OCCUPATIONAL LUNG DISEASES .pptx

OCCUPATIONAL LUNG DISEASES .pptx

1. OCCUPATIONAL LUNG DISEASES

2. PNEUMOCONIOSES Pneumoconiosis is the term used for lung diseases caused by inhalation of dust, mostly at work ( pneumo = lung; conis = dust in Greek). These diseases are, therefore, also called ‘dust diseases’ or ‘occupational lung diseases’. The type of lung disease varies according to the nature of inhaled dust. Some dusts are inert and cause no reaction and no damage at all, while others cause immunologic damage and predispose to tuberculosis or to neoplasia .

3. The factors which determine the extent of damage caused by inhaled dusts are as under: 1. size and shape of the particles; 2. their solubility and physicochemical composition; 3. the amount of dust retained in the lungs; 4. the additional effect of other irritants such as tobacco smoke; and 5. host factors such as efficiency of clearance mechanism and immune status of the host. In general, most of the inhaled dust particles larger than 5 μm reach the terminal airways where they are ingested by alveolar macrophages

4. Most of these too are eliminated by expectoration but the remaining accumulate in alveolar tissue. Particles smaller than 1 μm which are deposited in the alveoli most efficiently. Most of the dust-laden macrophages accumulated in the alveoli die leaving the dust, around which fibrous tissue is formed. Some macrophages enter the lymphatics and reach regional lymph nodes. The tissue response to inhaled dust may be one of the following three types: Fibrous nodules e.g. in coal-workers’ pneumoconiosis and silicosis. Interstitial fibrosis e.g. in asbestosis. Hypersensitivity reaction e.g. in berylliosis

5. Coal-Workers’ Pneumoconiosis This is the commonest form of pneumoconiosis and is defined as the lung disease resulting from inhalation of coal dust particles, especially in coal-miners engaged in handling soft bituminous coal for a number of years, often 20 to 30 years. It exists in 2 forms —a milder form of the disease called simple coal workers’ pneumoconiosis and an advanced form termed progressive massive fibrosis (complicated coal- miners’ pneumoconiosis ). Anthracosis , on the other hand, is not a lung disease in true sense but is the common, benign and asymptomatic accumulation of carbon dust in the lungs of most urban dwellers due to atmospheric pollution and cigarette smoke ( anthacite refers to coal).

6. PATHOGENESIS However, progressive massive fibrosis develops in a small proportion of cases (2-8%) of simple coal-workers’ pneumoconiosis. A number of predisposing factors have been implicated in this transformation as follows: 1. Older age of the miners. 2. Severity of coal dust burden engulfed by macrophages. 3. Prolonged exposure (20 to 30 years) to coal dust. 4. Concomitant tuberculosis. 5. Additional role of silica dust.

7. Activation of alveolar macrophage plays the most significant role in the pathogenesis of progressive massive fibrosis by release of various mediators : i ) Free radicals which are reactive oxygen species which damage the lung parenchyma. ii) Chemotactic factors for various leucocytes ( leukotrienes , TNF, IL-8 and IL-6) resulting in infiltration into pulmonary tissues by these inflammatory cells which on activation cause further damage. iii) Fibrogenic cytokines such as IL-1, TNF and platelet derived growth factor (PDGF) which stimulate healing by fibrosis due to proliferation of fibroblasts at the damaged tissue site.

8. The pathologic findings at autopsy of lungs in the major forms of coal-workers’ pneumoconiosis are considered below under 3 headings: 1 simple coalworkers ’ pneumoconiosis, 2 progressive massive fibrosis 3 rheumatoid pneumoconiosis ( Caplan’s syndrome).

9. SIMPLE COAL-WORKERS’ PNEUMOCONIOSIS. Grossly, the lung parenchyma shows small, black focal lesions, measuring less than 5 mm in diameter and evenly distributed throughout the lung but have a tendency to be more numerous in the upper lobes . These are termed coal macules , and if palpable are called nodules . The air spaces around coal macules are dilated with little destruction of alveolar walls Similar blackish pigmentations are found on the pleural surface and in the regional lymph nodes

10. Histologically , the following features are seen : 1. Coal macules are composed of aggregates of dust laden macrophages. These are present in the alveoli and in the bronchiolar and alveolar walls. 2. There is some increase in the network of reticulin and collagen in the coal macules . 3. Respiratory bronchioles and alveoli surrounding the macules are distended without significant destruction of the alveolar walls.

11. PROGRESSIVE MASSIVE FIBROSIS. Grossly, besides the coal macules and nodules of simple pneumoconiosis, there are larger, hard, black scattered areas measuring more than 2 cm in diameter and sometimes massive. They are usually bilateral and located more often in the upper parts of the lungs posteriorly . Sometimes, these masses break down centrally due to ischaemic necrosis or due to tuberculosis forming cavities filled with black semifluid resembling India ink. The pleura and the regional lymph nodes are also blackened and fibrotic

12. Histologically , the following features are present: 1. The fibrous lesions are composed almost entirely of dense collagen and carbon pigment. 2. The wall of respiratory bronchioles and pulmonary vessels included in the massive scars are thickened and their lumina obliterated. 3. There is scanty inflammatory infiltrate of lymphocytes and plasma cells around the areas of massive scars. 4. The alveoli surrounding the scars are markedly dilated.

13. RHEUMATOID PNEUMOCONIOSIS (CAPLAN’S SYNDROME) The development of rheumatoid arthritis in a few cases of coal-workers’ pneumoconiosis, silicosis or asbestosis is termed rheumatoid pneumoconiosis or Caplan’s syndrome. Grossly, the lungs have rounded, firm nodules with central necrosis, cavitation or calcification. Histologically , the lung lesions are modified rheumatoid nodules with central zone of dust-laden fibrinoid necrosis enclosed by palisading fibroblasts and mononuclear cells. The lung lesions in Caplan’s syndrome have immunological basis for their origin as evidenced by detection of rheumatoid factor and antinuclear antibodies.

14. Silicosis Historically, silicosis used to be called ‘knife grinders’ lung. Silicosis is caused by prolonged inhalation of silicon dioxide, commonly called silica. Silica constitutes about one-fourth of earth’s crust. Therefore, a number of occupations engaged in silceous rocks or sand and products manufactured from them are at increased risk. These include miners (e.g. of granite, sandstone, slate, coal, gold, tin and copper), quarry workers, tunnellers , sandblasters, grinders, ceramic workers, foundry workers and those involved in the manufacture of abrasives containing silica. Peculiar to India are the occupational exposure to pencil, slate and agate-grinding industry carrying high risk of silicosis (agate = very hard stone containing silica).

15. An infrequent acute form of silicosis called accelerated silicosis produces irregular fibrosis adjoining the alveoli which is filled with lipoproteinaceous exudate and resembles alveolar proteinosis . However, if not specified, silicosis refers to the common chronic form of the disease characterised by formation of small collagenous silicotic nodules.

16. PATHOGENESIS. Silicosis appears after prolonged exposure to silica dust, often a few decades. Besides, it depends upon a number of other factors such as total dose, duration of exposure, the type of silica inhaled and individual host factors. The mechanisms involved in the formation of silicotic nodules are not clearly understood. 1. Silica particles between 0.5 to 5 μm size on reaching the alveoli are taken by the macrophages which undergo necrosis. New macrophages engulf the debris and thus a repetitive cycle of phagocytosis and necrosis is set up.

17. 2. Some silica-laden macrophages are carried to the respiratory bronchioles, alveoli and in the interstitial tissue. Some of the silica dust is transported to the subpleural and interlobar lymphatics and into the regional lymph nodes. The cellular aggregates containing silica become associated with lymphocytes, plasma cells, mast cells and fibroblasts. 3. Silica dust is fibrogenic . Crystalline form, particularly quartz, is more fibrogenic than non-crystalline form of silica. 4. Simultaneously, there is activation of T and B lymphocytes. This results in increased serum levels of immunoglobulins ( IgG and IgM ), antinuclear antibodies, rheumatoid factor and circulating immune complexes as well as proliferation of T cells. 5. As noted above, silica is cytotoxic and kills the macrophages which engulf it. The released silica dust activates viable macrophages leading to secretion of macrophage derived growth factors such as interleukin-1 that favour fibroblast proliferation and collagen synthesis

18. MORPHOLOGIC FEATURES. Grossly, the chronic silicotic lung is studded with well-circumscribed, hard, fibrotic nodules, 1 to 5 mm in diameters. They are scattered throughout the lung parenchyma but are initially more often located in the upper zones of the lungs. These nodular lesions frequently have simultaneous deposition of coal-dust and may develop calcification. The pleura is grossly thickened and adherent to the chest wall. There may be similar fibrotic nodules on the pleura and within the regional lymph nodes. The lesions may undergo ischaemic necrosis and develop cavitation , or be complicated by tuberculosis and rheumatoid

19. Histologically , the following features are observed : 1. The silicotic nodules are located in the region of respiratory bronchioles, adjacent alveoli, pulmonary arteries, in the pleura and the regional lymph nodes. 2. The silicotic nodules consist of central hyalinised material with scanty cellularity and some amount of dust. The hyalinised centre is surrounded by concentric laminations of collagen which is further enclosed by more cellular connective tissue, dust-filled macrophages and a few lymphocytes and plasma cells. Some of these nodules may have calcium deposits.

20. 3. The collagenous nodules have cleft-like spaces between the lamellae of collagen which when examined polariscopically may demonstrate numerous birefringent particles of silica. 4. The severe and progressive form of the disease may result in coalescence of adjacent nodules and cause complicated silicosis similar to progressive massive fibrosis of coal-workers’ pneumoconiosis. 5. The intervening lung parenchyma may show hyperinflation or emphysema. 6. Cavitation when present may be due to ischaemic necrosis in the nodules, or may reveal changes of tuberculosis or rheumatoid pneumoconiosis ( Caplan’s syndrome), discussed already.

21. Asbestos Disease Asbestos is a Greek word meaning ‘unquenchable’. In general, if coal is lot of dust and little fibrosis, asbestos is little dust and a lot of fibrosis. Prolonged exposure for a number of years to asbestos dust produces three types of severe diseases: asbestosis of lungs, pleural disease and Tumours . There are two major geometric forms of asbestos: Serpentine Amphibole

22. PATHOGENESIS. 1. The inhaled asbestos fibres are phagocytosed by alveolar macrophages from where they reach the interstitium . Some of the engulfed dust is transported via lymphatics to the pleura and regional lymph nodes. 2. The asbestos-laden macrophages release chemo-attractants for neutrophils and for more macrophages, thus causing cellular reaction around them. 3. Asbestos fibres are coated with glycoprotein and endogenous haemosiderin to produce characteristic beaded or dumbbell-shaped asbestos bodies.

23. 4. All types of asbestos are fibrogenic and result in interstitial fibrosis. Fibroblastic proliferation may occur via macrophage derived growth factor such as interleukin-1. Alternatively, fibrosis may occur as a reparative response to tissue injury by lysosomal enzymes released from macrophages and neutrophils or by toxic free radicals. 5. A few immunological abnormalities such as antinuclear antibodies and rheumatoid factor have been found in cases of asbestosis but their role in the genesis of disease is not clear.

24. 6. Asbestos fibres are carcinogenic, the most carcinogenic being crocidolite . There is high incidence of bronchogenic carcinoma in asbestosis which is explained on the basis of the role of asbestos fibres as tumour promoters or by causing cell death of the airways so that it is exposed to the carcinogenic effect of cigarette smoke. The development of pleural mesothelioma in these cases is probably by carrying of asbestos fibres via lymphatics to the pleura

25. MORPHOLOGIC FEATURES. As stated already, overexposure to asbestos is associated with 3 types of lesions: asbestosis, pleural disease and certain tumours . A. ASBESTOSIS. The gross pulmonary fibrosis caused by asbestos exposure and histologic demonstration of asbestos bodies on asbestos fibres is termed asbestosis. Grossly, the affected lungs are small and firm with cartilage-like thickening of the pleura. The sectioned surface shows variable degree of pulmonary fibrosis, especially in the subpleural areas and in the bases of lungs . The advanced cases may show cystic changes.

26. Histologically , the following changes are observed: 1. There is non-specific interstitial fibrosis. 2. There is presence of characteristic asbestos bodies in the involved areas . These are asbestos fibres coated with glycoprotein and haemosiderin and appear beaded or dumbbell-shaped. The coating stains positively for Prussian blue reaction. 3. There may be changes of emphysema in the pulmonary parenchyma between the areas of interstitial fibrosis. 4. The involvement of hilar lymph nodes in asbestosis is not as significant as in silicosis.

27. B. PLEURAL DISEASE. Pleural disease in asbestos exposure may produce one of the following 3 types of lesions: 1. Pleural effusion. It develops in about 5% of asbestos workers and is usually serious type. Pleural effusion is generally accompanied by subpleural asbestosis. 2. Visceral pleural fibrosis. Quite often, asbestosis is associated with dense fibrous thickening of the visceral pleura encasing the lung. 3. Pleural plaques. Fibrocalcific pleural plaques are the most common lesions associated with asbestos exposure. Grossly, the lesions appear as circumscribed, flat, small ( upto 1 cm in diameter), firm or hard, bilateral nodules.

28. 3. There may be changes of emphysema in the pulmonary parenchyma between the areas of interstitial fibrosis. 4. The involvement of hilar lymph nodes in asbestosis is not as significant as in silicosis. B. PLEURAL DISEASE. Pleural disease in asbestos exposure may produce one of the following 3 types of lesions: 1. Pleural effusion. It develops in about 5% of asbestos workers and is usually serious type. Pleural effusion is generally accompanied by subpleural asbestosis.

29. 2. Visceral pleural fibrosis. Quite often, asbestosis is associated with dense fibrous thickening of the visceral pleura encasing the lung. 3. Pleural plaques. Fibrocalcific pleural plaques are the most common lesions associated with asbestos exposure. Grossly, the lesions appear as circumscribed, flat, small ( upto 1 cm in diameter), firm or hard, bilateral nodules. They are seen more often on the posterolateral part of parietal pleura and on the pleural surface of the diaphragm. Microscopically, they consist of hyalinised collagenous tissue which may be calcified so that they are visible on chest X-ray. Asbestos bodies are generally not found within the plaques.

30. C. TUMOURS. Asbestos exposure predisposes to a number of cancers, most importantly bronchogenic carcinoma and malignant mesothelioma . A few others are: carcinomas of oesophagus , stomach, colon, kidneys and larynx and various lymphoid malignancies. 1. Bronchogenic carcinoma is the most common malignancy in asbestos workers. Its incidence is 5 times higher in non-smoker asbestos workers than the nonsmoker general population and 10 times higher in smoker asbestos workers than the other smokers. 2. Malignant mesothelioma is an uncommon tumour but association with asbestos exposure is present in 30 to 80% of cases with mesothelioma ..

31. Berylliosis Berylliosis is caused by heavy exposure to dust or fumes of metallic beryllium or its salts. Beryllium was used in the past in fluorescent tubes and light bulbs but currently it is principally used in nuclear and aerospace industries and in the manufacture of electrical and electronic equipments. Two forms of pulmonary berylliosis are recognised — acute and chronic.

32. ACUTE BERYLLIOSIS. Acute berylliosis occurs in individuals who are unusually sensitive to it and are heavily exposed to it for 2 to 4 weeks. The pulmonary reaction is in the form of an exudative chemical pneumonitis in which the alveoli are filled with protein-rich fluid with formation of hyaline membrane. The patient develops sudden dyspnoea , hyperapnoea and substernal pain. Most patients recover completely. CHRONIC BERYLLIOSIS. Chronic berylliosis develops in individuals who are sensitised to it for a number of years, often after a delay of 20 or more years. The disease is a cell mediated hypersensitivity reaction in which the metal beryllium acts as a hapten .

33. The condition is characterised by development of non- caseating epithelioid granulomas like those of sarcoidosis . These granulomas are diffusely scattered throughout the lung parenchyma. The granulomas have giant cells which frequently contain 3 types of inclusions: 1. Birefringent crystals. 2. Concentrically-laminated haematoxyphilic Schaumann or conchoid bodies. 3. Acidophilic stellate -shaped asteroid bodies.

34. Others 1. Farmers’ lung is the classic example resulting from exposure to thermophilic actinomycetes generated by humid and warm mouldy hay. 2. Bagassosis occurs in individuals engaged in manufacture of paper and cardboard from sugarcane bagasse . Spores of thermophilic actinomycetes grow rapidly in mouldy sugarcane bagasse which are inhaled. 3. Byssinosis is an occupational lung disease occurring in workers exposed to fibres of cotton, flex and hemp for a number of years. The role of immunologic mechanisms in byssinosis is not as clear as in exposure to other organic dusts.

35. 4. Bird-breeders’ (Bird-fanciers’) lung occurs in pigeon breeders, parrot breeders, chicken farmers and bird-fanciers who are exposed to bird-droppings and danders from their feathers. 5. Mushroom-workers’ lung is found in mushroom cultivators exposed to mushroom compost dust. 6. Malt-workers’ lung is seen in distillery and brewery workers who are exposed to mouldy barley and malt dust. 7. Maple-bark disease occurs in those involved in stripping of maple bark and inhale mouldy maple bark (maple tree is grown in northern hemisphere for timber and its leaf is the national emblem of Canada)