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D. Christiani, M.D., M.S. PNEUMOCONIOSES Introduction 1867: Zenker - pneumo = lung conio = dust osis = state of 1874: Proust - "pneumoconiosis" = "dusty lung" 1950: A diagnosable disease of the lungs produced by inhalation of dust (aka mineral dusts) 1971: Accumulation of dust in the lungs with concomitant tissue reaction to its presence 1973: Industrial Injuries Advisory Council (England): pneumoconiosis is a permanent alteration of lung structure due to the inhalation of mineral dust and the tissue reactions of the lung to its presence, but should not include bronchitis and emphysema. 1982: WR Parkes: "pneumoconiosis" is defined as the non-neoplastic reaction of the lungs to inhaled mineral or organic dust and the resultant alteration in their structure excluding asthma, bronchitis, and emphysema. II. Asbestos-Related Lung Diseases A. Nature of Asbestos 1. Types: Group of fibrous silicates a. Chrysotile("serpentine") ^ b. Crocidolite } amphiboles ---- c. Amosite d. Other amphiboles:anthophyllite, tremolite, actinolite 1 HWBUI0003712 Indestructible a. Up to 800C b. Amosite 600-900C c. Add resistant World Production and Use a. Production (Metric Tons) Amosite Croddolite 1920 200 6,100 1970 100,000 135,000 1983 4,157,256 (all types) b. Consumption (Metric Tons) 1920-1970: fourfold increase in USA 1983: 217 metric tons Chiysotile 184,000 3,150,000 Asbestos cement products - tiles, roofing, water pipes, drain pipes Floor tiles (10-30% by weight) Insulation and fire-proofing (shipbuilding construction) Textiles Paper - insulating, gaskets, wall coverings, cooking mats, stove mats, etc. Friction products - brakes, clutches Mining and processing 2 HWBUI0003713 8. Other - respirator filters, cigarette filters (past), hair dryers (past) 9. Many approved uses. EPA now wants ban. D. Populations at Risk 1. Exposures .from mining to manufacture, use, removal, discarding 2. Number of workers exposed in manufacturing: 18,000 3. Construction/Renovation: 180,000 to 480,000 4. Automobile/Truck Repair: 2,000,000 5. Ship Repairs/Building: 4,000 6. Potential for current exposure: 2/3.5 million 7. Potential for past exposure: unknown E. Clinical Conditions 1. Asbestosis a. Definition: Pulmonary or parenchymal fibrosis, often accompanied by thickening of visceral and parietal pleura and calcification of the parietal pleura b. Pathology 1. macroscopic a. small, pale, firm and rubber in severe cases b. fibrostic, adherent pleura c. patchy (inhomogeneous) to diffuse fibrosis d. lower lobes predominantly affected e. Hilar nodes not enlarged 3 HWBUI0003714 microscopic a. peribronchiolitis (respiratory bronchioles) first lesions b. alveolitis (alveol: of respiratory bronchioles) c. spreads from lumen to interstitium d. asbestos bodies present UICC/DjO Grading (paraphrased) Grade O: no fibrosis in bronchioles Grade 1: fibrosis involves wall of respiratory bronchiole; no fibrosis in more distant alveoli Grade 2: Grade 1 plus involvement of alveolar ducts or alveoli Grade 3: fibrosis as in Grade 2, with coalescence of fibrotic alveoli Grade 4: Grade 3 plus formation of new spaces larger than alveolis ranging up to 1 cm. "Honey combing" or bronchiolectasis. Spaces may or may not be lined by epithelium. Asbestos bodies, or ferruginous bodies a. indicate exposure, not disease b. golden brown, up to 300 microns; average is 30-50 microns c. Asbestos fiber covered by layers of iron containing pigment d. dumbbell appearance e. Most fibers, especially chrysotile, are uncoated f. ratio of uncoated to coated ishigh: from 5:1 to 10,000:1 4 HWBUI0003715 c. Pathogenesis a. Inhaled fiber may exceed 100 microns in length; 0.1-0.2 microns in diameter. b. first effect on respiratory bronchioles, alveoli of respiratory bronchioles c. Exact mechanisms of pleuropulmonaiy fibrosis, mesothelioma and carcinoma of lung (and other organs) are not known. d. Theories: (1) direct physical irritation (2) response to released silicic acid and metallic ions (3) autoimmune reaction from antigens liberated through asbestos-macrophage interactions (4) free oxygen radical generation e. Like silica, asbestos becomes coated with protein as it is engulfed by macrophages. It is relatively soluble compared with quartz dust, which may explain the diffuse nature of the fibrosis and relative paucity of asbestos ("ferruginous") bodies in some cases of advanced asbestiosis. Hyalin Plaques a. bilateral, well circumscribed parietal pleura fibrosis. On CXR, may only see on one side. b. may calcify c. characteristic hyalin on pathology Diffuse Visceral Pleural Thickening a. usually after an asbestos pleural effusion b. may accompany parenchymal asbestiosis c. costophrenic angle blunting d. may lead to respiratory impairment, failure 5 4. Pleural Effusion a. "benign" b. may occur early, i.e., 10 years since exposure c. serofibrinous or sometimes hemorrhagic d. must rule out mesothelioma, other malignancies e. may resorb spontaneously, and reappear on other side f. asbestos bodies rare in fluid d. Clinical Presentation of Asbestosis 1. Symptoms a. dyspnea on exertion b. dyspnea greater than x-raysigns c. cough - common. Dry if no bronchitis. d. occasional pleuritic pain, chest tightness 2. Signs a. Bibasilar rales (50%) b. decreased chest expansion c. finger clubbing - in advanced disease d. pleural rub (occasional) e. Laboratory Findings 1. Lung function tests a. decreased volumes (TLC, FRC, RV, FVC) b. Impaired gas exchange. Decreased DLCO may be earliest sign and may occur only in exercise. 6` HWBUI0003717 c. Can have obstructive defect (decreased flows, FEVi) d. Progression: decline in volumes, DLCO; T(A-a)D02 2. Chest X-Ray a. fibrosis - linear; lower lobe predominance b. pleural plaques often present c. thickened visceral pleura also often present d. obscured heart border, diaphragm edge e. plaques often undetected on x-ray f. honeycombing may be present (later stages) f. Diagnosis of Asbestosis a. Clinical 1. history of exposure 2. latency (usually 15 years) 3. abnormal chest x-ray - linear fibrosis, plaques 4. restrictive pattern on PFT 5. impaired gas exchange 6. rales * 1. and 2. essential other criteria increase likelihood with number of positives Pathology 1. discussed above 2. even fine asbestos body is significant 7 HWBUI0003718 F. Complications/Other Diseases Associated with Exposure 1. bronchogenic carcinoma - all cell types, synergism with smoking 2. Ca of other organs - mesothelioma, GI, larynx 3. bronchitis and bronchiectasis 4. spontaneous pneumothorax - difficult re-expansion 5. Cor Pulmonale 6. TB - NO. G. Prevention 1. substitution: most effective in this case 2. proper removal - engineering, PPE, practices 3. standard enforcement. PEL = 0.2 fiber/cc 8 hr TWA; "action level" = 0.1 f/cc; STEL = under litigation as of 9/89 4. smoking cessation to minimize risk of cancer and other complications 8 HWBUI0003719 III. Talc A. Definition 1. hydrated magnesium silicate 2. in nature, "talc" is 1-99% talc up to 70% tremolite (asbestine) up to 30% quartz 3. therefore, platey and fibrous 4. New York State (NYS) talc is 70% tremolite 5. steatite - fine grained, pure 6. soapstone ore - talc substitute B. Exposures/Uses 1. mining/milling 2. paints 3. pharmaceutical - 10-40 microns 4. electronic ceramics 5. In Rubber as lubricant. Inner tubes - parting compound 6. chewing gum 7. paper filler (esp. fibrous talc) C. Epidemiology 1. poor information 2. NYS fibrous results in more disease than non-fibrous 3. Vermont - non fibrous 9 HWBUI0003720 D. Pathology 1. macroscopic a. fibrous adhesion of pleura b. grey-white fibrosis - soft modules with poor structure or diffuse interstitial 2. microscopic a. ill-defined nodules b. diffuse interstitial fibrosis c. foreign-body granuloma, "talc granuloma" E. Clinical Features 1. Symptoms a. occur late in process b. dyspnea on exertion c. cough 2. Signs a. asbestosis-like 3. Chest x-ray a. nodular: silicosis-like, 3-5 nun, with lobes b. diffuse - (asbestosis-like) fibrosis c. pleural plaques 4. Pulmonary Function Tests a. nodules late - impaired gas transfer (DLCO; t A-a D02 on exertion) b. restrictive picture in fibrosis 10 HWBUI0003721 G. Diagnosis 1. histoiy of exposure 2. chest x-ray 3. PFT H. Prognosis 1. NYS talc = diagnosis to death 26 years 2. slowly progressive 3. course may be fast with high exposure I. Complications 1. ?? cancer (asbesteiform) J. Control 1. 2. Silicosis Standard TLV non-fibrous fibrous 2 mg/m3 (respirable) 2 fibers/ce greater than 5/i A. Quartz 1. silicon dioxide (Si02) = "free silica" 2. earth's crust - silicates B. Sources of Exposure/Uses 1. mining, quarrying, tunneling 2. stone cutting and polishing 3. abrasives and abrasive blasting 4. glass manufacture 5. fillers for paints andrubber 6. foundries 11 HWBUI0003722 7. ceramics including refractory brick 8. boiler scaling 9. vitreous enameling C. Populations at Risk (numbers are approximate) 1. metal mining 76,000 2. coal mining 80,000 3. non-metallic minerals 95,000 4. stone and glass products 507,000 5. iron and steel foundries 188,000 6. non-ferrous foundries 69,000 7. agriculture ? 2,000,000 8. heavy construction 600,000 D. Disease Rate Estimates 1. no reporting, no standardized diagnosis 2. NIOSH estimates 3,000-5,000/year E. Pathology 1. macroscopic a upper lobepredominance b. nodules (2-6 mm) (i) intact with whirled pattern (ii) cavitation (without TB) rare (iii) conglomeration occurs c. lymph node calcification (proportional to amt of quartz per 100 gm node) 12 HWBUI0003723 d. can have fibrous, adherent pleura 2. microscopic a. quartz particles in and out of macrophages in alveolar walls, especially alveoli from respiratory bronchioles b. pathogenesis (theory): cell death - fibroblast proliferation -* reticulin formation concentric collagenous fibrosis .i c. nodule hyalinization with cellular capsule where silica is. Hyaline has high content of carbohydrate and phospholipid (like amyloid). 3. miscellaneous a. Amount of fibrosis is proportional to free silica content and duration of residence in lung. b. Normal lungs: free silica up to 1%. In silicotic lungs, up to 20%. c. Silica in lymph nodes may lead to characteristic "egg shell" calcification d. Fibrosis progresses after exposure has ceased. Clinical Presentation 1. symptoms a. initially, non-productive cough. Later, sputum and infection b. increasing dyspnea. Poor correlation with chest x-ray c. no chest or pleuritic pain 2. signs a. distant breath sounds b. no wheezes or rales c. finger clubbing uncommon d. advanced cases have signs of cor pulmonale 13 G. Evaluation 1. chest x-ray a. rounded opacities early in upper fields b. increase in size and profusion of nodules over time c. well-defined large opacities d. egg-shell calcifications of nodes 2. lung function a. no characteristic changes b. reduced VC or FVC first finding - less than chest x-ray suggests, (vs. asbestosis) c. reduced FEV,/FVC and TLC later d. impaired gas exchange (02 desaturation) with exercise and with conglomeration e. resting A-a 02 difference increases with advanced stages 3. other a. biopsy - rarely necessary - scalene node may suffice b. EKG - changes seen with cor pulmonale c. Rheumatoid factor and ANA (circulatingautoantibodies) may be present with or without arthritis. Larger necrotic nodules, positive RF = Caplan's Syndrome. H. Diagnosis 1. occupational history 2. chest x-ray 3. PFT 14 HWBUI0003725 4. exclusion of other conditions: e.g., isolated conglomeration -R/O Cancer. Calcification of nodes or nodules - R/O TB, histoplasmosis. I. Complications 1. tuberculosis - common * suspect with: sudden change of chest x-ray; productive cough; weight loss; hemophysis 2. atypical mycobacteria - supplanting M. Tb in many regions of USA 3. cor pulmonale - not common. Occurs after silico-Tb and pulmonaiy hypertension 4. scleroderma - ? related 5. cancer - ? caused, same evidence in humans suggestive, animals - yes. 6. spontaneous pneumothorax -uncommon J. Treatment 1. Poly-2-vinylpyridine-N-oxide (PVPNO) - prevents progression in animals, toxic and mutagenic.2 3 4 5 6 2. Tetrandrine - from root of stephania tetrandrina, American plant, used in China, appears to break down collagen, decreases opacities on chest x-ray. in monkeys, decreases hyalin in nodules, does not alter function. ? change progression (unlikely), no controlled studies. 3. corticosteroids - no help, potential harm (TB) 4. active TB - 3 drugs 5. positive PPD - prophylaxis for 9-12 months 6. heart failure - diuresis 15 HWBUI0003726 K. Prevention 1. PEL in mg/m3: respirable cone = 10 + [% resp quartz + 2] L. Acute Silicosis 1. Origins a. high exposures to free silica over short time b. free silica mostly of small particle size (1-2 microns) 2. Pathology a. macroscopic - widespread fibrosis b. microscopic - alveolar proteinosis identical to PAP. Birefringent particles can be demonstrated in areas - not diffuse fibrosis with silicotic nodules. If present, they are smaller and less organized. 3. Clinical Presentation a. symptoms - rapidly progressive breathlessness over a period of a few weeks, weight loss, productive cough, pleuritic chest pain b. signs - finger clubbing, rales 4. Evaluation a. PFT: restrictive pattern with marked decrease in TLC. impaired gas exchange, even at rest b. chest x-ray: diffuse alveolar air-space filling ("ground glass") appearance fir like miliary TB (fine nodular) 5. Diagnosis a. same as silicosis, except: b. lavage and biopsy more likely and are veiy useful c. rapidly fatal - within one year 16 HWBUI0003727 M. Other Aspects of Silicosis 1. free silica: a. quartz: stable up to 867C b. tridymite: stable from 867C to 1470C c. cristobalite: stable from 1470C - 1723C (melting point 1723C) Fibrogenic properties of silica increase from quartz through cristobalite. Quartz < Tridymite < Cristobalite 2. (b) and (c) are formed in: refractory bricks other highly silicous ceramics foundry sands straight and flux-calcined diatomite 3. Silicates = Si02 combined with various cations a. "silicatosis" of silicate pneumoconiosis - similar to silicosis in many respects b. compounds: diatomaceous earth kaolin clay (China clay) CoaJ/Carbonaceous Dust A. Terminology 1. coal worker's pneumoconiosis ("CWP") - 1942 2. "anthracosilicosis" - disease as a result of exposure to both anthracite and silica (carbon and silica)3 4 3. "black lung" - administrative term, includes any of the pulmonary conditions present in a miner's chest 4. CWP terminology a. simple CWP - discreet macules qt nodules < 5 mm b. complicated or infective pneumoconiosis = disease considered to be due to TB complicating CWP 17 c. progressive massive fibrosis ("PMF') = large confluent masses of dust and collagen fibrosis B. Sources of Exposure 1. coal mining - face workers a. surface work - low dust b. trimming - high dust 2. graphite = crystalline carbon and impurities (3-5% quartz) a. refractory ceramics and crucibles - heat resistant b. foundry facings - heat resistant c. steel and cast iron for hardness d. pencils, lubricants, electrodes 3. lamp black = smoke of hydrocarbon flame - amorphous carbon 4. carbon black = flames of natural gas or petroleum distillation, crystalline carbon, used as filler and color in rubber, plastics, records, printing inks, electrodes, decoloring agents C. Epidemiologic Highlights 1. prevalence of radiologic abnormalities a. simple vs. complicated cases: complicated more common in Eastern Pennsylvania; rare in Colorado b. rank related? iQ 2. Progression relates to profusion at first visit and presence of circulatory autoantibodies (e.g., RF).3 3. Simple does not carry increased mortality and pulmonary function usually normal. D. Pathology 1. Simple Pneumoconiosis 18 HWBUI0003729 a. macroscopic - dust macules interspersed with unpigmented upper lobe indurated nodules. 2-5 mm, and softer than silica b. microscopic - dust in and out of macrophages near respiratory bronchioles, some reticulin. nodules - random collagen (reticulin collagen greater than silicosis), centrilobular emphysema with dust - ? chemical significance in this setting .i 2. Progressive Massive Fibrosis (PMF) a. macroscopic - variable shape and does not respect architecture of the lung (upper lungs), hard, rubbery, black surface, coalescence greater than 3 cm is definition, cavitation - melanoptysis b. microscopic - same as simple CWP nodules, vessels obliterated, arterial obstruction may cause necrosis 3. Rheumatoid Coal Pneumoconiosis ("Caplan's Syndrome") a. generally, but not exclusively, accompanied by R.A. b. In one study, the prevalence of circulating RF was no different than the general population. c. pathology (i) macroscopic: 3-20 cm - more random distribution than above, still tends to upper cut surface, alternates black and grey-white to yellow bands (dust and necrotic collagen), can cavitate (necrotic) or calcify, coal dust macules or nodules uncommon (ii) microscopic: centers necrotic, then macrophages and fibroblasts; then collagen and plasma cells, strking endarteritis at periphery with plasma cells, no TB. 4. Diffuse Interstitial Fibrosis a. associated with heavy dust pigmentation 19 HWBUI0003730 E. Clinical Presentation 1. Symptoms a. none specific up through category A except probably chronic bronchitis b. PMF - cough, sputum c. rheumatoids may have hemoptysis (AFB negative) > d. DOE 2. Signs - more reflective of bronchitis or emphysema F. Evaluation 1. Lung Function a. miners have (slightly) lower FEVj and FVC than non miners b. simple CWP can have reduced DLCO and (A-a) D02 c. PMF - results variable, but can see jTLC, jVC, |RV, jDLCO and t(A-a) D02 d. rheumatoid nodule(s) - littleabnormality e. some physicians say ventilatoiy capacity is the best guide to disability 2. X-Ray a. q > r > p on ILO scheme b. profusion grades 1-3 associated with increased retained dust. Grade 3 spreads to whole lung. c. large opacities form d. rheumatoid nodule: 3-30 cm, irregular, calcified e. RF is positive in Caplan's. f. Cavitation requires search for TB. 20 HWBUI0003731 Diagnosis 1. occupational history 2. chest x-ray 3. differentiated Dx: a. TB b. cancer c. granulomatous lung disease 4. disability a. controversial b. Black Lung Law - legal norms discriminate against group c. "CWP" vs. "CWD" d. proof of exposure for 15 years e. MD's "evaluation" f. specific pulmonary function tests Complications 1. TB 2. chronic bronchitis 3. cor pulmonale Prognosis 1. variable Treatment - none Prevention 1. dust control 2. 2 mg/m3 of resp dust if Si 02 < 5% 21 HWBUI0003732 3. if Si 02 > 5% - silica standard Fibrous Glass A. Nature and Origin 1. thin streams of molten glass to steam 2. spinning off a centrifuge ( la cotton-candy) 3. add resin for insulation or bonding j B. Exposure 1. great variety depending on process 2. small % respirable 3. "VFP . veiy fine fibers made since 1969 4. primarily insulators, also production and manufacture of products C. Uses 1. insulation - pipe, rolls 2. textiles (draperies) 3. cords 4. reinforcement - cars, boats 5. refractory material D. Disease 1. Clinical a. upper respiratory tract irritation - severe b. skin - irritant contact dermatitis c. lower respiratory tract = VFF d. animal studies - VFF carcinogenic - similar to asbestos 22 HWBUI0003733 .2 Pathology a. minimal tissue reaction for large fibers b. VFF - ? alveolitis/fibrosis 3. Epidemiology a. x-ray negative for coarse fibers i b. one study of VFF showed 2-3% linear opacities c. mortality - equivocal, no follow-up yet done of VFF VII. Inert Dusts A. chest x-ray changes with little or no change in lung function: high radiodensity 1. iron (siderosis) 2. barium 3. antimony 4. zirconium 5. chromite B. low radiodensity - minimal chest x-ray changes and no lung function change 1. limestone 2. cement (non-silica containing) 3. gypsum (CaS0<-2H2O) 4. silicon carbide jdc/nmy 23 HWBUI0003734