PH2113 - Asthma

Question 1

What is asthma caused by?

Answer 1

Lung inflammation

Question 2

What are the steps in asthma development?

Answer 2

• sensitisation
• exposure
• inflammatory response
• bronchoconstriction (asthma attack)

Question 3

Describe the airways during an asthma attack

Answer 3

During an asthma attack, the airway is constricted due to smooth muscle contracting

Question 4

What is resistance to air flow proportional to?

Answer 4

1 / airway radius^4

Question 5

What is mucus plugging?

Answer 5

Airways completely blocked by mucus

Question 6

What causes a decreased airway diameter?

Answer 6

Airway smooth muscle contraction + increased mucus production

Question 7

What does airway resistance affect?

Answer 7

Airflow

Question 8

What determines airflow?

Answer 8

Respiratory drive

- metabolism

Question 9

How is airflow measured?

Answer 9

Spirometry

• peak flow
• FEV1 - the amount of air you can force from your lungs in one second

Question 10

What generates the pressure gradient in the lungs?

Answer 10

At rest - diaphragm

During exercise - diaphragm, internal and external intercostals

Question 11

What is resistance to airflow determined by?

Answer 11

Airway diameter

Question 12

What is peak flow?

Answer 12

Maximum rate of exhalation

Question 13

What is FEV1?

Answer 13

Volume of air that can be forcibly exhaled in 1 second

Question 14

What is the function of a reliever inhaler?

Answer 14

• cause bronchodilation (relieve acute asthma symptoms)

- no anti-inflammatory action (does not affect disease progression)

Question 15

What is the function of a preventer inhaler?

Answer 15

• do not cause bronchodilation (no acute relief from symptoms)
• anti-inflammatory action (limits disease progression)

Question 16

Which class of drugs are primarily in preventer inhalers?

Answer 16

Corticosteroids

• beclametasone
• fluticasone

Question 17

What is a combi-inhaler?

Answer 17

• contains both preventer (steroid) and reliever (long acting beta-agonist)
• provides long-term bronchodilation and prophylaxis

Question 18

How many people in the UK have asthma?

Answer 18

5.4 million people

Question 19

What proportion of households are affected by asthma?

Answer 19

1/5

Question 20

How many people die each day from asthma?

Answer 20

3 people a day die from asthma

Question 21

What percentage of asthma hospital admissions are avoidable?

Answer 21

75%

Question 22

What percentage of asthma deaths are preventable?

Answer 22

90%

Question 23

Why are asthma statistics so bad?

Answer 23

Poor asthma control
- increase rates of morbidity and mortality
Asthma is controlled by preventers (corticosteroids)
- corticosteroids are not effective? (steroid resistance)
- patients do not take their medication (poor adherence)
- as low as 50%
- confuse anabolic steroids and corticosteroids
- patients do not take their medication correctly (poor inhaler technique)
- needs to go to the bottom of the lung

Question 24

What type of hypersensitivity reaction is asthma?

Answer 24

Type 1

Question 25

What are the two main types of asthma phenotype?

Answer 25

Extrinsic - allergen induced Intrinsic - non-allergen induced

Question 26

Give examples of extrinsic asthma triggers

Answer 26

- pollen - house dust mite - mould - ragweed

Question 27

Give examples of intrinsic asthma triggers

Answer 27

- viral infection - cold, dry air - environmental pollution - aspirin - cigarette smoke - exercise

Question 28

What are the two phases of an asthma attack?

Answer 28

- early phase | - late phase

Question 29

What happens in the early phase of an asthma attack?

Answer 29

Immediate response to release of inflammatory mediators from mast cells

Question 30

What happens in the late phase of an asthma attack?

Answer 30

Continuation of inflammation characterised by an influx of eosinophils into the lungs

Question 31

What is hyperresponsiveness?

Answer 31

Increased response of the target cells (receptors)

Question 32

How does asthma sensitisation take place?

Answer 32

``` An allergen (foreign protein) triggers a dendritic cell (resident in the lungs) which migrates into the lymph nodes The dendritic cell presents the antigen to the Th0 helper lymphocytes which differentiate into Th2 lymphocytes This activates B cells which generates IgE antibodies ``` Upon re-exposure, the IgE receptors on mast cells in the lungs bind the IgE which starts the inflammation process

Question 33

What happens to mast cells when they are activated by an allergen binding to IgE?

Answer 33

Degranulation | - release of histamine and other mediators

Question 34

Describe the process of sensitisation

Answer 34

- allergen is recognised as foreign by dendritic cell - dendritic cells migrate to lymph nodes where they display the allergen to undifferentiated population of T cells - This then causes the T cells to differentiate into TH2 lymphocytes which then activate B cells. - B cells generate IgE immunoglobulins - IgE then binds to high affinity receptors on mast cells - preexposure of the allergen causes cross linking between multiple IgE binded to the mast cell which triggers mast cell degranulation

Question 35

What are the outcomes of the inflammatory cascade?

Answer 35

- bronchoconstriction - vasodilation - increased mucus production - increased vascular permeability - leukocyte recruitment

Question 36

What are the late phase responses of an asthma attack?

Answer 36

Continuation of the inflammatory response - oedema begun during early phase is more prominent - sensory nerve fibres release inflammatory agents that can cause bronchoconstriction - increased parasympathetic activation ACh and M3 receptors which cause bronchoconstriction

Question 37

What causes and drives asthma progression?

Answer 37

Inflammation

Question 38

What is airway remodelling?

Answer 38

Airway remodelling is an ongoing structural change caused by asthma that leads to thickened airway walls and the narrowing of the airway ``` Driven by chronic inflammation Generally makes airway thicker - reducing diameter of airway - increased obstruction of airway - increased resistance to airflow Lung less stretch - reduced capacity of lung - reduced elastic rebound when exhaling Chronic inflammation - more mucus from goblet cells Pulmonary angiogenesis - new blood vessels Smooth muscle hypertropy ```