L5 - asthma

Question 1

Asthma

Answer 1

chronic inflammatory disorder of the airways causing recurrent episodes of wheezing, breathlessness, chest tightness and coughing

Question 2

asthma episodes

Answer 2

usually associated with widespread but variable airway obstruction that is often reversible either spontaneously or with treatment

Question 3

asthma mechanism

Answer 3

airway inflammation –> Bronchial hyperresponsiveness –> recurrent reversible airway obstruction

Question 4

Hygiene hypothesis

Answer 4

exposure to microbial components early in life skews immune respons
Th2–> Th1

Question 5

Hygiene hypothesis limitations

Answer 5

respiratory allergies increased earlier than food allergies
Helminth infections
measles and respiratory viruses

Question 6

helminth infections

Answer 6

high Th2 levels but decreased allergic disease

Question 7

Measles and respiratory viruses

Answer 7

high Th1 levels but not protective against allergic disease and can increase risk

Question 8

Hygiene hypothesis year

Answer 8

1989

Question 9

Old friends hypothesis

Answer 9

early and regular exposure to harmless microorganisms train the immune system to react appropriately to threats

Question 10

Aspects of old friends

Answer 10

maternal microbes, childhood contact, hygiene, caesarians, pets, farms etc.
And genetics

Question 11

Old friends hypothesis year

Answer 11

2003

Question 12

Risk factors

Answer 12

respiratory infections, allergens, work, medication, genetics, food additives, pollutants, tobacco, obesity

Question 13

Asthma genetics

Answer 13

polygenic with over 150 related genes

Question 14

1 parent asthma risk

Answer 14

25%

Question 15

2 parents asthma risk

Answer 15

50%

Question 16

Asthma twin studies

Answer 16

70% variation in disease susceptibility

Question 17

Epigenetics

Answer 17

transcriptional dynamic alterations leading to changes in gene expression

Question 18

Asthma mutations in 4 areas

Answer 18

triggering and regulating immune system, regulation of Th2 differentiation, lung function remodelling and disease severity or positional cloning

Question 19

Th2 eosinophilic

Answer 19

early and later onset disease with severity range
associated with allergy
non-allergic variants

Question 20

Non-Th2 non-eosinophilic

Answer 20

obesity, smoking, neutrophilic

associated with more severe disease

Question 21

Asthma pathology

Answer 21

contracted smooth muscle, blood vessels infiltrated by immune cells, decreased lumen diameter, inflammation, swelling and excess mucus

Question 22

Airway inflammation

Answer 22

protection against invaders, recruitment of inflammatory cells, swelling, mucus secretion, airway constriction

Question 23

Bronchial hyperresponsiveness

Answer 23

hallmark of asthma
degree of this correlates with asthma severity
causes by inflammation
dynamic and reversible

Question 24

Acute asthma response

Answer 24

binding of allergen to membrane-bound IgE on mast cells

release of mediators and bronchoconstriction

Question 25

Late asthma response

Answer 25

~50% of patients

influx of inflammatory cells, mainly eosinophils leading to oedema and bronchoconstriction

Question 26

Airway remodelling

Answer 26

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

Question 27

Airway smooth muscle cells

Answer 27

hypertrophy and hyperplasia in response to growth factors released from inflammatory and epithelial cells leading to narrowing of the airway lumen
inflammatory mediators, irreversible fixed airflow obstruction

Question 28

Blood vessels in asthma

Answer 28

increased mucosal bloodflow
angiogenesis in response to growth factor VEGF
microvascular leakage from post-capillary venues - oedema and plasma exudation into lumen

Question 29

Mucus hyper secretion in asthma

Answer 29

hyperplasia of submucosal glands, increased epithelial goblet cells
mucus plugs occlude asthmatic airways

Question 30

Potent inducers of mucus hypersecretion

Answer 30

Il-13 and neutrophil elastase

Question 31

Fibrosis

Answer 31

aberrant repair to persistent epithelial injury

thickens basement membrane

Question 32

vascular remodelling with inner airway wall thickening

Answer 32

decreased baseline airway calibre and amplification of airway smooth muscle shortening

Question 33

Hypertrophy and hyperplasia of airway smooth muscle

Answer 33

increased smooth muscle strength and airway hyperresponsiveness

Question 34

Connective tissue deposition

Answer 34

increased airway smooth muscle constraint

Question 35

thickening and fibrosis of all layers

Answer 35

decreased airway distensibility and reduced effectiveness of bronchodilators

Question 36

hypertrophy and hyperplasia of mucus gland

Answer 36

decreased lumen calibre and amplification for airway smooth muscle shortening

Question 37

loss of alveolar attachments

Answer 37

predisposition closure and collapse

Question 38

Asthma treatments

Answer 38

usually controlled using inhaled corticosteroids and bronchodilators