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Physiologic and Genetic Determinants of Occupational Lung Dysfunction in the Swine Industry

This presentation explores the characteristics of the swine industry, respiratory health effects in workers, mechanisms of dysfunction, and interventions. It discusses the evolving nature of the industry, air quality in swine barns, and the role of dust and endotoxin in respiratory health. The presentation also presents case studies of occupational asthma in swine workers and the impact of chronic airflow limitation. The study concludes that swine farmers may experience more respiratory symptoms and reduced lung function compared to non-exposed individuals.

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Physiologic and Genetic Determinants of Occupational Lung Dysfunction in the Swine Industry

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  1. . Physiologic and Genetic Determinants of Occupational Lung Dysfunction- Experience in the Swine IndustryOccupational and Environmental Medical Association of Canada Annual Scientific Conference October 5, 2010 James A Dosman MD

  2. CREDITS A Senthilselvan Ernie Barber Chuck Rhodes Tom Hurst Shelley Kirychuk Liliane Chénard Yvon Cormier David Schwartz Leslie Holfeld Don Cockcroft Frank Froh Lorne Babiuk Phil Wilson Baljit Singh Alan Rosenberg Louise Hagel Kendra Ulmer Vaneeta Grover Josh Lawson Merry-Lynn MacDonald

  3. CREDITS The Medical Research Council of Canada National Health Research and Development Program The Canadian Institutes of Health Research Saskatchewan Health Research Foundation Saskatchewan Labour Saskatchewan Agriculture and Food

  4. OUTLINE OF PRESENTATION 1.Characteristics of the industry 2. Respiratory health effects 3. Mechanisms of dysfunction 4. Interventions

  5. THE SWINE INDUSTRY IN CANADA Annual sales: $4 Billion Number of pigs/yr: 31 Million Number of people in industry: 30,000

  6. AN EVOLVING INDUSTRY • From the family farm with outdoor or small scale production and a few hours per day exposure

  7. AN EVOLVING INDUSTRY • Large scale indoor animal confinement involving thousands of pigs and the “eight hour per day” employed worker Photo: Prairie Swine Centre, Floral, SK

  8. AIR QUALITY(n=54 – winter) • Total dust (mg/m3) 2.93 ±0.92 • Endotoxin EU/m3 11,443 ± 13,492 • NH3 (ppm) 11.3 ± 4.2 • CO2 (ppm) 2,632 ± 807 Zejda et al, JOM 36:49-56, 1994

  9. Animal feed Swine feces Swine dander Mold Pollen grains Insect parts Mineral ash DUSTS – CHARACTERISTICS (1) Median aerodynamic diameter, 2.2 um Donham et al, Am J Ind Med, 10:294-297,1986.

  10. DUSTS – CHARACTERISTICS (2) • Mold – 1.9 x 103 cfu/mg3 Penicillium Alternaria Aspergillus Fucarium Verticillium Scopulariopsis Donham et al, Am J Ind Med, 10:294-297, 1986

  11. DUSTS – CHARACTERISTICS (3) • Bacteria 1.7 x 104 cfu/m3 • Predominant type – gram-positive • Gram-negative count – 8.4 x 103 Donham et al, Am J Ind Med, 10:294-297, 1986

  12. DUST AND ENDOTOXIN • Dust particles are less than 5µ in mean aerodynamic diameter and can penetrate terminal bronchioles. • Endotoxin adheres to dust particles

  13. ENDOTOXIN • Soluble lipopolysaccharides (LPS) • Outer membrane gram negative bacteria • Aggregate to form micelles • Molecular weight 1,000,000 kd Reed CE, Milton DK. 2001. Mosby Inc.

  14. RESPIRATORY HEALTH EFFECTS Asthma Chronic airflow limitation Acute effects in new workers Healthy worker effect

  15. 6 weeks -severe wheezing 3 months - quit work 1.5 months after quitting - seen in clinic Past history - no asthma, allergy O/E - wheezes on forced expiration Dosman et al, Euro Resp J, 24:689, 2004 Chest X-ray clear FEV1 3.48; 10% BD Allergy test: weeds, grass, alfalfa PC20 1.03 mg/ml Diagnosis: asthma Rx: fluticasone prop CASE # 1, CAUCASIAN WOMAN, AGE 29 (1)

  16. Re-entry challenge - 2.5 mo after work cessation Spent less than 30 minutes in barn before severe coughing and wheezing forced end of challenge Pre-challenge PC20 1.03 mg/ml 3 hour post-challenge PC20 0.74 mg/ml Dx: occup asthma Rx: fluticasone prop Stay off work CASE # 1, CAUCASIAN WOMAN, AGE 29 (2) Dosman et al, Euro Resp J, 24: 698-702, 2004

  17. 4 months after work cessation Mildly symptomatic Off fluticazone prop PC20 1.23 mg/ml CASE # 1, CAUCASIAN WOMAN, AGE 29 (3) Dosman et al, Euro Resp J, 24: 698-702, 2004

  18. 7.5 mo after work cessation No symptoms Not on treatment Not working in barn PC20 5.9 mg/ml ( nearly normal) Dx: discharged CASE # 1, CAUCASIAN WOMAN, AGE 29 (4) Dosman et al, Euro Resp J, 24: 698-702, 2004

  19. CASE STUDY: Occupational asthma in newly employed workers in intensive swine confinement facilities” CASEONSETQUITOUTCOME 29 yr f 1.5mo 3 mo 7mo, no Rx 38 yr f 1 mo 4 mo 7mo, on Rx 44 yr f 6 mo 24 mo 5.5mo, on Rx 39 yr f 12 mo 30 mo days no Rx Dosman et al, Euro Resp J, 24: 698-702, 2004

  20. CHRONIC AIRFLOW LIMITATION

  21. Saskatchewan Farmers SurveyOrganized by Mr. Frank Froh n=504 swine farmers n=448 non-exposed Humboldt men Dosman et al, J Occ Med 30: 715-720, 1988

  22. Swine farmers in Saskatchewan had more respiratory symptoms than control men FarmersControlsSig (n=504) (n=448) age (yr) 42.2 39.7` p<.05 smoking (pk yr) 13.6 13.2 NS wheeze (%) 29.2 10.3 p<.001 sob (%) 32.1 19.4 p<.001 Dosman et al, J Occ Med 30: 715-720, 1988

  23. Swine farmers in Saskatchewan had lower values for lung function than control men FarmersControlsSig Test n=504) (n=448) FEV1 (pred) 95.5 103.6 p<.001 FVC (pred) 97.3 106.8 p<.001 Dosman et al, J Occ Med 30: 715-720, 1988

  24. INCREASED AIRWAY RESPONSIVENESS

  25. 20 Hutterite swine farmers (age 39.0±11.1 yrs) had more increases in airways responsiveness than did 20 blue collar city workers (age 40.1±8.5 years) Zhou et al, CHEST, 99:951-944, 1991

  26. ACROSS SHIFT CHANGES (n=54): Swine farmers had significant reductions in expiratory flow rates over an 8-hour work shift Zhou, C, PhD Thesis, University of Saskatchewan, 1994

  27. Over a four year period there was significant accelerated lung function decline in swine farmers vs non-exposed control subjects Senthilselvan et al, Chest, 111:1733- 41, 1997

  28. Annual Rate Change in FEV11990/91 – 1994/95 (vs 171 controls) βSESig Grain Farmers-16.4 7.33 p=0.03 (n=218),16 cc/year excess loss Swine Farmers -26.1 7.44 p<0.0005 (n=217), 26 cc/year excess loss Senthilselvan et al Chest 111:1733- 41, 1997

  29. The best predictor of annual decline in FEV1 over a four year period was 8 hr across-shift change in FEV1 on the initial observation Kirychuk et al, Can Resp J, 5: 472-478, 1998

  30. RESPIRATORY HEALTH STATUS IN SWINE PRODUCERS RELATES TO ENDOTOXIN IN THE PRESENCE OF LOW DUST LEVELS

  31. Respiratory Health Status in Swine Producers Relates to Endotoxin Exposure in the Presence of Low Dust Levels • n=54, Total Dust = 2.93 ± 0.92mg/m3 • FVC FEV1 • Airborne endotoxin -0.35* 0.17 • Airborne endotoxin x hrs/day -0.42* 0.28** • **p<.05 *p=.06 Zejda et al, JOM 36: 49-56, 1994

  32. Acute exposure of naïve volunteers for 5 hours in a swine barn resulted in evidence for acute inflammatory response at both high and low dust levels

  33. Dust and endotoxin concentrations (± SE) treatmentcontrol Total dust (mg/m3) 0.15 ± 0,02 2.41 ± 0.09* Endotoxin (EU/m3) 452.3 ± 65.8 3983.5 ± 498.3* NH3 (ppm) 18.3 ± 0.5 26.0 ± 0.6 * *p<.001 Senthilselvan et al, ARRCCM 156: 410-417, 1997

  34. Summary: Acute exposure to dust, endotoxin and NH3 results in evidence for acute inflammatory response: • Acute, reversible FEV1 decline • Elevation in total WBC, neutrophils and lymphocytes • Increase in cytokines in nasal wash and blood • Effects are reduced but not eliminated by sprinkling canola oil

  35. Mask Study Naïve subjects exposed 1. wearing a mask 2. not wearing a mask Dosman et al, Chest, 118: 852-860, 2000

  36. “Positive Human Health Effects of Wearing a Respirator in a Swine Barn” FEV1 % change no mask 8.12 ± 1.1 FEV1 % change with mask 0.32 ± 0.62 p<.001 Dosman et al, Chest, 118: 852-860, 2000

  37. N-95 mask provides similar protection than reducing dusts and endotoxin 10 fold

  38. Baseline and interim lung function predicts healthy worker survival in swine farmers.RESULTS OF A 14 YEAR FOLLOW UP IN SWINE FARMERSChenard et al, Chest, 131:245-254, 2006

  39. There is a significant healthy worker effect among farmers who continue to work in swine confinement facilities • Survival in the industry may be predicted by baseline and interim lung function. • Genetic make-up may be a factor in the healthy worker effect

  40. GENETICS Cellular innate recognition of endotoxin depends on membrane bound receptors including the Toll like receptors

  41. MD-2 CD14 LPS LBP TLR4 Cell Membrane NEMO IKKβ IKKα IκBβ or IκBα NF-B NF-B Nucleus Nucleus

  42. MD-2 TLR4 299 &/or TLR4 399 mutation(s) CD14 LPS LBP TLR4 Cell Membrane NEMO IKKβ IKKα IκBβ or IκBα NF-B NF-B Nucleus Nucleus x

  43. Arbour et al, Nature Genetics, 25(2): 187-191, 2000

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