Asthma and Respiratory Immunology 2 Flashcards
In an asthma attack what are you exposed to?
-Allergens
-Pathogens (viruses +/- bacteria)
-Pollution
-Tobacco smoke
Multiple events come together
What happens in an asthma attack if infection is the predominant exposure?
- Reduced anti-viral responses
- Increased viral replication result in prolonged illness
- Decrease IFN alpha, beta, lamda
- severity of illness is worse
What happens to spirometry in an asthma attack?
- Background airway obstruction is significantly exacerbated
- So if did spirometry in attack,
- Reduced peak expiratory flow rate
- Increased airway obstruction
- Resulting in acute wheeze
- Responsive to bronchodilators but not always
What happens to eosinophilia in airways in asthma attack?
- Increased airway eosinophilic inflammation
- Responsive to corticosteroids
- Treat with systemic high dose steroids in acute attack e.g. predisonoline
What is anti-IgE antibody therapy?
- Humanised anti-IgE monoclonal antibody
* Binds and captures circulating IgE – to prevent interaction with mast cells and basophils to stop allergic cascade
What is the result of anti-IgE antibody therapy?
•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
-Manage and control symptoms not cure
What is most common anti-IgE antibody therapy?
omalizumab
What is criteria for omalizumab?
- Severe, persistent allergic (IgE mediated) asthma in patients >6 years who need continuous or frequent treatment with oral corticosteroids
- 4 or more courses in the previous year
- Optimised standard therapy
- Documented compliance
What is bad for omalizumab?
- Fixed total serum IgE for which it can be prescribed: between 30-1500 - 2/3 of patients not even eligible
- Expensive: 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
When is omalizumab used?
-Effective for reduction in exacerbations
What is mepolizumab?
Anti-IL5-antibody
How does mepolizumab work?
- Anti-IL5 antibody for severe eosinophilic asthma
2. IL-5 regulates growth, recruitment, activation and eosinophil survival
When is mepolizumab lisenced?
Licensed for adults and children >6 years
What is the criteria for mepolizumab?
- Severe eosinophilic asthma
- Blood eosinophils >300 cells/mcl in the last 12 months
- At least 4 exacerbations requiring oral steroids in the last 12 months
- Trial for 12 months – 50% reduction in attacks, then continue
How was mepolizumab shown as effective?
DREAM tiral: Anti-Il-5 Ab in severe asthma
-Multi-centre RDBPC trial, 81 centres – 13 countries
•Patients aged 12-74 years
•Diagnosis of severe / refractory asthma (high dose ICS)
•>2 exacerbations in previous year
•Sputum eosinophils >3% or FeNO> 50ppb or blood eosinophils >0.3x109/ml
What were the results of DREAM trial?
Clinically significant exacerbations reduced with mepolizumab, not really dependent on dose
What are the characteristics of people to benefit from meplozumab in DREAM trial?
- elevated blood eosinophils
- number of previous exacerbations (lots)
- dose of inhaled steroids (been on high dose and haven’t responded)
