T2 L13: Restrictive lung diseases: fibrosis

• What is the interstitium of the lung?

  spaces in lungs between and around air sacs

  includes:

  • connective tissue (ie basement membrane)
  • patrolling immune cells and fibroblasts
  • blood and lymphatic vasculatures
• What is intralobular septa?

  connective tissue

  surround alveoli

  thin layer between alveoli and capillaries

  
• What is interlobular septa?

  outline secondary lobules

  contain lymphatics and veins of lungs

  only visible on CT when thickened from disease

  
• What is peri-bronchial interstitium?

  supports the thin terminal + respiratory bronchiole walls

  
• What is a secondary lobule?

  smallest functional unit in the lung that:

  • contains a central artery and a terminal bronchiole
  • is bound by a fibrous connective tissue

  
• What are interstitial lung diseases (ILDs)?

  diseases that cause inflammation or scarring

  starts at one of these locations:

  • intralobular / interlobular septa
  • respiratory bronchioles
  • capillary endothelial cells (vasculitis)
• What is the goal in ILD care?

  to make a specific diagnosis

  as many symptoms are non-specific (eg dyspnoea, cough, restriction, hypoxaemia)
• What is the difference in granulomas in tuberculosis vs ILD?

  in ILD little to no necrosis in granulomas
• What are granulomas?


  collection of macrophages, typically with lymphocytes in the outer rim

  
• What are nodules?

  lumps due to inflammation

  lymphatic distribution - along interlobar septa

  centrilobular distribution - do not touch fissures

  
• What are reticulations and ground glass opacities and how do they arise?

  seen on CT

  reticulations: fine lines

  ground glass opacities: fuzzy grey patches (due to air / fluid / fibrosis)

  manifest due to infiltration of lymphocytes along the intralobular septa (ie around alveoli)

  
• What is 'peribronchial infiltrate of lymphocytes'?

  areas of lymphocytes around air trapping

  occurs when air can't be adequately exhaled

  also where small bronchioles have congested and narrowed lumens

  
• What are 'collagen plugs'?

  collagen plug and inflammation in alveoli and around respiratory bronchioles

  cause 'consolidations': alveoli filled with inflammatory cells and collagen

  
• What are 'fibroblast foci'?

  collections of fibroblasts that make scarring collagen

  get activated permanently

  can't discrete on imaging

  
• What are fibrotic reticulations?

  fine lines formed from scarring in the intra-alveolar septal spaces

  
• What are honeycomb cysts?

  fibroblast foci create fibrosis

  which destroy normal lung tissue

  ultimately results in honeycomb cysts

  
• Terms related to inflammation

  granuloma

  nodules

  intralobular infiltrate of lymphocytes

  peribronchial infiltrate of lymphocytes

  collagen plugs
• Terms related to fibrosis

  fibroblast foci

  reticulations

  honeycomb cysts
• What is 'Non-specific interstitial pneumonia (NSIP)'?

  infiltration of lymphocytes along intralobular septa
• What is 'Organizing pneumonia' (OP)?

  plugs of collagen and inflammation in alveolar and respiratory bronchioles
• What is 'Usual interstitial pneumonia (UIP)?

  disease pattern

  includes fibroblast foci with tails of fibrosis
• What are the 3 pathology patterns?

  NSIP pattern (intralobular septa)

  Organizing pneumonia pattern (in alveoli)

  UIP pattern (fibroblast foci)
• What is Hypersensitive Pneumonitis?

  chronic inflammatory disease that can convert to fibrosis

  (less common: chronic HP - high antigen exposure, flu-like illness)

  causes: exposure to organic dust + genetic predisposition

  symptoms: shortness of breath, cough, wheeze
• How does hypersensitive pneumonitis show on imaging?

  nodules, granulomas, ground glass opacities

  
• How is hypersensitive pneumonitis treated?

  remove antigenic exposure (most important!!!)

  immunosuppression if:

  • symptomatic
  • extensive (lots of lung affected)
  • progressive (loss of lung function)
• What is Sarcoidosis?

  abundance of tightly packed (well circumscribed) granulomas in a lymphatic distribution

  Can affect almost any part of the body, but the lungs and thoracic lymph nodes are the most common

  unknown trigger

  symptoms: systemic (fever, weight loss, night sweats, fatigue, depression) likely due to elevated levels of cytokines in blood

  mainly affects adults ages 20-60 with black ppl having higher risk
• How does Sarcoidosis present upon examination?

  thickening along small airways from granuloma formation in airway lymphatics

  upper lung zones more affected than lower

  
• How is Sarcoidosis treated?

  immunosuppression meds (eg corticosteroids) if progressive (as have lots of side effects)

  monitored w/o treatment if stable
• What is CTD-ILD?

  Connective Tissue Disease-Interstitial Lung Disease

  • nearly any ILD pattern can happen in CTD (most common NSIP & organising pneumonia)
  • inflammatory CTD-ILD can convert, over time, to fibrosis (in UIP pattern)

  eg scleroderma, rheumatoid arthritis, dermatomyositis / polymyositis, Sjorgen's,
• How is CTD-ILD treated?

  immunosuppression if symptomatic, extensive, progressive

  treatment not always effective
• What is drug-related ILD?

  causes: chemotherapy meds, amiodarone, long-term use of nitrofurantoin

  imaging findings: ranging from mild inflammation to severe fibrosis

  diagnosis often made without biopsy (due to non-specific nature of inflammation)
• How is drug-related ILD treated?

  stop medication (MOST IMPORTANT)

  difficult decisions regarding stopping treatment but must be done

  treat with immunosuppression if symptomatic, extensive or progressive
• What is occupational lung disease?

  Work-related lung conditions.

  • asbestos-related disease
  • lung cancer
  • mesothelioma
• What is pneumoconiosis?

  Lung disease caused by inhaling dust particles.

  nodular disease is a common finding in silica & coal dust exposure, causing 'progressive massive fibrosis'

  asbestos fibres often get stuck in lymphatics near pleural, causing 'pleural plaques'

  
• What is 'asbestosis'?


  disease due to fibrotic response to asbestos fibres

  causes reticulations and honeycomb cysts on imaging

  
• What can asbestos cause?

  1. Asbestosis
  2. Mesothelioma (pleura cancer)
  3. Lung cancer

  can cause pleural plaques

  which increase risk

  highest risk of lung cancer = smoking + asbestos exposure

  
• What is 'coal miner's lung'?

  very small coal dust particles reach airsacs

  • engulfed by macrophages → inflammation
  • trigger massive fibrosis

  essentially lasts forever in lung

  
• What is the latency period for asbestos-related disease and coal-miner's lung?

  years after exposure

  asbestos-related: can be decades

  coal-miner's: within years
• Do all fibrotic ILDs start with inflammation?

  no

  IPF does not have typical inflammatory pro-dome phase
• What is Idiopathic Pulmonary Fibrosis (IPF)?

  reticulations + honeycomb cysts

  mostly affects lower + peripheral aspects of lung

  UIP pattern

  common, old age (rare before 50)

  most patients have smoked, but disease process not understood so 'idiopathic'