Cardio - Asthma + Resp Immunology Flashcards
What is the epidemiology of asthma in the UK?
→ 5.4 mil suffer from it
→ 1.1 mil are children
→ 3 per day die of asthma attack
What are the cardinal features of asthma?
→ Wheeze
→ Dry cough ( on exertion, worse w colds and allergen exposure)
→ Atopy / Allergen Sensitisation
→ Reversible airflow obstruction
→ Airway inflammation (with eosinophilia or lymphocytic Type2)
What are the airways like in someone with asthma?
→ In asthmatic airways:
→ Thickened walls due to eosinophilic inflammation
→ Relaxed smooth muscle
What happens to the airways during an asthma attack?
→ Tightened smooth muscle
→ Walls further thickened and inflamed
→ Air trapped in alveoli
How is reversible airflow obstruction proven?
→ BDR test (bronchodilator reversibility test)
→ administer bronchodilator and check
→ Change is seen between the flow volume loop before + after
What is the pathogenesis of allergic asthma?
→ allergens (e.g. pollen, dust mites, mold) irritate the bronchial epithelium
→ inflammation occurs + airway remodelling starts
What does airway remodelling in asthma consist of?
→ higher recruitment of inflammatory cells (especially eosinophils)
→ increase in goblet cells for increased mucus production
→ increase in matrix + amount and size of smooth airway muscle
→ creates a thicker airway wall
Why do only some people who are sensitised to allergens develop asthma?
→ genetic susceptibility to allergies and allergic diseases
→ environmental exposures except for allergens (e.g. infection, pollution)
What have GWA studies for asthma shown?
→ polygenic causes (ILL33, GSDMB)
→ multi-factorial regardless of genetics
→ gene therapy is not really a cure but can help with novel therapies
What are the cascade of reactions in Type 2 immunity is asthma?
→ allergen / antigen triggers dendritic cells int he lungs to become APCs with MHC class II → these recruit Th0 cells that differentiate into Th1 and Th2 → Th2 cells release IL-4, IL-5, IL-13
What are the different interleukins responsible for in the Type 2 immune response?
→ IL-4 helps convert plasma cells (B-cells) + encourages production of IgE
→ IL-5 recruits eosinophils + promotes their survival
→ IL-13 involved in mucus secretion
How do clinics test for asthma allergy sensitisation?
→ allergy skin tests (wheel + flare)
→ blood tests for specific IgE antibodies to allergens of interest
→ total IgE alone however is not sufficient to define atopy
How do asthma clinics test for eosinophilia?
→ blood eosinophil count ( >300 cells/mcl is abnormal)
→ induced sputum eosinophil count ( >2.5% eosinophils is abnormal)
→ exhaled nitric oxide breath test
How is exhaled nitric oxide used for diagnosis of asthma?
→ fractional conc. of exhaled FeNO is quantitative + non-invasive
→ measures airway inflammation
→ indirect marker of T2-high eosinophilic airway inflammation in asthma
How is exhaled nitric oxide used to test for adherence to medication for asthmatic patients?
conc. of exhaled FeNO should decrease if patient is adhering to steroids (very sensitive to steroids)