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Irritants and asthma variants Susan M Tarlo Toronto Western Hospital and

Irritants and asthma variants Susan M Tarlo Toronto Western Hospital and Gage Occupational and Environmental Health Unit, University of Toronto. Respiratory irritant effects.

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Irritants and asthma variants Susan M Tarlo Toronto Western Hospital and

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  1. Irritants and asthma variants Susan M Tarlo Toronto Western Hospital and Gage Occupational and Environmental Health Unit, University of Toronto

  2. Respiratory irritant effects • Sx which mimic asthma: e.g. transient eye / upper airway irritation, ? RUDS, sx of vocal cord dysfunction, IEI, ? GERD • Acute aggravation of underlying asthma • Irritant-induced asthma (IIA: includes RADS) • ? Increased risk of respiratory sensitization with concurrent allergen exposures • Other acute or chronic lung effects (ARDS, pneumonitis, bronchiolitis, bronchitis, COPD) Relate to exposure factors (levels, chemical, particle size etc, and host factors)

  3. Criteria for RADS (Brooks et al 1985) • No preceding respiratory complaints • Sx onset after a single specific exposure incident or accident • Exposure was to a gas, smoke , fume, or vapor in very high concentration and being an irritant • Sx onset <24h of exposure, lasting >3mo. • Sx simulate asthma • PFTs may show airflow obstruction • Methacholine challenge positive • Other lung disease excluded Many subsequent reports expanded the criteria, with the term IIA

  4. Acids Calcium oxide Chlorine gas Glacial acetic acid Ammonia Metam sodium Isocyanates Ethylene oxide Tear gas Phosgene Welding fumes Spray paint Smoke inhalation Locomotive exhaust Silo gas WTC dusts Agents reported to cause IIA or RADS

  5. Definitions will affect PrevalenceIrritant-induced asthma (IIA) • IIA: as for RADS but exposure extended to one or more exposures to a high concentration of inhaled respiratory irritant, and onset of sx within 24h of this (others have extended the onset time up to 7 days post-exposure or even longer) . • Prevalence of IIA in an occupational lung disease clinic (using criteria of 1 or more acute exposures), was 6% of 154 consecutive referrals (3% if restricted to RADS criteria, similar to Brooks’ prevalence) • 16% of all OA patients in the clinic had IIA, (8% RADS) (Chest 1989)

  6. Practical difficulties in diagnosis of IIA/RADS • Exposure levels often hard to assess • Emerg / physician visit may have been delayed • Usually no previous PFTs • Often a smoking or atopic history • PFTs / methacholine challenge may not have been done when sx were present • Often hard to exclude unrelated sx or disease • Pathology not clearly distinctive from other asthma

  7. Prevalence of Irritant asthma effects in aOntariocompensationpopulation • 9% of all accepted OA claims were for new-onset irritant-induced OA (IIA) [3% very probable, RADS] • 50% accepted work-related asthma claims were for aggravation of unrelated asthma (AA) • usually from moderate, allowable levels of respiratory irritants with previous asthma • Workplace inhalation accidents (19% of all accepted asthma claims) : • attributed symptoms shorter for AA v IIA ( 32d vs. 112d ), p<0.001 and less lost work (p<0.001). Chatkin et al, Chest 1999

  8. Surveillance studiesPrevalence, risks • Prevalence: • Ross and McDonald ‘96, 8% among all inhalation accidents reported to SWORD, (5% with PFT support) • Risk factors for an asthmatic response: • Blanc et al ‘93, poison centre, post- inhalation: self-reported wheeze increased with smoking (RR1.6) and prior asthma (RR1.3). Combined RR2.8 (CI 1.9-4.3)

  9. Is the risk of sensitizer-induced OA greater with spills? • Some sensitizers can be irritant in high levels • A few documented cases of IIA and concurrent sensitization to the same agent (e.g. diisocyanates) [Leroyer et al Thorax ‘98] • SWORD report, risk of new asthma with reported spills was highest with spills of sensitizers [Ross, Ann Occ Hyg 1996]

  10. Asthma RR with presumed non-massive irritant occupations (* significant risk)

  11. Radiographers in Ontario, • Cross-sectional questionnaire mail survey, MRTs, physiotherapists • Analyses involve 1110 MRTs and 1523 physiotherapists who never smoked Gary M. Liss, Susan Tarlo, J Purdham, J Doherty, M Kerr, L McCaskell OEM 2003

  12. RESULTS Asthma and Respiratory Symptoms * adjusted for age and gender † adjusted for age ** significant interaction with gender p=0.016 ‡ adjusted for gender, age and childhood asthma WR = work-related

  13. Examples of Work Tasks/ Exposures Past 12 months Associated with Respiratory Symptoms - Workplace Factors 0.3-0.8 0.4-0.7 0.4-0.95 0.2-0.6

  14. Examples of Work Tasks/ Exposures Past 12 Months Associated with Respiratory Symptoms - Tasks (1) 1.8-4.7 1.5-3.4 1.6-3.5 1.3-3.3 1.2-3.2 1.2-2.4 0.97-2.6 1.0-2.2 *  1/wk and daily vs never and < 1/wk

  15. Examples of Work Tasks/ Exposures Past 12 months Associated with Respiratory Symptoms - Tasks (2) 1.9-4.2 1.6-3.8 1.7-4.3 1.5-2.7 1.0-3.1 1.1-2.5 1.2-2.4 0.9-1.7

  16. Frequency of Exposures by Gender Past 12 months Percent Reporting

  17. ? Irritant effects • Increased new onset asthma among MRTs vs physios • Excess of resp symptoms among MRTs, • Only a subset of MRTs with asthma had IgE antibodies to GA • MRTs vs physios had induced sputum neutrophilia +/- respiratory symptoms but not eosinophilia • Associations with tasks and scenarios involving irritant exposures, but not with routine tasks, especially in men: • Workplaces of those with symptoms had higher levels of acetic acid and SO2 (although all levels were relatively low) • suggests work-related contribution due to possible irritants/ aerosol generation, especially among the men

  18. WTC cough in firefighters with at least 4 weeks off work Prezant DJ, et al N Engl J Med 2002;347:806-15. P<0.01

  19. New York Fire Fighters Oct 1-14 2001 Self reported symptoms among those with cough (similar % in those with cough among all 3 exposure levels) • new or worsened GERD (82-88%), • post-nasal drip (33-42%) • exertional dyspnoea (94-96%) • wheeze (57-77%) • chest discomfort (82-86%)

  20. Course of WTC cough • Medical attention for cough: incidence peaked 6-8 weeks after exposure • At that time cough was non-productive in 58% • 65% with cough but normal responsiveness returned to work vs 20% of those with hyperresponsiveness (RR 4.8 [CI 2.5-9.2]) mostly by 4-6 months after exposure: normal PFTs / methacholine responses by time of return

  21. Without WTC cough (103 firefighters) methacholine response RR exposure level 21.0 [CI 1.8-164] P=0.01

  22. 6 month follow-up of 179 workers (none with WTC cough at entry)(Banauch et al AJRCCM ’03) • Methacholine responses at 1,3,6 months • Significant differences with exposure groups only seen by 3 months • High exposure – 6.8 x increased risk of hyper-responsiveness at 6 mo (CI 1.8-25.2) (and dose-response slope rose 46% over time) • Hyper-responsiveness persisted to 6 months in 55% of those +ve at 1 or 3 months. • At 6 mo, 16% of all exposed had resp sx + hyper-responsiveness (20% with high exposure, 8% with moderate exposure).

  23. WTC airway effects • Cough may have had several contributing causes (GERD/ PN Drip/ airway hyper-responsiveness • Findings support development of irritant-induced asthma/hyperresponsiveness, but time-course differs from previous criteria • This is the largest group of exposed workers with preceding medical surveillance • Should criteria for IIA be revised?

  24. Endotoxin: irritant/? adjuvant? • Animal workers: 38-67% have rhinitis/asthma without animal sensitization • Pacheco et al (AJRCCM ‘03) in lab mouse workers found 22% had mouse-attributed sx but only 43% of these were sensitized to mice • Among those not sensitized, • rhinitis was associated with endotoxin (current and cumulative) but not mouse allergen. • Asthma was associated with both endotoxin and allergen even in non-sensitized workers

  25. Controversy with IIA • How commonly do irritants cause asthma? • Should our criteria change for diagnosis? • How can coincidental asthma-onset be excluded, especially if atopy/smoking are risk factors also for IIA? • Endotoxin / fungal glucans effects? • What criteria should be used for Aggravation of asthma (currently mostly history-based)? • Compensation implications

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