30 Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases

Question 1

Interstitial lung diseases

• Interstitial lung diseases
  
  • Affect…
  • Associated with…
  • The process often spills over into…
• There is a long list of lung insults and injuries that can lead to the development of interstitial lung disease

Answer 1

• Interstitial lung diseases
  
  • Affect the gas exchange surface of the lung
  • Associated with the accumulation of inflammatory cells, fibroblasts, and fluid in the interstitial space
  • The process often spills over into the alveoli and small airways, but it is the expansion of the interstitial space that is most prominent
• There is a long list of lung insults and injuries that can lead to the development of interstitial lung disease
  
  • Infection: viral pneumonia, mycoplasma pneumonia
  • Malignancies: lymphangitic carcinomatosis
  • Sarcoidosis
  • ARDS recovery (almost all will have varying degrees of ILD)
  • Pharmacologic (drug-induced): Amiodarone, Bleomycin, Busulfan, etc.
  • Hypersensitivity pneumonitis: Farmers lung, Pigeon breeders’ lung, etc.
  • Collagen Vascular Diseases: Rheumatoid Arthritis, Scleroderma, DM/PM, SLE, etc.
  • Occupational exposures: Asbestosis, Silicosis, Coal Workers
  • Pneumoconiosis
  • Eosinophilic Granuloma

Question 2

Interstitial lung diseases

• Idiopathic interstitial pneumonias (IIP)
• Members of this class include…
• Idiopathic pulmonary fibrosis (IPF)

Answer 2

• Idiopathic interstitial pneumonias (IIP)
  
  • Interstitial lung diseases that have no evident cause
  • A class of lung diseases characterized by the development of variable degrees of inflammation and fibrosis limited to the lung and involving principally the alveolar structures
• Members of this class include…
  
  • Acute interstitial pneumonia (AIP)
  • Nonspecific interstitial pneumonia (NSIP)
  • Desquamative interstitial pneumonia/respiratory bronchiolitis with interstitial lung disease (DIP/RBILD)
  • Cryptogenic organizing pneumonia (COP)
    
    • Formerly called bronchiolitis obliterans with organizing pneumonia
  • Idiopathic pulmonary fibrosis (IPF)
• Idiopathic pulmonary fibrosis (IPF)
  
  • One of the more common of the idiopathic interstitial pneumonias
  • Carries the poorest prognosis

Question 3

Idiopathic pulmonary fibrosis (IPF)

• General
• Gender
• Age
• Prevalence
• Geography and race
• Age-adjusted mortality rates

Answer 3

• General
  
  • The most common IIP encountered
• Gender
  
  • More males have been reported with IPF than females
• Age
  
  • ~2/3 of patients with IPF are over the age of sixty at presentation
  • The estimated prevalence of the disease in patients older than 75 years of age is approximately 175 cases per 100,000
• Prevalence
  
  • Old data: ~20.2 cases per 100,000 in males and 13.2 cases in females
  • More recent data: incidence in the U.S. is 220/100,000 or ~89,000 cases with 34,000 new cases per year
  • The difference is most likely a consequence of the frequent use of Chest CT scans in the evaluation of patients with lung disease
• Geography and race
  
  • No distinct geographical distribution or predilection for race or ethnicity
• Age-adjusted mortality rates
  
  • Appear to be higher in whites than blacks, but this may reflect inadequate reporting, healthcare availability or utilization, or, possibly, real differences in disease course

Question 4

Idiopathic pulmonary fibrosis (IPF)

• Patients usually present with…
• Physical examination reveals…
• The chest radiograph reveals…

Answer 4

• Patients usually present with…
  
  • Dyspnea on exertion that has been progressing slowly for months or even years
  • Paroxysmal, non-productive cough that is usually provoked by exertion or exposure to irritants
  • A small percentage will have cough productive of mucoid or whitish sputum
    
    • More common in those who have also smoked
• Physical examination reveals…
  
  • Loud (“Velcro”) inspiratory crackles at the lung bases in up to 80% of patients
  • Clubbing of the fingers and toes is seen in 25-50%
• The chest radiograph reveals…
  
  • Reticulonodular infiltrates in up to 90% of subjects with a predilection for the lung bases

Question 5

Idiopathic pulmonary fibrosis (IPF)

• The high-resolution CT scan
• Pulmonary function studies reveal…
• Patients usually experience…

Answer 5

• The high-resolution CT scan
  
  • The most useful non-invasive test to diagnose idiopathic pulmonary fibrosis
  • Typically demonstrates a sub-pleural distribution of infiltrates which usually consist of honeycombing fibrosis and areas of “traction bronchiectasis”
• Pulmonary function studies reveal a restrictive impairment.
  
  • Decreased FVC and FEV1
  • Normal to increased FEV1/FVC
  • Decreased DLco
  • Widened (A-a)PO2 gradient particularly with exertion
• Patients usually experience…
  
  • Desaturation of arterial blood with modest exercise when the DLco is less than 50% of predicted
  • Retention of carbon dioxide does not occur until the disease is very advanced

Question 6

Idiopathic pulmonary fibrosis (IPF):
Natural history

• Prognosis
• Survival is adversely affected by the presence of…
• Even in the absence of complicating disease, the median survival of biopsy-confirmed IPF is…
• Mortality

Answer 6

• Prognosis
  
  • Progressive illness
  • Median survival is unaffected by medical therapy
  • Earlier estimates suggesting a longer survival (and better response to therapy) were complicated by the inclusion of other types of IIPs that carry a more favorable prognosis and response to anti-inflammatory and immunosuppressive therapies
• Survival is adversely affected by the presence of…
  
  • Concomitant diseases in this elderly population, such as coronary atherosclerotic disease, smoking-related lung disease, chronic obstructive lung disease and bronchogenic carcinoma, and pulmonary infections
• Even in the absence of complicating disease, the median survival of biopsy-confirmed IPF is…
  
  • ~3½ years
• Mortality
  
  • Most frequently due to respiratory failure from progressive pulmonary fibrosis
  • Ischemic heart disease, bronchogenic carcinoma, infection, and pulmonary emboli accounted for some of the deaths in one series

Question 7

Idiopathic pulmonary fibrosis (IPF):
Natural history

• Natural history
• Some patients experience a gradual decline characterized by…
• Serial CT scans in such patients generally show…
• Some patients experience long periods of…
• A small proportion of patients experience rapid decline in lung function associated with…
• Lung histology, when available, shows…

Answer 7

• Natural history
  
  • Highly variable and largely unpredictable
• Some patients experience a gradual decline characterized by…
  
  • Worsening dyspnea and diminished exercise capacity as a consequence of progressive interstitial fibrosis and loss of lung function
• Serial CT scans in such patients generally show…
  
  • Progressive honeycomb changes extending centrally, with traction bronchiectasis and lung distortion
• Some patients experience long periods of…
  
  • Relative stability of lung function, occasionally punctuated by brief periods of accelerated decline
• A small proportion of patients experience rapid decline in lung function associated with…
  
  • Severe gas exchange impairment
  • The appearance of ground glass infiltrates on CT scanning
  • Death from respiratory failure within a few weeks to months
• Lung histology, when available, shows…
  
  • Diffuse alveolar damage superimposed on the UIP pattern of injury (formerly called Hamman-Rich syndrome), a syndrome now referred to as an acute exacerbation of IPF

Question 8

Idiopathic pulmonary fibrosis (IPF):
Pathology

• Hallmarks of usual interstitial pneumonia (UIP)
• Other findings
• The most destructive lesions are found…

Answer 8

• Hallmarks of usual interstitial pneumonia (UIP)
  
  • Geographic and temporal heterogeneity
  • Geographic heterogeneity dictates that there are areas of lung with marked loss of normal architecture such as honeycombing fibrosis adjacent to areas of nearly normal lung
• Other findings
  
  • Hyperplasia of smooth muscle within the interstitial space
  • Hyperplasia and metaplasia of epithelial cells in the alveoli and small airways
• The most destructive lesions are found…
  
  • In the subpleural and paraseptal areas of the lung

Question 9

Idiopathic pulmonary fibrosis (IPF):
Pathology

• Temporal heterogeneity implies that…
• Inflammation
• Principal inflammatory cells

Answer 9

• Temporal heterogeneity implies that…
  
  • Areas of inflammation and advanced scarring are seen in the same specimen
• Inflammation
  
  • An early event that progresses to fibrosis
• Principal inflammatory cells
  
  • Mononuclear cells, macrophages, lymphocytes, and plasma cells
  • There is a scattering of polymorphonuclear leukocytes, mainly neutrophils, within the interstitium
  • Occasionally, clumps of neutrophils are seen in dilated airways

Question 10

Idiopathic pulmonary fibrosis (IPF):
Pathology:
Features that characterize the fibrotic response

Answer 10

• The earliest is the “fibroblastic focus” where fibroblasts are undergoing replication
• These foci usually occur at an air-tissue interface where there is a junction between normal and scarred lung
• They are felt to be the source of the fibroblasts that lay down immature and mature collagen
• A large number of fibroblastic foci seem to portend a worse prognosis since they are a marker for the severity of the fibrotic response

Question 11

Idiopathic pulmonary fibrosis (IPF):
Prognosis

• Mean survival after diagnosis of IPF vs. non-specific interstitial pneumonitis (NSIP)
• The traditional concept of how IPF progresses
  
  • Previous hypothesis
  • Two additional patterns of disease progression

Answer 11

• Mean survival after diagnosis of IPF vs. non-specific interstitial pneumonitis (NSIP)
  
  • IPF: 3½ years (18% after 6 years, 5% after 17 years)
  • NSIP: much better (75% after 6 years, 50% after 17 years)
  • These differences highlight the importance of making a correct diagnosis
• The traditional concept of how IPF progresses
  
  • Previous hypothesis
    
    • Patients lost lung function is a linear manner over time
    • Eventually they reached the point where they either…
      
      • Developed terminal respiratory insufficiency with or without infection
      • Died of other causes prior to respiratory failure
  • Two additional patterns of disease progression
    
    • Patients with well-documented IPF actually may have periods of relative stability interrupted by accelerated declines in lung function over a period of several months
    • Approximately 15% of patients may also experience “acute exacerbations” where the decline in lung function is more precipitous (usually over a period of weeks)
      
      • These patients are often hospitalized with signs of acute respiratory failure associated with airspace disease on CT scan and (when biopsied) histologic evidence of diffuse alveolar damage

Question 12

Idiopathic pulmonary fibrosis (IPF):
Pathogenesis

• Current theories
• The causes of the initial and recurrent injury
• The risk of IPF seems higher in…

Answer 12

• Current theories
  
  • A repetitive injury to the alveolar microenvironment followed by abnormal wound healing
  • Instead of the normal sequence leading to repair and restoration of structure and function, progressive loss of alveoli is due to scarring
• The causes of the initial and recurrent injury
  
  • Oxidative stress probably plays a role
• The risk of IPF seems higher in…
  
  • Some occupational groups particularly sheet metal workers and workers with heavy sawdust exposure
  • But the majority of subjects with IPF have no occupational exposures

Question 13

Idiopathic pulmonary fibrosis (IPF):
Pathogenesis

• Tissue injury is often associated with inflammation
• Other roles

Answer 13

• Tissue injury is often associated with inflammation
  
  • Innate immune mechanisms may initiate the response
  • Adaptive immune mechanisms may also be recruited leading to release of immune lymphokines and cytokines
  • Activation of the cellular or humoral immune system in IPF
  • An imbalance between Th1 and Th2 cytokines may contribute to fibrosis.
• Other roles
  
  • Angiogenesis
    Growth factor production
  • Fibroblast phenotypes
  • Recruitment and maintenance of the myofibroblast
  • Abnormal turnover of extracellular matrix
  • Loss of epithelial cells may also be due to increased apoptosis of this cell type from mediators that the myofibroblasts release

Question 14

Idiopathic pulmonary fibrosis (IPF):
Pathogenesis

• Role of these factors in the IPF lung
• A familial form of IPF
  
  • Accounts for…
  • Inheritance
  • Male to female ratio
  • Mutation

Answer 14

• Role of these factors in the IPF lung
  
  • Upregulation of genes for TGF-β
  • Connective tissue growth factor (CTGF)
  • Matrix metaloproteinases (MMP’s), particularly MMP-7
  • The balance between angiostatic and angiogenic factors
• A familial form of IPF
  
  • Accounts for 2-10% of cases
  • An autosomal dominant gene with variable penetrance is the culprit
  • The male to female ratio in familial IPF is about equal
  • Recently a mutation of the gene for Surfactant C was detected in a kindred with…
    
    • Familial IPF associated with histological UIP
    • Nonspecific Interstitial Pneumonia (NSIP)

Question 15

Idiopathic pulmonary fibrosis (IPF):
Treatment

• Proven effective medical therapies for IPF
• Potentially promising medical therapies
  
  • High dose corticosteroids
  • Corticosteroids when combined with cyclophosphamide or azathioprine
  • Idiopathic interstitial pneumonias
  • Prednisone, azathioprine, and the antioxidant N-acetylcysteine
  • The short-term efficacy of regimens that combine steroids with colchicine, D-penicillamine, or both

Answer 15

• Proven effective medical therapies for IPF
  
  • At this time, there are no proven effective medical therapies for IPF
• Potentially promising medical therapies
  
  • High dose corticosteroids
    
    • Decrease mortality
    • Associated with significant and often irreversible side effects
  • Corticosteroids when combined with cyclophosphamide or azathioprine
    
    • Questionable improved survival compared to corticosteroids alone
  • Idiopathic interstitial pneumonias
    
    • More steroid-responsive
  • Prednisone, azathioprine, and the antioxidant N-acetylcysteine
    
    • Increase in mortality
  • The short-term efficacy of regimens that combine steroids with colchicine, D-penicillamine, or both
    
    • No significant difference in measures of lung function, gas exchange, or survival at the end of 2 years

Question 16

Idiopathic pulmonary fibrosis (IPF):
Treatment

• Therapies that target pathways involved in lung fibrosis
  
  • Pirfenadone
  • Endothelin receptor antagonism, interferon-gamma, etanercept, and sildenafil
  • Nintedanib
• Lung transplantation

Answer 16

• Therapies that target pathways involved in lung fibrosis
  
  • Pirfenadone
    
    • Not approved by the FDA in the U.S., but has gained approval in Japan, India, Europe, and Canada
  • Endothelin receptor antagonism, interferon-gamma, etanercept, and sildenafil
    
    • Failed to demonstrate efficacy
  • Nintedanib
    
    • A novel triple-kinase inhibitor
    • Promising results in the US, Europe, and Asia
• Lung transplantation
  
  • Currently the only therapeutic option offering long term survival in patients with IPF
  • Given the age of the population affected by this disease, only a limited number can avail themselves of the treatment

Question 17

Occupational lung disease (fibrogenic pneumoconiosis)

• A complex mix of diseases that occur as a consequence of…
• The clinical manifestations of occupational lung disease depend on…
• Dust exposures
• The term pneumoconiosis is restricted to exclude…

Answer 17

• A complex mix of diseases that occur as a consequence of…
  
  • Workplace exposure to agents that induce lung disease
• The clinical manifestations of occupational lung disease depend on…
  
  • The nature of the offending agent
  • The magnitude of exposure
  • The individual host susceptibility
• Dust exposures
  
  • Not all dust exposures lead to the development of pulmonary fibrosis or respiratory impairment
  • The tissue reaction may be fibrogenic or non-fibrogenic
• The term pneumoconiosis is restricted to exclude…
  
  • Neoplasms, asthma, bronchitis, and emphysema
  • All of which may be the result of occupational exposure

Question 18

Occupational lung disease (fibrogenic pneumoconiosis):
Silicosis

• Silicosis
• Silica
• Major cause of…
• At risk occupations

Answer 18

• Silicosis
  
  • Lung disease that occurs as a consequence of inhalation of silicon dioxide, or silica, in crystalline form (quartz) and, less commonly, cristobalite and tridymite
• Silica
  
  • Among the most fibrogenic dusts
  • Often leads to progressive severe disease after exposure
• Major cause of…
  
  • Morbidity and mortality in individuals exposed to silica dust in a wide variety of occupations
• At risk occupations
  
  • Mining, tunneling, excavating: miners, drillers, tunnelers
  • Quarrying: drillers, hammerer, digger
  • Stonework: cutters, drillers, polishers
  • Foundries: molders, fettlers, casters
  • Abrasives: crushers, pulverizes
  • Ceramics: workers exposed to dry products at any stage

Question 19

Occupational lung disease (fibrogenic pneumoconiosis):
Silicosis:
Clinical features

• Symptoms of silicosis
• Simple (chronic) silicosis
• Complicated silicosis (aka progressive massive fibrosis)

Answer 19

• Symptoms of silicosis
  
  • Nonspecific, like most of the pneumoconioses
  • Often develop 10 to 20 years after exposure
  • Most common: gradual development of dyspnea
  • Many patients are asymptomatic early in the course of their disease even with an abnormal chest X-ray
• Simple (chronic) silicosis
  
  • Diagnosed by the presence of nodules on chest x-ray that are < 1 cm in size
  • Associated with few symptoms or pulmonary function abnormalities
  • Chest X-rays often demonstrate hilar and mediastinal lymph node calcifications
• Complicated silicosis (aka progressive massive fibrosis)
  
  • Over time, the nodules may gradually coalesce to form larger nodules (> 1 cm in size)

Question 20

Occupational lung disease (fibrogenic pneumoconiosis):
Silicosis:
Clinical features

• The transition from simple silicosis to progressive massive fibrosis
• Acute silicosis

Answer 20

• The transition from simple silicosis to progressive massive fibrosis
  
  • Highly variable but may occur over a period of 5-20 years
  • When it occurs, the disease is slowly progressive leading to respiratory failure and death
  • In many patients with simple or complicated disease, more rapid progression may be indicative of concurrent mycobacterial infection (either M. tuberculosis or atypical mycobacterial disease)
    
    • These individuals appear to be more susceptible to mycobacterial disease, because of qualitative or quantitative deficiencies of alveolar macrophage function
• Acute silicosis
  
  • An uncommon manifestation of this disease
  • Seen in individuals with massive dust exposure (e.g. sand blasters)
  • They develop an acute airspace disease resembling alveolar proteinosis (airspaces fill with lipoproteinaceous debris)
  • Rapid progression to interstitial fibrosis, respiratory failure, and death
  • Less common now because of strict occupational standards limiting this degree of dust exposure

Question 21

Occupational lung disease (fibrogenic pneumoconiosis):
Silicosis:
Pathology

• The hallmark lesion of silicosis
• It is characterized by…
• Collagen fibers
• Silicotic islets

Answer 21

• The hallmark lesion of silicosis
  
  • The silicotic islet or nodule
• It is characterized by…
  
  • A cell-free and dust-free central area surrounded by concentrically arranged collagen fibers producing an “onion-like” appearance on cross-section
• Collagen fibers
  
  • More loosely arranged in the periphery of the nodule and dust-laden macrophages are often visible
  • Areas of interstitial fibrosis are also seen but are less specific
• Silicotic islets
  
  • May appear granulomatous, with multinucleated giant-cells
  • May be seen in the lung parenchyma, lymph nodes, where they may be encased in calcification, or impinging on or eroding into airways

Question 22

Occupational lung disease (fibrogenic pneumoconiosis):
Silicosis:
Radiographic features and pulmonary function testing

• Uncomplicated (simple) silicosis
• Complicated silicosis
• Both simple and complicated silicosis
• Acute silicosis
• Restrictive lung disease with a diminution in the diffusing capacity

Answer 22

• Uncomplicated (simple) silicosis
  
  • Characterized by small (< 1 cm) rounded opacities in the lung, usually with upper lung zone predominance
  • Patients often have normal pulmonary function
• Complicated silicosis
  
  • The rounded opacities gradually coalesce to eventually produce large conglomerate masses often in excess of 10-20 centimeters
  • These lesions may form cavities, a finding that often suggests either ischemic necrosis or concurrent infection with mycobacteria
• Both simple and complicated silicosis
  
  • Hilar calcifications (so called “eggshell” calcifications because of the cortical distribution within the lymph nodes)
• Acute silicosis
  
  • Results from a massive dose of silica exposure
  • Produces a distinct radiographic finding of alveolar filling disease (alveolar proteinosis) which progresses to diffuse pulmonary fibrosis
• Restrictive lung disease with a diminution in the diffusing capacity
  
  • The most common pulmonary function abnormality associated with this condition

Question 23

Occupational lung disease (fibrogenic pneumoconiosis):
Asbestosis

• Asbestos
• Forms of asbestos
• What the different forms of asbestos have in common
• Exposures associated with asbestos-related lung diseases

Answer 23

• Asbestos
  
  • An ancient mineral that has been exploited over time by humans because of its fibrous nature, heat resistance, and durability
• Forms of asbestos
  
  • Crysotile
  • Crocidolite
  • Amosite
• What the different forms of asbestos have in common
  
  • A fibrous nature, i.e. they occur in bundles of parallel, radiating, or interlaced fibers that can be easily separated for different manufacturing processes
• Exposures associated with asbestos-related lung diseases
  
  • Indirect occupational exposure as a consequence of working in the vicinity of individuals handling asbestos
  • Domestic exposure from handling asbestos-laden work clothes
  • Environmental exposure occurring as a consequence of living near plants containing asbestos

Question 24

Occupational lung disease (fibrogenic pneumoconiosis):
Asbestosis:
Clinical features

• Asbestosis is a term reserved for individuals who…
• The disease develops…
• Radiographically and pathologically the disease is virtually indistinguishable from…
• Clues to the diagnosis
• Asbestos bodies

Answer 24

• Asbestosis is a term reserved for individuals who…
  
  • Develop pulmonary fibrosis as a consequence of asbestos exposure
• The disease develops…
  
  • Insidiously with slowly progressive dyspnea and paroxysms of dry cough as the most common symptoms
  • Uncommonly results in death from respiratory failure
• Radiographically and pathologically the disease is virtually indistinguishable from…
  
  • Idiopathic pulmonary fibrosis
• Clues to the diagnosis
  
  • Careful occupational history
  • The concomitant presence of asbestos related-pleural disease in some but not all patients
• Asbestos bodies
  
  • The presence of asbestos bodies (protein coated asbestos fibers) in the lung does not necessarily implicate asbestos as the cause of pulmonary fibrosis

Question 25

Occupational lung disease (fibrogenic pneumoconiosis):
Asbestosis:
Pathology

• The asbestos body or coated asbestos fiber
• Asbestos bodies in the sputum
• Pulmonary fibrosis following asbestos exposure
• Asbestosis vs. pulmonary fibrosis

Answer 25

• The asbestos body or coated asbestos fiber
  
  • The hallmark of exposure to asbestos
  • Readily visible by light microscopy
• Asbestos bodies in the sputum
  
  • In humans, the number of asbestos bodies in the sputum correlates strongly with the number of fibers in the lung
  • The presence of more than one asbestos body in the sputum is still cited as an important criterion for the diagnosis of asbestosis, although this remains controversial
• Pulmonary fibrosis following asbestos exposure
  
  • Typically begins in the subpleural regions
  • Has a lower lobe predominance
• Asbestosis vs. pulmonary fibrosis
  
  • There are no specific pathologic features that distinguish asbestosis from other causes of pulmonary fibrosis, except for the presence of asbestos bodies
  • Unlike silicosis (and coal workers pneumoconiosis), the lymph nodes are not usually involved in this disease, and patients do not develop progressive massive fibrosis

Question 26

Coal worker’s pneumoconiosis (CWP):
Pathology

• Pneumoconiosis secondary to coal dust exposure
• Simple CWP
  
  • Diagnosis
  • Pulmonary function tests
  • Symptoms
  • Chest X-ray
• Complicated CWP (progressive massive fibrosis, PMF)

Answer 26

• Pneumoconiosis secondary to coal dust exposure
  
  • Has many features similar to silicosis although they are generally less severe
• Simple CWP
  
  • Diagnosed because of an abnormal chest X-ray in an individual with coal dust exposure
  • Pulmonary function tests in individuals with simple CWP may be normal or may show a mild restrictive pattern
  • Associated with few symptoms
    
    • The individuals may have symptoms of cough and sputum production as a consequence of dust-induced chronic bronchitis or concomitant cigarette smoking
  • Chest X-ray demonstrates small rounded opacities less than 1 centimeter in size
• Complicated CWP (progressive massive fibrosis, PMF)
  
  • In a small percentage of individuals, the nodules will coalesce to form large masses associated with severe progressive dyspnea and respiratory failure
  • When complicated CWP develops, the nodules coalesce to form large conglomerate masses that migrate centrally and to the upper lung zones
  • Cavitation of these masses sometimes occurs, and the disease process can be accelerated by concomitant mycobacterial disease in a similar fashion to silicosis

Question 27

Coal worker’s pneumoconiosis (CWP):
Pathology

• Develops as a consequence of…
• The main occupational risk for this disease
• The primary lesion in CWP: The coal macule
• As the lesion enlarges,…
• As the lesion enlarges with PMF,…
• The progression from simple to complicated disease

Answer 27

• Develops as a consequence of…
  
  • The deposition of coal dust in the lungs
• The main occupational risk for this disease
  
  • Coal mining
  • Exposure to coal dust continues to be a major contributor to respiratory diseases in this country
• The primary lesion in CWP: The coal macule
  
  • A small, pigmented lesion in the lung usually < 4 mm in diameter
  • Formed by an aggregation of dust-laden macrophages and fibroblasts accumulating around respiratory bronchioles
• As the lesion enlarges,…
  
  • The bronchial wall weakens and dilates producing an area of focal emphysema
  • Tattooing of the parietal and visceral lymphatics by coal dusts also occur
  • Sometimes subpleural dust deposits and enlarged hilar and mediastinal lymph nodes are present
• As the lesion enlarges with PMF,…
  
  • They impinge on blood vessels and obliterate airways, frequently cavitating as a result of ischemic necrosis
• The progression from simple to complicated disease
  
  • Occurs less commonly in CWP compared to silicosis
  • Determined by a variety of as yet undefined host factors and/or concomitant mycobacterial disease