Lecture 13: Asthma

Question 1

Give an overview of asthma:

Answer 1

Very heterogenous disease therefore different outcomes for different people.

Question 2

What is the most common symptom of asthma?

Answer 2

Wheeze is most common symptom (very common for many conditions)

Question 3

Write some notes on asthma epidemiology;

Answer 3

Huge problem globally, big problem in NZ

Question 4

Are there disparities of asthma in NZ?

Answer 4

Ethnic and sex disparities in asthma prevalence in NZ

• Children more than adults
• Maori more than european

Question 5

What is the definition of asthma?

Answer 5

Characterised by chronic airway inflammation. It is defined by the history of respiratory symptoms i.e a wheeze, chest tightness, cough that varies with time and intensity together with variable expiratory airflow limitation.

Question 6

What are the key asthma features?

Answer 6

• Chronic airway inflammation
• Variable symptoms of airway obstruction

Use a scale for diagnosis to determine likelihood of asthma diagnosis. (Diagnosis approach is different for adults and children)

Question 7

In asthma diagnosis what can be done on first presentation?

Answer 7

First presentation

1) History taking
2) Physical examination
3) Spirometry
4) Additional lab tests (eosinophils, FeNO, allergy)
5) Radiological investigation to exclude alternative diagnosis

Question 8

Whats important in history taking for asthma?

Answer 8

1. Asthma symptoms: Wheezing, coughing, shortness of breath, chest tightness
2. Symptom variation, time, intensity, triggers
3. Family history of asthma / allergies
4. Other allergic diseases, esp. in children i.e eczema, allergic rhinitis

Term wheeze is not present in every language or culture

Question 9

Whats of note for physical examination of asthma?

Answer 9

1. Expiratory wheeze on the auscultation (might be absent during remission)
2. Possibly Nasal polyps
3. Possible multiple symptoms

Question 10

Whats difficult about spirometry?

Answer 10

• Children under 5 cant
• Older children its possible with highly skilled technician
• Reference values for normal lung functions vary based on ethnicity, age, sex

Question 11

How is the reversibility of airflow limited?

Answer 11

After administration of bronchodilators:

• An increase in FEV1 >12% and >200mL from baseline
• If provocative test is used - 20% drop in FEV1

Question 12

What are some additional investigational tests?

Answer 12

1. Blood eosinophils (Not all patients would have elevated eosinophils)
2. Allergy test - Skin prick test, specific IgE
3. Provocative tests with methacholine, histamine, or exercises can also be used to assess variability of airflow limitation

Question 13

What are the three groups of risk factors for asthma?

Answer 13

1. Risk of asthma incidence (newly developed asthma)
2. Risk of asthma exacerbation (Triggers)
3. Risk of asthma hospitalisations (Prognosis)

Question 14

What are some triggers for asthma exacerbation?

Answer 14

Inflam factors

• Allergens
• Resp. infection

Irritants

• Exercise
• Cold air
• Temp changes

Others

• Tobacco
• Medication

Question 15

What are the two types of asthma from a signalling perspective?

Answer 15

T2 High asthma

• Allergic asthma
• Non-allergic T2 Asthma

Non-T2-Type Asthma

Question 16

Describe the signalling mechanism of T2 High allergic asthma

Answer 16

1) Allergen contacts Epi (dysf alreadY0
2) Causes release of intracellular TSLP, IL33, IL25 signalling molecules
3) Activates dendritic cells (these have processes extending to epi) which then sample allergen
4) DC presents allergen to T cells
5) These activated T Helper cells which in turn can activate (via IL in specific IL4)
- Epi defences
- Eosinophil cells
- Smooth muscle
- B cells to produce IgE (Not IgG)

Mast cells can also contribute to the T helper activation

Check updated slides

Question 17

Describe non-allergic T2 asthma:

Answer 17

Virus, pollutants, tobaco smoke can stimulate epithelium to release IL which activates ILC2 (not T cells) these in turn activate

• SM
• Eosinophils
• Goblet cells

Question 18

Is asthma a single disease?

Answer 18

No, asthma is no longer considered a single disease but an umbrella of diseases with different underlying molecular pathology and clinical course

Question 19

Describe asthma phenotypes and endotypes

Answer 19

Asthma phenotypes: Age of onset, exercise induced, obesity induced etc define this

Asthma endotypes: Usually represent the molecular pathways: This is an active area of research

Question 20

What are some treatments for the chronic airway inflammation?

Answer 20

• Inhaled corticosteroids

- Biologics

Question 21

What are some treatments for the variable symptoms of airway obstruction?

Answer 21

• Short or long acting beta agonists
• Luekotriene modifiers
• Muscarine receptor antagonists

Question 22

What are some potential drug targets in the molecular pathway of asthma?

Answer 22

• Target smooth muscle to dilate or prevent constriction
• Inhibit epi signalling of inflam
• Inhibit DC presentation
• Inhibit eosinophil activation
• Inhibit mast cell activation
• Inhibit T cells
• Inhibit B cells