Silicosis

1) Silicosis: It results from exposure to crystalline silica when workers chip, cut, drill or grind objects that contain crystalline silica. High risk jobs such as abrasive blasting, sandblasting, foundry work, stone cutting, rock drilling, quarry work and tunneling. Following types are seen:

Chronic/classic silicosis: It is the most common, occurs after 15–20 years of moderate to low exposures to respirable crystalline silica. Symptoms associated with chronic silicosis include shortness of breath upon exercising, fatigue, chest pain, or respiratory failure.

Accelerated silicosis: It can occur after 5-10 years of high exposures to respirable crystalline silica. Symptoms include severe shortness of breath, weakness, and weight loss.

Acute silicosis: It occurs after a few months or as long as 2 years following exposures to extremely high concentrations of respirable crystalline silica. Symptoms of acute silicosis include severe disabling shortness of breath, weakness, and weight loss, which often leads to death.

In silicosis, the lung is studded with fibrotic nodules, accompanying pleura is fibrotic and thickened and may show pleural nodules. Microscopically, nodules show central hyalinization, calcification, cavitation and are surrounded by laminated collagen. CxR shows bilateral ground glass opacities, reticulo-nodular opacities, hilar and mediastinal lymphadenopathy with characteristic “egg-shell calcification”, pleural lesions and pleural effusion. Changes are more pronounced in the upper lobes. There is an increased risk of tuberculosis. Crystalline silica is a carcinogen and can cause lung cancer. The risk is multiplied in smokers with silicosis.

2) Asbestosis: Crocidolite, chrysotile and amphibole fibres are most commonly implicated types of asbestos fibres. Asbestosis occurs after occupational exposure to asbestos over a period of years. It may contaminate clothing and skin and can cause asbestosis in close contacts like family members. As in all other pneumoconiosis, alveolar macrophages are activated by asbestos fibres, in the process they release cytokines and growth factors which result in inflammation and severe fibrosis. Asbestosis is initially asymptomatic, followed by dyspnea, dry cough, fatigue, clubbing, bibasilar crackles and cor pulmonale in advanced cases. Disease may progress even after exposure is stopped. On gross examination, the lungs are small and shrunken , fibrotic, pleura is thickened with prominent changes in the basal areas. Microscopically, asbestos or ferruginous bodies are seen. Asbestos bodies are dumbbells or drumstick shaped or beaded, golden brown, with a transparent, fibrous core made of amphibole type of asbestos fibers coated with glycoproteins and hemosiderin. They will look blue with Prussian blue stain. Pleural plaques characteristically on diaphragmatic pleura, which may be calcified, pleural fibrosis and effusions may be present. Asbestosis predisposes to malignant mesothelioma and bronchogenic carcinoma, especially in smokers. Carcinomas of the esophagus, stomach, colon, kidneys , lymphomas and leukemias may occur. There is a higher chance of RA (Caplan’s syndrome). CxR shows bilateral reticular opacities, pronounced in lower lobes, pleural plaques, honeycombing. Nodules and lymphadenopathy are not pronounced. HRCT, lung biopsy and BAL are preferred investigations for diagnosis.

3) Berylliosis: It is seen following occupational exposure to beryllium via inhalation of airborne beryllium or skin contact in the aerospace, electronics and nuclear industries. Berylliosis may manifest as beryllium sensitization, chronic beryllium disease (CBD) and lung cancer. Beryllium sensitization is asymptomatic, but sensitized individuals are at higher risk to develop CBD. CBD is a chronic granulomatous lung disease that presents with dyspnea, unexplained coughing, fatigue, weight loss, fever and night sweats. Symptoms may appear quickly or after a few months to years. Microscopically, noncaseating epithelioid granulomas with Schaumann bodies (similar to sarcoidosis), are seen in the lung. Schaumann bodies are calcium and protein inclusions inside of Langhans giant cells in the granuloma. Acute beryllium disease (ABD) is a potentially fatal, rapid onset form of chemical pneumonia that results from breathing high airborne concentrations of beryllium.

4) Hypersensitivity pneumonitis: Hypersensitivity pneumonitis is an allergic or immune reaction in the lung occurring in response to a variety of inhaled organic antigens. Different types of fungal, bacterial, protozoal, animal and insect antigens normally present in the environment have been implicated. Most commonly implicated antigens are thermophilic actinomycete species, fungi (Aspergillus and Penicillium), and bird proteins. It may have an acute, subacute or chronic presentation, depending on the dose of initial antigenic exposure. Examples are farmer’s lung, bagassosis, byssinosis etc. Polymorphisms in HLA-DR and DQ, TAP genes etc determine individual susceptibility to hypersensitivity pneumonitis. Th1 response, IL 12, gamma interferon, IL 17, type III or IV hypersensitivity contribute to pathogenesis. Microscopically infiltration of alveoli with lymphocytes, plasma cells and macrophages is seen, followed by foreign body granuloma formation. In chronic cases, interstitial fibrosis and honeycombing is seen. Clinical features include cough, dyspnea, fatigue, myalgia, chills, clubbing, low-grade fever, cor pulmonale. Restrictive pattern is seen on spirometry. CxR may be normal or may show ground-glass opacities; HRCT shows ground-glass opacities, bronchiectasis or honeycombing.

5) Pulmonary alveolar proteinosis (PAP): It is characterized by the buildup of surfactant in the alveoli leading to interference with gas exchange in the lungs. It may be primary (includes autoimmune and hereditary) , secondary or congenital. It presents with dyspnea, peripheral cyanosis, cough, fatigue, malaise, weight loss and chest pain. Primary PAP is caused by reduced GM-CSF stimulation of alveolar macrophages leading to disturbance in surfactant homeostasis and surfactant buildup in alveoli. In autoimmune PAP, often seen in smokers, B cells produce auto-antibodies to GM-CSF. In hereditary PAP, GM-CSF receptors on alveolar macrophages are defective. It is inherited as an AR disorder. In secondary PAP, conditions such as myelodysplasia, HIV, chemotherapy, inhalation injury from silica, titanium, aluminium etc., damage the alveolar macrophages so that surfactant cannot be re-absorbed. In congenital PAP, mutations are seen in genes coding for surfactant proteins such as genes SFTPB, SFTPC, ABCA3 or NKX2.1. On gross examination, the lungs are filled with turbid fluid. Microscopically, homogenous, granular, PAS positive, eosinophilic ,material with occasional cholesterol clefts fills the alveoli. CxR shows opacities, typically not involving the apical zones and costophrenic angle, in a “batwing” distribution. Some cases may show diffuse consolidation. HRCT shows ground glass opacities and thickening of interlobular and intralobular septa.

6) Idiopathic pulmonary fibrosis or cryptogenic fibrosing alveolitis: It is a type of diffuse interstitial pneumonia with poor prognosis, characterized by pulmonary interstitial fibrosis and inflammation not caused by infection or cancer. It is seen more commonly in middle aged or older males. It presents with dyspnea, chronic dry cough, velcro-like crackles on auscultation and clubbing. Bilateral reticular infiltrates and hazy opacities are seen on CxR especially in the lower lung zones. Mutations in TERT, TERC, PARN and RTEL1 genes confer higher risk. Overexpression of mucin 5B in small airways is seen. Macrophages containing lamellar bodies are present. Diffuse fibrosis and honeycombing is seen in advanced cases.

7) Hypereosinophilic syndrome (HES): It is characterized by persistent and marked blood eosinophilia for more than 6 months along with eosinophil-induced organ damage, in the absence of allergic, parasitic and malignant causes of eosinophilia. Sporadic hematopoïetic stem cell mutation, leading to primitive clonal expansion of cells belonging to the myeloid lineage with preferential eosinophil differentiation or overproduction of eosinophilic poietic cytokines like IL5 by an activated population of T cells (Th2 cells) can cause HES. Skin, heart, lungs, and central and peripheral nervous systems are more commonly involved. Eosinophil cationic protein and major basic protein, peroxidases, elastases, collagenases and free radicals cause local tissue damage. Clinical features depend on the organ systems involved and can present with urticaria, angioedema, pruritis, heart failure, restrictive cardiomyopathy, endomyocardial fibrosis, peripheral neuropathy, encephalopathy, stroke, pulmonary fibrosis, hepatosplenomegaly etc. Therapy is with imatinib, corticosteroids, hydroxycarbamide, alpha interferon or mepolizumab.