2- overview of obstructive airways disease

Question 1

what is
a) obstructive disease?
b) restrictive disease?

Answer 1

a) airways problem
b) lung problem

Question 2

what are the obstructive airway syndrome?

Answer 2

• asthma
• chronic bronchitis
• emphysema

Question 3

what is ACO?

Answer 3

asthma/COPD overlap syndrome i.e. smokers with features of both asthma & COPD

• COPD with blood eosinophilia
• responds better to inhaled corticosteroids which help exacerbation reductions
• more reversible to salbutamol
• difficult to distinguish ACO from type 2 asthmatic smokers who have airway remodelling

Question 4

what does atopic mean?

Answer 4

allergy

Question 5

what are extrinsic and intrinsic asthma triggers?

Answer 5

extrinsic trigger like allergen or intrinsic if no obvious trigger factor

Question 6

what are the 3 key principles of asthma?

Answer 6

1. type 2 inflammation = characterised predominantly by eosinophils in mucosa and submucosa in 95% of cases (type 2 high). some cases where eosinophils not predominant and more neutrophil (type 2 low asthma)
2. airway hyperresponsiveness = because of type 2 inflammation, sensitive airway to become unstable, twitching and obstruction in response to stimuli
3. reversible airflow obstruction = melt away eosinophil with corticosteroid or relax muscle with medication →reverses obstruction

Question 7

what is the evolution of asthma?

Answer 7

bronchoconstriction = brief symptoms
type 2 airway inflammation = exacerbations
if don’t treat type 2 eosinophilic inflammation the body lays down collagen (scar tissue = fibrosis) in the mucosa and in basement membrane - no drug dissolves it = airway remodelling

Question 8

what happens in remodelling of airways in asthma?

Answer 8

there is thickening of basement membrane and collagen deposition in mucosa, submucosa and basement membrane
= also smooth muscle hypertrophy & hyperplasia

Question 9

what is the process of type 2 inflammation?

Answer 9

allergen binds to dendritic cell (antigen presenting cell) via chemical mediator, TSLP. moves to nearest lymph node where activates nearest T cells to become activated and they can interact with B cells and Th2 cells release cytokines (3 key ones: IL-4, IL-5, IL-13)

IL-5 is attractant for eosinophils (they protect body from parasites) - when eosinophils apoptose they release basic proteins (cytotoxic), leukotrienes & cytokines

Mast cells & basophils link with Ig and release histamine

Leukotrienes stimulate goblet cells in epithelium to produce lots of mucus and affect mucociliary clearance

IL-4 stimulates IgE production

IL-13 affects smooth muscle

Question 10

what does IL 4,5 & 13 do?

Answer 10

IL 4 = stimulates IgE production
IL 5 = attractant for eosinophils
IL 13 = affects smooth muscle

Question 11

what are 3 biomarkers that indicate type 2 inflammation?

Answer 11

• blood/sputum eosinophilia (IL-5)
• raised FeNO (fractional exhaled nitric oxide) (IL-13)
• raised total or specific IgE (IL-4)

Question 12

what drugs to patients with type 2 high respond to?

Answer 12

respond well to corticosteroids & biologics (which act on type 2 pathway)

Question 13

what is management for eosinophilic inflammation (part of inflammatory cascade)?

Answer 13

anti-inflammatory medication = corticosteroids & theophylline

Question 14

what is management for mediators & Th2 cytokines (in inflammatory cascade for asthma)?

Answer 14

antileukotrienes or antihistamines
(anti-IgE, anti-interleukin 5)

Question 15

what is management for twitchy smooth muscle (hyperreactivity) as a result of inflammatory cascade in asthma?

Answer 15

bronchodilators = beta 2 agonists, muscarinic antagonists

Question 16

what is difference about appearance of normal vs asthma pathology of cells?

Answer 16

normal is the structured, neat looking respiratory epithelium (pseudostratified columnar epithelium) and asthma is all jumbled and chaotic looking

Question 17

what is the only drug shown to normalise the the appearance of jumbled asthma cell pathology?

Answer 17

corticosteroids

Question 18

what are the triggers of asthma?

Answer 18

allergens (animal dander, dust mites, pollens, moulds)

other things: exercise, viral infection, smoke, cold, chemicals, drugs (NSAIDs, beta blockers)

Question 19

how does asthma present clinically?

Answer 19

• episodic symptoms & signs
• diurnal variability (worse in morning)
• non productive cough
• wheeze due to turbulent airflow
• family history of asthma
• ask about associated comorbidites

Question 20

what are associated type 2 inflammation comorbidities?

Answer 20

• allergic rhinoconjunctivitis (hay fever)
• chronic rhinosinusitis with nasal polyps
• atopic dermatitis (eczema)
• eosinophilic esophagitis
• urticaria (hives - skin rash)

Question 21

what is used to help assist diagnosis of asthma?

Answer 21

• history & examination
• diurnal variation of peak flow rate
• reduced forceful expiratory ratio = reversibility to inhaler salbutamol
• provocation testing →bronchospasm
  
  • exercise
    -histamine/methacholine/mannitol

Question 22

what is involved in COPD development?

Answer 22

noxious particles or gases (smoking or certain gas stoves) = inflammation →tissue damage & mucociliary dysfunction

Question 23

what are symptoms of COPD?

Answer 23

breathlessness & worsening quality of life

Question 24

what are characteristics of COPD?

Answer 24

• exacerbations
• reduced lung function

Question 25

what is type 2 high inflammation?

Answer 25

eosinophilic inflammation

Question 26

what is type 2 low inflammation?

Answer 26

neutrophilic inflammation

Question 27

what happens type 2 low inflammation in COPD?

Answer 27

neutrophilic inflammation (type 2 low normally) = sticky mucus that blocks airway, smooth muscle hypertrophy, loose alveolar

Question 28

what is disease process in COPD low?

Answer 28

1. the toxins activate alveolar macrophage to release neutrophil chemotactic factors like cytokine IL-8 2. neutrophils arrive and release mediators, oxygen radicals & proteases (like trypsin) 3. cause alveolar wall destruction (emphysema) and mucus hypersecretion (chronic bronchitis) = progressive airflow limitation

Question 29

what is chronic bronchitis?

Answer 29

type of COPD involving mucus hypersecretion & mucociliary dysfunction = characterized by chronic neutrophilic inflammation (type 2 low)

Question 30

what are some affects of chronic bronchitis?

Answer 30

- altered lung microbiome due to chronic inflammation & mucus accumulation - in response to chronic inflammation & irritation, the smooth muscle spasm & hypertrophy = further narrowing the airways

Question 31

is chronic bronchitis reversible?

Answer 31

- some aspects of chronic bronchitis are partially reversible with treatment e.g. bronchodilators help relax smooth muscle & improve airflow

Question 32

what is emphysema?

Answer 32

progressive lung disease that primarily affects the alveoli - an effect of COPD the neutrophils produce proteases which destroy the alveoli making impaired gas exchange and loss of bronchial support (this is irreversible)

Question 33

what is genetic problem that can cause emphysema?

Answer 33

antiprotease

Question 34

what should be assessed in COPD for diagnosis & management?

Answer 34

- assess symptoms - assess degree of airflow limitation using spirometry - assess risk of exacerbations - assess comorbidities

Question 35

what are the chronic symptoms of COPD?

Answer 35

- Daily productive cough - Progressive breathlessness - Frequent infective exacerbations viral/bacterial - Chronic bronchitis-mucous hypersecretion - Emphysema- reduced breath sounds

Question 36

is COPD atopic or non atopic?

Answer 36

non-atopic (non-allergic)

Question 37

what is the chronic cascade in COPD?

Answer 37

progressive fixed airflow obstruction →impaired alveolar gas exchange →respiratory failure (decreased oxygen and increased CO2) →pulmonary hypertension→RV hypertrophy/failure →death