1. Bronchiolitis Obliterans and Food Flavorings - Diacetyl Kathleen Kreiss, MD Division of Respiratory Disease Studies kkreiss@cdc.gov 304-285-5800 Kathleen Kreiss, MD Division of Respiratory Disease Studies kkreiss@cdc.gov 304-285-5800 “The findings and conclusions in this report are those of the author and do not necessarily represent the views of the National Institute for Occupational Safety and Health” No relationships to disclose

2. 2 Context for Recognition of Bronchiolitis Obliterans  Irreversible airways obstruction  Endemic and rare  Severe: lung transplant listing  490,000 food production workers  Irreversible airways obstruction  Endemic and rare  Severe: lung transplant listing  490,000 food production workers

3. 3 Overview  Epidemiologic risk factors  Effective interventions  Extent of risk in food production  Extent of risk in flavoring and chemical production  Challenges of surveillance  What’s next in prevention  Epidemiologic risk factors  Effective interventions  Extent of risk in food production  Extent of risk in flavoring and chemical production  Challenges of surveillance  What’s next in prevention

4. 4 Epidemiologic risk factors Job titles:  Mixers of flavorings; quality control workers  Powder compounders in flavoring plants*  Process operators in diacetyl manufacture** Diacetyl:  Cumulative and average  Peak *Kanwal R. AJRCCM 2007;175:A27 **van Rooy F. AJRCCM 2007;176: in press Job titles:  Mixers of flavorings; quality control workers  Powder compounders in flavoring plants*  Process operators in diacetyl manufacture** Diacetyl:  Cumulative and average  Peak *Kanwal R. AJRCCM 2007;175:A27 **van Rooy F. AJRCCM 2007;176: in press

5. 5 Effective interventions: Reducing flavoring exposure  Company implementation of engineering controls  ConAgra company- wide program  CA flavoring companies’ exposure assessment  Respiratory protection  Company implementation of engineering controls  ConAgra company- wide program  CA flavoring companies’ exposure assessment  Respiratory protection Average Diacetyl Concentrations by Survey Date and Job 0.001 0.01 0.1 1 10 100 00- NOV O1- APR O1- SEP O1- NOV O2- MAR O2- AUG O3- JAN O3- JULY DATE PPM MIXERMACHINE OPQC

6. 6 Preventing flavoring-related BO  Prevention of decrements in FEV 1  Only 1 reported case in microwave popcorn since 2003 Kreiss K.Current Opin Aller Clin Immunol 2007;7:162-7  Prevention of decrements in FEV 1  Only 1 reported case in microwave popcorn since 2003 Kreiss K.Current Opin Aller Clin Immunol 2007;7:162-7 0 20 40 60 80 100 120 140 160 200120022003 Annualized loss (ml/year) FEV 1 Decrements by Follow-up Year

7. 7 Effective interventions: Secondary prevention by screening  Affected workers removed from exposure in microwave popcorn plants  Screening implemented in flavoring plants  Pulmonary function quality improvement  Affected workers removed from exposure in microwave popcorn plants  Screening implemented in flavoring plants  Pulmonary function quality improvement ↓ Left employment Sep-01 Percent Predicted FEV 1 by Survey Date )

8. 8 Extent of risk in food production: 6 microwave popcorn plants*  5 plants had BO cases  19.2% of ever-mixers (>12 mo.) obstructed  14% of packaging workers where mixing tanks not isolated  85% QC workers in index plant  Maintenance workers had excess symptoms * Kanwal. AJOEM 2006;48:149-157  5 plants had BO cases  19.2% of ever-mixers (>12 mo.) obstructed  14% of packaging workers where mixing tanks not isolated  85% QC workers in index plant  Maintenance workers had excess symptoms * Kanwal. AJOEM 2006;48:149-157

9. 9 Other food production risks Popcorn popping plant *  3 of 3 workers had work-related asthma  2 of 3 had findings consistent with BO  Exposure profile different: aldehydes predominant  Diacetyl present but unmeasurable Food production with heated flavors  Hard candy, potato chips * Sahakian. Yatsko Health Hazard Evaluation Popcorn popping plant *  3 of 3 workers had work-related asthma  2 of 3 had findings consistent with BO  Exposure profile different: aldehydes predominant  Diacetyl present but unmeasurable Food production with heated flavors  Hard candy, potato chips * Sahakian. Yatsko Health Hazard Evaluation

10. 10 Extent of risk in diacetyl and flavoring production Netherlands diacetyl manufacturing cohort*  4 severe BO cases in 102 workers Flavoring manufacturing workers in 11 companies**  19% obstructed among 650 flavoring workers Case reports  NJ, MD, OH, CA in flavoring manufacturing workers  Cal/OSHA and CA Dept of Health Services mandated screening*** * van Rooy F. AJRCCM 2007;176: in press **Rose C. AJRCCM 2007;175:A17 ***Materna B. MMWR 2007;56:390-3 Netherlands diacetyl manufacturing cohort*  4 severe BO cases in 102 workers Flavoring manufacturing workers in 11 companies**  19% obstructed among 650 flavoring workers Case reports  NJ, MD, OH, CA in flavoring manufacturing workers  Cal/OSHA and CA Dept of Health Services mandated screening*** * van Rooy F. AJRCCM 2007;176: in press **Rose C. AJRCCM 2007;175:A17 ***Materna B. MMWR 2007;56:390-3

11. 11 Medical surveillance example in California flavoring company October 2006 screening  2 of 12 production workers obstructed  Case 1: FEV 1 17.9% predicted (ratio 37.4%)  Case 2: FEV 1 86.5% predicted (ratio 64.4%) March 2007 screening  Case 2: 1 liter drop FEV 1 to 64.5% predicted (ratio 51.3%) October 2006 screening  2 of 12 production workers obstructed  Case 1: FEV 1 17.9% predicted (ratio 37.4%)  Case 2: FEV 1 86.5% predicted (ratio 64.4%) March 2007 screening  Case 2: 1 liter drop FEV 1 to 64.5% predicted (ratio 51.3%)

12. 12 Case 1  1995: 26 year old man with dyspnea 1 year into employment  2003 rhinitis; 2004 bronchitis  2005 FEV 1 20%; ratio 47%; no BD response  Bronchiectasis, 2 hospitalizations  2006 FEV 1 17.9%; ratio 37.4%  Bronchiolitis obliterans syndrome  1995: 26 year old man with dyspnea 1 year into employment  2003 rhinitis; 2004 bronchitis  2005 FEV 1 20%; ratio 47%; no BD response  Bronchiectasis, 2 hospitalizations  2006 FEV 1 17.9%; ratio 37.4%  Bronchiolitis obliterans syndrome Plastic curtain Exhaust hood Ribbon blender

13. 13 Case 2  25 year old man without symptoms 2 years into employment  10/31/06: abnormal ratio of 64.4%  3/14/07: fixed FEV 1 64.5% predicted; ratio 51.3%  Relocated to warehouse  25 year old man without symptoms 2 years into employment  10/31/06: abnormal ratio of 64.4%  3/14/07: fixed FEV 1 64.5% predicted; ratio 51.3%  Relocated to warehouse

14. 14 What’s next in prevention of flavoring-induced bronchiolitis obliterans?  Control technology study for flavoring industry  Improvement of sampling method for diacetyl  Inhalation toxicology of additional flavoring ingredients  OSHA special emphasis program  Regulatory approaches  Control technology study for flavoring industry  Improvement of sampling method for diacetyl  Inhalation toxicology of additional flavoring ingredients  OSHA special emphasis program  Regulatory approaches