty Jobs 1.0% ( %) 0.03 % Ever Smokers 1.1% ( %)

15 Table 1. Chronic obstructive pulmonary disease among residents of an historically industrialised area Darby, Waterhouse, Stevens, Billings, Billings, Burton, Young, Wight, Blanc, Fishwick; Thorax 2012; 67:901-7 Cigarette/ VGDF Exposure Subject n (1183) Probability COPD Excess Prob. Adjusted OR Never/No (REF) Never/Yes (2.6-12) Low/No ( ) Low/Yes (7.6-32) High/No (4.9-22) High/Yes (16-64) Low = 20 Pack-years or less; High=>20 Pack-years; VGDF=Vapors, Gas, Dust, or Fumes by Job Exposure Matrix COPDGene Study Cohort COPD Risk I van Koeverden, PD Blanc, RP Bowler, M Arjomandi. J Chronic Obstr Pulm Dis [2015;12:182-9] Multivariate analysis in 1400 ever employed subjects all current or former smokers, with or without COPD. COPD risk from secondhand smoke (SHS) and occupational exposures (job exposure matrix). Adjusted for direct smoking, sex, age CT Scan Evidence for the Occupational Burden for Emphysema, COPD, and Airway wall Thickening Marchetti N et. al. Am J Respir Crit Care Med 2014 [COPDGene] More CT Scan Evidence (COPDGene Study) Occupational Burden for Emphysema, COPD, and Airway Wall Thickening D Stinson, N Marchett, JE Hart, PD Blanc, et. al. Risk of Chronic Respiratory Symptoms, QCT Measures of Disease, and COPD Attributable to Occupational Factors is Similar for Job Exposure Matrix, Self-reported Exposure, and Lower Educational Level as an Exposure Surrogate in COPDGene. Am J Respir Crit Care Med 2015:191:A2592 (Abstract) Figure 3. Effect of occupational exposure on the presence of gas trapping greater than 20% and emphysema greater than 6% as measured by quantitative computed tomography assessment. Analyses were adjusted for age, race, pack-years of smoking, education, body mass index, and current smoking status. The odds ratios were similar in men and women for (A) % gas trapping and (B) % emphysema. End Point Self-Report Dust and Fumes Exposure (Exposed n=4,633) JEM Exposure by Main Occupation (Exposed n=3,398) OR (95% CI) p-value OR (95% CI) p-value COPD (GOLD 2,3,4) 1.46 ( ) < ( ) <.0001 % Emphysema > 6% 1.62 ( ) < ( ) Effect of occupational exposure on the presence of gas trapping greater than 20% and emphysema greater than 6% as measured by quantitative computed tomography assessment. Analyses were adjusted for age, race, pack-years of smoking, education, body mass index, and current smoking status. % Gas Trapping > 20% 1.36 ( ) < ( ) <.0001 Pi10 > 3.75mm 1.23 ( ) ( ) <

16 Occupational Exposure and COPD Severity (Spiromix Study) Paulin LM, Diette GB, Blanc PD, et. al. Occupational exposures are associated with worse morbidity in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015; 191: Other COPD Data Since 2008 [Never smoker data in red] Location, YR, Pub Key Findings of Occupational Risk for COPD USA, 2008; Weinmann, JOEM Smokers (n= 644)PAR 19%; (n=100 never smokers) PAF 43% Italy, 2008; Boggia, JOEM (n=2019) Significant occupation*cigarette interaction p<0.001 Spain, 2008; Rodriguez, CHEST (n=195) OR vs. GOLD I (referent): Gold IV, 6.9; III, 1.7; II, 1.0 Columbia, 2008; Caballero, CHEST (n=5539) Univariate OR: Gas/fume, 1.9; Dusts, 1.4) UK, 2010; Melville, ERJ (n=185) OR=3.0 [PAF 50%] S Africa, 2011; Govender, Thorax (n=212) OR 5.9 (Dust); 3.6 (Gas/fumes); PAR 27% International (BOLD), 2011; Lamprecht, CHEST USA (COPDGene), 2011; Hersh, CHEST (n=4291 all never smokers). COPD GOLD II, FEV1/FVC < LLN: organic dust exposure OR women, 2.6; men, 2.6 [PAR 18%] 821 COPD (LLN) [50 pkyrs] vs. 776 referent smokers [27 pkyrs w/o COPD; smoking adjusted OR occupation (self report)=1.5 Switzerland, 2012; Mehta, AJRCCM (n=4267) Incidence GOLD II, OR[IRR]=1.5 PAF 24% (n=1740 never smokers) Incidence GOLD II, OR=3.3 PAR 51% China, 2012; Lam, Respir Med (n=8216) OR =1.4; PAF 10.4% Russia 2012; Mazitova, Arch Hig (n=1375, all industrial workers) OR=5.9; PAF 65% Rada Toksikol (n=776 never smokers) OR= 22.2; PAR=81% Finland 2014; Pallasaho, COPD (n=4302, f/u population sample) OR 2.1 ( ) USA 2014 (MESA);Doney, COPD Denmark 2015; Würtz, Occup Environ Med (n=3686) VGDF+cig, OR=7.0; VGDF no cig, OR=2.4 (n=1575 all never smokers). COPD by FEV1/FVC <LLN; VGDF OR 3.7, PAF=48% Location, YR, Pub Spain, 2014, Rodrigues, PLOS One New Zealand, 2014; Hansell, JOEM Of Note: Recent Negative Studies Key Findings 1 st time Hospitalized for COPD (n=338) Occupational exposure not associated with airflow obstruction or decreased DLco (associated with better DLco in long term quitters/never smokers) Highest exposure higher FEV 1 (n=750 with lung function); protective (NS) for MD diagnosed COPD (n=1017); increased risk (NS) for chronic bronchitis [after adjustment including SES (deprivation index)]. Other data from same study [unpublished] VDGF risk of COPD by Lower Limit Normal OR 1.62 ( ) but adjusted for demographics including social deprivation, OR 1.07 ( ) Note: Both studies used the same Job Exposure Matrix system (ALOHA) Another Recent Negative Study Nigeria BOLD Cohort 875 Adults; 7.7% COPD; 90% never smokers Multivariate logistic regression of chronic airflow obstruction (FEV1/FVC <LLN) Variable OR 95% CI P value Ex Smoker Current Firewood or coal for cooking or heating Ever engaged in farming (n=386; 44.2%) Ever worked in dusty job (n=309; 35.3%) Location, YR, Pub Nigeria, 2015, Obaseki DO, et. al. Chronic Airflow Obstruction in a Black African Population: Results of BOLD Study, Ile Ife, Nigeria. COPD Feb; 13:42 9. Key Findings Discussion: We did not observe any association between occupational exposures and CAO [chronic airflow obstruction]. Farmers who have a variable occupational exposure to dust, fumes and other chemicals like pesticides, made up 43.5% of the respondents (data not shown) and they were not at increased risk of CAO (OR: 0.8, 95%CI: 0.4, 1.6). Working in a dusty job was also not a significant determinant of airflow obstruction in our population, probably reflecting the fact that Ile Ife is a non industrial city. 16

17 Mazitova N.N. OCCUPATIONAL FACTORS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A META ANALYSIS FUNDAMENTAL RESEARCH 2011; 9: Emerging Meta Analyses of COPD and Occupation 2011, 2015, 2016 PAR % of occupational COPD 15 % ; OR = 1.59 (95 % CI ) Ryua J Y et al. Chronic Obstructive Pulmonary Disease (COPD) and Vapors, Gases, Dusts, or Fumes (VGDF): A Meta analysis. COPD 2015; 12: Sheikh M. Alifa SM et. al. Occupational exposure and risk of chronic obstructive pulmonary disease: a systematic review and meta analysis. Expert Rev Respir Med 2016; 10: Overall association between exposure to VGDF and COPD in random effects model meta analysis (n = 11) (analyzed by subgroup of study design). ES = effect size. Limited to studies using a single JEM (ALOHA) 5 pubs for PFTs; 3 for chronic bronchitis, the analysis shown here. 17

18 Relevant Industry Specific Exposures Coal mining emphysema (autopsy based) Coal mining COPD per dust years exposure Cotton dust Stage IV byssinosis = COPD Vanadium Bronchitis Biomass fuel smoke COPD, bronchitis Omlanda Ø, Würtz ET, Aasen TB, Blanc P, et. al. Occupational COPD: a systematic literature review. Scan J Work Health Environ 2014; 40:19 35 Exposure, Location of Study Occupational Exposure Annual Loss in FEV1 Cigarette Smoking Annual Loss in FEV1 Coal miners, UK 4 8 ml 11 ml Coal miners, USA 7 ml 9 ml Industrial workers, Paris 8 ml 11 ml Silica, various countries 4 ml 7 ml Steel workers, USA 5 ml 9 ml Metal fumes, Norway 4 ml 7 ml Wood dust, Denmark ( ) 4ml 8 ml Other specific exposures with data indicating COPD risk: Welding, coke ovens, asphalt, cement, tunneling, glass, bleach, cotton, flax, jute, grain, wood, paper, rubber, farming (endotoxin) Summary of Data Multiple studies, worldwide, various methods: occupation COPD, chronic bronchitis Both COPD and chronic bronchitis: PAR% estimates yield a median value ~ 15% COPD in non-smokers (n=8 values) PAF: 18, 26, 30, 42, 43, 51, 53, 81 median=42.5%] Emphysema: data are limited, but suggestive Exposure may COPD severity and morbidity among those with COPD Clinical Implications An occupational history should be obtained in all COPD patients Exposure to vapors, gas, dusts, or fume may be a reasonable screening question In smokers, occupation can still contribute to COPD onset and/or progression In non-smokers, the proportional role is Smoking + VGDF additive (no synergy) 18

19 Policy Implications By consistency, strength of association, and biologic plausibility: occupational exposure is causally related to COPD This is a worldwide problem affecting men and women COPD could be reduced by at least 15% if the causal exposures were controlled In non-smokers the impact may be greater Clinical and Policy Goal: Cutting Out a Piece of the Pie COPD PAR% Occupation Smoking Other Collaborators ATS Committee: John Balmes MD, Margaret Becklake MD, Paul Henneberger PhD, Kathleen Kreiss MD, Cristina Mapp MD, Giovanni Viegi MD, Don Milton MD, David Schwartz MD, Kjell Torén MD Post-ATS Literature Review: Kjell Torén MD UCSF Initial COPD Study and Further Exploration of Links : Edward Yelin PhD, John Balmes MD, Laura Trupin MPH, Mark Eisner MD, Patti Katz PhD, Gillian Earnest MS FLOW Study: Mark Eisner MD (PI), Carlos Iribarren MD, Edward Yelin PhD, Patti Katz PhD Ecological Analysis: Ana Menezes MD, Estel Plana PhD, David Mannino MD, Pedro Hallal PhD, Kjell Torén MD, Mark D. Eisner MD, Jan-Paul Zock PhD Sheffield Study: Anthony Darby MD, David Fishwick MD, Judith Waterhouse RN, along with V. Stevens, Clare Billings, Catherine Billings, C Burton, C. Young, and J. Wight COPDGene Analysis: Ian van Koeverden, Russell Bowler, and Mehrdad Arjomandi Danish Working Group: TB Aasen, J Brisman, MR Miller, Ø Omland, OF Pedersen, V Schlünssen, T Sigsgaard, CS Ulrik, S Viskum, ET Würtz. 19

20 1. What is the best estimate of the occupational burden of COPD and CB? A. 7% B. 30% C. 15% D. <5% 2. COPD and CB only partially overlap because: A. COPD and CB both require a physician s diagnosis B. COPD is defined by airflow; CB by symptoms C. COPD requires both lung function and a radiographic findings D. COPD responds to medication, CB does not 3. Future trends are most likely to change the work-associated PAF for COPD and CB by: A. Smoking reduction increasing the relative contribution of work and other factors B. Eliminating the PAF relevant exposures C. Increasing the PAF because of nanoparticles D. Genetic drift will increase resistance to COPD REFERENCES 1. Balmes J, Becklake M, Blanc P, et. al. American Thoracic Society statement: occupational contribution to the burden of airway disease. Am J Respir Crit Care Med 2003; 167: Trupin L, Earnest G, San Pedro M, Balmes JR, Eisner MD, Yelin E, Katz PP, Blanc PD. The occupational burden of chronic obstructive pulmonary disease. Eur Respir J 2003; 22: Blanc PD, Eisner MD, Trupin L, Yelin EH, Katz PP, Blames JR. The association between occupational factors and adverse health outcomes in chronic obstructive pulmonary disease. Occup Environ Med 2004; 61: Blanc PD, Torén K. Occupation in COPD and chronic bronchitis: an update. Int J Tuberc Lung Dis 2007;11: Blanc PD, Iribarren C, Trupin L, Earnest G, Katz PP, Balmes J, Sidney S, Eisner MD. Occupational exposures and the risk of COPD: dusty trades revisited. Thorax 2009; 64:

21 6. Blanc PD, Menezes A-M B, Plana E, et. al. Occupational exposures and COPD: An ecological analysis of international data. Eur Respir J 2009;33: Blanc PD, Eisner MD, Earnest G, Trupin L, Balmes JR, Yelin EH, Gregorich SE, Katz PP. Further exploration of the links between occupational exposure and chronic obstructive pulmonary disease. JOEM 2009; 51: Blanc PD. COPD and occupation: a brief review. J Asthma 2012; 49: Darby AC, Waterhouse JC, Stevens V, Billings CG, Billings CG, Burton CM, Young C, Wight J, Blanc PD, Fishwick D. Chronic obstructive pulmonary disease among residents of an historically industrialised area. Thorax Thorax 2012; 67: Blanc PD, Hnizdo E, Kreiss K, Toren K. Chronic obstructive airways disease due to occupational exposure. In: Asthma in the Workplace 4th Boca Raton: CRC Press, Taylor & Francis Group, 2013, Omland O, Würtz ET, Aasen TB, Blanc P, et al. Occupational chronic obstructive pulmonary disease: a systematic literature review. Scand J Work Environ Health. 2014; 40: Koeverden Iv, Blanc PD, Bowler RP, Arjomandi M. Secondhand tobacco smoke and COPD risk in smokers: A COPDGene Study Cohort subgroup analysis. COPD. 2015;12: Paulin LM, Diette GB, Blanc PD, et. al. Occupational exposures are associated with worse morbidity in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015; 191: Stinson D, Marchetti N, Hart JE, Blanc PD, et. al. Risk of chronic respiratory symptoms, Qct measures of disease, and COPD attributable to occupational factors is similar for job exposure matrix, self-reported exposure, and lower educational level as an exposure surrogate in COPDgene. (Abstract) Am J Respir Crit Care Med :A Blanc PD, Toren K. COPD and occupation: Resetting the agenda. Occup Environ Med. 2016; 73: Reviews by others: 1. Balmes JR. Occupational contribution to the burden of chronic obstructive pulmonary disease. J Occup Environ Med 2005; 47: Fishwick D, Barber CM, Darby AC. Chronic Obstructive Pulmonary Disease and the workplace. Chron Respir Dis 2010; 7: Naidoo RN. Occupational exposures and chronic obstructive pulmonary disease: incontrovertible evidence for causality? Am J Respir Crit Care Med. 2012;185: Diaz-Guzman E, Aryal S, Mannino DM. Occupational chronic obstructive pulmonary disease: an update. Clin Chest Med. 2012; 33: