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TTS 2010 Istanbul – 16 May 2010 Human-made fibres and health consequences

TTS 2010 Istanbul – 16 May 2010 Human-made fibres and health consequences. B. Nemery, MD, PhD Occupational, Environmental & Insurance Medicine and Pneumology K.U.Leuven Belgium ben.nemery@med.kuleuven.be. Fibres. “Natural” fibres Mineral fibres Vegetal fibres “Man-made” fibres

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TTS 2010 Istanbul – 16 May 2010 Human-made fibres and health consequences

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  1. TTS 2010Istanbul – 16 May 2010Human-made fibres and health consequences B. Nemery, MD, PhD Occupational, Environmental & Insurance Medicine and Pneumology K.U.Leuven Belgium ben.nemery@med.kuleuven.be

  2. Fibres • “Natural” fibres • Mineral fibres • Vegetal fibres • “Man-made” fibres • Man-made mineral (vitreous) fibres • Synthetic organic fibres • Nanofibres

  3. Mineral fibres

  4. Natural mineral fibres • Asbestos fibres • Other natural mineral fibres

  5. Asbestos • Broad commercial term for a group of naturally occurring hydrated silicates that crystallize in a fibrous habit • “fibre” determined by aspect ratio(length:diameter) • mineralogy: aspect ratio > 10:1 • medical-environmental-legal: aspect ratio >3:1 • “WHO fibre” = length > 5 µm, diameter < 3 µm

  6. Asbestos types • serpentine (curly) • chrysotile (white asbestos) Mg6Si4O10(OH)8 • amphiboles (straight) • crocidolite (blue asbestos) Na2(Fe3+)2(Fe2+)3Si8O22(OH)2 • amosite (brown asbestos) (Fe,Mg)7Si8O22(OH)2 • anthophyllite, tremolite, actinolite • differences in morphology, chemistry, durability • differences in biological effects

  7. Biopersistence Deposition Fibre biopersistence Physiological clearance Physicochemical processes • Translocation • to • Larynx • Interstitium • Lymphatics • Pleura • Biodurability • Dissolution • Leaching • Breaking • Splitting Retention T1/2

  8. Pathogenesis of asbestos-induced lesions Fibre dimensions “Stanton fibre” length > 8 µm, diameter < 0.25 µm “frustrated phagocytosis by macrophages” Chemical composition oxidative stress (Fe) Fibre biopersistence chrysotile ↔crocidolite Mg6Si4O10(OH)8 Na2(Fe3+)2(Fe2+)3Si8O22(OH)2

  9. Health effects of asbestos exposure • asbestosis (diffuse fibrosis of lung parenchyma) • non malignant pleural disease • pleural effusion • pleural plaques • diffuse pleural thickening • rounded atelectasis • malignant mesothelioma • lung cancer

  10. Asbestos induced lesions Past exposure Specificity • asbestosis +++ + • bronchopulmonary cancer ++? - • pleural effusion ++ - • diffuse pleural thickening ++ -/+ • rounded atelectasis ++ + • pleural plaques + +++ • malignant mesothelioma + +++

  11. Yearly mean mesothelioma deaths 2000-2004 Lin et al. Lancet 2007 369, 844-9 Flanders 106/3x106 Nawrot et al. Lancet 2007, May 19, 369, 1692 20 BEL Deaths/106/y Belgium+Lux 53,790 T 5.5 1 2 3 4 5 6 0 Yearly mean asbestos consumption 1960-1969 (kg/head/year)

  12. Pan XL et al. Residential proximity to naturally occurring asbestos and mesothelioma risk in California. Am J Respir Crit Care Med. 2005,172, 1019-25 [+ Editorial] • California, 1988-1997 • 2908 incident cases of malignant mesothelioma >35 y • 2908 sex- & aged-matched controls with pancreatic cancer • Home address at time of diagnosis (GIS) • Probability of occupational exposure to asbestos derived from longest held occupation

  13. Pan XL et al. Residential proximity to naturally occurring asbestos and mesothelioma risk in California. Am J Respir Crit Care Med. 2005,172, 1019-25 [+ Editorial]

  14. Kurumatani N, Kumagai S. Mapping the risk of mesothelioma due to neighborhood asbestos exposure. Am J Respir Crit Care Med. 2008, 178, 624-9 • Amagasaki City, Japan, asbestos cement pipe (1957-1975) • 96 mesotheliomas without (para-)occupational asbestos exposure (1995-2006) 39 36

  15. Fibrous silicates palygorskite attapulgite sepiolite wollastonite zeolite erionite Minerals with potential fibre (tremolite) contamination vermiculite talc some metal ore deposits Other natural mineral fibres

  16. Human-made mineral fibres Man-made mineral fibres (MMMF) Man-made vitreous fibres (MMVF)

  17. Man-made vitreous fibres (MMVF) • Filaments • Continuous glass filament • Wools • Glass wool (insulation wool; special purpose wool) • Rock (stone) wool • Slag wool • Refractory ceramic fibres (RCF) • Other fibres [Alkaline Earth Silicate (AES) wools; High-Alumina, Low-Silica wools (HT)]

  18. Health risks of MMVF • Glass wool & rock/slag wool • Refractory Ceramic Fibres (RCF)

  19. Glass wool & rock/slag wool • Irritation of skin & eyes & upper airways (coarse fibres + binders) • No evidence of lung fibrosis • No evidence of non-malignant pleural changes

  20. Glass wool & rock/slag wool • Carcinogenicity ? • Animal data • Mesothelioma if direct injection of high doses in peritoneum • No lung tumours or mesothelioma in long-term inhalation studies

  21. IARC overall evaluation • Group 1: agent is carcinogenic to humans = sufficient evidence in humans • Group 2A: probably carcinogenic to humans limited evidence in humans + sufficient in animals • Group 2B: possibly carcinogenic to humans limited evidence in humans + insufficient in animals orinadequate ev. in humans, but sufficient in animals • Group 3: not classifiable as to carcinogenicity • Group 4: probably not carcinogenic to humans

  22. Glass wool & rock/slag wool • Carcinogenicity ? • Human data Two large cohort studies (USA & Europe) + nested case-control studies of workers from manufacturing plants • Overall, no evidence for increased risk of lung cancer or mesothelioma • IARC evaluation (2002): GROUP 3

  23. Refractory Ceramic Fibres (RCF) • Irritation of skin & eye & upper airways

  24. Retrospective clinical study (unpublished) • 1991-93 • Assembly of high temperature probes, made with “sleeves” composed of RCF • 12 workers • 10 women, 2 men • 26-49 y • 2 atopics • 3 smokers

  25. 0.59 f/ml 0.005-0.04 f/ml 0.009-0.06 f/ml 0.003-0.45 f/ml 0.08-0.29 f/ml

  26. Symptoms • Work-related symptoms • Skin irritation in 11/12 • Eye irritation in 1/12 • Throat irritation in 5/12 • Cough in 7/12 • Chest tightness in 2/12 • Dyspnea in 2/12

  27. Pulmonary function • Spirometry • Normal, except in 1 heavy smoker • Histamine test • Abnormal (PC20 < 8 mg/ml) in 8/10 subjects

  28. Follow-up • Symptoms disappeared in most subjects after implementation of hygiene measures to lower levels to < 0.01 f/ml • No deterioration of spirometry or histamine test during follow-up

  29. Two subjects with disease • Two subjects had more pronounced symptoms • Very severe cough • “Cough-variant asthma” • No evidence for allergy (to binding agent), “irritant-induced asthma” • Persisted even after removal from exposure • Slight increase in lymphocytes in BAL • No evidence of parenchymal or pleural disease (follow-up?)

  30. RCF & pleura Lockey J. et al. Refractory ceramic fiber exposure and pleural plaques. Am J Respir Crit Care Med 1996, 154, 1405-1410 • Retrospective + nested case-control study of 652 workers in manufacture of RCF • Chest X-rays • 19 workers with plaques; 1 worker with diffuse pleural thickening • Risk of plaques increased with latency (> 20 y) and cumulative exposure • Not due to asbestos exposure

  31. RCF & cancer? • Human data: no adequate data yet • Animal data: • Lung tumours and mesotheliomas in long-term inhalation studies (rat, hamster) • IARC evaluation (2002): GROUP 2B (possibly carcinogenic in humans)

  32. Organic fibres

  33. Natural organic fibres • Vegetal fibres (cellulose) • Silk • Cotton • Flax • Hemp • Jute

  34. Byssinosis Occupational respiratory disease in cotton (flax, hemp) workers chest tightness and dyspnoea (“asthma-like”) initially, only in beginning of week later, “chronic bronchitis” with disability (COPD) not due to allergy, but probably to toxic-inflammatory response to microbial contamination (endotoxin) risk mainly in early stages (high dust) of cotton processing (opening bales, carding) higher risk in smokers

  35. COPD and organic dust high prevalence of chronic bronchitis in jobs involving exposure to organic dust grain handling farming, harbours, mills intensive pig farming dairy farmers animal feed industry some clinical features of byssinosis

  36. Synthetic organic fibres • Artificial fibres (> cellulose) • Cellulose acetate, Viscose, Rayon • Synthetic textile fibres: fibrous polymers • Nylon • Acrylic • Olefins (polyethylene, polypropylene) • Polyester (polyethylene terephthalate, ...) • Carbon/graphite fibres • Aramid fibres (Kevlar, …)

  37. Synthetic fibres • Monomers used for the synthesis of synthetic polymers are often reactive substances with high toxic, sensitizing and/or carcinogenic potential • Synthetic polymers are much less reactive and, hence, they are generally devoid of substantial toxicity by themselves • Generally, the size of dusts from synthetic polymers does not lead to significant aerosolization and/or deposition in the respiratory tract

  38. “Flock worker’s lung”

  39. Production and use of nylon flock • nylon “tow” (continuous nylon rope,  15-20 µm) dyed & fixed • tow rinsed, dipped in finishing bath (tannic acid, ammonium ether of potato starch, fatty alcohol) and cut (2 mm) by rotary precision cutters: flock • flock dried & stored • coating (electrostatic + adhesive) of fabric with flock, curing oven, further finishing & processing

  40. “Nylon flock worker’s lung” • 1994-96: D. Kern: 2 cases of ILD (35y, 28y) in textile workers from a nylon flocking plant, RI • 1990-91: 5 cases of ILD in plant from same company in Ontario: “mycotoxicosis” (Lougheed et al. Chest 1995, 108, 1196-200) • further case-finding Kern et al. (Ann. Int. Med. 1998, 129, 261-272) • hygiene study & survey of workforce (NIOSH) Health Hazard Evaluation Report 96-0093, April 1998

  41. Flock-worker’s lung - 8 patients • x-ray: no pneumoconiosis, diffuse reticulonodular infiltrates (4), patchy consolidation (1) • HRCT: peripheral honeycombing (2), patchy (mild) ground glass (6), with consolidation (2) • LFT: restrictive (5), reduced DLco (5) • biopsies (7): 6 NSIP (lymphocytes), 1 BOOP • not HP (no granulomas) or other pneumoconiosis • BAL (6): lymphocytes (2); eosinophils (3) Kern et al. Ann. Int. Med. 1998, 129, 261-72

  42. Flock worker’s lung - HRCT Pt. 8 Pt. 4 Pt. 2 Kern et al. Ann. Int. Med. 1998, 129, 261-72

  43. Flock worker’s lung - pathology Pt. 2: NSIP Pt. 8: BOOP Pt. 4: NSIP Nodular, peribronchovascular interstitial lymphoid infiltrates, lymphocytic bronchiolitis, lymphocytic infiltration of alveolar septa, mild fibrosis Kern et al. Ann. Int. Med. 1998, 129, 261-72

  44. Flock-worker’s lung - 8 patients 1 2 3 4 5 6 7 8 FVC 56% 74% 59% 50% 82% 93% 100% 64% 44% 45% 29% 43% 85% 84% 84% 36% DLco HRCT Gr Gl Gr Gl Gr Gl Gr Gl Gr Gl Gr Gl HonC HonC consol µnod consol nd n 35% ly 35% n 10% ly 58% BAL nl nd e 40% e 25% e 28% n 8% Biopsy NSIP nd NSIP NSIP NSIP NSIP NSIP BOOP OL /TB Kern et al. Ann. Int. Med. 1998, 129, 261-72

  45. Industrial hygiene evaluation • total dust 0.1 to 141 mg/m3 • respirable dust 0.05 to 40 mg/m3 • highest in flocking rooms & during blowdown • underestimates (inlet clogging, electrostatic clinging) • vertical elutriator: large nylon flock fibers + fine (respirable) irregular fibers formed by shredding • endotoxin & microbiological contamination: low • other gaseous contaminants: none (formaldehyde) NIOSH HETA 96-0093

  46. Nylon flock microfibres Scanning electron microscopy of bulk nylon fiber ends NIOSH HETA 96-0093

  47. Nylon flock-worker’s lung • Further references: • Eschenbacher et al. (AJRCCM, 1999, 159, 2003-8): workshop summary (NIOSH): characteristic lymphocytic bronchiolitis & peribronchiolitis • Burkhart et al. (J Toxicol Environ Health, 1999, 57, 1-23): industrial hygiene study • Porter et al. (J Toxicol Environ Health, 1999, 57, 25-45): i.t. instillation in rats: marked inflammation • Kern et al.(Chest, 2000, 117, 251-9): 5 further cases (?), importance of precision-cut flock (guillotine) vs random-cut flock (rotary cutters)

  48. Flock worker’s lung • Barroso et al. Polyethylene flock-associated interstitial lung disease in a Spanish female. Eur Respir J 2002, 20:1610-2. • Atis S. et al. The respiratory effects of occupational polypropylene flock exposure. Eur Respir J 2005, 25, 110-117.

  49. Atis S. et al. ERJ, 2005, 25, 110-7 • Cross-sectional survey, polypropylene plant, Turkey • 50 workers exposed to polypropylene flock (32.2 y) – 45 non-exposed controls (33.9 y) • Questionnaire • Spirometry & DLco • Chest x-ray and HRCT (10 subjects with low DLco) • Serum TNF- and IL-8 • Dust measurements and microscopy of flock

  50. Atis S. et al. ERJ, 2005, 25, 110-7 10 µm Inhalable dust 4.4 mg/m3 Respirable dust < 0.2 mg/m3

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