Asthma and Respiratory Immunology Flashcards
What are the cardinal features of asthma?
- wheeze (on exertion, worse with colds and allergen exposures)
- (possible) dry cough and dyspnoea
- Atopy/allergen sensitisations
- reversible airflow obstruction
- airway inflammation (Eosinophilia and T2-Lymphocytes, CD4+ cells)
What does an untreated asthma airway look like?
- abnormal even at baseline
- thickened wall caused by inflammation
- increase in airway smooth muscle
- reduced lumen causes turbulent airflow, leading to wheeze
How is a reversible airflow obstruction diagnosed?
- lung function test (spirometry)
- flow volume loop with scooped black line (red is normal)
- changes to normal with treatment
What must be tested in the diagnosis of asthma?
- evidence of inflammation, eosinophilia (biopsy)
What causes asthma?
- suspetibility to asthma
- exposure and sensitisation to pathogens
- inflammation and airway remodelling (changes in the structure)
- changes in epithelium (increased goblet cells)
- increased matrix
- increased size and number of smooth muscle cells
Why do only some people that are sensitized develop disease?
need the underlying genetic susceptibly to develop it.
What genes have been consistently shown to cause an increased susceptibility to asthma?
- IL33
- GSDMB
Is one gene enough to cause a susceptibility to asthma?
no - multifactorial cause
Why is type II immunity important in allergic asthma?
determines the tests done
What is the pathway of an antigen causing eosinophilic airway inflammation?
- antigen presented to antigen presenting cell (MHC class II)
- MHCII activates Th0
- Th0 differentiates into Th1 and Th2
- TH2 releases IL-4, IL-5 and IL-13
- interleukins cause eosinophilic airway inflammation
What does IL-5 do?
recruitment and survival of eosinophils
What does IL-4 do?
conversion of B cells to secrete IgE
What does IL-13 do?
involved in mucus secretion
What happens when a patient is sensitised to an allergen and is the exposed to allergen again?
- build an allergic immune response
- IgE binds to mast cells that release growth factors, cytokines, histamines and chemokines
- causing the allergic reactions
How do you test for allergic sensitization?
- skin prink tests
- blood tests
What happens in a skin prick test?
- intradermal injection of a positive control and compare to the allergen.
- measure the size of the swelling caused by the allergic reaction
What tested in the blood tests for allergic sensitisation?
- IgE antibodies to allergens of interest
- total IgE alone is not sufficient to define atopy
What tests are done for eosinophilia?
- blood test (when stable)
- induced sputum test
- exhaled nitric oxide.
What blood eosinophil count (when stable) is indicative of asthma?
> 300 cells/mcl is abnormal
What induced sputum eosinophil count is abnormal?
> /= 3%
What is exhaled nitric oxide?
a non-invasive biomarker of airway (type-2) eosinophilic inflammation
How is exhaled nitric oxide used to diagnosis asthma?
Fractional concentration of exhaled nitric oxide
- quantitative
- non-invasive
- safe
- indirect marker of T2-high eosinophilic airway inflammation in asthma
When should exhaled nitric oxide not be used in the diagnosis of asthma?
when steroids have been use
What can exhaled nitric oxide also do?
- prediction of steroid responsiveness
- assessing adherence to inhaled corticosteroids
What is needed to confirm eosinophilic inflammation?
- symptoms
- lung function test
- blood/airways eosinophils
- exhaled nitric oxide