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 14-30

• Maximum of 1½ packs per day

• Quit 40 years previously

• Under 25 pack years total

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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 (1989-94)

• Less exposure 1994-1998, 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

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

While at work: 99mls loss FEV1/yr [p<0.01]; After exposure cessation: FEV1 ∆ NSWhile at work: FVC ∆ NS; After exposure cessation 109 mls loss FVC/yr [p<0.01]

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Other Data

• Serum alpha1anti-trypsin (AIAT) assay

• Electrophoresis with agarose immuno-fixation

• ZZ phenotype

• Quantified value: 24 units (normal ≥90).

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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 [FEV1]

– And/or its ratio to the total breath [FEV1/FVC]

• Cut-points use to define COPD vary:– FEV1/FVC < 0.70 [GOLD Stage I]

– FEV1/FVC < 0.70 + FEV1<80% pred [Gold II]

– FEV1/FVC < 0.60 [some older studies]

– FEV1/FVC <90th %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

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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”

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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: COPDBreathlessness (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. ’

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UCSF COPD StudyTrupin, Earnest, San Pedro, Balmes, Eisner, Yelin, Katz, Blanc

Eur Respir J 2003 22:462-9

• 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 55-75

• National USA (48 contiguous states)

• Over-sampling in regions with higher

COPD-related mortality

• Supplemental recruitment of subject-

reported 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

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702

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Figure 1. Telephone Area Codes Corresponding to “Hot Spot” Health Service

Areas with Highest Age-Adjusted COPD Mortality Rates, 1982 - 1993

1,001 (48%)

Interview completed

17,442

Total contacts

2,081

Potential participants

National RandomSample

“Hot Spots”Random Sample

Figure 2. Recruitment of Study Participants in Three Cohorts

16,042

Total contacts

1,002 (54%)

Interview completed

1,850

Potential participants

“Hot Spots”Condition Sample

155Potential participants (with airway condition)

7,583

Total contacts

110 (71%)

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”

Figure 3. Specific and Global VGDF

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Diagnosis By Exposure Status Risk of COPD by ExposureAll 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

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Occupational Factors as Predictors of COPD Outcomes

Blanc et al. Occup Envrion Med 2004; 61:661-7

• 12 month follow-up, airways disease cohort

• 517 at baseline352 (69%) re-interviewed

• 267 of 352 (76%) with COPD

• 242 with any work history/ 234 complete data

Risk of Health Utilization for Respiratory DiseaseAdjusted 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 (0.3 -2.4) 2.1 (0.5 – 8.4)

Prior job change due to breathing 1.2 (0.3 – 5.0) 6.3 (1.2 – 33.0)

Both risk factors 3.9 (1.4 – 10.5) 7.6 (1.8 – 32.1)

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 updateBlanc & Torén, Int J Tuberc Lung Dis (IJTLD) 2007; 11:122-33

• 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

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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; 60:645-651)

• 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 (1.4-7.1) [PAR% >45%]

Mineral dust by JEM: OR 1.07 (0.46-2.45) [PAR% 2%]

Gases and fumes by JEM: 1.3 (0.57 -2.8) [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

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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 40-65

• 30 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 COPD n=1202

Controlsn=302

OR (95% CI) PAR%

Exposure to VGDF

58% 39% 1.9 (1.4-2.5) 27%

[GOLD ≥ 2]

Exposure to VGDF

[n=742]

60%

[n=302]

39% 1.9 (1.3-2.6) 27%

Exposure by Job Exposure Matrix (JEM) on Longest Held Job

Multiple logistic regression adjusted for smoking, age, race, sex

JEM Exposure

COPD n=1202

Controlsn=302

OR (95% CI) PAR%

Intermediate Exposure

9% 7% 1.3 (0.7-2.2) 2%

High Exposure

23% 11% 2.1 (1.5-3.5) 13%

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Smoking-Occupation EffectsAll COPD vs. Controls

Cigarette/Work VGDF

Exposure

Subject n

Probability COPD

Excess Prob.

Adjusted OR

Never/No 178 0.44 0 1.0 (REF)

Never/Yes 145 0.60 0.16 2.0 (1.3-3.1)

Ever/No 512 0.83 0.40 6.7 (4.6-9.8)

Ever/Yes 669 0.91 0.47 14.1 (9.3-21)

Further Exploration of the Links Between Occupational Exposure and COPD

Blanc et al. J Occup Environ Med 2009 51:804-10

• 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 (FEV1/FVC <0.70) among 98 cases and 1652 Referents

Risk Group OR (95% CI)

No smoking up to 10 pack-years and no occupational exposure

1.0 (Referent)

No or minimal smoking; occupational exposure

2.0 (0.9-4.6)

Smoking>10 pack years; No occupational exposure

3.7 (1.9-7.1)

Smoking and occupational exposure

5.9 (2.9-12.0)

Occupational Exposures and COPD: An Ecological Analysis of International Data

Blanc et al. Eur Respir J. 2009; 33:298-304

Study Cohort (n)

NationsIncluded

StudySites

Study Subject Number per Site

Men Women

N n Median (Range) Median (Range)

BOLD (8775)

12 12 334 (206-685) 343 (237-435)

ECRHS II (4648)

14 28 70.5 (30-179) 78.5 (35-79)

PLATINO (5671)

5 5 442 (380-474) 632 (558-983)

All (19094) 31 45 111 (65-324) 108 (72 -334)

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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 per 10% ↑ EXP

p value

All study sites/strata (n=90)

% Ever Held Dusty/Dirty Jobs 0.8% (0.3-1.3%) 0.003

% Ever Smokers 1.3 (0.7-1.8%) <0.001

Men only (n=45 sites)

% Ever Held Dusty/Dirty Jobs 0.8% (0.3-1.3%) 0.004

% Ever Smokers 0.9% (0.1-1.8%) 0.04

Women only (n=45 sites)

% Ever Held Dusty/Dirty Jobs 1.0% (0.1-11.9%) 0.03

% Ever Smokers 1.1% (0.4-1.8%) 0.005

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Chronic obstructive pulmonary disease among residents of an historically industrialised areaDarby, 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 530 0.02 0 1.0 (REF)

Never/Yes 302 0.08 0.06 5.6 (2.6-12)

Low/No 248 0.07 0.05 4.0 (1.8-8.9)

Low/Yes 279 0.18 0.16 15.7 (7.6-32)

High/No 186 0.15 0.13 10.4 (4.9-22)

High/Yes 338 0.31 0.29 32 (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 RiskI 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]

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.

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.

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)

End PointSelf-Report Dust and

Fumes Exposure(Exposed n=4,633)

JEM Exposure by MainOccupation

(Exposed n=3,398)

OR (95% CI) p-value OR (95% CI) p-value

COPD (GOLD 2,3,4) 1.46 (1.30 - 1.63) < .0001 1.46 (1.30 - 1.64) < .0001

% Emphysema > 6% 1.62 (1.43 - 1.84) < .0001 1.14 (1.00 - 1.30) 0.0422

% Gas Trapping > 20% 1.36 (1.22 - 1.53) < .0001 1.36 (1.21 - 1.52) < .0001

Pi10 > 3.75mm 1.23 (1.10 - 1.38) 0.0004 1.43 (1.27 - 1.61) < .0001

Table 1.

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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; 191:557‐65. 

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

(n=4291 all never‐smokers). COPD ≥GOLD II, FEV1/FVC < LLN:  organic dust exposure OR women, 2.6; men, 2.6 [PAR ≈18%]

USA (COPDGene), 2011; Hersh,CHEST 

821 COPD (LLN) [50 pkyrs] vs. 776 referent smokers [27 pkyrsw/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 HigRada Toksikol

(n=1375, all industrial workers) OR=5.9; PAF 65%                            (n=776 never‐smokers)  OR= 22.2; PAR=81%

Finland 2014; Pallasaho, COPD (n=4302, f/u population sample) OR 2.1 (1.3‐3.4)

USA 2014 (MESA);Doney, COPD (n=3686) VGDF+cig, OR=7.0; VGDF no cig, OR=2.4

Denmark 2015; Würtz, OccupEnviron Med

(n=1575 all never‐smokers). COPD by FEV1/FVC <LLN;         VGDF OR 3.7, PAF=48%  

Of Note: Recent Negative Studies

Location, YR, Pub Key Findings

Spain,  2014, Rodrigues , PLOS One 1st 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)  

New Zealand, 2014; Hansell,  JOEM

Highest exposure  higher FEV1 (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 (1.01 – 2.62) but adjusted for demographics including “social deprivation,”  OR 1.07 (0.64 – 1.81)

Note: Both studies used the same Job Exposure Matrix system (ALOHA) 

Another Recent “Negative” Study

Location, YR, Pub Key Findings

Nigeria, 2015, Obaseki DO, et. al. Chronic Airflow Obstruction in a Black African Population: Results of BOLD Study, Ile‐Ife, Nigeria. COPD. 2016 Feb; 13:42‐9.

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.”

Nigeria BOLD  Cohort875 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  0.8 0.2  ‐ 2.9 0.78

Current  2.4 0.4  ‐ 12.5 0.31

Firewood or coal for cooking or heating 1.2 0.5 ‐ 2.7 0.66

Ever engaged in farming (n=386; 44.2%)  0.8 0.4  ‐ 1.6 0.60

Ever worked in dusty job (n=309; 35.3%)  1.5 0.7  ‐ 3.0 0.27

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Emerging Meta‐Analyses of COPD and Occupation

2011, 2015, 2016

Mazitova N.N. OCCUPATIONAL FACTORS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A META‐ANALYSIS FUNDAMENTAL RESEARCH 2011; 9: 599‐92

PAR % of occupational COPD  15 % ; OR = 1.59 (95 % CI 1.48–1.72)

Ryua J Y et al. Chronic Obstructive Pulmonary Disease (COPD) and Vapors, Gases, Dusts, or Fumes (VGDF): A Meta‐analysis. COPD 2015; 12: 374‐80

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.  

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: 861 ‐72.  

Limited to studies using a single JEM (ALOHA) 5 pubs for PFTs; 3 for chronic bronchitis, the analysis shown here.

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Relevant Industry Specific Exposures

• Coal miningemphysema (autopsy‐based)

• Coal miningCOPD per dust years exposure  

• Cotton dustStage IV byssinosis = COPD

• VanadiumBronchitis

• Biomass fuel smokeCOPD, 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 

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)

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

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)

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Policy Implications

• By consistency, strength of association, and biologic plausibility: occupational exposure is causally related to COPD

• This is a worldwide problem affecting menand 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 MDPost-ATS Literature Review: Kjell Torén MDUCSF 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 MSFLOW Study: Mark Eisner MD (PI), Carlos Iribarren MD, Edward Yelin PhD, Patti Katz PhDEcological 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. WightCOPDGene Analysis: Ian van Koeverden, Russell Bowler, and Mehrdad ArjomandiDanish Working Group: TB Aasen, J Brisman, MR Miller, Ø Omland, OF Pedersen, V Schlünssen, T Sigsgaard, CS Ulrik, S Viskum, ET Würtz.

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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: 787-797.

2. 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: 1-9.

3. 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; 61:661-7.

4. Blanc PD, Torén K. Occupation in COPD and chronic bronchitis: an update. Int J Tuberc Lung Dis 2007;11:1-7.

5. 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; 64:6-12.

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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;33:298-304.

7. 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: 804-810

8. Blanc PD. COPD and occupation: a brief review. J Asthma 2012; 49:2-4.

9. 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; 67:901-7

10.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, 375-391.

11.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; 40:19-35

12.Koeverden Iv, Blanc PD, Bowler RP, Arjomandi M. Secondhand tobacco smoke and COPD risk in smokers: A COPDGene Study Cohort subgroup analysis. COPD. 2015;12:182-9.

13.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; 191:557-65

14.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 2015 191:A2592.

15.Blanc PD, Toren K. COPD and occupation: Resetting the agenda. Occup Environ Med. 2016; 73:357-8.

Reviews by others:

1. Balmes JR. Occupational contribution to the burden of chronic obstructive pulmonary disease. J Occup Environ Med 2005; 47:154-160.

2. Fishwick D, Barber CM, Darby AC. Chronic Obstructive Pulmonary Disease and the workplace. Chron Respir Dis 2010; 7:113-22

3. Naidoo RN. Occupational exposures and chronic obstructive pulmonary disease: incontrovertible evidence for causality? Am J Respir Crit Care Med. 2012;185:1252-4

4. Diaz-Guzman E, Aryal S, Mannino DM. Occupational chronic obstructive pulmonary disease: an update. Clin Chest Med. 2012; 33:625-36