Document zQY7zqGOe1nVnmkLN6aDvKr36

Agenda item 7 - 14th meeting of ttie Medical Advisory Panel. 4th Draft - klk/ZZ/'/Z/r.. August 1985 THE DIFFERENTIAL DIAGNOSIS CF ASBESTOSIS Preamble Asbestosis, a diffuse interstitial pulmonary fibrosis is a known Occupational disease in workers who are occupationally exposed to Asbestos fibre, such as in mining, milling and manufacture of asbestos containing products. The signs and symptoms of asbestosis are similar to those of other forms of diffuse interstitial pulmonry fibrosis, hence nay not be helpful in distinguishing between them. In addition there is no specific investigation that confirms the diagnosis of asbestosis Hence, the object of this paper is to focus on the importance of making a distinction between asbestosis and other forms of diffuse interstitial fibrosis, since this will affect therapy, medical management, workers compensation and other issues. DEFINITIONS Asbestosis Asbestosis is a diffuse interstitial pulmonary fibrosis caused due to occupational exposure to respirable airborne asbestos fibres, over a longer period. The fibrosis is irreversible, and the process of fibrosis may progress even after exposure has ceased, in sane. :2: Diffuse interstitial pulmonary fibrosis(DIPF) The term diffuse interstitial pulmonary fibrosis is applied to a heterogenous group of diseases grouped together because of cannon clinical, radiological, Patho-physiological features. The disease consists of bilateral diffuse fibrosis which chiefly affects the gas-exchange region of the lungs. The most prevalent diseases under this head are provoked by a variety of causes, grouped under three sub heads, non-occupational, occupational, and unknown. Criteria for diagnosis of Asbestosis The diagnosis of asbestosis is based upon a history of adequate exposure, radiographic evidence consistent with diffuse interstitial pulmonary fibrosis, a predcminently restrictive than a mixed pulmonary function defect and the prescence of persistant bilateral based endinspiratory crepitations in the lungs. Dyspnoea, cough, sputum production, chest pain and clubbing of the fingers are usually late, non-specific symptoms. The chest radiograph shows small irregular reticular, linear Opacities in lower and mid zones of lung field. A profusion of over 1/0 as per ILO international classification of radiographs of pneumoconiosis(1980), and above is suggestive of a possible case of asbestosis. But these opacities are not characteristic of asbestosis, hence cannot differentiate from other diffuse interstitial pulmonary fibrosis cases. Sane normal adults will A0 K03 :3: exihibit these radiographic patterns as a part of aging, especially in persons v*io tad repeated pulmonary infections (eg: bronchitis, pneumonitis). As there will be an overlap in the frequency distribution of snail irregular opacity profusion in normal and pneumoconiotic individuals at the low levels of profusion(8), a positive diagnosis may not be possible without further observation and investigation. Higher levels of profusion of snail irregular opacities nay also pose problems of interpretation in the absence of an adequate occupational exposure history. Scleroderm, lipoid pneumonia, desquamative interstitial pneumonitis and sarcoidosis may produce basal irregular patterns similar to those seen in asbestosis(8!. Pleural plaques are fibrot.c areas mainly affecting the parietal pleura. They are usually bilateral, smooth or nodular and discrete. They are more frequently seen on the posterolateral or anterolateral chest walls, run along the rib margins (most caitronly the sixth-tenth ribs) and are also found on the danes of the diaphragm. Calcification nay occur as the years go by. They are considered to be a unique radiographic sign presumptive of t asbestos etiology(7). The working group cn Asbestos of American college of Radiology, describe nany other diagnostic features of value in raking a diagnosis of asbestosis and they point out the differences between early and late findings, in their monograph(7). A0 1 403 i :4: Pulmonary function tests, spiremetry, transfer factor, show a restrictive defect in asbestosis, which is again ccmmon to all cases of diffuse interstitial pulmonary fibrosis. But in presence of other criteria for diagnosing asbestosis, it serves as an important guideline specially if pre-employment and periodic medical examination test values are available. Presence of persistant bilateral basal endinspiratory crepitations, is an early sign of asbestosis. All other possible causes associated with this sign to be ruled out before confirming asbestosis, as this sign is also not specific. Diagnosis of Diffuse Interstitial Pulmonary fibrosis(DIPF) DIPF cases can be broadly classified into two groups, i.e. known and unknown etiological factors. To quote Fulmer, there is no occupation in which the worker is imnune to non occupational diseases. Hence it is a matter of grate concern in judging the cause of DIPF, in a worker veto's Occupation is also supposed to result in such condition. AO H 1 C / :5: Causes of Diffuse Interstitial Pulmonary Fibrosis DIPT cases can be broadly classified into two groups, i.e.known and unknown etiological factors. [After Fulmer(l) D.Geraint James and Peter R.Study (2) and W.Raymond Park.es(3) ] Known Etiology: 1) Inhalants a) Inorganic (See table 3) b) Organic (See table 4) c) Fumes, gases vapours, aerosols(See table 5) 2) Ingestants or parenetaerally administered materials. a) Drugs (See table 6) b) Poisons - Paraquat - Kerosene 3) Infectious agents (See table 7) 4) Neoplastic causes (See table 8) 5) Metabolic causes like uraemic pneumonitis. Hypercalcemia. 6) Circulatory causes (See table 9) 7) Physical agents like Post irradiation fibrosis, thermal injury,(Boiler Operator, Sauna takers) Oxygen toxicity, blast injury. 8) Incomplete resolution of pneumonias. Unknown Etiology 1) Idiopathic Pulmonary Fibrosis (Familial Pulmonary Fibrosis or Hannan - Rich Syndrome). 2) Inherited disorders - tuberous sclerosis - Neuiofibranatosis A01 4 1 1 :6: 3) Collagen disorders - Scleroderma - Rheumatoid arthritis - Lupus erythematosus - Progressive systemicsclerosis - Periarteritis nodosa - Sjogren's syndrome - ankylosing spondylitis - Wegner's granulomatosis - Derma tcryositis 4) Miscellaneous - Sarcoidosis - Histiocytosis x - Letterer sieve disease - Hand - Schuller - Christian disease - Eosinophilic granuloma - Idiopathic haemosiderosis - Pulmonary alveolar proteinosis - Amyloidosis - Veno - occlusive disease - Iymphangioleionycmatosis. :7: TRRTF - 3 OCCUPATIONAL INTERSTITIAL LUNG DISEASES CAUSED BY INORGANIC INHALANTS INORGANIC DUST Aluminium Asbestos Beryllium Cadmium Coal Diatcraoeousearth Graphite Kaolin Mica Iron Qxide(Siderosis) Mercury vapour Silica Talc Titanium Barium Tin Vanadium Silver Manganese INDUSTRIAL HAZARD Grinding Mining Milling Insulation Industry Product Manufacturing Alloys Electronics Nuclear workers Mining Processing Polishing Welding Mining and manufacturing Drilling, blasting Foundry and glass workers. Ceramics and cosmetics Paint A0 1 4 1 3 :8: TABIE - 4 NATURE AND SOURCE CF ORGANIC DUST ANTIGENS IN DIPF Disease Dust exposure Nature of antigen to which praecipitin shown Farmers' lung Mouldy overheated hay Fog-fever in Cattle Bagassosis Mouldy hay Mouldy overheated sugar-cane bagasse Mushroom workers' lung Mushroom compost dust Malt workers'lung Mouldy barley or malt Bird fanciers' lung Pigeon and budgerigar droppings Wax ooating feathers'pigeon bloom' Pituitary snufftakers' lung Powder of porcine and bovine posteriorpituitary extract Wheat weevil disease (Millers' lung) Infested vrtieat flour Maple strippers' lung Maple bark Thermophilic actinamycetes Micropolyspora faeni Thermbactincmyces vulgaris Micropolyspora faeni Mouldy bagasse Thermoacti ncnyces sachani Thermophilic actincmycetes (See farmers' lung) Aspergillus fumigatus Aspergillus clavatus Avian serum protein antigens Serum protein and pituitary antigens Sitophilus granarius Cryptostrcma (Ccniosporium) corticale AO 1 414 :9: Disease Exist exposure Nature of antigen to which precipitin shon Sequoiosis Mouldy redwood sawdust Aaureobasidium (Pullularia) -pullulans -graphium Suberosis Oak bark, cork dust Mouldy oak bark P. frequentans Woodworkers'lung Sawdusts of oak,cedar, etc. Sawdust extracts Cheese-washers' lung Moulds on cheese Penicillium casei 'New Guinea' lung Mouldy thatch dust Extracts of thatch Smallpox-handlers' Smallpox scabs lung Paprika splitters' Mouldy paprika pods lung Macor stolonifer Humidifier or forced-airsystem lung Fungal spores in airconditioning ducts and in home humidifiers T.candidus T.vulgaris Naegleria gruberi Coptic lung Cloth wrappings of mumues Poultry handlers' lung Coffee and tea growers' disease Poultry feathers and products t Green coffee bean Tea fluff Turkey and chicken proteins Sewage slixlge disease Dust of heat treated sludge Gram-negative bacteria Sauna takers' disease Contaminated steam Aaureobasidium pullulans Dry rot lung Mould dust Merulins lacrynans 401415 Disease : 10 : Dust exposure Fish meal workers' lung Di isocyanate alveolitis Fish meal dust Dust and gas in nanufacture of seme adhesives paints etc. Naturae of antigen to which prseacipitin shown Fish proteins 1DI and HDI TABLE - 5 FUMES CAUSING INTERSTITIAL LUNG DISEASE Exposure Swinming pools Ore-smelting Nose drops Vineyard spray Insecticides Silo-Filler's disease Vapour inhaled Chlorine gas Sulphur dioxide Oil Bordeaux mixture of copper sulphate and lime Pyrethrum Nitrogen dioxide Aimonia Phosgenes Aoetylen Carbon tetrachloride Bromine Hydrochloric acid Nitre acid Picric acid. AO U 1 6 : 11 TABLE - 6 CAUSES CF DRUG-INDUCEE CHRONIC INTERSTITIAL LUNG DISEASE Aminosalicylic acid Bischloroethylnitrosousea Bleaiycin Busulphan Chlorambucil Cyclophosphamide Diphenylhydantoin 5 Fluorouracil and Mitomycin C Gold salts Hexamethonium Mocamylamine Melphelan Methotrexate Methysergide Nitrofurantoin Nitrosoureas Paraquat Penicillin Pentolinium Practolol Procarbazine Sulphonamides Vincristine AO 1 417 : 12 : TABLE - 7 INFECTIOUS AGENTS CAUSING INTERSTITIAL LUNG DISEASES A. VIRUSES - Infleuenza - Cytomegalovirus - Measles - Varicella Zoster B. BACTERIA - Miliary tuberculosis - Staphyllococcal infections - Streptococcal infections - Klebsiella infection - Mycoplasma infection - Brucellosis - Salmonellosis - Shigellosis - Pertussis - Psittacosis - 0 Feret - RMS Fever - Nocardiosis A0 I 4 1a 13 : C. FTJfGI - Histoplasmosis - Coccidiodanycosis - Blastomycosis - Cryptococcosis - Candidiasis - Aspergillosis - Geotrichosis - Sporotrichosis D. PARASITES - Sdiistoscmiasis - Pneumocystitis carini - Filariasis - Toxoplasmosis - Paragomniasis - Ascariasis - Trichinosis - Hook worm infestation AO 1 4 1 g 14 TABLE - 8 NEOPLASTIC CAUSES CF DIPF Bronchioloalveolar carcinoma Haematogenous metastasis Lymchangitic carcinaratosis Leukaemia Lymphoma Polycythemia vera AO 1 420 : 15 : TABLE - 9 Circulatory system diseases resulting in Interstitial Pulmonary Fibrosis - Haemodynamic - Pulmonary edema - Chronic passive congestion(Possibly Haemosiderosis and or bane deposition) - Thranboembolic - Multiple Pulmonary emboli - Fat embolism - Sickle - cell anaemia - Lymphangiography - Foreign body vasculitis. t A0 1 42 1 16 : Clinical features of DIPF: Irrespective of the etiology of the diffuse interstitial pulmonary fibrosis, the clinical presentation is virtually the same in all cases. Breathlessness usually first noted cn exertion, is the initial recognisable symptom in the majority of cases and is invariably present once the disease process has become fairly extensive. Investigations and interpretation: The chest radiograph at this stage will be that of a diffuse infiltrative lesion. The pulmonary fibrosis which develops affects the gas exchanging area of the lungs and in some cases a reduction in the carbon monoxide diffusing capacity may be the earliest indication of the disease process. The interstitial lung diseases are characterised by impairment of gas transfer and a restrictive ventilatory defect. The histological appearances in the final stages of the interstitial lung diseases are non specific and are those of a progressive diffuse chronic pulmonary fibrosis with few, if any, distingusihing diagnostic features. The disease process involves the alveoli and associated connective tissues. (Table 1) A0 1 422 17 TRRTF - I Schema of possible pathways of pathogenesis of DIPF(W.R.Parkes) INHALED SYSTEMIC AND AGENTS CONNECTIVE -- | |-------- TISSUE DISORDERS BLOOD-BORNE AGENTS {including drugs) CHRONIC ALVEOLAR WALL OEDEMA CRYPTOGENIC INORGANIC ORGANIC Beryllium Asbestos Minerals Hard metal Aluminium!?) UNRESOLVED PNEUMONIA (Including treated tuberclosis) Sarcoid granulomas Muralfibrosing (?) Desquamative fibrosing 'alveolitis' ------1-------------- 1 > DIPF > AO 1423 Differential Diagnosis : 18 : Murphy et al.(4) pointout that minimal interstitial pulmonary fibrosis caused by the inhalation of asbestos can be difficult to detect. They state that symptomatology is subjective and pulmonary function studies are often nonspecific. X-rays are usually not able to indicate the etiological factors responsible in the production of diffuse pulmonary fibrotic lesions. Symptoms and signs per se, do not enable asbestosis to be differentiated fran other fibrotic lung diseases which are around 130 in number (keogh et al 5, Crystal et al 6) and it is necessary in each and every case to obtain a detailed medical history and occupational history. There are same features of asbestosis and some details in the medical history which tray assist in the differential diagnosis. Fulmer(1) discusses the diagnostic approach to patients with interstitial lung disease and emphasizes the need for a systematic approach stating that "A detailed occupational history is mandatory in diagnosing the inorganic dust diseases". Sane of the issues which should be considered covered then taking the medical history include the following few examples: 1. Detailed occupational history - the long latent interval between first exposure to asbestos and development of disease mist be recognized and taken into account - farmers' lung and psittacosis nay be suggested by a history of exposure to moldy hay or bird droppings respectively AO 1424 : 19 : - other organic dust exposure possibilities such as use of home humidifiers, vaporizers, saunas - exposure to organic chemicals 2. Detailed drug use history. - Three itajor groups of drugs are responsible for most drug-induced interstitial diseases. They are listed by Fulmer as the cytotoxic and immunosuppressive agents (bleanycin, nitrosoureas, methotrexatae, etc,); the neuroactive and vasoactive agents (methysergide, Phenytoxin, etc.) and antimicrobial agents (Nitrofurantoin, sulfonamides, etc.) (Refer Table - 6) 3. Family history - sarcoidosis - collagen vascular disorders . mixed connective tissue disease . rheunatoid lung (Skin and eye manifestations of sarcoidosis, collagen- vascular disorders, neurofibrcnatosis and Wegener's granulcmatosis may help in the differential diagnosis). 4. Investigations Investigating the patient with an interstitial lung disease my include, in addition to the medical history, interpretation of chest radiographs, and pulmonary function evaluation. Special investigations such as serological studies, bronchoalveolar lavage, conjunctival, skin and lymph AO H2S / 20 node biopsy, fiberoptic bronchoscopy and transbronchial biopsy andfinaUy, open lung biopsy may be indicated. In the case of a suspected occupational lung disease, where the diagnosis will determine eligibility for compensation, and where death benefits nay be payable to defendants, the opportunity to confirm the clinical diagnosis at autopsy should be vigorously pursued. The chest x-ray is of diagnostic value in only a few types of diffuse interstitial pulmonary fibrosis. According to Fulmer, diffuse interstitial infiltrates with sparing of the costophrenic angles in a young male is suggestive of histiocytosis-X. In a young black patient in the USA hilar adenopathy with uveitis and skin lesions is thought to be diagnostic of sarcoidosis. Thus all endemic diseases are to be considered in preferential order.(Table 10). Pulmonary function studies are generally not helpful in the differential diagnosis of interstitial lung disease,including occupational lung diseases. Serological studies are of value in the diagnosis of collagen-vascular disorder and sarcoidosis. Circulating istnune complexes ac antibasement membrane antibody can also be of use if studied in conjunction with lung tissue or lavage cellular analysis. Interest in the later procedure has grown recently with regard to the diagnosis of : 21 : interstitial diseases. Thus far it has proved to be of value only in alveolar proteinosis and the pulmonary hemorrhage syndromes. Haemosiderin-laden macrophages (indicative of pulmonary hemorrhage) and the presence of circulating antibasemant membrane antibodies are necessary to diagnose Goodpasture's syndrome. Brocho-alveolar lavage promises to develop into a useful diagnostic procedure. Two distinct cellular patterns have been described. Predominant lymphocytosis is suggestive of sarcoidosis, organic dust disease, acute idiopathic pulmonary fibrosis, certain collagen-vascular disorders, and acute histiocytosis-X. A predominant finding of polymorphonuclear leukocytosis may be seen in inorganic dust diseases, idiopathic pulmonary fibrosis, collagen-vascular disorders and advanced sarcoidosis. Further studies are required before this procedure becomes useful in the differential -diagnosis of interstitial lung diseases. An Asbestosis casef shows the presence of higher count of Asbestos bodies in addition to Macrophages. Ferruginous bodies sure also demonstrated in the lavage in urban population who are not exposed to asbestos occupationally. Transbronchial biopsy nay be useful in the diagnosis of interstitial lung disease. Sane conditions which may be Aon 2? : 22 : diagnosed by this procedure are listed in Table - 11 (Fulirer's Table - 4 (1). Open lung biopsy is hardly ever justified unless the possibility exists that the outcone will affect treatment of a potentially curable condition. AO 14-28 : 23 : TABUS - 10 RADIOLOGIC WVSQUERADERS CF ASBESTOSIS Adult Respiratory distress Syndrane Alveolar Proteinosis Aityloidosis Bilharziasis Bronchiectasis Universalis Bronchioalveolar carcincma Chemical Pneumonia Cholesterol Pneumonitis Drug Infiltrates Goodpasture's Syndrane Hannan-rich Syndrane Histiocytosis Idiopathic Pulmonary Hemosiderosis Inclusion Body Pneumonia Miliary tuberculosis Parenchymal Hodgkins Disease Pneumoncystis Carinii Pseudolymphoma Pulmonary Edema Rheumatoid Lung Sarcoidosis Scleroderma Tbesaurosis 40 j INSTERSTITIAL LONS DISEASES THAT CAN BE DIAGNOSED BY TRANSBRONOOAL BIOPSY.* Sarcoidosis Organic dust diseases (hypersensitivity pneumonitides) Histiocytosis-X Pulmonary hemorrhage syndrcries Inorganic dust diseases Eosinophilic pneumonias Drug-induced interstitial diseases Lymphangioleicmyanatosis Infectious agents *This list includes diseases in whhich diagnostic tissue can be obtained, as well as those in vhhich tissue is suggestive but the diagnosis must be made by clinical and laboratory correlation. . : 25 : Recaimendations 1. Obtain a detailed medical history, including a meticulous exposure history. 2. Radiographs oust be of good quality, serial films should be available and interpretation should be by a radiologist -expert in the diagnosis of pneumoconiosis in particular and chest disorders in general. 3. Pulmonary function tests should only be used to confirm the presence of a restrictive syndrome once there are no specific physiological differences between the many varieties of interstitial lung disorders. 4. Other diagnostic tests should be considered and used in all doubtful cases to rule out conditions v*iich can masquerade as ashestosis. -:o0o:- AO H3 1 / : 26 : References 1. Fulmer, Jack D., The interstitial Long diseases. Chest 1982; 82: 172 - 178. 2. D. Geraint James and Peter R. Study, color atlas of Respiratory diseases, chapter 18, Pages 161 - 182 Published by year book Medical Publishers Inc., Chicago. 1982. 3. H. Raymond Parkas "The Ooccupational Lung diseases" 4. Murphy, Raymond L-H et al., crackles in the ffiirly detection of Asbestosis. Am.Rev.Resp.Dis.1984; 129: 375-379. 5. Keogh BA, crystal RG, chronic Interstitial Lung disease. In Sunions DH, ed current Pulmonology Vol.3, New York, wiling 1981: 237-340. 6. Crystal RG, Gadek JE, Ferrans VJ, Fulmer JD, Line BR, Runninghake GW, Interstitial Lung disease: current concepts of Pathogenesis, .68 staging and therapy. Am J Med 1981; 70:542- 7. Asbestos related diseases:clinical. Epidemiologic, pathologic and radiologic characteristics and manifestations. Prepared by the Asbestos working group (Chairman Russel H.Morgan). Published by American College of Radiology, 20 North Waeker Drive, Chicago, Illinois 60606.(1982) 8. Morgan, R.R., Danner, M.W, Gayler, B.W., et al: Decision processes and observer error in the diagnosis of pneumoconiosis by chest roentgenography. Am. Jr. Roentgenol. 1973; 117: 757-764. DRRAOl A01432