[PDF] - Goals Occupational COPD and Chronic Bronchitis Define COPD and PDF Document

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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

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

Volume in Liters (FEV1, FVC) Flow in Liters Second -1 (FEF25-75)

0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14 FVC FEV FEF 1 2 3 4 5 6 2/1/2005 6/1/2005 10/1/2005 2/1/2006 6/1/2006 10/1/2006 2/1/2007 6/1/2007 10/1/2007 2/1/2008 6/1/2008 10/1/2008 2/1/2009 6/1/2009 10/1/2009 2/1/2010 6/1/2010 10/1/2010 2/1/2011 6/1/2011 10/1/2011 2/1/2012 6/1/2012 10/1/2012 2/1/2013 6/1/2013 10/1/2013 2/1/2014 6/1/2014

DLco/VA

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: 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%)

f 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 Study

Trupin, 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)
f 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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702 740 Colorado 719 New Mexico Arizona Nevada Texas Oklahoma Kansas Utah Wyoming Idaho Montana Oregon North Dakota South Dakota Minnesota Nebraska Iowa Missouri Arkansas Tennessee Washington Illinois Kentucky Louisiana Wisconsin Ohio Pennsylvania WV Virginia 304 814 IN Alabama MS South Carolina North Carolina Florida 904 850 New York VT NH MD MA CT RI 802 207 530 760 909 916 NJ DE 302 MI Maine 209 559 661 Georgia

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 Random Sample “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 155 Potential 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

0% 5% 1 0% 1 5% 20% 25% 30% 35% 40% 45% 50%

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Specific VGDF Exposure % reporting

global exp no global exp

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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

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Occupational Factors as Predictors

f COPD Outcomes

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

12 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 (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 update

Blanc & 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

Controls

n=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

Controls

n=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 Effects

All COPD vs. Controls

Cigarette/ Work VGDF Exposure Subject n Probability COPD Excess Prob. Adjusted OR Never/No 178 0.44 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
f 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;

ccupational exposure

2.0 (0.9-4.6) Smoking>10 pack years; No

ccupational 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) Nations Included Study Sites 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 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 530 0.02 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 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]

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 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 (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:

rganic 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 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 Rada 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, Occup Environ 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

f BOLD Study, Ile‐Ife, Nigeria.
COPD. 2016 Feb; 13:42‐9.

Discussion: “We did not observe any association between

ccupational 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 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

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.

SLIDE 18

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 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:
ccupation  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
btained 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 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.

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1. What is the best estimate of the
ccupational 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

f 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.

SLIDE 21

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;33:298-304.

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

bstructive 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

bstructive 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
bstructive 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
bstructive pulmonary disease: an update. Clin Chest Med.