Asthma and Respiratory Immunology Flashcards
what are the cardinal features of asthma?
- Wheeze +/- dry cough- on exertion, worse with colds, with allergen exposure- most important
what are the tests for asthma?
- Atopy/ allergen sensitisation
- Reversible airway obstruction
- Airway inflammation
- Eosinophilia
- Type 2- lymphocytes
what is the pathophysiology of asthma?
- Reversible airway obstruction
- Thickened airway due to increased smooth muscle and inflammation
Wheeze due to narrow airway causing turbulent airflow
what can be used to determine airway flow?
spirometry
red- mornal, black= asthma
asthmatics can change from black to red with treatment
what is the pathogenesis of allergic asthma?
asthma requires genetic susceptibility to develop allergic disease rather than an allergy
If have the susceptibility when exposed to allergen/infection/pollution causes allergy, reversible airflow obstruction and inflammation
Genome studies have shown there are specific genes increased in the expression of asthma (GSDMB and IL33)
- Polygenic disease so gene therapy not a solution for asthma
what immune respone is generated in allergic asthma?
Type 2 immunity in allergic asthma:
- Exposed to inhaled allergy (antigen)
- Presented to APC- dendritic cells in lungs
- Carry antigen via MCHII to mediastinal lymph nodes where naive Th0 cells differentiate into Th1 and Th2 cells
- Th2 cells secrete cytokines IL4,5 and 13
- IL-5 recruits eosinophils into airways and promotes eosinophil survival
- IL-4 helps conversion plasma cells or B-cells to secrete an IgE
- IL-3 is involved in mucus secretion
- When exposed to same allergen again will recognise and produce allergic response
how can you test for allergic sensitisation?
- Intradermal injection of positive control (histamine) and saline (negative control) and compare to allergens
- Will develop a wheal and flare reaction and measure size of wheal to determine whether sensitized
- Can look in blood for specific IgE antibodies to allergens of interest
- Total IgE alone not sufficient to define atopy
how can you test for eosinophilia?
- Blood eosinophilia count when stable
- >300 cells/mcl is abnormal
- Induced sputum eosinophilia count
- >2.5% eosinophils is abnormal
what is the allergen pathway to allergic asthma?
what can be used as a biomarker for type 2 inflammation?
exhaled nitric oxide
diagnosis
- fractional concentration of exhaled nitric oxide (FeNO) is a quantative, non-invasive and safe measure of airway inflammation
- indirect marker of T2-high eosinophilic airway inflammation in asthma
what can be measures for adherence and steroid response?
- FeNO has a role in aiding asthma diagnosis, predicting steroid responsiveness and assessing adherence to inhaled corticosteroids
- Elevated if not taking medication (steroids)
what is the order of tests in allergic asthma?
- Spirometry
- Repeat tests every 6 to 12 months and treat on observation if unable to perform spirometry
- Exhaled nitric oxide if diagnostic uncertainty remained after spirometry and BDR
- If diagnostic uncertainty after FeNO, monitor peak flow variability for 2-4 weeks
what results on objective tests indicate asthma?
- airway obstruction on spirometry
- FEV1/FVC ration <0.7
- reversible airway obstruction-bronchdilator reversibility >12%
- exhaled nitric oxide (FeNO)
- >35ppb (children)
- >40ppb (adults)
what is the management of asthma?
- Reduce airway eosinophilic inflammation
- Inhaled corticosteroids (ICS)- target eosinic inflammation
- Leukotriene receptor antagonists -reduce type 2 inflammation
- Acute symptomatic relief
- Beta-2-agnosts (smooth muscle relaxation)
- Anticholinergic therapies (smooth muscle relaxation)- ipratropium bromide
- Severe asthma- steroid sparing therapies
- Biologic targeted to IgE
- Anti-IgE antibody
- Biologics targeted to airway eosinophils
- Anti-interleukin-5 antibody
- Anti-interleukin-5 receptor antibody
- Biologic targeted to IgE
Must give a preventative and then give an as needed bronchodilator- do not give bronchodilators only!
what is the mechanism of action of corticosteroids?
what is the pathogenesis of an acute lung attack?
how does Anti-IgE antibody therapy work?
- Humanised anti-IgE monoclonal antibody
- Bind and captures circulating IgE – to prevent interaction with mast cells and basophils to stop allergic cascade
- IgE production can decrease with time when patients given anti-IgE Ab
- Reduction in serum IgE over time means the therapy may not need to be used indefinitely
- No evidence yet that stopping anti-IgE Ab after some time is a long-term solution
- Example= omalizumab
what does a prescription of omalizumab require?
- severe, persistent allergic asthma in patients >6 yrs who need continuous of frequent treatment with oral corticosteroids
- total serum IgE between 30-1500
- Dosing based on weight and serum IgE 2-4 weekly s/c injections
- Min 75mg 4 weekly = £1,665 /patient/year
- Max 600mg 2 weekly = £26,640 /patient/year
how does an anti-IL5 antibody work?
- IL-5 = eosinophil recruitment, growth, activation and prolonged survival
- Steroid decrease eosinophil recruitment and promote apoptosis
what anti-IL5 antibody is used during asthma?
mepolizumab
- Anti- IL5 antibody for severe eosinophilic asthma
- Blood eosinophils >300 cells/mcl in last 12 months
- At least 4 exacerbations requiring oral steroids in last 12 months
- Trial for 12 months- if 50% reduction in attacks then continue
- Characteristics of responders:
- Elevated blood eosinophils
- Number of previous exacerbation
- Dose of inhaled steroids
- Characteristics of responders:
- Licenced for adults and children >6 years
