Lecture 13: Asthma Flashcards
Give an overview of asthma:
Very heterogenous disease therefore different outcomes for different people.
What is the most common symptom of asthma?
Wheeze is most common symptom (very common for many conditions)
Write some notes on asthma epidemiology;
Huge problem globally, big problem in NZ
Are there disparities of asthma in NZ?
Ethnic and sex disparities in asthma prevalence in NZ
- Children more than adults
- Maori more than european
What is the definition of asthma?
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.
What are the key asthma features?
- 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)
In asthma diagnosis what can be done on first presentation?
First presentation
1) History taking
2) Physical examination
3) Spirometry
4) Additional lab tests (eosinophils, FeNO, allergy)
5) Radiological investigation to exclude alternative diagnosis
Whats important in history taking for asthma?
- Asthma symptoms: Wheezing, coughing, shortness of breath, chest tightness
- Symptom variation, time, intensity, triggers
- Family history of asthma / allergies
- Other allergic diseases, esp. in children i.e eczema, allergic rhinitis
Term wheeze is not present in every language or culture
Whats of note for physical examination of asthma?
- Expiratory wheeze on the auscultation (might be absent during remission)
- Possibly Nasal polyps
- Possible multiple symptoms
Whats difficult about spirometry?
- Children under 5 cant
- Older children its possible with highly skilled technician
- Reference values for normal lung functions vary based on ethnicity, age, sex
How is the reversibility of airflow limited?
After administration of bronchodilators:
- An increase in FEV1 >12% and >200mL from baseline
- If provocative test is used - 20% drop in FEV1
What are some additional investigational tests?
- Blood eosinophils (Not all patients would have elevated eosinophils)
- Allergy test - Skin prick test, specific IgE
- Provocative tests with methacholine, histamine, or exercises can also be used to assess variability of airflow limitation
What are the three groups of risk factors for asthma?
- Risk of asthma incidence (newly developed asthma)
- Risk of asthma exacerbation (Triggers)
- Risk of asthma hospitalisations (Prognosis)
What are some triggers for asthma exacerbation?
Inflam factors
- Allergens
- Resp. infection
Irritants
- Exercise
- Cold air
- Temp changes
Others
- Tobacco
- Medication
What are the two types of asthma from a signalling perspective?
T2 High asthma
- Allergic asthma
- Non-allergic T2 Asthma
Non-T2-Type Asthma
Describe the signalling mechanism of T2 High allergic asthma
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
Describe non-allergic T2 asthma:
Virus, pollutants, tobaco smoke can stimulate epithelium to release IL which activates ILC2 (not T cells) these in turn activate
- SM
- Eosinophils
- Goblet cells
Is asthma a single disease?
No, asthma is no longer considered a single disease but an umbrella of diseases with different underlying molecular pathology and clinical course
Describe asthma phenotypes and endotypes
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
What are some treatments for the chronic airway inflammation?
- Inhaled corticosteroids
- Biologics
What are some treatments for the variable symptoms of airway obstruction?
- Short or long acting beta agonists
- Luekotriene modifiers
- Muscarine receptor antagonists
What are some potential drug targets in the molecular pathway of asthma?
- 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
