Medical Surveillance for Occupational asthma (OA) Susan M Tarlo MB BS FRCP(C) Toronto Western Hospital, and Gage Occupational and Environmental Health Unit

Primary – avoidance Secondary – early detection (best medical outcome for sensitizer-induced OA is with early diagnosis and removal from exposure when asthma is relatively mild) Medical Surveillance - early identification by worker/ physician) Medical Surveillance - early identification by worker/ physician) Tertiary – optimal treatment Prevention

No clinical studies have looked at medical surveillance for OA as an isolated intervention All include exposure controls, education All include exposure controls, education Usually a resp questionnaire, spirometry and when feasible skin tests/specific serum IgE Usually a resp questionnaire, spirometry and when feasible skin tests/specific serum IgE The combination of interventions has shown benefit The combination of interventions has shown benefit

Examples of effective interventions that include medical surveillance for OA Natural rubber latex (NRL): -also included primary prevention with changes in gloves to low-protein low- powder or non-latex gloves, and also included worker education Natural rubber latex (NRL): -also included primary prevention with changes in gloves to low-protein low- powder or non-latex gloves, and also included worker education Incident reports for NRL allergy in the largest Ontario hospital fell from a peak of 45 per year (with surveillance) in ’94 to 1 in ’99 (after glove changes). Incident reports for NRL allergy in the largest Ontario hospital fell from a peak of 45 per year (with surveillance) in ’94 to 1 in ’99 (after glove changes). The onset of symptoms had been relatively steady between ’89 and ’94 (4-9 cases per year) but were not reported until surveillance began in ‘94 The onset of symptoms had been relatively steady between ’89 and ’94 (4-9 cases per year) but were not reported until surveillance began in ‘94 Tarlo et al, JACI 2001

Ontario MOL Surveillance requirements for diisocyanate-induced OA (from 1983) 1. Workplace air monitoring for TWA 0.005ppm diisocyanates, TLV 0.02 ppm. 2. Medical surveillance Pre-employment respiratory questionnaire, physical exam and spirometry. Pre-employment respiratory questionnaire, physical exam and spirometry. 6 monthly questionnaires, at least 2- yearly spirometry. 6 monthly questionnaires, at least 2- yearly spirometry. Physician referral: symptoms or 15% fall in FEV1 or FVC. Physician referral: symptoms or 15% fall in FEV1 or FVC.

Diisocyanate OA and medical surveillance in Ontario Workers’ compensation (WSIB) claims for diisocyanate-induced OA ’80-’87 comprised ~50% of all accepted OA claims, rose from 30/year to 58/year by 1988 (likely effective case finding), then progressively fell to 21 (vs 39 other OA) in 1993 and 10 in 2002 Workers’ compensation (WSIB) claims for diisocyanate-induced OA ’80-’87 comprised ~50% of all accepted OA claims, rose from 30/year to 58/year by 1988 (likely effective case finding), then progressively fell to 21 (vs 39 other OA) in 1993 and 10 in 2002 An earlier diagnosis of diisocyanate-induced OA occurred after the surveillance program was introduced An earlier diagnosis of diisocyanate-induced OA occurred after the surveillance program was introduced Tarlo et al OEM ’97, OEM ’02, Buyantseva et al PATS (abst) ’08

If medical surveillance is medically effective, how cost-effective is it? Wild, Redlich, Paltiel, OEM ‘05 A simulation model of yearly diisocyanate asthma surveillance (Markov model) A simulation model of yearly diisocyanate asthma surveillance (Markov model) Input data from several published sources, but some estimates from “expert opinion” Input data from several published sources, but some estimates from “expert opinion” Ranges used for sensitivity analyses Ranges used for sensitivity analyses

Model input parameters Sensitization rate Sensitization rate Time to diagnosis Time to diagnosis no surv no surv with surveillance with surveillance Chance of removal Chance of removal If diagnosed If diagnosed If not diagnosed If not diagnosed Likelihood of disability Likelihood of disability If removed If removed If still exposed If still exposed 2.8% per year ( %) 2.7y ( y) 1.7y ( y) 71% at 6 mo (<15-99%) 24% at 1y (0-71%) 30% disabled at 4y (0-69%) 60% disabled at 4y (expert panel)

Cost estimates Lost productivity Lost productivity Employer Employer society society Diagnosis costs Diagnosis costs Screening Screening confirmation confirmation Medical absenteeism costs Medical absenteeism costs Symptomatic Symptomatic Chronic Chronic Disabled Disabled $0 (?? Could not estimate) $28% loss x 10y at 50K/y (28-56%) $104 (50-200%) $454 $42.60/mo (50-200%) $85.24/mo $ /mo

Model results For 100,000 workers over 10y vs passive case finding, surveillance would result in For 100,000 workers over 10y vs passive case finding, surveillance would result in 683 fewer disabled workers 683 fewer disabled workers 3.3 million more symptom-free days 3.3 million more symptom-free days 1831 additional QALYs 1831 additional QALYs Additional costs of $44 million Additional costs of $44 million (~ 50% of the additional costs for surveillance and confirmation were offset by reductions in meds, absenteeism and disability costs)

Cost-effectiveness estimate From the employer perspective From the employer perspective $24K per QALY (a cited threshold is $50K/QALY) $24K per QALY (a cited threshold is $50K/QALY) $13.3 per symptom-free day $13.3 per symptom-free day $64K per case of disability prevented $64K per case of disability prevented From the society perspective surveillance was cost saving (including lost wages) From the society perspective surveillance was cost saving (including lost wages)

Sensitivity analyses Benefits increase with: Benefits increase with: High incidence of OA High incidence of OA High likelihood of becoming disabled High likelihood of becoming disabled Rapid removal after diagnosis Rapid removal after diagnosis Faster diagnosis with surveillance vs passive case finding Faster diagnosis with surveillance vs passive case finding Variations in above can change the difference in disability cases vs passive finding, from Variations in above can change the difference in disability cases vs passive finding, from If sensitization rate is 0.7%/y then surveillance has a CER >$50K per QALY from both employer and society perspective, i.e. not cost effective If sensitization rate is 0.7%/y then surveillance has a CER >$50K per QALY from both employer and society perspective, i.e. not cost effective

Other factors Benefits also relate to predictive values, sensitivity and specificity of instruments used (questionnaires, spirometry, immunologic tests) – will determine the number of false positive and false negative results Benefits also relate to predictive values, sensitivity and specificity of instruments used (questionnaires, spirometry, immunologic tests) – will determine the number of false positive and false negative results Frequency of surveillance can affect cost- effectiveness Frequency of surveillance can affect cost- effectiveness Job-security may affect self-reporting of symptoms on questionnaire Job-security may affect self-reporting of symptoms on questionnaire Extent of participation can affect results Extent of participation can affect results Costs can vary widely by country/system Costs can vary widely by country/system

Other examples of medical surveillance for OA Complex platinum workers – skin tests are highly predictive for OA Complex platinum workers – skin tests are highly predictive for OA Detergent enzymes: routine skin prick testing used to indicate inadequate exposure Detergent enzymes: routine skin prick testing used to indicate inadequate exposure Bakers: 4% asthma sx after 1 y, 9% after 2y Bakers: 4% asthma sx after 1 y, 9% after 2y - good results of surveillance in UK research study - good results of surveillance in UK research study poor results in actual practice (poor participation, and not admitting to sx) poor results in actual practice (poor participation, and not admitting to sx) - estimated that asthma was 7x under-recognized in practice in bakers and 4x in all bakery workers (Brant ’05) - estimated that asthma was 7x under-recognized in practice in bakers and 4x in all bakery workers (Brant ’05)

When should medical surveillance for OA be introduced? ? All workplaces with sensitizer exposures and reliable tests available or all higher risk companies? ? All workplaces with sensitizer exposures and reliable tests available or all higher risk companies? - medical surveillance program feasibility and limitations should be considered - medical surveillance program feasibility and limitations should be considered - need valid tests: questionnaires, well-performed spirometry, specific IgE - need valid tests: questionnaires, well-performed spirometry, specific IgE - include worker education in the program - include worker education in the program - address group analyses as well as individual results - address group analyses as well as individual results - need to initially establish reporting mechanisms, action levels, action plans - need to initially establish reporting mechanisms, action levels, action plans

Conclusion Medical surveillance as a component of preventive strategies can be effective for medical outcome but should be carefully implemented and evaluated prospectively Medical surveillance as a component of preventive strategies can be effective for medical outcome but should be carefully implemented and evaluated prospectively For many current “higher risk” occupations, such as cleaners and nurses where the specific sensitizer is often unclear, and work settings are widespread, this would be difficult to implement For many current “higher risk” occupations, such as cleaners and nurses where the specific sensitizer is often unclear, and work settings are widespread, this would be difficult to implement