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)
What are the disadvantages of FeNO?
a single non-invasive biomarker does not reflect airway eosinophilic inflammation
What clinical assessments need to be done for asthma according to the NICE guidelines?
→ history + examination
→ assess/ confirm wheeze when acutely unwell
What are the order of diagnostic tests that need to be done for asthma according to the NICE guidelines?
→ airway obstruction through spirometry
→ BDR test is spirometry shows obstruction
→ if diagnostics are still uncertain, do FeNO
→ if diagnostics are still uncertain, do peak flow variability
How are children tested for asthma if they’re unable to perform objective tests?
→ treat based on observation + clinical judgement
→ try doing tests agains every 6 months
What test results are needed for a diagnosis of asthma objectively?
→ airway obstruction on spirometry (FEV1/FVC ratio < 0.7)
→ reversible airway obstruction - (BDR > 12%)
→ exhaled nitric oxide > 35 ppb in children or 40 ppb in adults
What test results are needed for a diagnosis of asthma objectively in children and young people (5-16 yrs)?
→ FeNO level of 35 ppb or more + positive peak flow variability OR
→ obstructive spirometry + positive BDR
What are the 3 main aspects of asthma management?
→ reduce airway eosinophilic inflammation
→ acute symptomatic relief
→ severe asthma prevention
How is airway eosinophilic inflammation reduced?
→ inhaled corticosteroids (ICS)
→ leukotriene receptor agonists
How is acute symptomatic relief given to asthmatic patients?
→ beta-2-agonists (smooth muscle relaxation)
→ anticholinergic therapies (smooth muscle relaxation)
What are some steroid sparing therapies? (Biological)
→ Anti-IgE antibodies (biological targeting of IgE)
→ Anti-IL-5 antibodies or Anti-IL-5 receptor antibodies (biological targeting of airway eosinophils)
What is the mechanism of action of corticosteroids on inflammatory cells?
→ reduces no. of eosinophils through apoptosis
→ reduces T-lymphocyte cytokine production
→ reduces no. of mast cells
→ reduces macrophage cytokine production
→ reduces no. of dendritic cells
What is the mechanism of action of corticosteroids on structural cells?
→ reduces no. of cytokines + mediators produced by epithelial cells
→ reduces leakage from endothelial cells
→ increases beta-2 receptors but reduces cytokines from airway smooth muscle
→ reduces mucus secretion from mucus glands
What is the most important factor in asthma management?
adherence to inhaled corticosteroids
What is the regular starting treatment for asthma?
low dose ICS (inhaled corticosteroid)
What is the initial add-on therapy for asthma?
addition of LABA to low-dose ICS (fixed dose or MART)
What are additional controller therapies?
→ increasing ICS to medium dose OR
→ adding LTRA
→ if no response to LABA, scrap it
When are biological therapies offered to asthmatic patients?
→ when they don’t respond to baseline steroids
→ when they have severe asthma
What is the pathogenesis of an acute lung attack?
→ reduced anti-viral responses (due to infection) + increased viral replication = prolonged illness
→ reduced peak expiratory flow rate + increased airway obstruction resulting in acute wheeze, responsive to bronchodilators
→ increased airway eosinophilic inflammation, responsive corticosteroids
What can trigger an asthma attack?
accumulation of: → allergens → pathogens (viral/bacterial) → pollution → tobacco smoke
What is anti-IgE antibody therapy?
→ humanised anti-IgE MAB
→ binds + captures circulating IgE
→ prevents interaction with mast cells + basophils to stop allergic cascade
→ IgE production decreases over time
What is the anti-IgE antibody therapy commonly prescribed in the UK?
omalizumab
What is the criteria for anti-IgE antibody therapy?
→ severe, persistant allergic IgE mediated asthma in patients >6 years who need continuous or frequent treatment w oral corticosteroids → optimised standard therapy → documented compliance → total serum IgE between 30-1500 → dosing based on weight and serum IgE
What are the advantages + disadvantages to anti-IgE antibody therapies?
→ definite reduction in exacerbations
→ very expensive
→ many people don’t fit into the criteria for it
When is anti-IL5-antibody therapy prescribed?
→ for severe eosinophilic asthma
→ licensed for adults + children over 6
→ blood eosinophils > 300 cells/mcl in the last 12 months
→ a least 4 exacerbations requiring oral steroids in the last 12 months
