Asthma and respiratory immunology Flashcards
What are the cardinal features of asthma? (3)
-Atopy / allergen sensitisation
-Reversible airflow obstruction
-Airway inflammation
Eosinophilia
Type 2 - lymphocytes
What type of immune cells do you see infiltrating asthmatic airways?
Eosinophils
Describe the pathogenesis of allergic asthma
-An allergen gets introduced into the airway bronchial epithelium which sensitizes it causing, inflammation and remodeling.
-Recruitment of inflammatory cells (mostly eosinophils) leads to increase in mucous secreting goblet cells.
-Amount of MATRIX and MUSCLE CELL SIZE then increase.
Why are only some people who are sensitised develop the disease of asthma?
Due to genetic susceptibility to asthma
Circled genes are more expressed in asthma patients
- What does this show about the genetic cause of asthma?
That it’s a multigene disorder and is polyfactorial
What does MHC stand for and what is MHC class II and its function
Major histocompatibility complex:
-It is present on the surface of certain immune cells, such as dendritic cells, B cells, and macrophages
-Presents antigens to T helper cells
How does type 2 immunity reaction come about in allergic asthma? (3 STEPS)
- Patients with asthma have exposure to inhaled allergen
- This allergen binds to lung dendritic cells and are carried via MHC class II to mediastinal lymph nodes
- Naive T cells in nodes differentiate into Th2 cell which secretes IL4, 5 and 13
What does IL-4 do?
Helps conversion of B plasma cells to secrete IgE
What does IL-5 do?
IL-5 recruits eosinophils into airways and promotes their survival- causing eosinophilia
What does IL-13 do?
Involved in mucous production
If a patient is already sensitised to allergen- what happens if they’re exposed to it again?
- There’s an allergic immune response
- IgE recognises circulating antigen and binds to mast cells
- Mast cells degranulate and release histamines, cytokines, chemokines, growth factors, enzymes, eicosanoids
How do we test for allergic sensitisation? (2) (what reaction to we look for)
-Blood tests for specific IgE antibodies
-Allergy skin prick tests, look for WHEAL AND FLARE REACTION.
How do we test for eosinophilia? (3)
- Blood eosinophil count when stable → ≥300 cells/mcl is abnormal
- Induced sputum eosinophil count: ≥2.5% eosinophils is abnormal
- Exhaled nitric oxide
What objective tests are done to diagnose asthma? (3)
- Airway obstruction on spirometry- FEV1/FVC ratio <0.7
- Reversible airway obstruction- bronchodilator reversibility ≥12%
- Exhaled NO (FeNO) >35ppb (children), >40ppb (adults)
What are the 3 areas of asthma management?
-Reduce airway eosinophilic inflammation
-Acute symptomatic relief
-Treat severe asthma
How do we reduce airway eosinophilic inflammation?
- Inhaled corticosteroids- target and reduce eosinophilic inflammation
- Leukotriene receptor antagonists- can reduce type 2 inflammation
How do we give acute symptomatic relief?
- Beta-2 agonists (smooth muscle relaxation)
- Anticholinergic therapies (smooth muscle relaxation)
How do we treat severe asthma?
Steroid sparing therapies
- Biologics targeted to IgE e.g. anti-IgE antibody
- Biologics targeted to airway eosinophils e.g. anti-interleukin-5 antibody and anti-interleukin-5 receptor antibody
Why do we use corticosteroids? (what things do they do?) (2)
- Reduce eosinophil numbers through apoptosis
- Reduce mast cell numbers
How do we measure adherence objectively?
Electronic adherence monitoring
What is the order of treatment for asthma patients?
How do we treat acute asthma attacks?
- With systemic high dose steroids like prednisolone
- Inhaled steroids in maintenance therapy isn’t good enough
How does anti-IgE antibody therapy work?
- Binds and captures circulating IgE- prevents its interaction with mast cells and basophils to stop allergic cascade
- IgE production can decrease with time when patients given anti-IgE Ab
What is Omalizumab?
- The commonly used anti-IgE antibody given as subcutaneous injections
- Is very expensive
- Is effective at reducing exacerbations compared to placebo
