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  • Environmental lung disease should mean lung disease caused by things in the environment. But this isn't so, we limit the use of this phrase - most lung disease is caused by things in the environment e.g. we don't include infections or malignancies (even though these are caused by environmental things e.g. pathogens and carcinogens. Focused on physical and chemical causes
  • Interested in acute/chronic systemic toxicity, or physical injury - lung is a major target because it's exposed to everything in the atmosphere, as well as particulates in the atmosphere that can cause physical injury - most particulates in the atmosphere produce both chemical and physical injury (due to adsorbed particles).
    • Other targets of environmental disease: kidney (excretion), bone (non-excreted toxins), CNS (lipid-soluble toxins). Some toxins are particularly likely to affect rapidly dividing cells.
    • Lung is the most important target for environmental injurious agents

Causes of death

Doesn't include morbidity!

  • CVD
    • IHD
    • CerebroVD
  • Malignant neoplasms
  • Respiratory disease
    • Chronic lower respiratory diseases - most is one entity which is mostly triggered by one syndrome
    • Pneumonia and influenzza
  • Accidents, poisoning and violence
  • Diabetes mellitus


  • The #1 cause of environmentally induced lung disease is tobacco smoke (usually self-inflicted)
    • Passive smoking is also an issue; includes not only malignancy, but also COPD (pattern of disease)
  • There is only a limited number of ways the lung can respond to environmentally induced injury (we talk about 4)
    • NB: ARDS is in dyspnoea next week, asthma was in phase 1.
    • chronic bronchitis is a misnomer
    • pulmonary fibrosis is not a specific disease but is a

NB: lung disease ranks high in morbidity

Smoking

  • COPD & chronic bronchitis are the two we focus on
  • Smoking causes
    • Carcinomas of urinary tract, carcinomas of larynx and esophagus, lungs, pancreatic carcinoma, carcinoma of kidney, atherosclerosis
    • Lots of morbidity: e.g. chopped off limbs, dyspnoea

Chronic bronchitis

  • Part of the spectrum of COPD
  • Clinical syndrome of chronic cought with enhanced production of mucus, may be associated with airflow obstruction; overlaps with other syndromes
  • How particulates in air are managed in the respiratory tree; remember also the adsorbed chemicals
    • Large particulates are trapped in the nasopharynx (turbinates, mucus, humidification). These particles is diameter >5u (diameter is the effective aerodynamic diameter - depends on how it is carried in the air)
    • Past the nasopharynx, particles are carried in a laminar branch stream through 17 branchings. Each branchpoint has a little turbulence and the rate of airflow decreases - so at each branchpoint there are some particles that drop out - acts like a sieve. (1-5u)
    • Therefore the particles that reach the alveoli are very small (<1u reach the exchange part of the respiratory tree)
  • Mucus catches most of the particles, and mucociliary escalator brings it up and swallows it. 150mL made each 24 hours.
  • Past the conducting airway system (distal to terminal bronchioles) there is no mucus
  • Very little particles are not handled like this - they behave like a gas (ultrafine particles) - no hard data
  • Any larger particles that make it to the alveoli are phagocytosed by alveolar macrophages
  • Particles that go down the airstream and deposit in the airways can act as irritants
    • Causes increased mucus production - in the airway wall

Some triggers of chronic "bronchitis"

Major cause of cough in chronic bronchitis is mucus. The inflammation is not in the bronchi, so it is a misnomer.

  • Operational definition, by absence of any other diagnosis (see the definition)

Triggers

  • Smoking
    • Carbon deposits stuck in alveoli - collects pollutants etc.
  • Atmospheric pollution (sulphur dioxide, particulates)
  • Occupation exposure to chemicals and dusts (plastics, cotton and grain, minerals)
    • We are conscious of this in Australia - controls are quite good
  • Superimposed infections (no evidence that infection starts the process, but there is evidence that it triggers it over the top)


  • Diagram of large conducting airway
    • Cartilage therefore conducting
    • Aggregates of glands - bronchial mucus glands (hypertrophy/hyperplasia) --> more mucus --> cough
    • Chronic bronchitis is not primarily about inflammation or obstruction - so why is it part of COPD?

Patterns of chronic bronchitis

  • Simple - cough with mucus, without any other identifiable cause
  • Asthmatic - wheezy
  • Mucopurulent - because of superimposed infections; then it's a true bronchitis due to inflammation
  • Obstructive - this is the big deal; this isn't about mucus overproduction, but changes in small airways of conduction
  • with Cor Pulmonale


  • Slide of a small conducting airway
    • Evidence of airflow obstruction
    • Small airways disease (right) involves membranous bronchioles <2 mm in diameter and respiratory bronchioles. Histological abnormalities include epithelial loss, smooth muscle hyperplasia, fibrosis, mural inflammation, luminal exudate and decreased numbers of alveolar wall attachments.
    • Small airway disease is the main form of chronic bronchitis; this is the critical component of COPD w.r.t. conducting airways
      • flow directly proportional to r^4
    • Should be called chronic bronciolitis
    • Alveolar organisation and attachments keep the alveoli open
  • You best demonstrate airflow obstruction associated with chronic bronchitis using spirometry
    • Physical exam is useless
    • Six minute walk test is nonspecific to chronic bronchitis
    • CXR is hopelessly insensitive
    • CT and MRI can show you damage to lung but no functional impairment

Spirometry

  • Deep breath in, blow out as hard and fast as you can
  • FEV1 = forced expiratory volume in one second
  • FEV1/FVC fraction is a direct measure of airflow obstruction
  • Normal FVC = 5 L, FEV1 = 4 L
    • FEV1/FVC = 80%
  • Obstructive FVC = 3L
    • FEV1 = 1.2L
    • FEV1/FVC = 40%
  • Restrictive
    • FEV1 = 2.7
  • Most obstruction to flow in COPD is destruction of small airways. In emphysema, there is loss of alveolar recoil.
  • Restrictive lung disease doesn't have Low FEV1/FVC (it's high) but has low FVC due to restriction). Reduced
  • Obstructive cutoff is 70% FEV1/FVC
  • Airflow obstruction in chronic bronchitis is caused by peribronchiolar fibrosis (this is small airways disease)
    • Mucous gland hyperplasia causes cough
    • Mucus plugging of bronchi is a variation of the same thing
    • Chronic inflammation of the bronchi is WRONG - misnomer
    • Alveolar wall destruction is emphysema


  • COPD
    • Disrupted alveolar attachments - air trapping - can't get out (obstruction)
    • Mucosal inflammation and fibrosis
    • Mucus hypersecretion

Emphysema

  • Irreversible destructive dilation of airspaces distal to terminal bronchioles
  • Exchange airways in the lung
  • Last place that particles will drop out will be the first order branching of the respiratory bronchioles (beyond this they act as a gas)
    • Particles here cause inflammation, destruction and a little scarring
    • This is in the centre of the lobular acinus - the pattern is centriacinar/centrilobular emphysema. Over time it can get worse and involve the whole acinus
    • A small subset of people have the emphysema starting distally (panacinar/panlobular emphysema)
  • Normal lung looks like a sponge - emphysema has huge holes with no gas exchange
    • The ones on the surface look like emphysematous bullae (can pop and cause pnemothorax). Bullae tend to form at the apex
  • Second emphysema gough section = panacinar emphysema
  • Late emphysema = hyperinflated lungs (visible on CXR) - pulmonary arterial hypertension, cor pulmonale (causing right ventricular hypertrophy)
    • Cor pulmonale is a late complication of emphysema
  • Pathophys: particles attract white cells that make enzymes that damage
    • Matrix metalloproteinases - collagenases and elastases. Elastic tissue is irreplacable (that's why skin goes wrinkly) - then your alveolar recoil and capacity to breathe out is gone. This results in functional obstruction
    • Chronic airflow limitation is a better name for COPD
      • Either little airway narrowing, or loss of elastic recoil
  • Normally there are good antiprotease mechanisms (secreted proteases locally and plasma proteases i.e. alpha-1 antitrypsin)
    • So we have increased proteases and decreased antiproteases
    • Genetic emphysema = alpha-1 antitrypsin deficiency
    • Environmental emphysema = centriacinar, genetic emphysema = panacinar
  • Emphysema patients have decreased FEV1/FVC
    • Decreased residual volume occurs as a late complication

Triggers to hypersensitivity pneumonitis

  • Immunologically mediated interstitial pneumonitis, usually triggered by inhaled inorganic dusts
  • Some inorganic molecule triggers a mixed type 3 and type 4 hypersensitivity reaction
    • This is interstitial pneumonitis (in the alveolar walls, not in the alveoli)

Triggers

  • Thermophilic actinomycetes in hay and grain
  • Other microorganisms associated with dusts
  • Bird feathers and droppings
  • Sawdust
  • Grasses

Histo

  • Thick alveolar walls
  • They don't expand and contract very well
    • Become breathless and can't exchange gas
  • Becomes granulomatous and fibrotic
  • Widespread opacification on CXR because of thickening of alveolar wall
  • Pulmonary fibrosis is a convergence of many restrictive diseases
    • Most common causes is unknown
  • Dense fibrosis, alveoli have come together
  • interstitial and/or intra-alveolar deposition of collagen with irregular collapse and irreversible reorganisation of airspace architecture, following parenchymal inflammation
  • Can be caused by a lot of inflammatory events, one of which is hypersensitivity pneumonitis.
    • Note there are non-environmental causes

Pulmonary Fibrosis

  • Interstitial and/or intra-alveolar deposition of collagen with irregular collapse and irreversible reorganisation of airspace architecture, following parenchymal inflammation

Dust diseases

  • Silicosis and asbestosis
  • Coal miner: silicosis: black fibrotic nodules, fibrosis of pleura.
  • Asbestosis: very highly inflammatory resulting in fibrosis
    • Asbestos bodies: hemosiderin is deposited on top of them. They are long (50um), but a very small cross section
      • Later consequence = mesothelioma
  • Interstitial lung disease has reduced compliance