Lecture 12

Question 1

What is asthma?

Answer 1

Chronic inflammatory disease of the airways.

Question 2

What are the symptoms of asthma?

Answer 2

Wheezing, cough, sputum production, cheese tightness and shortness of breath. Sometimes symptoms become worse during night.

Question 3

Describe variable episodic airflow obstruction in terms of asthma?

Answer 3

Asthma is reversible either spontaneously or with treatment.

Question 4

Describe facts about asthma?

Answer 4

1. Most common chronic disease in the world.
2. 1/6 adults and 1/4 children have asthma symptoms in NZ. With more than 600,000 kiwis having asthma.
3. Over 500,000 kiwis take asthma medication.
4. $800 million annual economic burden of asthma.
5. Most common cause of admission to hospital for children.
6. Hospitalisation rates have doubled in past 30yrs.
7. The higher-ranking disease in terms of Years Lost to Disability in males, 3rd for females.

Question 5

Describe the features of asthma?

Answer 5

Episodic - patients may have no symptoms period between each episodes of attack. And sometimes it depends on the season.
Chronic - persistent airflow obstruction.
Life-threatening - if not treated properly can cause death (slow-onset or fast-onset and fatal within 2 hours).

Question 6

How do you diagnose asthma?

Answer 6

1. Physical examination: Wheezing (high pitched whistling sounds).
2. History of any of the following:
   - Cough, recurrent wheeze.
   - Recurrent dyspnea.
   - Recurrent chest tightness.
   - Reversible airflow limitation and diurnal variation.
3. Lung function test: evidence of variable airflow obstruction.
4. Symptoms occur or worsen due to:
   - Exercise.
   - Viral infection.
   - Animals with fur or feathers.
   - House-dust mites.
   - Moulds, smoke, pollen.
   - Changes in weather.
   - Strong emotional expression (laughing or crying hard, beathing heavily).
   - Airborne chemicals or dust.
5. Other things:
   - Family history of asthma.
   - History of atopic disease: allergic rhinitis, urticaria or eczema.

Question 7

Describe an atypical presentation of asthma?

Answer 7

1. Dyspnea without wheezing.
2. Chronic cough.
3. Increased shortness of breath at nighttime.
4. Allergic rhinitis with wheezing.

Question 8

What are the laboratory studies for asthma?

Answer 8

1. Lung function tests.
2. Skin allergy test and serologic studies.
3. Radiographic studies.

Question 9

Describe lung function tests?

Answer 9

1. Peak expiratory flow (PEF).
2. Spirometery: FEV1 is a better measure for asthma. Can be used to distinguish between COPD and asthma, and not suitable to young patients.

Question 10

Describe FEV1 test?

Answer 10

In asthma FEV1/FVC is reduced. Use post-bronchodilator reversibility test. If in FEV1 it increases by more than 400ml then you can say it could be asthma.

Question 11

Describe blood tests in regards to diagnosing asthma?

Answer 11

1. Eosinophil count: >4% or 300-400/mm3 and if >800/mm3 then it suggests the presence of other disorders.
2. Increased Serum IgE level.

Question 12

Describe allergy tests in regards to asthma?

Answer 12

1. Tree, grass, weed and flower pollens.
2. Dust mites.
3. Mold and mold spores.
4. Animal dander.
5. Insect allegens.
6. Smoking.

Question 13

What are the current pathogenesis of asthma?

Answer 13

1. Allergy model.
2. Non-allergy models.
   Up to 90% of asthma could be due to allergies.

Question 14

Describe atopic asthma?

Answer 14

1. The most common type of asthma.
2. Usually begins in childhood, early-onset.
3. Triggered by environmental antigens.
4. A positive family history.
5. Often preceded by allergic rhinitis, urticaria or eczema.

Question 15

What are the cells identified in airway inflammation?

Answer 15

1. Eosinophils - late phase response to the allergen (cause chronic asthma).
2. Mast cells - aid in acute phase responses.
3. Macrophages - activate and release pro-inflammatory mediators.
4. T cells - central role in control of the inflammatory response especially in late phase response.
5. Neutrophils - resistance.
6. Basophils - last response to the allergen.
7. Dendritic cells - the presenting of allergen to the inflammatory cells.

Question 16

Describe the asthmatic airway?

Answer 16

Epithelia cells, smooth muscle cells and goblet cells all are changed.

Question 17

Describe the acute-phase response of asthma?

Answer 17

Inhalation of allergen causes an immediate fall in lung function (5-10minutes). Sometimes the functions can recover themselves. After 2 hours the lung function recovers.

Question 18

Describe the late-phase response of asthma?

Answer 18

Beginning about 4-6 hours after allergen challenge. Lasts for about 18-20 hours.

Question 19

Describe dual phase?

Answer 19

The lung function begins to drop and then exposed again the response happens again and lasts longer. FEV1 drops to about 30%, even worse than late-phase.

Question 20

Describe the mechanism of asthma?

Answer 20

Inhaled allergens, once inside the airway, either stick to the dendritic cells or activate the mast cells. Once mast cells are activated they will release histamine, cysteine leukotrienes and prostaglandin D which will cause bronchoconstriction (construction of bronchioles). The dendritic cells will release CCL22/17, which willa activate T-helper cells, which will release IL5 (activate eosinophils) or IL-13 which will activate B cell which will produce IgE which will then activate Mast cells and then bronchiole constriction.

Question 21

Describe asthma genetics?

Answer 21

1. the major eitology factors of allergic asthma are genetic predisposition to Th2 (T helper cells) rather than Th1.
2. Th cells: Helper T cells, T lymphocytes that belong to CD4+ subset.
3. Th1 cells: produce IFN-gamma, IL-2 and TNF-beta.
4. Th2 cells: secrete cytokines (e.g. IL-4, IL-5, IL-9, IL 13 etc).

Question 22

Describe Th2 cells pathway?

Answer 22

1. Causes type 1 hypersensitivity/atopy: such as eczema (atopic dermatitis), hay fever (allergic rhinitis), asthma.
2. Chronic airway inflammation.
3. Bronchial hyper responsiveness.

Question 23

Describe nonatopic asthma?

Answer 23

1. The majority of late-onset asthma are nonatopic.
2. It may be associated with respiratory tract infections, such as mycoplasma pneumoniae and chlamydia pneumoniae.
3. other risk factors: medications induced asthma (e.g.NSAIDs, beta blockers and aspirin).

Question 24

What are the key mediators in asthma: leukotrienes?

Answer 24

1. De novo synthesis of ams cells, eosinophils.
2. Very potent mediator (e.g. LTC4, LTb4) cause prolonged bronchocosntriction.
3. Increase mucus secretion and vascular permeability which generates oedema in the airway.
4. Leukotriene receptor antagonists (e.g. singular) is currently recommended as a second-line in the treatment of asthma.

Question 25

Describe prostanoids?

Answer 25

Potent bronchoconstrictors (PGD2, PGF2 and TxA2) that are produced by eosinophils and mast cells.

Question 26

Describe acetylcholine (ACh)?

Answer 26

1. Released from intrapulmonary motor nerves. 2. Causing smooth muscle constriction in airways. 3. Stimulating muscarinic receptors.

Question 27

Describe chemokine?

Answer 27

The function of chemokine is to recruit or chemotaxis of inflammatory cells. Chemokine receptor inhibitors for CCR3 and CCR4 and others are in development as potential therapy for asthma.

Question 28

Describe IgE in regards to Asthma?

Answer 28

Triggers the mast cell and causes airway inflammation. Humanised monoclonal antibody targeting IgE is developed for asthma therapy (Xolair).

Question 29

Describe Nitric Oxide in regards to asthma?

Answer 29

there are higher levels of NO in asthma. The production of NO reflects the level or severity of airway inflammation. Exhaled NO measurement has been used to monitor the extent of airway inflammation for asthma control.

Question 30

Describe Granule Proteins?

Answer 30

1. Mast cells, basophils, eosinophils, neutrophils, can release granule proteins. 2. Major basic protein (ECP). 3. Eosinophil cationic protein (ECP).

Question 31

Describe adhesion molecules in inflammation?

Answer 31

Integrates are the primary mediators of cell-extracellular matrix adhesion. Interns are important for trans-endothelial migration of inflammatory cells into the airways.