Asthma and Respiratory Immunology 2

Question 1

In an asthma attack what are you exposed to?

Answer 1

-Allergens
-Pathogens (viruses +/- bacteria)
-Pollution
-Tobacco smoke
Multiple events come together

Question 2

What happens in an asthma attack if infection is the predominant exposure?

Answer 2

1. Reduced anti-viral responses
2. Increased viral replication result in prolonged illness
3. Decrease IFN alpha, beta, lamda
   - severity of illness is worse

Question 3

What happens to spirometry in an asthma attack?

Answer 3

1. Background airway obstruction is significantly exacerbated
2. So if did spirometry in attack,
   - Reduced peak expiratory flow rate
   - Increased airway obstruction
   - Resulting in acute wheeze
   - Responsive to bronchodilators but not always

Question 4

What happens to eosinophilia in airways in asthma attack?

Answer 4

• Increased airway eosinophilic inflammation
• Responsive to corticosteroids
• Treat with systemic high dose steroids in acute attack e.g. predisonoline

Question 5

What is anti-IgE antibody therapy?

Answer 5

• Humanised anti-IgE monoclonal antibody

* Binds and captures circulating IgE – to prevent interaction with mast cells and basophils to stop allergic cascade

Question 6

What is the result of anti-IgE antibody therapy?

Answer 6

•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

Question 7

What is most common anti-IgE antibody therapy?

Answer 7

omalizumab

Question 8

What is criteria for omalizumab?

Answer 8

1. Severe, persistent allergic (IgE mediated) asthma in patients >6 years who need continuous or frequent treatment with oral corticosteroids
2. 4 or more courses in the previous year
3. Optimised standard therapy
4. Documented compliance

Question 9

What is bad for omalizumab?

Answer 9

1. Fixed total serum IgE for which it can be prescribed: between 30-1500 - 2/3 of patients not even eligible
2. 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

Question 10

When is omalizumab used?

Answer 10

-Effective for reduction in exacerbations

Question 11

What is mepolizumab?

Answer 11

Anti-IL5-antibody

Question 12

How does mepolizumab work?

Answer 12

1. Anti-IL5 antibody for severe eosinophilic asthma

2. IL-5 regulates growth, recruitment, activation and eosinophil survival

Question 13

When is mepolizumab lisenced?

Answer 13

Licensed for adults and children >6 years

Question 14

What is the criteria for mepolizumab?

Answer 14

• 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

Question 15

How was mepolizumab shown as effective?

Answer 15

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

Question 16

What were the results of DREAM trial?

Answer 16

Clinically significant exacerbations reduced with mepolizumab, not really dependent on dose

Question 17

What are the characteristics of people to benefit from meplozumab in DREAM trial?

Answer 17

• elevated blood eosinophils
• number of previous exacerbations (lots)
• dose of inhaled steroids (been on high dose and haven’t responded)