Occupa&onal Lung Disease

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1 Occupa&onal Lung Disease Situa&on, Preven&on, Rehabilita&on Thomas H Gassert, MD, MSc Harvard University School of Public Health University of MassachuseCs Medical School 08 May 2013

2 Preven&on Primary Prevent exposure at the source Occupa&onal (Industrial) Hygiene & Safety Hierarchy of Controls, including Management Tobacco- Free Workplace Secondary Medical Fitness & Surveillance Respiratory Protec&on Biological Monitoring Tobacco Cessa&on and Wellness Programs Ter/ary Correct Diagnosis Removal from Exposures, including Tobacco Correct Treatment Prevent Complica&ons Physical and Occupa&onal Rehabilita&on 08 May 2013 Gassert Occupa&onal Lung Disease 2

3 Primary Preven&on Hierarchy of Controls Management SOPs (procedures, regulatory compliance) Bipar&te OSH CommiCees (labor + management) Union bargaining Engineering and Design Subs&tu&on, Elimina&on, Containment Hazard Communica&on + Training Emergency Preparedness & Response Ven&la&on Personal Protec&ve Equipment Inspec&ons Industrial Hygiene consulta&on Medical clearance, case management, and safe return to work 08 May 2013 Gassert Occupa&onal Lung Disease 3

4 OEM Tools and Toxic Torts Cases (injuries, illnesses, deaths) Epidemiology (popula&on studies) Toxicology (human, animal, cell experiments) Regulatory aspects (OSHA, case law) In USA Daubert Rules of Evidence 08 May 2013 Gassert Occupa&onal Lung Disease 4

5 Overview Mechanisms (pathogenesis) Differen&al Diagnosis Defini&ve Diagnosis Treatment Strategies Pulmonary Rehabilita&on Lung transplant Preven&on 08 May 2013 Gassert Occupa&onal Lung Disease 5

6 Scope Surveillance and lung tes&ng Asthma Hypersensi&vity pneumoni&s Byssinosis (cocon dust) Pneumoconioses: Asbestos, silica, coal, nanopar&cle lung diseases 08 May 2013 Gassert Occupa&onal Lung Disease 6

7 Pneumoconioses Asbestos Disease and Mesothelioma Coal Workers (Black) Lung Silicosis Chronic Beryllium Disease Nano- Par&cle Lung Disease Flock lung (nylon) Others (some rela&vely benign) 08 May 2013 Gassert Occupa&onal Lung Disease 7

8 Lung Anatomy Bronchi Bronchioles Alveoli 08 May 2013 Gassert Occupa&onal Lung Disease 8

9 Medical Surveillance for Lung Disease OSHA Standards for asbestos and silica; MSHA for coal Other agents consider: beryllium, cocon, allergens Medical history, ques&onnaire and physical examina&on Pulmonary Func&on Tes&ng Chest X- ray or HRCT scan; ILO classifica&ons Serology and skin tes&ng for sensi&zing agents 08 May 2013 Gassert Occupa&onal Lung Disease 9

10 Medical History & Physical Exam ATS standardized ques&onnaire Epidemiology Standardiza&on Project (American Thoracic Society) Asbestos ques&onnaire (OSHA) Respiratory Protec&on ques&onnaire (OSHA) Add addi&onal informa&on on specific trades Tobacco use and counseling Periodic (annual) administra&on Physical examina&on: skin, upper airway, lungs, lymph nodes, limbs (CCE) 08 May 2013 Gassert Occupa&onal Lung Disease 10

11 Tests Pulmonary Func&on Restric&on vs. Obstruc&on Oxygen satura&on Pulse oximetry, Arterial blood gas Imaging Chest x- ray, High Resolu&on CT (not MRI for dusts) Biopsy and/or BAL (lavage) Transbronchial (bronchoscopy) or open lung Blood BeLPT (beryllium), precipi&ns, rheumatoid, T- Spot Skin TST for TB 08 May 2013 Gassert Occupa&onal Lung Disease 11

12 ILO Classifica&on Standardized Chest X- Ray B Reader Cer&fica&on and Comparison Standard Films Single PA view, or 4 views for staging Quality (penetra&on and scapulae raised) Pleura Thickening, Calcifica&on Parenchyma Nodules (distribu&on, size, shape) Other Findings Lymph Nodes, Masses, Effusions (fluid), Heart, etc. 08 May 2013 Gassert Occupa&onal Lung Disease 12

13 Pulmonary Func&on Tests PFTs measure: Air flow (simple spirometry) Lung volumes Gas diffusion (DLCO) Allow for categoriza&on and severity: Obstruc&ve (air flow impaired) Restric&ve (reduced volume) Fibrosis (reduced gas exchange) 08 May 2013 Gassert Occupa&onal Lung Disease 13

14 Pulmonary Func&on Tes&ng 08 May 2013 Gassert Occupa&onal Lung Disease 14

15 Case 38- y.o. metal worker complains of recent onset of cough, wheeze, shortness of breath, chest &ghtness, and itchy skin rashes on wrists, ankles and neck. Symptoms worsen at work and improve at home and on vaca&on. Operates a Class- IV laser to cut and shape large jet engine metal components. Metal fumes and par&culates are visible in air and on surfaces. Analysis of metal amalgam aerosol demonstrated chromium, nickel, vanadium, iron and cobalt. 08 May 2013 Gassert Occupa&onal Lung Disease 15

16 Asthma Facts: Mortality / Morbidity 17 million in U.S. Deaths: > 5,000 each year Hospitaliza&ons: ½ million / year Emergency department visits: 2 million / year Healthcare costs: > $11 billion / year Lost work &me: 3 million days / year Es&mates of occupa&onal asthma range from 2-15% Background community prevalence ~5%, life&me incidence ~15% 08 May 2013 Gassert Occupa&onal Lung Disease 16

17 Asthma - Defini&on Chronic inflammatory disease of the airways involving cells and their products, resul&ng in recurrent reversible episodes of airflow limita3on and bronchial hyperreac3vity manifest as wheezing, breathlessness, chest &ghtness and cough. 08 May 2013 Gassert Occupa&onal Lung Disease 17

18 Asthma Types 1. Sensi&zed (immune, latency period) 2. Irritant (RADS, no latency) 08 May 2013 Gassert Occupa&onal Lung Disease 18

19 Causes of Asthma Over 250 agents reported to cause asthma (most are high or low MW sensi&zers) Examples HMW LMW Irritants Proteins/Polysaccharides Inorganic cpds Irritants Animal dander Pla&num Acids B. sub3lus enzyme Epoxy resins Bases Castor beans Nickel Smoke Vegetable gum Latex Isocyanates Formaldehyde 08 May 2013 Gassert Occupa&onal Lung Disease 19

20 Peak Flow (PEFR) Meters 08 May 2013 Gassert Occupa&onal Lung Disease 20

21 Peak Flow Diary h1p://www.chestnet.org/health.science.policy/images/chest f01.gif 08 May 2013 Gassert Occupa&onal Lung Disease 21

22 Asthma: Goals of Therapy Control chronic and nocturnal symptoms Maintain normal ac&vity and exercise levels Maintain normal pulmonary func&on Prevent acute exacerba&ons Prevent need for emergency care and hospitaliza&on Avoid adverse effects of asthma medica&ons Prevent death due to asthma 08 May 2013 Gassert Occupa&onal Lung Disease 22

23 Byssinosis Byssus = fine, silk- like filament Exposure: carding, threading, spinning cocon, flax, hemp, sisal Cause: Gram- nega&ve bacillus endotoxin Pathology: Obstruc&ve inflammatory lung disease, leads to scarring ater prolonged exposure Presenta&ons: acute and chronic Dyspnea (short of breath) Dry cough, chest &ghtness Wheeze (airway obstruc&on) +/- mild fevers Worse on Mondays Treat: removal, bronchodilator, cor&costeroids as needed 08 May 2013 Gassert Occupa&onal Lung Disease 23

24 08 May 2013 Gassert Occupa&onal Lung Disease 24

25 Schilling Criteria Grade 0: No symptoms Grade ½: Occasional chest &ghtness or dyspnea on Monday exposure Grade 1: Chest &ghtness or dyspnea on all first days of the work week Grade 2: Chest &ghtness or dyspnea on first and other days of the work week 08 May 2013 Gassert Occupa&onal Lung Disease 25

26 Byssinosis Diagnosis Typical symptom pacern Wheeze may be present Cross- shit FEV 1 decline 08 May 2013 Gassert Occupa&onal Lung Disease 26

27 Byssinosis Epidemiology Prevalence varies widely, 3-80% depending on exposure Shanghai cohort study showed that cross- shit FEV 1 decline predicts long- term FEV 1 in both smokers and non- smokers Other occupa&ons with similar syndromes - > grain elevators, sewage treatment, plywood making, animal confinement,?cleanup workers (e.g. New Orleans) 08 May 2013 Gassert Occupa&onal Lung Disease 27

28 Byssinosis Epidemiology E&ologic agent endotoxin a strong candidate Chamber studies, animal studies, and Shanghai cohort suggest that endotoxin, possibly in associa&on with other dust components, caused COPD in tex&le workers 08 May 2013 Gassert Occupa&onal Lung Disease 28

29 Pneumoconioses Diseases due to an increased dust burden in the lungs From Greek: PNEUMON = LUNG, KONIS =DUST Inflammatory reac&on of small airways and alveoli to dust deposi&on in lung Cell ac&va&on Macrophages ac&vated cytokine mediators inflamma&on fibrosis Restric&ve disease 08 May 2013 Gassert Occupa&onal Lung Disease 29

30 ILO X- Ray B- Reader Report 08 May 2013 Gassert Occupa&onal Lung Disease 30

31 ILO Digital X- Ray System 10 years to create, just completed Valida&on studies against hard films verified Accessible via internet, thus rela&vely cheap and reaches out to all with internet access B- Reader interpreta&on assured Computerized interpreta&on not yet developed No more chemical film development; safer Easy digital storage and sharing See: hcp://blogs.cdc.gov/niosh- science- blog/2009/06/xray/ 08 May 2013 Gassert Occupa&onal Lung Disease 31

32 Lung Biopsy Histology Normal Abnormal Emphysematous bullae (COPD) Inters&&al fibrosis consistent with pneumoconiosis 08 May 2013 Gassert Occupa&onal Lung Disease 32

33 Asbestos Diseases ARPD Asbestos- Related Pleural Disease (pleural) Asbestosis (parenchymal) Cancer (all asbestos types, lung and GI tract) Mesothelioma (not dose dependent) Associated right heart failure (cor pulmonale) 08 May 2013 Gassert Occupa&onal Lung Disease 33

34 Asbestos > 107,000 work- related deaths worldwide each year Thousands more from environmental exposure 125M people exposed at work now (mining, building materials, brake linings) 90% of use today is in cement construc&on materials and pipes Major mining: Russia, Kazakhstan, China, Brazil, Canada, Zimbabwe All fiber types cause lung disease and cancer (zero threshold, IARC) Cancer in animals: only 7 hours high- dose inhala&on, all fiber types Much higher risk of cancer among smokers WHO and ILO urge all na&ons to ban all forms of asbestos mining and use Iceland first country to ban asbestos 1983; 54 other na&ons since Japan banned asbestos 2004; South Korea banned asbestos 2009 US and Canada: severely restricted use (almost no use now), lawsuits have prevented ban, Canada + China remain a major mine source and exporter Much safer subs&tutes 08 May 2013 Gassert Occupa&onal Lung Disease 34

35 Global Asbestos Produc&on May 2013 Gassert Occupa&onal Lung Disease 35

36 Trend Finland Use and ARDs 08 May 2013 Gassert Occupa&onal Lung Disease 36

37 Asbestosis Mortality USA: May 2013 Gassert Occupa&onal Lung Disease 37

38 Asbestos Timeline in USA 1925: Asbestosis appears in medical literature 1927: MassachuseCs Worker Compensa&on granted for asbestos disease 1935: Two US surveys 25% and 53% of asbestos factory workers have asbestosis 1964: Major conference in US high excess death rates from asbestosis and cancers 1972: US OSHA Asbestos Standard 1973: US EPA emission standard for asbestos 1974: Man dies from mesothelioma, only exposure one day sawing boards to build chicken coups 1978: Legal cases unearth asbestos industry cover- up disease risk, including cancer, s 1982: Largest US asbestos company seeks bankruptcy protec&on from lawsuits 1989: US EPA rules to phase out all major uses by 1997 (overturned by industry lawsuit in 1991) 1989: Construc&on workers union federa&on (now Building & Wood Workers Interna&onal) calls for global ban of asbestos (17 years later, 2006, WHO and ILO call for global ban) 1994: US OSHA lowers PEL (8- hour/day TWA) for airborne asbestos from 5.0 to 0.1 fiber/cc (ml) [Source: B. Castleman, 2012, personal communica&ons] 08 May 2013 Gassert Occupa&onal Lung Disease 38

39 Asbestos Fibrous silicates: 1. Serpen&ne: chryso&le 2. Amphiboles: amosite/ crocidolite, tremolite, anthophylite Forms: spayed, weaved, molded, embedded Uses: construc&on industry, boilermakers, auto repair Insula&on / filters / fric&on products (brakes, clutches) / pipes, beams / flooring / roofing/ fillers in paints / hazardous waste ~ 1 million persons in U.S. had direct or bystander exposure in WWII shipyards Environmental Exposures: Hurricane Katrina, New York WTC collapse May 2013 Gassert Occupa&onal Lung Disease 39

40 Asbestos Exposure Risk Construc&on work (outdoors and indoors) Using power tools to cut asbestos- containing pipes and sheets: upwards of 250 fibers/cc (ml) Demoli&on of A- C wall and ceiling sheets: huge levels of contamina&on U&lity work repairing A- C pipes: avg. 92 fibers/cc US OSHA daily average exposure limit 0.1 fiber/cc; short- term peak exposure limit 1.0 fiber/cc WHO rejected claim that controlled use of A- C construc&on materials is a realis&c expecta&on 08 May 2013 Gassert Occupa&onal Lung Disease 40

41 Asbestos Exposure USA 8 million workers exposed since 1960 OSHA established 5 fiber/ml limit in 1970 Lowered in 1994 to 0.1 fibers/ml limit (only for fibers 5 microns long) Per OSHA Asbestos and Respirator Standards, employers have duty to: Conduct air sampling Provide PPE, including respirators with medical clearance, fit tes&ng, training, and a wricen management program Medical surveillance 08 May 2013 Gassert Occupa&onal Lung Disease 41

42 Asbestos Disease USA 8% asbestos workers will die of asbestos Average asbestos worker has 50% chance of dying from cancer, compared to 18% of general popula&on Nearly all cases are primary lung cancer or mesothelioma Life&me risk of mesothelioma is 10% Latency for mesothelioma is years Non- occupa&onal environmental exposure to natural asbestos was associated with lung cancer in California study Tobacco smoking increases cancer risk 60 &mes over matched controls with no smoking or asbestos exposure history Asbestos also causes peritoneal mesothelioma 08 May 2013 Gassert Occupa&onal Lung Disease 42

43 Asbestosis Pathology Ferruginous (asbestos) bodies on biopsy: Small brown nodules in the septum of the alveolus. Asbestos fibers surrounded by iron- rich material from proteins such as ferri&n and hemosiderin, believed to be formed by macrophages 08 May 2013 Gassert Occupa&onal Lung Disease 43

44 Asbestosis and ARPD 08 May 2013 Gassert Occupa&onal Lung Disease 44

45 Asbestosis Progression Above: small re&culonodular opaci&es at lung bases sugges&ng mild asbestosis Below: coarse linear opaci&es at lung bases, L > R, obscuring diaphragm and heart ( shaggy heart sign) 08 May 2013 Gassert Occupa&onal Lung Disease 45

46 Asbestosis and ARPD ARPD = Asbestos Related Pleural Disease 08 May 2013 Gassert Occupa&onal Lung Disease 46

47 Asbestos Related Pleural Disease Fibrous, tan- white, pleural plaques on the pleural side of the diaphragm Latency > 10 yr +/- restric&on, symptoms (courtesy of Dr. Edward KlaC)

48 Cancer Risk: Asbestos and Smoking ASBESTOS CIGARETTES RISK NO NO 1 YES NO ~5 NO YES ~10 YES YES ~50-90x *SELIKOFF, ET AL 08 May 2013 Gassert Occupa&onal Lung Disease 48

49 Mesothelioma Epidemiology Malignant mesothelioma: uniformly fatal cancer of the lung lining (pleurae) or abdominal lining (peritoneum) Originate in pleura, peritoneum, pericardium, tunica vaginalis (male testes) 80% of cases are pleural (lung lining); 70% pleural cases (and 85% all cases): proven asbestos exposure No rela&on to cigarece smoking In USA: Yearly incidence = 3,300 new cases Peak year was 2000, now declining Drama&c increases are predicted where asbestos is mined, used in building materials, and wherever not banned or carefully contained Occurs among family members and communi&es nearby 08 May 2013 Gassert Occupa&onal Lung Disease 49

50 Mesothelioma Rare Causes Radia&on treatment above the diaphragm (e.g., medias&num) for other cancers, especially if younger than 25 (rarely done now) Hodgkin and non- Hodgkin lymphoma Tes&cular cancer (RR=4) Breast cancer treatment data are conflic&ng Viral oncogenes: Simian virus- 40 (?) Thorotrast (thorium dioxide intrapleural) Other silicates: erionite, zeolite (Turkey) Carbon nanotubes: in studies mice, mesothelioma- like changes following intraperitoneal injec&on Gene&c factors: loss or inac&va&ng muta&on of BAP- 1 (nuclear deubiqui&nase) enzyme 08 May 2013 Gassert Occupa&onal Lung Disease 50

51 Mesothelioma 08 May 2013 Gassert Occupa&onal Lung Disease 51

52 Mesothelioma Mortality Globally US data are well reported. China mesothelioma data are absent. Hong Kong and Taiwan are reported, along with Japan, South Korea, India, Russia and many others. Source: Environmental Health Perspec&ves, April 2011, Vol.19, Issue 4, pp May 2013 Gassert Occupa&onal Lung Disease 52

53 Pleural Mesothelioma Mexico May 2013 Gassert Occupa&onal Lung Disease 53

54 Exposure and Mesothelioma Deaths United Kingdom 08 May 2013 Gassert Occupa&onal Lung Disease 54

55 Prognosis Extremely poor Median survival Untreated: 4-13 months Treated (all types): 6-18 months Histology is significant: Sarcomatoid and Biphasic have worst outcomes Small number and heterogeneity in studies limits iden&fica&on for biomarkers for prognosis Gene expression profiling in future 08 May 2013 Gassert Occupa&onal Lung Disease 55

56 New Non- Chemo Therapies Molecular targeted: Epidermal growth factor receptor (EGFR) pathway 2 objec&ve responses with gefi&nib, none with erlo&nib Angiogenesis inhibitors Sorafenib (VEGF) limited benefit Bevacizumab no benefit Cediranib under study Imi&nib mesylate minimal benefit Vatalanib limited benefit Thalidomide no improvement Suni&nib limited benefit Histone deacetylase inhibi&on Vorinostat no benefit Vector- Gene systems (viral and nanopar&cle vectors) 08 May 2013 Gassert Occupa&onal Lung Disease 56

57 Treatment of Isolated Disease Limited to hemithorax: Surgical vs Non- Surgical Surgical (pallia&ve vs cura&ve): Diagnos&c: video thoracoscopy (VATS) or OLBx Allows for earlier diagnosis and selec&on of candidates Relieve pain, dyspnea, effusions Poten&al for significant morbidity No RCT studies yet to show if actual survival benefit Observa&onal studies suggest some survival benefit Modali&es: Tube thoracostomy (or VATS) with talc pleurodesis (effusions) Radical pleurectomy and decor&ca&on (PD) Radical extrapleural pneumonectomy (EPP) 08 May 2013 Gassert Occupa&onal Lung Disease 57

58 Pleurectomy & Decor&ca&on Allows for expansion of trapped lung More effec&ve than talc pleurodesis Reduces chance of recurrent effusions Neither open lung nor thoracoscopic procedures reduce survival 08 May 2013 Gassert Occupa&onal Lung Disease 58

59 Extrapleural Pneumonectomy Complete ipsilateral hemithoracic resec&on: Lung, pleural, pericardium, hemi- diaphragm Achieves greatest cancer cell reduc&on, improving V/Q mismatch Only interven&on that leads to disease- free long- term survival in highly- selected cases with favorable prognos&c indices Not candidates for EPP: + nodes or sarcomatoid histology Complex, high peri- opera&ve M+M 4% mortality, even with very extensive aggressive care 60% had complica&ons in a series of 328 cases at Harvard s Brigham and Women s Hospital (Boston) 40% suffered poorly treatable atrial fibrilla&on Heart and abdominal hernia&ons into lung space Vocal cord dysfunc&on with voice loss Bronchopleural fistula Empyema (infec&on) Prolonged respiratory failure Overall, median survival < 2 years; about 15% have 5- year survival EPP does not improve survival on its own: combine with adjuvant XRT and/or chemotherapy (pemetrexed plus cispla&n) 08 May 2013 Gassert Occupa&onal Lung Disease 59

60 Pa&ent Selec&on for Combina&on Therapy Age over 60 years usually not good candidate No metastases or posi&ve lymph nodes Thoracic imaging (CT + PET) with saggital views Pulmonary func&on tes&ng Echocardiography Medias&noscopy, laparascopy, and/or endoscopy with ultrasound guided fine needle biopsy to rule out medias&nal and intraperiotoneal spread Tumor expressed gene/protein analysis may become useful markers for selec&on in the future Tumor type: not sarcomatoid 08 May 2013 Gassert Occupa&onal Lung Disease 60

61 Human Gene Therapy Intrapleural ins&lla&on of replica&on- deficient recombinant adenovirus vector to deliver: Herpes simplex virus thymide kinase gene Makes tumor cells sensi&ve to nontoxic ganciclovir Human type- I interferon genes (beta/alpha) Induce humoral and cellular an&- tumor immune responses 08 May 2013 Gassert Occupa&onal Lung Disease 61

62 Addi&onal Costs of Asbestos First lawsuits in the USA filed against manufacturers Since then li&ga&on costs in the US$ Billions 08 May 2013 Gassert Occupa&onal Lung Disease 62

63 WHO- ILO Na&onal Asbestos Profiles Document: Current regula&ons Import and consump&on, forms, use, per year Import of A- C materials per year Domes&c produc&on of asbestos per year Domes&c produc&on of A- C materials per year Es&mated total number of workers exposed Full list of industries with asbestos exposure List of industries with high risk; number of workers Es&mate of burden of asbestos deaths Prevalence of asbestosis 08 May 2013 Gassert Occupa&onal Lung Disease 63

64 WHO- ILO Na&onal Asbestos Profiles Incidence of lung cancer among exposed workers Incidene of mesothelioma Es&mates on % house stock and vehicles Number of workers eligible for compensa&on Enforceable exposure limits for chryso&le System for inspec&on and limits enforcement Es&mated economic losses due to asbestos diseases Major epidemiologic studies in the country 08 May 2013 Gassert Occupa&onal Lung Disease 64

65 Asbestos Subs&tutes Polyvinyl alcohol (PVA) fibers Nearly all fibers micron diameter None are respirable size (<10 microns) Most are too large to be inhaled beyond upper airway One study of exposed workers: no cancer Polypropylene (PP) fibers Some respirable size: evidence of bronchioli&s, no fibrosis Cellulose / vegetable fibers (bamboo, sisal, racan, etc.) Long, 1-10mm length, 12 micron diameter Combina&ons: PVA- cellulose, PP- cellulose Polyacrylonitrile (PA) fibers microns diameter 08 May 2013 Gassert Occupa&onal Lung Disease 65

66 Cost of Asbestos Subs&tutes Eliminates huge current and future costs of: regulatory enforcement, exposure controls, environmental contamina&on, building remedia&on, waste disposal, medical monitoring, illness, suffering, compensa&on, death, li&ga&on (lawsuits) Fiber- cement sheets made with PVA- cellulose or PP- cellulose are currently about 5-10% more expensive than A- C sheets Micro- concrete &les are much cheaper to make for use in roofing, ceilings, floors, etc.; can be made at the worksite Non- asbestos construc&on subs&tutes are lighter, less bricle, nail and cut becer Iron pipes are easier to transport, much more durable, last longer than asbestos- cement pipes Can recycle and can use power tools on asbestos subs&tutes 08 May 2013 Gassert Occupa&onal Lung Disease 66

67 Case 56 year- old man, worked 5 years in early 1980s as a machinist making beryllium- copper alloy pipe. Health was good un&l 2001 when he developed cough and shortness of breath (dyspnea). Symptoms gradually worsened. In 2005, HRCT revealed confluent apical infiltrates in both lungs and mid- zone granularity. Pulmonologist diagnosed sarcoidosis. Stress test revealed exercise induced oxygen desatura&on. 08 May 2013 Gassert Occupa&onal Lung Disease 67

68 Case Referred for further evalua&on Bronchoscopy with transbronchial biopsy BAL and serum BeLPT: both posi&ve BAL T- lymphocytes CD8 > CD4 Diagnosis: Chronic Beryllium Disease (CBD) Treatment: prednisone 40mg alternate days with almost immediate resolu&on of dyspnea Titrated down over 6 months to a low maintenance dose BeLPT = Beryllium Lymphocyte Prolifera&on Test 08 May 2013 Gassert Occupa&onal Lung Disease 68

69 Beryllium Use: high tech, aerospace, electronics, defense Granulomatous, non- casea&ng inters&&al disease Cell- mediated immunity (sensi&zing) 4-20% exposed develop sensi&za&on Latency months to years for symptoms Lifelong risk >50% (30-100%) of those sensi&zed Pathology similar to sarcoidosis Lymphocyte transforma&on test (LPT) BAL, serum 08 May 2013 Gassert Occupa&onal Lung Disease 69

70 Chronic Beryllium Disease Epidemiology in USA: Acute form extremely rare. Chronic form affects ~ 16,000. Pathology: Virtually iden&cal to sarcoidosis. Diagnosis: Upper and mid- lung granuloma. Posi&ve BeLPT of blood and BAL. BAL T- lymphocytes CD8 > CD4. Source: University of Pennsylvania School of Medicine Lung Center 08 May 2013 Gassert Occupa&onal Lung Disease 70

71 Coal Worker s Pneumoconiosis No respiratory protec&on. Tobacco adds to CWP COPD risk; and increases cancer risk. 08 May 2013 Gassert Occupa&onal Lung Disease 71

72 Coal Worker s Pneumoconiosis Mixture of Anthraco&c pigment and fibrosis (courtesy of Dr. Edward KlaC) 08 May 2013 Gassert Occupa&onal Lung Disease 72

73 Coal Worker s Pneumoconiosis CWP risk is higher for exposure to higher carbon rank coal: anthracite coal compared to bituminous coal Silica content increases risk of CWP 08 May 2013 Gassert Occupa&onal Lung Disease 73

74 Progressive Massive Fibrosis (PMF) in CWP PMF lesions > 10 mm diameter Calcified (eggshell) hilar lymphadenopathy Symmetric or unilateral Irregular non- calcified opaci&es Posterior upper and middle lobes Hilar retrac&on PMF lesions migrate toward medias&num causes peripheral trac&on emphysema Cavita&on predisposes to Tuberculosis and necrosis 08 May 2013 Gassert Occupa&onal Lung Disease 74

75 CWP and Dust Control: Reduc&on in CWP since the 1969 Coal Mining Health & Safety Act (MSHA) US NIOSH Mine Safety & Health Coal Workers Health Surveillance Program 08 May 2013 Gassert Occupa&onal Lung Disease 75

76 CWP Morbidity by Tenure: Percentage of underground miners with coal workers pneumoconiosis (ILO 1/0+) US NIOSH Coal Workers X- ray Surveillance Program 08 May 2013 Gassert Occupa&onal Lung Disease 76

77 Coal Worker Compensa&on Black Lung Benefits Act Monthly payments and medical treatment for workers totally disabled by pneumoconiosis Monthly payments for survivors of miners, mine construc&on and transport workers who die Mine operators (owner, supervisor, contractor) are liable for payments Medical providers must report to employer and federal government within 30 days of the first treatment, or payment for care can be denied Link to compliance guide: hcp://www.dol.gov/compliance/guide/blklung.htm#who 08 May 2013 Gassert Occupa&onal Lung Disease 77

78 Cause of Silicosis SILICON = Si = the element SILICA = SiO 2 = Silicon dioxide Crystalline ( free silica ): Quartz Cristobalite Trydymite Amorphous (e.g., glass) rela&vely non- toxic Silicates - combined forms, e.g. Asbestos/talc 08 May 2013 Gassert Occupa&onal Lung Disease 78

79 Chronic Silicosis Nodules contain collagen bundles 08 May 2013 Gassert Occupa&onal Lung Disease 79

80 Silicosis Hilar adenopathy with eggshell calcifica&on is highly sugges&ve of silicosis 08 May 2013 Gassert Occupa&onal Lung Disease 80

81 Silicosis Simple silicosis: 2-5mm rounded nodules, upper and middle lobes Silicosis with PMF: lucencies of emphysema due to PMF migra/on 08 May 2013 Gassert Occupa&onal Lung Disease 81

82 Infec&on Silicosis Complica&ons Rapid worsening of symptoms or chest x- ray Tuberculosis (TB) must be ruled out Fungal (mycetoma), e.g., Aspergillosis Autoimmune Disease Rheumatoid arthri&s (Caplan syndrome) Cancer of lung: IARC Group 1 (known human carcinogen) 08 May 2013 Gassert Occupa&onal Lung Disease 82

83 Silicosis Epidemiology USA Reality is largely unrecorded Es&mated 200,000 miners and 1.7 million others have experienced occupa&onal exposure Worst epidemic , Gauley Bridge tunnel in West Virginia 2000 who drilled rock: 400 died of acute silicosis, nearly all survivors developed chronic silicosis Recently, in 1996, silicosis reported in 60 of 1072 workers in automo&ve factory Among those employed > 30 years, 12% developed silicosis Declined from 12/M in 1968, to 2/M in1997 (underes&mated) [per Million of general popula&on] 08 May 2013 Gassert Occupa&onal Lung Disease 83

84 Silicosis Mortality May 2013 Gassert Occupa&onal Lung Disease 84

85 Silicosis Management Remove from silica and other inhala&on exposures Stop smoking Treat co- morbi&es (asthma, infec&ons) Pulmonary rehabilita&on: Can improves quality of life, but not survival Cor&costeroids do not work Whole lung lavage has proven ineffec&ve: High rate of complica&ons, including death Silica is embedded in lung; cannot be washed out 08 May 2013 Gassert Occupa&onal Lung Disease 85

86 Nano- Par&cles High surface to size ra&o (1-100nm) High poten&al for molecular level interac&on Fiber- like structures behave like asbestos fiber Health effects (carbon nanotubes; nanofibers): Binding with biochemicals to create free radicals leading to oxida&ve stress, chronic inflamma&on Fibrogenesis leading to pneumoconiosis Mesothelioma postulated risk US NIOSH recommends control as if asbestos 08 May 2013 Gassert Occupa&onal Lung Disease 86

87 Defini&on Nanopar&cles : one dimension < 100 nm 1 nanometer = 1 billionth meter (invisible to eye) Human hair diameter = 100, ,000 nm Average grain of sand = 1 million nm Red blood cell = 10,000 nm Hydrogen atom = 0.1 nm 08 May 2013 Gassert Occupa&onal Lung Disease 87

88 C60 transistor C nano- structures Source: Ecole Polytechnique de Montréal, Département de génie physique; hcp://nanostructures.phys.polymtl.ca/galerie.html 08 May 2013 Gassert Occupa&onal Lung Disease 88

89 Forms and Structures Powders Solu&ons Slurries Suspensions Composites Fullerenes (Bucky balls) 60 carbon atom cages Nanotubes Nano- injec&on Quantum dots Semiconductor materials that fluoresce (MRI, US) Composites Titanium oxide alloys 08 May 2013 Gassert Occupa&onal Lung Disease 89

90 Products Produced now: TiO 2 Cosme&c an&- wrinkle facial creams TiO 2 Transparent sunscreens Nano- silica dental fillers Nano- clay tennis balls Nano- whisker stain and wrinkle free fabrics TiO 2 Coa&ngs for self- cleaning glass, bicycles, cars An&cipated: Self- cleaning clothes Fire retardants Microscopic fuel cells High efficiency filters Wearable sensors coupled with wireless technology Lab- on- chip analyzers Opto- electronic devices for diagnosi&cs in vivo TargeCed sensors and vehicles for drug and vaccine delivery to specific organs or tumors 08 May 2013 Gassert Occupa&onal Lung Disease 90

91 Engineering Building from bocom up ( growing ) as living cells do Efficiency of resource use (grow a table rather than cut a tree) Less waste product Scaffolding using biodegradable polymers Linking of dry (electronic or alloy) and wet (biologic), e.g., cell sensors, &ssue/organ building NBIC (Natl Sci Found) convergence of Nanotech / Biotech (genes) / Infotech (computers) / Cognotech (brains) 08 May 2013 Gassert Occupa&onal Lung Disease 91

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