L6 - COPD

Question 1

COPD

Answer 1

chronic and progressive disease characterised by the development of airflow limitation that is not fully reversible and by an accelerated decline in lung function

Question 2

COPD usually results from…

Answer 2

an abnormal inflammatory response of the lungs to noxious particles or gases

Question 3

chronic bronchitis

Answer 3

usually seen in COPD

inflammation and excess mucus in the lung

Question 4

Emphysema

Answer 4

usually seen in COPD

alveolar membrane breakdown

Question 5

COPD established risk factors

Answer 5

smoking, occupational exposure, a1-antitrypsin deficiency, air pollution

Question 6

smoking first degree relatives

Answer 6

increases risk 3 fold of COPD

Question 7

Non-smoking first degree relatives

Answer 7

does not increase risk

Question 8

COPD genetics

Answer 8

20+ genomic loci associated with lung function (FEV1 levels)

Several of these also associated with COPD susceptibility

Question 9

a1-antitrypsin deficiency gene

Answer 9

SERPINA1

Question 10

a1-antitrypsin deficiency genetics

Answer 10

autosomal recessive inherited disorder affecting 1 in 2000-5000 persons in eyrioe

Question 11

a1-antitrypsin role

Answer 11

coats lungs, protecting from neutrophil elastase

Question 12

neutrophil elastase

Answer 12

produced by white blood cells too break down harmful bacteria, potentially damaging to the lungs

Question 13

a1-antitrypsin deficiency

Answer 13

lungs lack coating, so open to damage from neutrophil elastase - lung damage
a1-antitrypsin is trapped in the liver so there is liver damage

Question 14

?% of COPD patients are or were smokers

Answer 14

90%

Question 15

Smoking and emphysema mechanism

Answer 15

harmful particles trapped in alveoli
inflammatory response triggered
inflammatory chemicals dissolve the alveolar septum
large air cavity lined with carbon deposits formed
emphysema

Question 16

COPD pathology

Answer 16

alveoli destruction, excess mucus, narrowed bronchiole, mucus hyper secretion, exudate, mucus inflammation and fibrosis, disrupted alveolar attachments

Question 17

Airway inflammation

Answer 17

chronic inflammation affecting peripheral airways and lung parenchyma
inflammation increases with disease progression

Question 18

Inflammatory process in epithelial cells

Answer 18

fibroblast then fibrosis formation

Question 19

inflammatory process in macrophages

Answer 19

forms monocytes and Th1 cells.
Also Tc1 cells leading to alveolar wall destruction
neutrophil and proteases –> alveolar wall destruction
proteases to form mucus hypersecretion

Question 20

Pattern recognition receptors

Answer 20

pro inflammatory cytokines and chemokines
reactive oxygen species
proteolytic enzymes –> neutrophil elastase, matrix metalloproteases

Question 21

Oxidative stress

Answer 21

Increased by exogenous, i.e. cigarette smoke, and endogenous, i.e. inflammatory cell activation

Question 22

Inflammation in oxidative stress

Answer 22

Increase in NK-kB and P38 MAPK, also autoantibodies

Question 23

Ageing and cancer in oxidative stress

Answer 23

decrease in SIRT1 and DNA damage

Question 24

Steroid resistance and oxidative stress

Answer 24

decreased MD2

Question 25

fibrosis and emphysema in oxidative stress

Answer 25

decrease in antiproteases and increase in TGFB

Question 26

Oxidative stress leads to…

Answer 26

telomere shortening, cellular senescence, DNA damage, mitochondrial dysfunction, decreased autophagy, stem cell exhaustion and decrease in anti-ageing molecules

Question 27

Airway colonisation

Answer 27

bacterial pathogens that drive chronic airway and systemic inflammation

Question 28

Healthy airway colonisation

Answer 28

bacterial clearance and resolution of inflammation

Question 29

Airway colonisation in COPD

Answer 29

bacterial colonisation with defective phagocytosis and persistence of inflammation due to defective effercytosus

Question 30

Defective phagocytosis leads to…

Answer 30

bacterial colonisation

Question 31

Defective effercytosis leads to…

Answer 31

persistence of inflammation

Question 32

Exacerbation trigger

Answer 32

viruses, bacteria or pollutants

Question 33

Exacerbations

Answer 33

results in heightened inflammation –> oxidative stress, bronchoconstriction, oedema and mucus

Question 34

Exacerbation treatment

Answer 34

antibiotics, steroids and bronchodilators

Question 35

Exacerbations result in…

Answer 35

increased symptoms, hospitalisation, decreased quality of life, increased risk of future exacerbations, increased disease progression or death

Question 36

Frequent exacerbations cause…

Answer 36

worse progress, faster disease progression, more hospital emissions and worse health status

Question 37

Airway remodelling

Answer 37

development of specific structural changes in the airway wall in COPD accompanying long-standing and severe airway inflammation

Question 38

airway remodelling through…

Answer 38

mucus hyper secretion, neutrophils in sputum, squamous metaplasia of epithelium, no basement membrane thickening, goblet cell hyperplasia, increased macrophages and CD8+ lymphocytes, mucus gland hyperplasia and little increase in airway smooth muscle

Question 39

Asthma-COPD overlap syndrome

Answer 39

poorly-defined and understood, includes several phenotypes

Question 40

COPD patients with increased eosinophil counts treatment

Answer 40

high dose ICS, Il-5, IL-13, IL-33 blocking antibodies

Question 41

Asthmatic patients with severe disease or are current smokers with predominantly neutrophilic inflammation treatment

Answer 41

CXCR2 antagonists, phosphodiesterase-4-inhibitors, p38-MAPK inhibitors, IL-3 and IL-17 blocking antibodies, macrolides

Question 42

Asthmatic patients who have had largely irreversible airway obstruction and might have increased inflammation treatment

Answer 42

inhaled combination therapy of corticosteroids, long-acting B2-agonist, long acting muscarinic antagonist

Question 43

Management of stable COPD

Answer 43

reducing exposure to irritants and pulmonary rehabilitation
Relief of symptoms through bronchodilators and for long-acting muscarinic receptor antagonists
Reduces risk of exacerbations

Question 44

management of exacerbations

Answer 44

Oral antibiotics and sometimes oral corticosteroids

bronchodilators