Mohammad Tohidi M.D.

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Mohammad Tohidi M.D. Professor of Internal
Medicine Department of Pulmonary Medicine Ghaem
Hospital MUMS Mashhad IRAN
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Silicosis

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Case Scenario(1)

• 57 year old retired non-smoker man referred with
  the cc of dry cough for 1year.In addition he has
  had mild ED but no other complaint. Past Hx
  system review were negative.His VS,general PE
• chest exam were normal.Chest X ray showed
  diffuse reticulonodular pattern There were no
  hilar enlargement calcification.

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Case Scenario(2)

• HRCT scan of the lung revealed small rounded
  opacities thickening of alveolar septa
• no ground glass pattern,hilar adenopathy
• pleural effusion.He had gt30 years Hx of
  stone cutting grinding.With this Hx immaging
  studies, in the absence of another
  causes,diagnosis of simple silicosis was apparent.

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DEFINITION

• Silicosis is a fibrotic lung disease attributable
  to the inhalation of crystalline silica, usually
  in the form of quartz and, less commonly, as
  cristobalite and tridymite
• Amorphous silica is relatively nontoxic

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Introduction

• Silicosis (also known as Grinder's disease and
  Potter's rot) is a form of occupational lung
  disease caused by inhalation of crystalline
  silica dust, and is marked by inflammation and
  scarring in forms of nodular lesions in the upper
  lobes of the lungs.

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Wheres it come from?

• Crystalline forms of silica (Silicon Dioxide or
  SiO2) include quartz, cristobalite, and
  tridymite. Quartz is the most common type, and is
  a major component of rocks including granite,
  slate, and sandstone.

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Silica

• Silica is the second most common mineral on
  earth. It is found in sand, many rocks such as
  granite, sandstone, flint and slate, and in some
  coal and metallic ores.

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Silica

• The cutting, breaking, crushing, drilling,
  grinding, or abrasive blasting of these materials
  may produce fine silica dust.

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Silicosis history

• This respiratory disease was first recognized in
  1705 by Ramazzini who noticed sand-like
  substances in the lungs of stonecutters

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Silicosis history

• Full description by Bernardino Ramazzini
  (1633-1714) in early 18th century. ...when the
  bodies of such workers are dissected, they have
  been found to be stuffed with small stones.
  Diseases of Workers (De Morbis Artificum
  Diatriba, 1713).

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Silicosis history

• The name silicosis (from the Latin silex or
  flint) was attributed to Visconti in 1870

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Silicosis - history

• First U.S. description in 19th century.
• Term silicosis introduced in 1870, from Latin
  silex, or flint.
• Prevalence increased markedly with introduction
  of mechanized mining.
• Came to national attention 1930-1931 with
  construction of Hawks Nest Tunnel in Gauley
  Bridge, West Virginia. Called the worst
  industrial accident in U.S. history. At least
  764 tunnel workers died from silicosis. Hawks
  Nest disaster led to Congressional hearings in
  1936, and new laws protecting workers in many
  states.
• Prevalence of silicosis has greatly declined in
  recent decades because of effective industrial
  hygiene measures.

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Silicosis - history

• The full name for this disease when caused by the
  specific exposure to fine silica dust found in
  volcanoes is pneumonoultramicroscopicsilicovolcano
  coniosis, and at 45 letters it is the longest
  word in any of the major English dictionaries.

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Silicosis - history

• The prevalence of silicosis led some men to grow
  what is called a miner's mustache, in an attempt
  to intercept as much dust as possible.

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Diseases Associated with Exposure to Silica
Dust(1)

• Silicosis
  Chronic silicosis
  Accelerated silicosis
  Acute silicosis (silicoproteinosis)(fine
  dust, intense exposure , high
  silica)
• Progressive massive fibrosis
• Chronic Obstructive Pulmonary Disease Emphysema
  
  Chronic bronchitis
  Mineral dust-induced small airway disease

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Diseases Associated with Exposure to Silica
Dust(2)

• Lung Cancer
  Mycobacterial Infection Mycobacterium
  tuberculosis Nontuberculous Mycobacteria
  Immune-Related Diseases Progressive systemic
  sclerosis Rheumatoid arthritis
  Chronic renal disease
  Systemic lupus erythematosus

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Pulmonary Toxicology

• Particle size is critical.
• Peak dust inhalation
• occurs with particles
• having a diameter of 0.5 to
• 3 microns (µm).
• RCS is invisible to the
• human eye.
• Pulmonary clearance
• mechanisms
• macrophages the
• mucociliary escalator

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• The induction period between initial silica
  exposure and development of radiographically
  detectable nodular silicosis is usually 10 years.
  Shorter induction periods are associated with
  heavy exposures, and acute silicosis may develop
  within 6 months to 2 years following massive
  silica exposure.

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• Silicosis is an occupational hazard to mining,
  sandblasting, quarry, ceramics and foundry
  workers, as well as grinders, stonecutters and
  those continually exposed to silica dust.

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Variety of occupations

• Construction, and surface and underground rock
  drilling
• Foundries are also a main source of silica dust
• workers involved with the repair, rehabilitation,
  or demolition of concrete structures

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Variety of occupations

• New types of pneumoconiosis often turn out to be
  silicosis in an industry not previously thought
  to be at risk or a mixed-dust pneumoconiosis in
  which silica is implicated with other dusts
• Silicosis is often the result of exposure in the
  remote past and not in the current workplace

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Pathology(1)

• When small silica dust particles are inhaled,
  they can embed themselves deeply into the tiny
  alveolar sacs and ducts in the lungs, where
  oxygen and carbon dioxide gases are exchanged.
  There, the lungs cannot clear out the dust by
  mucous or coughing

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Pathology(2)

• Characteristic lung tissue pathology in nodular
  silicosis consists of fibrotic nodules with
  concentric "onion-skinned" arrangement of
  collagen fibers, central hyalinization, and a
  cellular peripheral zone, with lightly
  birefringent particles seen under polarized light

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Pathology(3)

• In acute silicosis, microscopic pathology shows a
  periodic acid-Schiff positive alveolar exudate
  (alveolar lipoproteinosis) and a cellular
  infiltrate of the alveolar walls

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Silicosis
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PATHOGENESIS(1)

• There is agreement that freshly fractured silica,
  such as that generated during sandblasting, is
  more toxic to the alveolar macrophages than is
  "aged" silica
• clay components, may adhere to the surfaces of
  silica particles, producing "coated" silica,
  which is less toxic than uncoated silica dust
• the incidence of silicosis is decreased by
  concomitant exposure to other dusts

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PATHOGENESIS(2)

• 4 The intensity of the exposure determines the
  nature of the lung injury. Low-intensity exposure
  generally produces aggregates of fibrosis with
  relative sparing of the lung architecture,
  whereas high-intensity exposure causes widespread
  pulmonary inflammation and collagen deposition
• 5 Individual susceptibility to the disease
  may play a role

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• Particles engulfed by macrophages
• transported upward and removed from lungs
  retained in the lung Frustrated Phagocytosis
• cascade of toxic effects
• inflammatory process
• 
  pneumoconiosis
  
  
• fibrosis in the lung tissue

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Pathogenesis(3)

• When fine particles of silica dust are deposited
  in the lungs, macrophages that ingest the dust
  particles will set off an inflammation response
  by releasing tumor necrosis factors,
  interleukin-1, leukotriene B4 and other
  cytokines. In turn, these stimulate fibroblasts
  to proliferate and produce collagen around the
  silica particle, thus resulting in fibrosis and
  the formation of the nodular lesions

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Pathogenesis(4)

• Furthermore, the surface of silicon dust can
  generate silicon-based radicals that lead to the
  production of hydroxyl and oxygen radicals, as
  well as hydrogen peroxide, which can inflict
  damage to the surrounding cells

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• Silicosis
• MC chronic occupational disease in the world
• caused by inhalation of crystalline silicon
  dioxide (silica).
• Acute silicosis -accumulation of a
  lipoproteinaceous material within alveoli
• Chronic silicosis - slowly progressing, nodular,
  Fibrosing pneumoconiosis
• Pathogenesis
• crystalline forms -more fibrogenic (quartz
  worst)
• silica particles ?lung macrophages ingest them ?
  activation and release of mediators ? IL-1, TNF,
  oxygen-derived free radicals
• Anti-TNF monoclonal antibodies can block lung
  collagen accumulation in mice
• Morphology.
• Early stages tiny nodules in the upper zones
• disease progresses nodules coalesce into hard,
  collagenous scars ?central softening and
  cavitation (due to superimposed tuberculosis or
  to ischemia)
• X-ray egg shell calcification in the lymph
  nodes
• Advanced stage - PMF
• Histology
• Nodular lesions -concentric layers of hyalinized
  collagen surrounded by a dense capsule
• Birefringent silica particles in polarized
  microscopy

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EPIDEMIOLOGY

• The prevalence of silicosis is difficult to
  estimate
• the reported cases have been estimated to
  represent only one third of the total cases of
  silicosis
• In calculating an individual's risk for
  silicosis, duration and intensity of exposure are
  of primary interest but peak exposure also may be
  important.

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EPIDEMIOLOGY(contd)

• In the United States, NIOSH has estimated that at
  least 1.7 million workers are exposed to silica,
  of whom between 1500 and 2360 will develop
  silicosis each year

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Prevalence

• Silicosis is the most common occupational lung
  disease worldwide, it occurs everywhere but is
  especially common in developing countries

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Silicosis deaths - decliningwww.cdc.gov/mmwr
1,157 (1968) 148 (2002)
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CLINICAL FEATURES(1)

• The main symptom is breathlessness, first noted
  during exertion and later at rest as the large
  working reserve of the lung is diminished. In
  chronic silicosis, in the absence of other
  respiratory disease, even this symptom may be
  absent
• a patient with chronic silicosis may present
  without symptoms for assessment of an abnormal
  chest radiograph

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CLINICAL FEATURES(2)

• The appearance of breathlessness may mark the
  development of a complication such as progressive
  massive fibrosis or tuberculosis, or may reflect
  associated airway disease
• Cough and sputum production are common symptoms
  and usually relate to chronic bronchitis, but may
  reflect the development of tuberculosis or lung
  cancer

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CLINICAL FEATURES(3)

• Chest pain is not a feature of silicosis, nor are
  systemic symptoms such as fever and weight loss,
  which should be attributed to tuberculosis or
  lung cancer until proven otherwise.
• Clubbing is also not a feature of silicosis

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CLINICAL FEATURES(4)

• In accelerated and acute silicosis, the time
  scale of symptom evolution is in years or months
  rather than decades. In acute silicosis,
  breathlessness may become disabling within
  months, followed by impaired gas exchange
  Cyanosis
• Cor pulmonale
• Respiratory insufficiency

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• Patients with silicosis are particularly
  susceptible to tuberculosis (TB) infection -
  known as silicotuberculosis. The reason for the
  increased risk - 10-30 fold increased incidence -
  is not well understood. It is thought that silica
  damages pulmonary macrophages, inhibiting their
  ability to kill mycobacteria

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Types of Silicosis

• (1) Chronic silicosis
• Occurs after 15-20 years of exposure to moderate
  to low levels of silica dust. Chronic silicosis
  itself is further subdivided into
• simple
  
• complicated silicosis(PMF)

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Chronic silicosis

• This is the most common type of silicosis.
  Patients with this type of silicosis may not have
  obvious symptoms, so a chest X-ray is necessary
  to determine if there is lung damage.

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• (2) Asymptomatic silicosis
• Early cases of the disease do not present any
  symptoms

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• (3) Accelerated silicosis
• Silicosis that develops 5-10 years after high
  exposure to silica dust. Symptoms include severe
  shortness of breath, weakness, and weight loss

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• (4) Acute silicosis
• Silicosis that develops a few months to 2
  years after exposure to very high concentrations
  of silica dust.

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Diagnosis of Silicosis

• In general, three key elements play a role in the
  diagnosis of silicosis
• A history of silica exposure sufficient to cause
  the degree of illness and the appropriate latency
  from the time of first exposure
• Chest imaging (usually a conventional chest
  radiograph) that shows opacities consistent with
  silicosis
• Absence of another diagnosis more likely to be
  responsible for the observed abnormalities

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Diagnosis of Silicosis

• Abnormal chest X-ray (or chest CT scan)
  consistent with silicosis
• History of significant exposure to silica dust
• Medical evaluation to exclude other possible
  causes of abnormal chest x-ray
• Pulmonary function tests are helpful to gauge
  severity of impairment, but NOT for diagnosis.
• Lung biopsy rarely indicated (since no effective
  treatment, biopsy is done only when other
  diagnoses are being considered)

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Silicosis can be misdiagnosed

• Silicosis can mimic
• Sarcoidosis (benign inflammation of unknown
  cause)
• Idiopathic pulmonary fibrosis (lung scarring of
  unknown cause)
• Lung cancer
• Several other lung conditions (chronic infection,
  collagen-vascular disease, etc.)
• Can usually make right diagnosis with detailed
  history (occupational medical) or, rarely, a
  lung biopsy.

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LUNG FUNCTION

• The lung function profile is determined by the
  extent of silicosis as well as associated or
  concomitant airway and vascular changes
• In chronic silicosis, spirometric tests (FEV1,
  FEV1/FVC, and maximal midexpiratory flow) usually
  reflect airflow limitation.

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LUNG FUNCTION

• In the accelerated and acute forms, functional
  changes are more marked and progression is more
  rapid. In acute silicosis, lung function shows a
  restrictive defect and impairment of gas
  exchange, which leads to respiratory failure and
  eventually to death from intractable hypoxemia

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LUNG FUNCTION

• Reduction in diffusing capacity is generally
  apparent in more advanced chronic silicosis and
  probably reflects associated emphysema.
• It is possible that most of the lung function
  changes associated with chronic silicosis can be
  attributed to the associated emphysema.

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Chest imaging

• The three main radiographic presentations of
  silicosis are
• simple silicosis progressive massive
  fibrosis
• silicoproteinosis

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Simple silicosis 

•  Simple silicosis refers to a profusion of small
  (less than 10 mm in diameter) nodular opacities
  (nodules). The nodules are generally rounded but
  can be irregular, and are distributed
  predominantly in the upper lung zones

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Progressive massive fibrosis 

• Progressive massive fibrosis (PMF, or
  conglomerate silicosis) occurs when these small
  opacities gradually enlarge and coalesce to form
  larger, upper- or mid-zone opacities more than 10
  mm in diameter

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PMF

• The hila are retracted upward in association
  with upper lobe fibrosis and lower lobe
  hyperinflation
• Hilar adenopathy with prominent calcification is
  often present. The opacities of PMF can be
  asymmetrical, and may mimic a neoplastic process.
  Cavitation may also be present in advanced
  disease, or in the setting of mycobacterial
  superinfection

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Silicoproteinosis

• Silicoproteinosis occurs following overwhelming
  exposure to respirable crystalline silica over a
  short time, and is the radiographic hallmark of
  acute silicosis The chest radiograph demonstrates
  a characteristic basilar alveolar filling
  pattern, without rounded opacities or lymph node
  calcifications.

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HRCT

• There is general agreement that CT/HRCT is
  superior to conventional chest radiography for
  documentation of PMF lesions and emphysematous
  changes associated with silicosis

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• pleural effusions are unusual,but pleural
  thickening appears to be common, especially among
  patients with more severe disease. In a series of
  110 patients with biopsy proven silicosis
  followed for a mean of 14 years, pleural
  effusions were noted in 12 patients (11 percent),
  but pleural thickening was present in 64 patients
  (58 percent)

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Normal Simple
silicosis
noal chest x-ray
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Accelerated Silicosis ( Progressive Massive
Fibrosis) normal chest x-ray
PMF
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Accelerated Silicosis (PMF)chest x-ray
CT scan

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Eggshell calcification almost exclusively
silicosis
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RADIOGRAPHIC FEATURES(2)

• Silicotic nodules are usually, although not
  invariably, symmetrically distributed and tend to
  occur first in the upper zones .later, although
  not invariably, other zones are involved.
  Occasionally the nodules are calcified,
  resembling microlithiasis

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RADIOGRAPHIC FEATURES(3)

• Enlargement of the hilar nodes may precede the
  development of the parenchymal lesions.
  "Eggshell" calcification, when present, is
  strongly suggestive although not pathognomonic,
  of silicosis
• Pleural plaques may occur but are not a common
  feature.

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RADIOGRAPHIC FEATURES(4)

• Progressive massive fibrosis is characterized by
  the coalescence of small rounded opacities to
  form larger lesions they are graded on the ILO
  scale according to size and extent (categories A
  to C).

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RADIOGRAPHIC FEATURES(5)

• CT assessment is superior to the chest radiograph
  not only in assessing the presence and extent of
  silicotic nodulation, but also in revealing early
  conglomeration.
• With time, the mass lesions tend to contract,
  usually to the upper lobes, leaving
  hypertranslucent zones at their margins and often
  at the lung bases. In this process, small rounded
  opacities, previously evident, may disappear,
  resulting in a picture that needs to be
  distinguished from tuberculosis

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RADIOGRAPHIC FEATURES(6)

• The rapid development of several large lesions
  suggests rheumatoid silicosis, but new lesions,
  especially if cavitated, should be regarded as
  evidence of mycobacterial disease
• Acute silicosis is characterized radiologically
  by diffuse changes that usually display an air
  space and interstitial pattern rather than the
  usual nodularity

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Diagnosis Serology

• Hypergammaglobulinemia
• RF
• ANF
• S-ACE
• Increased incidence of systemic sclerosis
• described in SA gold miners

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Treatment

• Silicosis is an irreversible condition with no
  cure. Treatment options currently focus on
  alleviating the symptoms and preventing
  complications

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Treatment

• The disease will generally progress even without
  further exposure,but the rate of deterioration is
  probably reduced

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Treatment

• There is currently interest in the use of lung
  lavage to remove silica from the lung, but a
  favorable impact on progression of acute or
  chronic silicosis has not been demonstrated.

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Treatment

• Treatment of all forms of silicosis should be
  directed toward control of mycobacterial disease.
  This is especially true for acute and accelerated
  silicosis and silicosis in workers with human
  immunodeficiency virus infection
• All patients with silicosis should have a
  tuberculin skin test and, if it is positive, be
  offered treatment for latent tuberculosis
  infection

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Treatment

• Interventions to interrupt the inflammatory
  process that leads to chronic silicosis including
  the inhalation of aluminum or polyvinylpyridine-N-
  oxide and oral tetrandine have not been shown to
  be successful

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Treatment

• The interaction between silica exposure and
  smoking in the development of COPD makes it
  particularly important to implement smoking
  cessation programs in the workplace

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Treatment

• Because acute and accelerated silicosis carry
  such a poor prognosis and tend to occur in
  younger persons, consideration should be given to
  lung transplantation in such cases

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Prevention

• The best way to prevent silicosis is to identify
  work-place activities that produce crystalline
  silica dust and then to eliminate or control the
  dust. Water spray is often used where dust
  emanates. Dust can also be controlled through dry
  air filtering

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Prevention

• The most important aspect of the management of
  silicosis relates to its prevention
• a sustained effort must be made to increase
  awareness of silicosis. Recent deaths from
  silicosis in younger individuals in the United
  States have occurred after exposure in the
  construction and manufacturing sectors, with none
  from mining

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• Silicosis
• MC chronic occupational disease in the world
• caused by inhalation of crystalline silicon
  dioxide (silica).
• Acute silicosis -accumulation of a
  lipoproteinaceous material within alveoli
• Chronic silicosis - slowly progressing, nodular,
  Fibrosing pneumoconiosis
• Pathogenesis
• crystalline forms -more fibrogenic (quartz
  worst)
• silica particles ?lung macrophages ingest them ?
  activation and release of mediators ? IL-1, TNF,
  oxygen-derived free radicals
• Anti-TNF monoclonal antibodies can block lung
  collagen accumulation in mice
• Morphology.
• Early stages tiny nodules in the upper zones
• disease progresses nodules coalesce into hard,
  collagenous scars ?central softening and
  cavitation (due to superimposed tuberculosis or
  to ischemia)
• X-ray egg shell calcification in the lymph
  nodes
• Advanced stage - PMF
• Histology
• Nodular lesions -concentric layers of hyalinized
  collagen surrounded by a dense capsule
• Birefringent silica particles in polarized
  microscopy

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