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Work-Related AsthmaMOEMA 9/23/2016
Kenneth D. Rosenman, M.D.
Professor of Medicine
Michigan State University
www.oem.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: [email protected] 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