Disclosures New onset and exacerbation I have nothing to disclose - PDF document

Work-related asthma: Disclosures New onset and exacerbation I have nothing to disclose Robert Harrison, MD MPH California Department of Public Health Occupational Health Branch and University of California, San Francisco Division of Occupational and Environmental Medicine TEL 415 717 1601 Email: robert.harrison@ ucsf.edu WRA: Increasing recognition and improving intervention efforts • California Department of Public Health • Carolina Espineli (research assistant) • Jennifer Flattery (epidemiologist) • Eleana Martysh (research assistant) • Debbie Shrem (health educator) • Justine Weinberg (industrial hygienist) • National Institute for Occupational Safety and Health (NIOSH) • Margaret Filios and Patricia Schleiff 1

Clinical definition of WRA Clinical classification • Variable airflow limitation and/or airway hyperresponsiveness due to exposure to a specific agent or conditions in the work environment • Sensitizer and irritant-induced asthma Tarlo et al; Chest 134: 1S-41S; 2008 2

New onset asthma (I) Surveillance case definition • Occupational asthma • Health care professional diagnosis consistent with asthma, AND • Workplace exposure to an agent previously associated with occupational asthma? • An association between symptoms of “ Yes ” or “ No ” asthma and work AND • Includes both new onset (OA, RADS) and work-aggravated asthma • Objective evidence of work-relatedness?: “ Yes ” or “ No ” New onset asthma (II) Work-aggravated asthma • Reactive airways dysfunction • Preexisting asthma that was syndrome (RADS) symptomatic and/or treated with asthma medication within 2 years • New asthma symptoms within 24 prior to entering the occupational hours after one-time high-level setting exposure, persists > 3 months 3

Epidemiology Epidemiology • Median PAR = 17.6% • > 250 agents reported to cause (Toren and Blanc, 2009) OA (Chan-Yeung 1994) • Occupations at high risk: painters, bakers, • Most common type of woodworkers, welders, chemical workers occupational lung disease in • Most common exposures: isocyanates, population based studies flour/grain, wood, latex, glutaraldehyde, lab (McDonald 2000) animals Classification of Confirmed Cases Work-related asthma in California, 1993-2012 (N=2,991) Work- 8RADS Aggravated 7% 9Sensitizer 46% 10% Irritant 37% 4

Exposures among Occupations w ith the highest rates Occupation Most Common Exposures Firefighters Smoke Science Technicians Acids, chemicals, indoor air, rat antigens, glues, dust Glutaraldehyde, chemicals, smoke, latex, dust, Medical Assistants & Support perfume, paint Smoke, chemicals, pepper spray, mace, cleaning Correctional Officers & Bailiffs chemicals Respiratory Therapists Cleaning chemicals, latex, pharmaceuticals Medical Records Technicians Dust, smoke, perfume Smoke, pepper spray, dust, indoor air, mold, animal Police Officers antigens Telephone Operators Chemicals, perfume, paint, carpet dust Chemical Technicians Solvents, acids, chemicals Govt Program Eligibility Workers Roofing tar, chemicals, indoor air, toner, perfume, dust 15 Most Common Exposures Reported by Cases Most Common Asthmagens Dust Bleach Unspecified Chemicals Chlorine Smoke Ammonia Mold Latex Indoor Air Pollutants Isocyanates Cleaning Agents Formaldehyde Paint Sulfuric Acid Indoor Air Pollutants from Building Glutaraldehyde Renovation Rat Antigens Perfume Quaternary Ammonium Compounds Pesticides Epoxies Glues Hydrochloric Acid Bleach California Redwood Diesel Exhaust Flour Asphalt X-ray Fixative Cigarette Smoke 5

Pathogenesis: sensitizer-induced Pathogenesis: sensitizer-induced • High molecular weight ( ≥ 5,000 Da) • High molecular weight [continued] • IgE-mediated (ex: flour dust, latex) • Release of cytokines/chemokines • Bind to specific IgE on mast cells, • Activation of inflammatory mediators basophils (histamine, leukotrienes, prostaglandins) • Act as complete antigens • Antibodies detected by circulating IgE (RAST) or skin prick testing Pathogenesis: sensitizer-induced Pathogenesis: sensitizer-induced • Low molecular weight • Effector cells (eosinophils, mast cells, epithelial cells, neutrophils) cause smooth muscle • IgE-mediated (Ex: acid anhydrides, platinum) contraction, mucus hypersecretion, airway or non IgE-mediated (ex: isocyanates) inflammation, and epithelial injury • React with proteins to produce complete • Genetic polymorphisms for major antigen, mechanism poorly characterized histocompatibility complex class II proteins may • Key role for T lymphocytes in inflammatory determine specificity of response process 6

Pathogenesis: irritant-induced Risk factors for WRA • Localized inflammatory response with • Duration of exposure (sensitizer subepithelial fibrosis, eosinophils and T cells induced) infiltration • Activation of nonadrenergic, noncholinergic • Atopic history and cigarette smoking pathways via axon reflexes and mast cell (IgE-dependent) degranulation • Recruitment of inflammatory cells • Level of exposure to irritant • Altered epithelial permeability Diagnosis of WRA Diagnosis: sensitizer-induced • Symptoms occur • Asthma = intermittent respiratory months to years after symptoms and reversible/variable airways exposure onset obstruction • Early, late or biphasic • Cough, chest tightness, shortness of responses breath, dyspnea on exertion • HMW: early and biphasic • Rhinoconjunctivitis (more common with • LMW: late and HMW substances) biphasic Tarlo et al; Chest 134: 1S-41S; 2008 7

Isocyanate exposure - packing department Isocyanate exposure - packing department Flour dust in bakery Red cedar dust - pencil manufacturing plant 8

Egg protein exposure - breaking room Red cedar dust - pencil manufacturing plant Cleaning agent exposure - hospital 9

Diagnosis: irritant-induced • Symptoms occur promptly following exposure • May be preceded by “ chemical bronchitis ” 10

Airway disease in 9/11 rescue/recovery workers Bus cleaner removing graffiti • Lung function decline, symptom recovery, BHR c/w exposure intensity • Asthma a/w co-morbid conditions: GERD, OSA, mental health disorders Airway disease in wildland firefighters Diagnosis of WRA • Medical history • 63 wildland FFs in • Asthma, allergies, atopic dermatitis, cardiac 5 Hotshot crews history • Tobacco and medication use • Decrease in lung • Occupational factors function and increase in BHR • Temporal relationship between work and symptoms • Bandana remains • Identification of work processes, job duties, chemicals (MSDS), PPE PPE of choice ARRD, December 1992 11

Diagnosis of WRA Diagnosis of WRA • Physical examination: nasal polyps, • Decrease of 10% in wheezing, crackles, rhonchi FEV 1 across work shift • Objective tests • > 20% diurnal variability in peak • CXR: bronchial wall thickening expiratory flow (PEF) • Spirometry: >12% improvement or • Airway absolute increase > 200 ml in FEV 1 hyperresponsiveness with inhalation after bronchodilator (ATS 1991) challenge testing (histamine or Tarlo et al; Chest 134: 1S-41S; 2008 methacholine) Diagnosis of WRA Management of WRA • Objective tests [continued] • Prompt diagnosis and removal from exposure (especially in sensitizer-induced • Specific inhalation challenge tests asthma) (precise etiology, test new agent) • Follow published guidelines for asthma • Skin prick tests for HMW aeroallergens management (NHLBI) • Specific IgE antibodies against HMW • Inhaled corticosteroids improve outcome and some LMW sensitizers (ex: following removal from exposure (Malo 1996) diisocyanates, acid anhydrides) 12

Management of WRA WRA and disability • Incomplete recovery common with • High rates of job loss/job change determined sensitizer-induced asthma (Chan-Yeung 1999) by working conditions (Blanc 1996) • Early removal increases likelihood of • Substantial income reduction after 3 years in recovery (Cote 1990) >50% affected (Ameille 1997) • Improved PFTs 1-2 years following • Impaired quality of life: increased symptoms, removal from sensitizer exposure activity limitation, emotional dysfunction • Persistent sxs > 2 years following irritant- (Gassert 1998) induced asthma (Bherer 1994) Preventing WRA Preventing WRA • Primary prevention • Secondary prevention • Detect early to minimize severity and duration • Substitute with less hazardous • Tertiary prevention substances • Provide appropriate health care: workers • Change work processes compensation claims • Reduce exposure: engineering controls, • Early removal from exposure PPE as last resort • Permanent impairment guidelines (ATS 1993) • Worker education and training • Long-term follow-up 13

Preventing WRA: w orkplace Chemical policies surveillance • Early detection works to prevent • “ Green chemistry ” initiatives morbidity and disability (Tarlo 1999) • “ cradle to grave ” or “ life cycle ” • Medical surveillance: symptom and the workplace questionnaires, spirometry, PEF records, skin-prick testing for HMW antigens • Occupational and environmental (flours, proteolytic enzymes, animal advocacy proteins) • Exposure monitoring of hazards Is it easy to be green? Before After Green Seal – third party certification for cleaning 14