asthma Flashcards
What are the key features of asthma?
- wheeze (due to bronchial constriction) +/- dry cough 2. atopy/allergen sensitisation 3. reversible airway obstruction 4. airway inflammation (eosinophilia t2 lymphocytes)
Pathophysiology of asthma?
Normal airway has laminar flow but asthmatic airway has thickened walls and increased smooth muscle so narrow lumen causes turbulent flow (wheeze). In spirometry expiration scooped showing airway obstruction.
What is spirometry and why is it hard for young children?
Exhalation through mouth as fast and hard as possible. Require effort and coordination so hard for young children.
What is a local allergen challenge and what does it show in asthma?
Inject allergens directly into airway and see the occlusion and inflammation of the airway lumen.
What is the pathogenesis of asthma? What structural changes happen as a response?
Have susceptibility to asthma + allergen sensitisation. There is inflammation causing airway remodelling. Inflammatory cells (mostly eosinophils) reqruited to airway. Structural changes include 1. increased goblet cells in epithelium secreting mucus 2. amount of matrix increases 3. amount & size of smooth muscle cells increase. So thicker wall & inflammation
Genetic basis of asthma?
Genetic predisposition to asthma + exposure to allergens –> asthma
What are some genes increasingly expressed in asthma patients?
IL33 and GSDMB - mutligene & polyfactorial
What happens in asthma when exposed to allergen?
Allergen (Antigen) presented to APC (dendritic cells in lungs) and taken to mediastinal lymph nodes where naïve t cells differentiate into Th2 cells & secrete cytokines (IL-4,5,13)
What does IL-5 do in asthma?
IL-5 recruites esoinophils and prolongs their survival
What does IL-4 do in asthma?
IL-4 help b cells convert to IgE.
What does IL-13 do in asthma?
Aids mucus secretion
Once they are sensitised what happens when asthmatics are exposed to the same allergen again?
Allergic response. IgE binds to mast cells causing degranulation of mast cells releasing inflammatory cytokines and chemokines eg. Histamine, t2 mediators.
What are some tests for allergic sensitization? What do you see in each case?
- Skin prick test - intradermal injection of allergen + control - if allergic reaction wheel and flare - measure. 2. IgE antibodies against specific allergens (not total IgE) blood test.
During stable disease what eosinophil count is abnormal?
> 300 cells/mcl
What tests can be done for eosinophilia? What is recommended?
Can look in airway for eosinophil using sputum sample. Recommended exhaled nitric oxide
What is exhaled nitric oxide and what is it used for? What is it a marker of and what can it imply?
Exhaled nitric oxide is non-invasive biomarker of type 2 airway inflammation. Used for diagnosis & to see if adhering to ICS - if they arent it is very high
What tests needed for a NICE asthma diagnosis?
- clinical assesment - history & examination to confirm wheeze when unwell 2. objective tests 1. airway obstruction on spirometry FEV1/FVC ratio <0.7. 2. reversible airway obstruction - bronchodilator reversiblity >12%. 3. exhaled nitric oxide FeNO >35ppb children >40ppb in adults
How can you diagnose asthma in children/young people (age 5-16)? (2 ways)? How many tests are needed to confirm diagnosis?
- symptoms of asthma, FeNO levels >35ppb & positive peak flow variability 2. obstructive spirometry & positive bronchodilator reversibility. need at least 2 tests
What is management for asthma? What to do in severe asthma not responding to treatments?
- reduce eosinophilic inflammation (inhaled corticosteroids, leukotriene receptor antagonists for T2 inflammation) 2. acute symptomatic relief ( beta-2 agonists (smooth muscle relaxation) & anticholinergics) 3. if severe not responding to treatment - biologicals (anti-IgE antibodies, anti-IL5 antibody)
What do inhaled corticosteroids do in asthma?
- reduce eosinophil numbers via apoptosis 2. reduce T2 mediators released by th2 cells 3. reduce mast cell numbers 4. help remodelling
What are 3 things needed for good management?
- optimal device and technique 2. clear plan 3. adherence to IcS
How can you check if patients are adherent to their corticosteroids?
Electronic adherence monitoring on their inhaler
What is a regular preventor in asthma? What if they don’t respond to it?
Anti-inflammaotry treatment (eg. ICS, leukotriene receptor antagonist) . If don’t respond specialist
What can happen if asthmatics don’t take their maintenance therapy?
Acute attack can lead to death
What is the pathogenesis of an acute lung attack?
Background allergen exposure + infection and other factors. If infection have reduced antiviral responses and IFN. Background airway obstruction increases - may not be completely reversible with increased eosinophilia
How do we treat acute asthma attacks?
High dose steroids - eg. Prednisolone
What does anti-IgE antibody therapy do? When is it used?
Used when unresponsible to IcS. Binds IgE to prevent degranulation of mast cells and mediators released. Can decrease IgE production over time
What is omalizumab? When is it used?
Anti-IgE antibody used in severe persistent IgE mediated asthma in those 6 and over Who need frequent steroids (4 or more courses in previous year). Document compliance
What is mepolizumab? What does it do? When is it used
Anti-IL5 antibody. For severe eosinophilic asthma. Adults & kids above 6. blood eosinophils 300 or more in last 12 months . At least 4 exacerbations requiring oral steroids in last 12 months. Trial for 12 months - 50% reduction in attacks - continue
