The Pathology of Lung Diseases

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The Pathology of Lung Diseases

• I. RESTRICTIVE LUNG DISEASES
• II. OBSTRUCTIVE LUNG DISEASES

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I.RESTRICTIVE LUNG DISEASES-Diffuse
Interstitial Lung Disease-Infiltrative Lung
Disease-Fibrosing alveolitis-Honeycomb lung
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• Restrictive lung diseases are characterized by
  reduced lung volume,
• an alteration in lung parenchyma
• a disease of the pleura or chest wall
• a disease of neuromuscular apparatus
• In physiological terms, restrictive lung diseases
  are characterized by
• reduced lung capacity
• reduced total lung capacity (TLC)
• reduced vital capacity
• reduced resting lung volume

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• The many disorders that cause reduction or
  restriction of lung volumes may be divided into 2
  groups based on anatomical structures
• 1. Intrinsic lung diseases (or diseases of the
  lung parenchyma),
• 2. Extrinsic disorders (or extraparenchymal
  diseases).

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• 1.
• Intrinsic lung diseases or diseases of the lung
  parenchyma
• The diseases cause inflammation or scarring of
  the lung tissue (interstitial lung disease) or
  result in filling of the air spaces with exudate
  and debris (pneumonitis).

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• 2.
• Extrinsic disorders or extraparenchymal diseases
• Nonmuscular diseases of the chest wall, and
  neuromuscular disorders
• The chest wall, pleura, and respiratory muscles
  are the components of the respiratory pump, and
  they need to function normally for effective
  ventilation.
• If not
• impaired ventilatory function,
• respiratory failure.

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Intrinsic lung diseases or Diseases of the lung
parenchyma

• RESTRICTIVE LUNG DISEASES

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• These diseases can be characterized according to
  etiological factors
• Acute restrictive pulmonary diseases (acute lung
  injury)
• Acute Respiratory Distress Syndrome (ARDS)
• Acute Hypersensitivity Pneumonitis
• Chronic restrictive pulmonary diseases
• Idiopathic fibrotic diseases
• Connective tissue diseases
• Drug-induced lung disease
• Primary diseases of the lungs (including
  sarcoidosis)

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Acute restrictive pulmonary diseases
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Acute Lung Injury

• 1. Diffuse Alveolar Damage (Acute Respiratory
  Distress Syndrome - ARDS)
• 2. Acute Hypersensitivity Pneumonitis (Extrinsic
  Allergic Alveolitis)

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1. Diffuse Alveolar Damage (Acute Respiratory
Distress Syndrome - ARDS)

• Diffuse alveolar damage (DAD) refers to a pattern
  of reaction to injury of alveolar epithelial and
  endothelial cells from a variety of acute
  insults.
• The clinical counterpart of severe DAD is the
  acute respiratory distress syndrome (ARDS).
• In this disorder, a patient with apparently
  normal lungs sustains pulmonary damage and then
  develops rapidly progressive respiratory failure.
  
• The condition reflects decreased lung compliance
  (usually requiring mechanical ventilation) and
  hypoxemia and features extensive radiologic
  opacities in both lungs (white-out).
• The overall mortality of ARDS is more than 50,
  and in patients older than 60 years, it is as
  high as 90.

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Nonthoracic Trauma
Shock due to any cause
Fat embolism
Infection
Gram-negative septicemia
Other bacterial infections
Viral infections
Aspiration
Near-drowning
Aspiration of gastric contents
Drugs and Therapeutic Agents
Heroin
Oxygen
Radiation
Paraquat
Cytotoxic drugs
ETIOLOGY Important Causes of the Acute
Respiratory Distress Syndrome
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Acute Respiratory Distress Syndrome Pathogenesis

• Endothelial/capillary injury ?
• alveolar capillary membrane damage ? increased
  vascular permeability ?
• edema (interstitial/alveolar) ?
• increased synthesis of neutrophil chemotacatic
  activating agents (IL) ?
• activated neutrophils ?
• oxidants, proteases, PAF, leukotriens ?
• tissue damage ?
• other mediators stimulating collagen production ?
• Fibrosis

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Pathology

• Exudative phase (0-7 days)
• congestion,
• necrosis of alveolar epithelial cells,
• edema,
• hemorrhage,
• neutrophils in capillaries,
• Destruction of type I pneumocytes
• permits exudation of fluid into alveolar spaces,
  where deposition of plasma proteins results in
  formation of fibrin-containing precipitates
  (hyaline membranes) on the injured alveolar walls

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• congestion
• necrosis of alveolar epithelial cells
• edema

• hemorrhage
• neutrophils in capillaries
• hyaline membranes

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• If the patient survives the acute phase of ARDS
• Proliferative phase (1-3 weeks)
• Proliferation of type II pneumocytes
• Cleaning of remnant hyaline membranes by
  pulmonary macrophages
• Expansion of alveolar septa
• Proliferation of fibroblasts
• Collagen tissue production
• Healing or Fibrosing
• Fibrosing phase
• Diffuse interstitial fibrosis
• Honeycomb lung

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• Proliferation of type II pneumocytes
• Cleaning of remnant hyaline membranes by
  pulmonary macrophages
• Expansion of alveolar septa
• Proliferation of fibroblasts

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• Diffuse interstitial fibrosis
• Honeycomb lung.

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2. Acute Hypersensitivity Pneumonitis (Extrinsic
Allergic Alveolitis)

• A response to inhaled antigens
• Farmer's lung occurs in farmers exposed to
  Micropolyspora faeni from moldy hay
• Bagassosis results from exposure to
  Thermoactinomyces sacchari in moldy sugar cane
• Maple bark-stripper's disease is seen in persons
  exposed to the fungus Cryptostroma corticale from
  moldy maple bark
• Bird fancier's lung affects bird keepers with
  long-term exposure to proteins from bird
  feathers, blood and excrement
• Hypersensitivity pneumonitis may also be caused
  by fungi growing in stagnant water in air
  conditioners, swimming pools, hot tubs, and
  central heating units.
• Skin tests and serum precipitating antibodies are
  often used to confirm the diagnosis.
• In many cases, especially in the chronic form of
  hypersensitivity pneumonitis, the inciting
  antigen is never identified.

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Chronic restrictive pulmonary diseases
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CHRONIC INTERSTITIAL LUNG DISEASES

• Characterized by
• - decreased lung volume
• - decreased oxygen-diffusing capacity on
  pulmonary function studies

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• A large number of pulmonary disorders are grouped
  as interstitial, infiltrative, or restrictive
  diseases
• They are characterized by inflammatory
  infiltrates in the interstitial space and have
  similar clinical and radiologic presentations
• These diverse maladies
• (1) are of known or unknown etiology, and
• (2) vary from minimally symptomatic conditions to
  severely incapacitating and lethal interstitial
  fibrosis

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Etiology

• Occupational/environmental diseases (24)
• Sarcoidosis (20)
• Idiopathic pulmonary fibrosis (15)
• Collagen-vascular diseases (8)
• The remainder have more than 100 different
  causes and associations.

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• The most striking findings are
• Longstanding inflammatory damage
• Fibrosis of the alveolar walls
• Fibrosis finally wipes out groups of alveoli
• Scar contraction of respiratory bronchioles
• The radiographic and autopsy diagnosis of
  "honeycomb lung"

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ORGANIC DUST EXPOSURE

• Chronic Hypersensitivity Pneumonitis
• Chronic form of Acute Hypersensitivity
  Pneumonitis
• The prototype of hypersensitivity pneumonitis is
  farmer's lung
• Cause Inhalation of thermophilic actinomycetes
  that grow in moldy hay
• Patients with the chronic form of
  hypersensitivity pneumonitis have a more
  nonspecific presentation, with indolent onset of
  dyspnea and cor pulmonale.

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• Pathology
• The main microscopic features of chronic
  hypersensitivity pneumonitis include
• bronchiolocentric cellular interstitial pneumonia
  
• noncaseating granulomas (in two thirds of cases)
• organizing pneumonia
• The bronchiolocentric cellular interstitial
  infiltrate
• lymphocytes
• plasma cells
• macrophages

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• Patchy mononuclear cell infiltrates,
• Lymphocytes
• Plasma cells
• Epitheloid histiocytes
• Interstitial noncaseating granulomas,
• Interstitial fibrosis.

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INORGANIC DUST EXPOSURE

• Pneumoconioses
• Dust inhalation
• Silicosis
• Asbestosis
• Talcosis
• Historically, knife grinder's lung (silicosis).

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Mineral dust-induced lung diseases

• Coal dust (upper lobe)
• Silica (upper lobe)
• Asbestos (lower lobe)
• Beryllium

Coal workers Stone, Ceramics,
Sandblasting Mining, Milling, Insulation
Nuclear energy, Aircraft industry
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• Particles over 10 µm in diameter deposit on
  bronchi and bronchioles and are removed by the
  mucociliary escalator.
• Smaller particles reach the acinus, and the
  smallest ones behave as a gas and are exhaled.
• Alveolar macrophages ingest the inhaled particles
  and are the primary defenders of the alveolar
  space.
• Most phagocytosed particles ascend to the
  mucociliary carpet and are expectorated or
  swallowed.
• Others migrate into the interstitium of the lung,
  then into the lymphatics.

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Air particulate exposure

• Pneumoconioses
• Pulmonary fibrosis
• Asthma
• Chronic bronchitis
• Lung cancer

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• INORGANIC DUST EXPOSURE Silicosis
• Inhalation of silicon dioxide (silica)
• History Dyspnea in metal diggers was reported by
  Hippocrates
• Early Dutch pathologists wrote that the lungs of
  stone cutters sectioned like a mass of sand.
• The major cause of death in workers exposed to
  silica dust for the first half of the 20th
  century
• Sandblasters
• Stone cutting
• Polishing and sharpening of metals
• Ceramic manufacturing
• Foundry work

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• After their inhalation, silica particles are
  ingested by alveolar macrophages
• Silicon hydroxide groups on the surface of the
  particles form hydrogen bonds with phospholipids
  and proteins, an interaction that is presumed to
  damage cellular membranes and thereby kill the
  macrophages
• The dead cells release free silica particles and
  fibrogenic factors ? progressive massive fibrosis
  
• The released silica is then reingested by
  macrophages and the process is amplified

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• The nodular lesions consist of concentric layers
  of hyalinized collagen
• Surrounded by a dense capsule of more condensed
  collagen
• Examination of the nodules by polarized
  microscopy reveals the birefringent silica
  particles.

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• INORGANIC DUST EXPOSURE Coal Workers'
  Pneumoconiosis (CWP)
• Coal dust is composed of amorphous carbon and
  other constituents of the earth's surface,
  including variable amounts of silica.
• Anthracite (hard) coal contains significantly
  more quartz
• Amorphous carbon by itself is not fibrogenic
• Silica is highly fibrogenic, and inhaled
  anthracotic particles may thus lead to
  anthracosilicosis.

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• Asymptomatic anthracosis
• Simple CWP
• Coal macules
• Coal nodules
• Complicated CWP
• Caplan syndrome

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Asymptomatic anthracosis
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• CWP
• Simple CWP
• Complicated CWP (progressive massive fibrosis)
• Coal-dust macules and coal-dust nodules
• Both are typically multiple and scattered
  throughout the lung as 1- to 4-mm black foci
• Microscopy
• Coal-dust macule numerous carbon-laden
  macrophages
• Coal-dust nodule round or irregular dust-laden
  macrophages associated fibrotic stroma
• Focal dust emphysema

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Coal workers pneumoconiosis (CWP)
Coal-dust nodule
Focal dust emphysema
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• Caplan syndrome
• Rheumatoid nodules (Caplan nodules) in the lungs
  of coal miners with rheumatoid arthritis.
• Nodular lesions (1-10 cm in diameter)
• Multiple, bilateral, and usually peripheral
• Microscopy
• Rheumatoid nodule dust deposits
• Rheumatoid nodules consist of large, central,
  necrotic areas surrounded by a border of chronic
  inflammation and palisading macrophages.

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• INORGANIC DUST EXPOSURE Asbestosis
• Asbestos - a group of fibrous silicate minerals
• Insulation
• Construction materials
• Automative brake linings

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• Asbestos is a naturally occurring fibrous
  silicate that was widely used in the past for
  commercial applications because of its
  heat-resistance properties.
• Geometric forms of asbestos
• 1. Amphibole (straight, stiff, and brittle
  fibers).
• 2. Serpentine (curly and flexible fibers 90
  used in wide-world).

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• Asbestos exposure has been industrial or
  occupational and primarily affects workers
  involved in
• mining or processing asbestos
• shipbuilding
• construction
• textile
• insulation-manufacturing industries
• However, because the latency period between an
  initial exposure and the development of most
  asbestos-related disease is 20 years or longer,
• Asbestos-related disease remains an important
  public health issue.

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• Exposure to asbestos can cause a number of
  thoracic complications
• Asbestosis
• Benign pleural effusion
• Pleural plaques
• Diffuse pleural fibrosis
• Rounded atelectasis
• Mesothelioma
• Lung carcinoma

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Asbestos-Related Lung Disease

Pleural lesions  Benign pleural effusion  Parietal pleural plaques  Diffuse pleural fibrosis  Rounded atelectasisInterstitial lung disease  AsbestosisMalignant mesotheliomaCarcinoma of the lung (in smokers)
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• ASBESTOSIS
• Asbestosis is diffuse interstitial fibrosis
  resulting from inhalation of asbestos fibers
• The development of asbestosis requires heavy
  exposure to asbestos
• Asbestos may produce obstructive as well as
  restrictive defects
• As the disease progresses, fibrosis spreads
  beyond the peribronchiolar location and
  eventually results in an end-stage or (honeycomb)
  lung
• Asbestosis is usually more severe in the lower
  zones of the lung

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• Pathology
• Lower lobes and subpleural
• Diffuse pulmonary interstitial fibrosis
• Asbestos bodies (golden brown, fusiform or beaded
  rods with a translucent center and knobbod ends)
• Asbestos fibers coated with an iron-containing
  proteinaceous material (ferruginous body)

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• Lower lobes and subpleural
• Diffuse pulmonary interstitial fibrosis

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• Asbestos fibers coated with an iron-containing
  proteinaceous material (ferruginous body)

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Asbestos-Related Lung Disease Complications
Pleural lesions  Benign pleural
effusion  Parietal pleural plaques  Diffuse
pleural fibrosis  Rounded atelectasis Interstiti
al lung diseaseAsbestosis Progressive
fibrosis Pulmonary hypertension and cor
pulmonale Malignant mesothelioma (80 pleural
20 peritoneal in origin) Bronchogenic carcinoma
(20-25 of heavily exposed asbestos worker)
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Berryliosis

• Aerospace industry
• Dusts/fumes of berrylium
• Acute pneumonitis (high doses)
• Pulmonary/systemic granulomatous lesions
• Progressively fibrotic lung pathology

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Primary or Unclassified diseases

• SARCOIDOSIS
• A granulomatous disease of unknown etiology
• Sarcoidosis can involve many systems and organs
• bilateral hilar lymphadenopathy (75-90 )
• lung involvement (90)
• eye and skin lesions
• Most sarcoid patients are young adults
• Exact pathogenesis of sarcoidosis remains obscure
  
• T lymphocyte response to exogenous or autologous
  antigens
• These cells accumulate in the affected organs,
  where they secrete lymphokines and recruit
  macrophages, which participate in the formation
  of noncaseating granulomas.

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• Pathology
• Multiple sarcoid granulomas are scattered in the
  interstitium of the lung.
• Frequent bronchial or bronchiolar submucosal
  infiltration by sarcoid granulomas accounts for
  the high diagnostic yield (lt90) on bronchoscopic
  biopsy.
• The cellular granulomatous phase of sarcoidosis
  can progress to a fibrotic phase.
• Significant necrosis is usually absent, small
  foci of necrosis are seen in one third of open
  lung biopsies.
• Asteroid bodies (star-shaped crystals)
• Schaumann bodies (small calcifications with a
  lamellar structure)

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Kveim test

• Kveim test, which involves taking ground-up
  spleen from someone with sarcoidosis and
  injecting it into the dermis,
• If a granuloma forms, the living patient
  supposedly has sarcoidosis,
• 80 sensitive, 95 specific.

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• noncaseating granulomas
• Schaumanns bodies
• asteroid bodies

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IDIOPATHIC PULMONARY FIBROSIS

• Usual Interstitial Pneumonia (UIP)
• Syn Chronic interstitial pneumonitis,
  Interstitial pneumonitis, Idiopathic pulmonary
  fibrosis, Cryptogenic fibrosing alveolitis
• One of the most common types of interstitial
  pneumonia
• Middle-aged men
• Unknown etiology (?)
• Viral (flu-like illness)
• Genetic (familial UIP UIP-like diseases in
  neurofibromatosis and Hermansky-Pudlak syndrome)
• Immunologic factors (collagen vascular diseases
  autoimmune disorders)

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• Circulating autoantibodies (e.g., antinuclear
  antibodies and rheumatoid factor).
• Immune complexes (antigen?)
• circulation,
• inflamed alveolar walls,
• bronchoalveolar-lavage specimens.
• Immune complexes ? activated alveolar
  macrophages ? phagocytosis of immune complexes ?
  release of cytokines ? neutrophil migratrion ?
  damage of alveolar walls ? progression ?
  interstitial fibrosis

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Pathology

• The histologic hallmark patchy chronic
  inflammation and interstitial fibrosis with areas
  of dense scarring and honeycomb cystic change
• The lungs are small
• Fibrosis tends to be worse in the lower lobes,
  subpleural regions, and along interlobular septa

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• The honeycomb cystic spaces
• lined by bronchiolar or cuboidal epithelium
• contain mucus, macrophages, or neutrophils
• interstitial chronic inflammation
• lymphoid aggregates, sometimes containing
  germinal centers, in UIP associated with
  rheumatoid arthritis

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• Vascular changes
• intimal fibrosis
• thickening of the media
• Progressive fibrosis of lungs ? respiratory
  insufficiency ? pulmonary hypertension ? cor
  pulmonale ? cardiac failure

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• Desquamative Interstitial Pneumonia (DIP)
• Pathologically described entity
• A diffuse lung disease characterized by marked
  accumulation of intraalveolar macrophages
• intra-alveolar cells were desquamated epithelial
  cells, whereas they are now recognized as
  macrophages
• The macrophages contain a fine golden-brown
  pigment.
• Alveolar walls show mild thickening by chronic
  inflammation and interstitial fibrosis.
• Scattered lymphoid aggregates also may be
  present.
• Hyperplasia of type II pneumocytes is often
  prominent.

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• In cigarette smokers
• The radiographic picture of DIP is not specific
  but is most frequently described as bilateral
  ground glass infiltrates with a lower lobe
  predominance
• DIP has a much better prognosis than UIP
• Most patients respond well to steroid therapy and
  smoking cessation

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Collagen-Vascular Diseases Drugs and other
Treatments

• Nonspecific Interstitial Pneumonia (NSIP)
• Etiology
• infection
• collagen vascular disease
• hypersensitivity pneumonitis
• drug reaction, and others)
• or it may be idiopathic.

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• Pathology
• Diffuse uniform changes in the lung
• NSIP
• Cellular type alveolar septa are diffusely
  involved by a mild to moderate lymphcytic
  infiltrate.
• Fibrosing type septa are diffusely involved by
  fibrosis, with or without significant associated
  inflammation.