L34 Environmental Lung Disease

• -Retention of and pathologic effects from inhalation of dust particles
• -typically due to inorganic dusts
• -most don't develop disease

• -Complex syndromes with various antigens
• -Organic antigens (proteins from bacteria, mold, fungi, myocbacterium)

• Development depends on:
• 1. Amount of dust retained in the lung -concentration
• -duration of exposure
• -effectiveness of clearance mechanisms

• 2. Size, shape and buoyancy of particles
• -1-5um
• -asbestos is larger by narrower width
• -curly fibers not dangerous

• 3. Particle solubility and physiochemical properties
• -smaller/soluble: dissolve in blood
• -larger/non-soluble: inflammation and fibrosis
• -quartz: interact with free radicals

• 1. Tortuous passages of upper airways
• 2. Bronchoconstriction
• 3. Entrapment in mucus blanket
• 4. Mucocilliary clearance
• 5. Phagocytosis by macrophages
• 6. Transport to lymphatics
• 7. Metabolic modifications

• -typical reaction to chronic injury is fibrosis
• -mechanism depends on agent
• -some directly injure lung parenchyma
• -some trigger macrophages --> inflammatory response
• -fibrosis may lead to pulmonary HTN and death from respiratory failure or RHF

-"black lung"

• Range of Disease:
• 1. Asymptomatic anthracosis
• 2. Simple coal workers pneumoconiosis
• 3. Complicated coal workers pneumoconiosis/Progressive Massive Fibrosis

• -asymptomatic
• -coal workers lung, urban dwellers, tobacco smokers
• -carbon pigment taken up in MPs which accumulate in lymphatics in CT and LNs
• 

• -usually asymptomatic
• -may have chronic productive cough with blank-tinged sputum

• Coal macules
• -1-2mm
• -carbon laden macrophages
• 

• Coal nodules
• -<1cm
• -collagen fibers and carbon laden macrophages
• 

-develops in the background of simple CWP

• Symptoms:
• -dyspnea
• -cough
• -sputum
• -may develop R sided congestive HF

*may progress even after exposure is stopped

• Diagnosis:
• -coal nodules > 1cm
• -nodules contain dense collagen and pigment and may have central necrosis
• 

• -most prevalent pneumoconiosis in the world
• -sandblasters, mine workers
• -inhalation of silicon dioxide

• Two forms of silica:
• 1. Crystalline (more fibrogenic)
• 2. Amorphous (can cause fibrosis with heavy burden)

• Pathogenesis:
• -silica is toxic to macrophages
• -fibrosis
• -lesions in upper portion of lungs

• Gross:
• -hard collagenous scars
• 

• Histology:
• -concentric layers of hyalinized collagen
• -particles visible under polarized light
• 

*Increased susceptibility to TB (maybe due to depressed cell mediated immunity)

• Different types of fibers
• 1. Serpentines
• -curly and flexible
• -get stuck in upper respiratory tract and cleared
• 2. Amphobiles
• -straight stiff and brittle
• -less prevalent
• -more pathogenic (mesothelioma)

• Pathophysiology:
• -crystals activate macrophages
• -stimulate production of ROS and cytokines
• -promote fibroblast and mesothelial cell proliferation

• Histology:
• -Ferruginous bodies: iron from phagocyte ferritin coats fibers
• -more commonly in lung parenchyma
• 

• Pathology of chronic exposure:
• 1. Benign pleural effusions (asbestos pleurisy)
• 2. Focal or diffuse pulmonary interstitial fibrosis (lower lobes)
• 3. Parietal pleural plaques
• 4. Mesothelioma

• -affects lower lobes and subpleural lung first
• -begins as fibrosis around respiratory bronchioles
• -extends to involve adjacent alveolar sacs and alveoli
• -fibrosis creates enlarged airspaces enclosed within thick fibrous walls

• -most common manifestation of asbestos
• -typically parietal
• -typically do NOT contain ferruginous obides
• -eventually calcify
• -dense periauricular collagen with slit like retraction spaces parallel to pleural surface
• 

• Epidemiology:
• -rare neoplasm
• -2-10% of pts with heavy asbestos exposure
• -long latency: 25-45yrs
• -other risk factors: radiation, chronic inflammation

*No increase in risk in asbestos workers who smoke

• Clinical Presentation:
• -pleural effusion
• -chest pain
• -dyspnea

• Pathogenesis:
• -asbestos causes chronic irritation of mesothelial cells
• -generate ROS --> DNA damage
• -can eventually encase the lung

• Gross:
• -multiple gray-white ill defined noduels
• -diffusely thickened pleura
• 

• Three Main Histological Types:
• 1. Epithelial (resembles adenocarcinoma)
• 2. Sarcomatoid (spindle cells)
• 3. Mixed or biphasic
• *has no prognostic value

• -sheets of rounded cells infiltrating down into fat
• 

• -can mimic adenocarcinoma
• 

• -spindle fibers
• -not in sheets

• -most frequent malignancy in asbestos exposure
• -risk for developing lung carcinoma is exacerbated by cigarette smoking (50-90X)
• -carcinogens from smoke may absorb into asbestos fibers
• -1/5 exposed die of lung carcinoma
• -1/10 die of mesothelioma
• -1/10 die of GI carcinomas

All the funny names

• -Immunologic reaction to inhaled organic antigens
• -both type III and type IV hypersensitivity responses

• Type III
• -immune complex mediated
• -abs present in blood
• -C' and Ig in vessel walls

• Type IV:
• -cell mediated
• -"attempt" to form a granulomatous response
• -increased chemokines and T cells in BAL
• -non-caseating granulomas are present

• Diagnosis:
• -known exposure
• -BAL with T lymphocytosis (CD8>CD4)
• -positive inhalation test

• Histopathology:
• -diffuse mononuclear cell infiltrates (lymphocytes)
• 

• -poorly formed non-caseating granulomas (peribronchiolar localization)
• 

-interstitial fibrosis and obliterative bronchiolitis in advanced cases

• -remove source of antigen
• -corticosteroids
• -prognosis good unless fibrosis has already developed

• Drugs:
• Bleomycin
• Methotrexate
• AMiodarone
• Nitrofurantoin
• Aspirin
• β-blockers

Radiation