Work-Related AsthmaMOEMA 9/23/2016

Kenneth D. Rosenman, M.D.

Professor of Medicine

Michigan State University

www.oem.msu.edu

Rosenman@msu.edu

517 353-1846

OBJECTIVES

Highlight the Importance of Considering Occupational and Environmental Exposures in Diagnosis and Treatment of Asthma

Discuss Approaches to Diagnosing Work- Related Asthma

Work-Related Asthma (WRA)

Work Aggravated Asthma (WAA)

New-Onset Work-Related Asthma (NOA)

Occupational Asthma

Irritant-Induced Asthma Reactive Airways

Dysfunction Syndrome (RADS)

Work-Related Asthma

Work-Related Asthma

Variable airway narrowing related to exposure in the working environment to airborne dusts, gases, vapors for fumes. ~36.5% of adult asthma is work-related.

Aggravation Pre-Existing Asthma – 21.5% Adult AsthmaDirect effect on the irritant receptors in bronchi (eg. cold air,particulates)

New Onset - 15% Adult AsthmaNo Latency Period -Reactive Airways Dysfunction Syndrome (RADS) Acute inflammatory bronchoconstriction from exposure to highconcentrations of an irritant (e.g. acids, hydrogen sulfide, smoke).

With Latency Period – Occupational (Allergic)Immune mediated effect which develops after a variable periodof symptomless exposure to a sensitizing agent.

Mechanisms Involved in Sensitizer-Induced Asthma and Irritant-Induced Asthma.

Tarlo SM, Lemiere C. N Engl J Med 2014;370:640-649

What Percentage of Asthma is Work-Related?

Consensus Statements American Thoracic Society

Am J Resp Crit Care Med 2003;167:787-797Am J Resp Crit Care Med 2011;184:368-378

New Onset Asthma

21 studies - range 4-58%, 15% median

Work Aggravated Asthma

12 studies - range 13-58%, 21.5% median

Estimates of Current Asthma Attributable to Work by Selected Definitions, Adults (18 Years) with Current Asthma: MI, MN, & OR

1. Yes to at least one of questions 1, 2, 3, or 4

2. Yes to at least one of questions 5 or 6

3. Yes to at least one of the 6 questions

(Lutzer etal. J Asthma, 2010)

CHEST SupplementDIAGNOSIS AND MANAGEMENT OF WORK-RELATED ASTHMA: ACCP CONSENSUS STATEMENT

Diagnosis and Management ofWork-Related AsthmaAmerican College of Chest PhysiciansConsensus Statement

Susan M. Tarlo, MBBS, FCCP; John Balmes, MD, FCCP;Ronald Balkissoon, MD; Jeremy Beach, MD; William Beckett, MD, MPH, FCCP;David Bernstein, MD; Paul D. Blanc, MD, FCCP; Stuart M. Brooks, MD;Clayton T. Cowl, MD, MS, FCCP; Feroza Daroowalla, MD, MPH, FCCP;Philip Harber, MD, MPH; Catherine Lemiere, MD, MSc;Gary M. Liss, MD, MS; Karin A. Pacheco, MD, MSPH;Carrie A. Redlich, MD, MPH, FCCP; Brian Rowe, MD, FCCP;and Julia Heitzer, MS

CHEST / 134 / 3 / SEPTEMBER, 2008 SUPPLEMENT 1s-41s

1. “In all individuals with new-onset or worsening asthma, take a history to screen for WRA (OA and WEA). Then confirm the diagnosis of asthma and investigate to determine whether the patient has WRA, performing these tests, whenever possible, prior to advising the patient to change jobs.”

1)Were there changes in work processes in the period preceding the onset of symptoms?

2)Was there an unusual work exposure within 24 h before the onset of initial asthma symptoms?

3)Do asthma symptoms differ during times away from work such as weekends or holidays or other extended times away from work?

4)Are there symptoms of allergic rhinitis and/or conjunctivitis symptoms that are worse with work?

Questions Recommended By ACCP Consensus Statement

For Adults with Lifetime Asthma who Report Asthma was Caused/Aggravated by Any Job, the Proportion who Discussed

with a Health Professional that Their Asthma was Work-Related: MI, MN, & OR

(Lutzer etal. J Asthma, 2010)

Severity of Asthma Symptoms by Duration of Exposure to Allergenic Substance

Sev

erit

y o

f S

ym

pto

ms

Duration of Exposure

WE=Weekend

WE

WE

Mast Cell Mediators

PerformedMediators

NewlySynthesized Mediators

Neutrophilchemotactic factor

Platelet activating factor

Eosinophilchemotactic factor

Leukotriene B4, C4, and D4

Histamine PGD2

Tryptase Thromboxanes

Kininogenases Cytokines (IL-3,4,5,6, TNF-)

(Asthma+ Allergy Proc 1997; 18:227-233

Primary Care Doctor05/03 “asthma, increase Advair”07/03 “poorly controlled asthma”, increase Advair dose09/03 “asthma about the same”11/03 “He notices chemicals at work seem to trigger his asthma. He does

wear a respirator and had talked to the occupational health doctor at the job site. They are monitoring his breathing. He doesn’t seem to have trouble outside the office.”

09/04 “was exposed to chemical at work again”11/04 “exposed isocyanate”08/05 “trouble with dyspnea from bronchospasm from occupational

exposure to lung irritants. This has been going on for some time. He has been on prednisone, averaging one taper per month. It seems that this is not the best route to go long term. He is considering leaving his work but if he leaves voluntarily on his ownhe loses his severance pay, so he is wondering if there is any way medical reason for leaving his job might help him to retain his severance. I recommend that we have him see a pulmonologist for further evaluation at this point.”

Company Doctor

10/3

Noted under care for asthma with medication

10/4

“Doesn’t work with isocyanates but when incidentally exposed flares up. Happens every 3 months, own doctor treats antibiotics and bronchodilator”

Abnormal spirometry – urged to stop smoking

Company Medical Screening

Date FEV1 Pred % Predicted

January 2002 3.75 L 3.94 95

September 2002 3.60 L 3.77 96

October 2003 3.27 L 3.74 87

October 2004 2.58 L 3.54 73

Prevalence of 1 Asthma ED/UC Visit (1 year) by Work-Relatedness, Adults (18 Years) with Current Asthma:

MI, MN, & OR

19.4 14.7 1112.4 90

10

20

30

MI (n=331; 238) MN (n=171; 147) OR (n=348;305)

Pe

rce

nt

WRA** Non-WRA

*

(Lutzer etal. J Asthma, 2010)*p<0.0001

**Yes to at least one of the 6 questions §Data suppressed due to estimate stability.

ED=Emergency Department; UC=Urgent Care

§

Web Based Listing of Agents Associated with New Onset Work-Related Asthma

Rosenman KD, Beckett WSRespiratory Medicine May 2015; 109: 625–631

http://www.sciencedirect.com/science/article/pii/S0954611115001031

http://www.aoecdata.org/ExpCodeLookup.aspx

Work Processes, in the Automotive Manufacturing

Industry with Possible Exposure to

Agents that Cause Asthma

Vehicle Parts Manufacturing

Work Process Exposure

Metal Parts Core/Mold Production Isocyanates

Machining Metal Working Fluids

Forging/Stamping Drawing Compounds

Polyurethane

foam

Foam Production for Seats,

Arm Rests

Isocyanates

Plastic Parts Extrusion/Injection Molding Styrene

Polyvinyl Chloride

Formaldehyde

Vehicle Assembly

Body Shop Welding Welding Fumes

Nox, Ozone,

Particulates

Paint Line Painting Isocyanates

Assembly Gluing Isocyanates

Epoxies

New Causes of Occupational Asthma

ChemicalsColistin (polymixin antibiotic) manufacture

5-Amino salicylic acid manufacture

Rhodium salts in electroplating facility

Triglycidyl isocyanurate in electrostatic powder painting

Insects Amblyseius californicius predatory mites in tomato greenhouse

Caddis flies around hydroelectric dams

FungusChrysonilia sitophilia in coffee grounds

PlantsCabreua wood used in parquet floors

Rice powder

(Current Opinion Allergy Clinical Immunology 2011; 11:80-85)

Material Safety Data Sheet

1. PRODUCT IDENTIFICATION

PRODUCT NAME…………………………………………INSTANT-LOK (R)

2. HAZARDOUS INGREDIENTS

INGREDIENT NAME/CAS NUMBER/PERCENTAGEEXPOSURE LIMITS

PARAFFIN WAX OSHA….. 2 mg/m3CAS NUMBER……………………8002-74-2 ACGIH….2 mg/m3OSHA PERCENTAGE………….. >1 STEL…....6 mg/m3

CEILING..none

Chlorine

Acid + Hypochlorite = Chlorine Gas(Bleach)

4H+ + 2OCl- = +Cl2 + 2H2O

Chloramine

Ammonia + Hypochlorite = MonoChloramine

(Bleach)

NH3 + OCl- = NH2Cl + OH-

Dichloramine

NH3 + 2OCl- = NHCl2 + 2OH-

Mixture of Acid or Ammonia and Bleach

Generation of Disinfection By-Products

Uyan ZS, et al. Swimming Pool, Respiratory Health, and Childhood Asthma: Should We Change Our Beliefs? Pediatric Pulmonology 2009; 44:31-37

Highest Concentrations of DBP

Chronic Exposure to DBP and Respiratory Effects

Competitive Swimmers• Increased prevalence of asthma in elite swimmers

• Greater proportions of eosinophils and neutrophils in sputum than controls specific antigen testing

• Higher bronchial responsiveness than controls

• Bronchial hyperresponsiveness was attenuated or disappeared in swimmers who stopped training during a 5-year follow-up

Swim instructors, lifeguards, and maintenance• Asthma documented specific antigen testing

• Irritant induced eye, nose, and throat symptoms associated with trichloramine levels

Occupational Asthma

MethacholineChallenge Test

Yes No

Positive 125 179Positive Predictive Value 41.1%

Negative6 120

Negative Predictive Value 95.2%

Total 131 299

Sensitivity 95.4% Specificity 40.1%

False Negative 4.6% False Positive 59.9%

(Adapted Pralong et al J Allergy and Clinical Immunology 2015)

Sensitivity, Specificity & Predictive Value of MethacholineChallenge Tests in Those Still at Work

Occupational Asthma

Methacholine Challenge Test

Yes No

Positive 98 209Positive Predictive Value 31.9%

Negative49 226

Negative Predictive Value 82.2%

Total 147 435

Sensitivity 66.7% Specificity 52.0%

False Negative 33.3% False Positive 48.0%

(Adapted Pralong et al J Allergy and Clinical Immunology 2015)

Sensitivity, Specificity & Predictive Value of MethacholineChallenge Tests in Those No Longer at Work

Change in FEV1 After Challenge to Control Lactose, Fresh Sugar Beet Pulp and Moldy Sugar Beets Pulp

(Rosenman et al, Chest 1992)

FEV1 (% Predicted) Values, 3/7 -12/16/2014

3.25

2.07

2.48

2.91

1.95

2.99

0

0.5

1

1.5

2

2.5

3

3.5

4

3/7/14 10/29/14 11/4/14 11/12/14 11/13/14 12/16/14

Lit

ers/

seco

nd

(68%)

(82%)

(113%)

(64%)

(99%)(91%)

8/27/14 Began Work

Symptoms Began –ED Visit,10/28

Removal from Production Area 10/29 Returned to

Production Area –Symptoms

within 3 Hours 11/13

Chemicals For Which There Are Commercially Available Serum RASTs

Chemical

Isocyanates

TDI – Toluene Diisocyanate

MDI – Diphenylmethane Diisocyanate

HDI – Hexamethylene Diisocyanate

Formaldehyde

Phthalic Annhydride

Latex Rubber

Sensitivity and Specificity of Diagnostic Tests For Work-Related Asthma

Sensitivity Specificity

Clinical History 94% 33-45%

Pre-Post Work Change in FEV1 (5-10%) 22-85% 56-89%

Serum IgE Tests17-72%*

90%**60-85%

Peak Flow (q2h) www.occupationalasthma.com/default.aspx

73% 74-100%

Serial Methacholine 62-67% 54-78%

The range of percentages for the sensitivity and specificity reflect the results from different studies.

*Low molecular weight (chemical) **High molecular weight (animal, plant)

Peak Flow Monitoring

% Variation

Day

4 16 11 6 7 8 4 11 12 4 3 5 7 4 1

-- -- -- -- -- -- -- work -- -- -- -- -- -- -- -- work --

A

<0.1

Dose of Methacholine Needed to Induce20% Decrease in FEV1

12. “An individual diagnosis of OA represents a potential sentinel health event:

Evaluate the workplace to identify and prevent other cases of OA in the same setting; and

For work environments with potential exposure to sensitizers, the Panel advises secondary preventive measures including medical surveillance using tools such as questionnaires, spirometry, and, where available, immunologic tests.”

Breathing Symptoms Among Co-Workers of

3,025 Confirmed WRA Patients,

Michigan 1988-2011# %

Companies Inspected 747

Companies w/Employee on OSHA Log

Workers on OSHA log with Resp. Prob.

131577

17.5

Workers Interviewed 9,785

Daily or Weekly SOB, Wheezing or

Chest Tightness at Work 1,527 15.6

Total 2,095*

*Nine individuals were both on the co-worker questionnaire and the OSHA Log.

Review of 18 of 20 Surviving Employees

Concerns about 5 individuals

3 had abnormal spirometry

1 had significant loss in FEV1 over time

1 had asthma, and was increasing medication

Interviewed 14 employees

1 had daily chest tightness at work

(only 1 of 5 individuals above were interviewed)

Examples of Occupational Respiratory Health Disparities

Condition Results Reference

Lung CancerChromium Smelter Workers

Coke Oven Workers

Uranium Miners

80 vs 15 increased risk, AA vs C3.08 vs 1.94 increased risk, AA vs C

8.18 times increased risk for AA

28.6 times increased risk for Navajo Indians

US PHS, 1953; Rosenman and Stanbury 1996

Lloyd, 1971

Gilliland et al, 2000

SilicosisTunnel Workers

Foundry Workers

South African Gold Miners

Acute Silicosis among AA

Silicosis incidence 5.5 increased risk for AA

Silicosis prevalence, AA 71.6% vs. C 6.88%

Cherniak, 1986

Rosenman et al, 2012

Irwig and Rocks, 1978

Work-Related AsthmaAll Workers

All Workers

Incidence of WRA, AA 4.8 vs C 2.5

Prevalence of WRA, AA 12.53%, H 10.43%, C 8.3%

Stanbury and Rosenman, 2014

MMWR, 2012

*AA=African American, C=Caucasian, H=Hispanic

Prevalence of Current Asthma1 for Adults (≥18 Years),Detroit and Michigan, 2012‐2014

• Current asthma prevalence amongadults in Detroit was significantly higherthan in Michigan (15.5% vs. 11.0%).

Source: 2012‐2014 Michigan Behavioral Risk Factor Surveys, MDHHS.

0

2

4

6

8

10

12

14

16

18

20

Detroit Michigan

Perc

ent

11.0 %

15.5%

Ten Most Common Occupations for African American, Asian, Caucasian and Hispanic Workers, Michigan 2011.*

Hispanic Workers (# employed: 161,489)Agricultural workers (9.8%)

Assemblers and fabricators (4.1%)Grounds maintenance workers (3.1%)

Retail salespersons (3.0%)Janitors (2.8%)Cooks (2.5%)

Food preparation workers (2.2%)Packers and packagers, hand (2.2%)

Waiters/waitresses (1.9%)Secretaries (1.8%)

African American Workers (# employed: 435,105)Nursing/home health aides (4.6%)

Janitors (3.1%)Assemblers and fabricators (3.1%)

Personal and home care aides (2.8%)Cashiers (2.8%)Laborers (2.5%)

Customers service reps (2.4%)Retail salespersons (2.3%)

Cooks (2.2%)Bus drivers (2.1%)

Asian Workers (# employed: 129,414)Mechanical engineers (9.8%)Software developers (7.5%)

Postsecondary teachers (4.3)Computer/information systems managers (3.9%)

Physical therapists (3.9%)Managers (3.4%)

Nurses (3.1%)Cooks (2.9%)

Accountants (2.9%)Physicians (2.7%)

Caucasian Workers (# employed: 3,558,662)Drivers/sales workers and truck drivers (2.8%)

Cashiers (2.4%)Retail salespersons (2.4%)

Secretaries (2.3%)Managers, all other (2.1%)

Nurses (2.1%)Elementary/middle school teachers (2.1%)Supervisors of retail sales workers (1.9%)

Waiters/waitresses (1.6%)Assemblers and fabricators (1.5%)

* Rankings of most common occupations are from the 2011 Current Population Survey, U.S. Bureau of Census(http://www.census.gov/people/io/methodology). Percentages in the table represent the percent of all employedmembers within that race/ethnicity group who work in that particular occupation. (Table adapted from Stanbury andRosenman, 2014)

Ways to Report

Web site: www.oem.msu.edu E-Mail: ODREPORT@ht.msu.edu Fax: 517-432-3606 Telephone: 1-800-446-7805 Mail: Michigan Occupational Safety & Health

Administration (MIOSHA) Management and Technical Services DivisionPO Box 30649Lansing, Michigan 48909-8149

Reporting forms can be obtained by calling (517)-284-7777 or 1-800-446-7805

Summary WRA is Common (15-50%)

Health Care Providers Not discussing with their Patients (≤ 25%)

Consequences of Not Considering or Delay in Considering

- Death

- Increased Morbidity

- Missed Opportunity for Primary Prevention