Asthma and Respiratory Immunology Flashcards
What are the main features of asthma?
Wheeze Bronchoconstriction Dry cough Sensitisation by allergens Reversible airflow obstruction Airway inflammation
What cells cause inflammation in asthma?
Eosinophils mainly
Type 2 lymphocytes
How do genes play a part in asthma?
There must be underlying genetic susceptibility- a lot of people are allergic but won’t develop asthma unless they have genetic susceptibility
Describe the basic pathophysiology of asthma
There is bronchoconstriction due to increased airway smooth muscle and allergen sensitisation, this causes a wheeze and narrowing of the lumen, which results in turbulent flow
How do we test for reversible flow obstruction?
Do spirometry
How will a flow volume loop of an asthmatic look different?
There right side of the peak in the positive axis will be more scooped
What is airway remodelling?
Change in the structural cells in the airway
What type of cells will the epithelium make more of in asthma?
Goblet cells
Smooth muscle cells
Matrix cells
What type of immunity is present in those with asthma?
Type 2
Describe an asthma flare up pathway starting at the asthmatic being exposed to an allergen
An antigen presenting cell takes up the antigen on the allergen
The APC displays the antigen on their MCH II
They carry this to the lymph nodes
Naive T0 cells in the nodes differentiate into Th2 cells
Th2 cells make IL 4, 13, 5
Interleukins recruit eosinophils to the airway and promote their survival
IL 13 is involved with causing IgE release from eosinophils
On second exposure to the allergen, IgE binds to mast cells
Mast cells release cytokines and chemokines
Eventually histamine is released and this is what causes an attack
What do APCs cause in lymph nodes in those with asthma?
The differentiation of naive t0 cells into th2 cells
In asthmatics what do th2 cells make?
IL 4, 13, 5
What recruits eosinophils to airways in asthma?
Interleukins produced by th2 cells
Which interleukin is involved in IgE release?
IL 13
What 2 tests can be done for asthma?
Skin prick
Blood tests
How do skin prick tests work?
Intradermal injection of positive control (histamine) is given
This is compared to other allergens in question
How do blood tests work in terms of asthma diagnosis?
It is possible to screen for IgE however screening for total doesn’t tell you anything you have to screen for specific allergens and their antibodies
What are the 3 ways to test for eosinophilia?
Blood eosinophils
Sputum sample analysis
Exhaled nitric oxide
What does exhaled nitric oxide indicate for asthmatics?
It is a non invasive biomarker of type 2 airway inflammation
What are the 3 objective tests that can lead to a diagnosis of asthma according to asthma guidlines?
Airway obstruction on spirometry
Reversible airway obstruction
Exhaled nitric oxide
A least 2 tests are needed to confirm a diagnosis
What test can be used to see if someone is taking their asthma medication? Why?
Exhaled nitric oxide
It is very sensitive to steroids so if someone is taking their medication it cannot be sky high
When managing asthma, what is given to reduce airway eosinophilic inflammation?
Inhaled corticosteroids
Leukotriene receptor antagonists
When managing asthma, what is given for acute symptomatic relief? Describe how they work
Beta 2 agonists for smooth muscle relaxation
Anticholinergic therapies for smooth muscle relaxation
What must be given with anti inflammatory medication in asthmatics and why?
Bronchodilators or there could be asthma death
What therapy is given for severe asthma?
Steroid sparing therapies eg biologics targeted to IgE or targeted to airway eosinophils
How do corticosteroids work?
They reduce numbers of eosinophils by causing apoptosis
They reduce type 2 mediators released by Th2 cells
Reduce mast cell numbers
Overall reduce type 2 inflammation
How may adherence to inhaled corticosteroids be monitored?
Via electronic device fitted to the inhaler
What happens in an acute asthma attack
There is background sensitisation to allergens
There are also other contributing factors eg pathogen (virus), bad day of pollution
If an infection is the predominant precipitant then theres reduced antiviral response
Interferon production is reduced, viral replication increases and infection is prolonged
Background airway obstruction is significantly exacerbated
Eosinophilia in the airways is much worse
How are acute asthma attacks treated?
Systemic high dose steroids (usually given with prednisolone)
How does anti IgE antibody therapy work?
Humanised anti IgE monoclonal antibody is given its captures and binds circulating IgE so it doesnt interact with mast cells and basophils so allergic cascade doesnt occour
What is the name of the main anti IgE antibody therapy?
Omalizumab
When can omalizumab be given?
In severe persistant allergic asthma in patients over 6 years of age, they must need frequent oral corticosteroid treatment and must have good adherence to their standard therapy
How is omalizumab given?
Subcutaneous injection 2-4 weekly
How does anti IL5 antibody work?
IL5 results in eosinophil recruitment and prolonged eosinophil survival so blocking it prevents this
What is the name of the anti IL 5 antibody?
Mepolizumab
When is mepolizumab used?
For those with severe eosinophilic asthma
Who can mepolizumab be given to?
Those over the age of 6, blood eosinophils are in the required range, there have been at least 3 exacerbations requiring oral corticosteroids in the past year
