Local immunomodulation in asthma Flashcards
What are the variables in asthma?
- Age of onset
- Gender
- Allergic sensitization
- Virus infections
- Transient/persistent wheeze
- Response to asthma medication (corticosteroids)
What is the recent change in the approach to treating asthma?
Instead of treating symptoms, target the underlying cause. Focus on endotype. If you understand the underlying mechanism (endotype), you can apply the right treatment.
What are the two phenotypes in asthma and what are their characteristics?
Eosinophilic and non-eosinophilic.
Eosinophilic: Th2 predominant, eosinophilia in blood and sputum, allergic sensitization and airway inflammation (FeNO)
Non-eosinophilic: neutrophilia, Th1/Th17 cells and airway inflammation (FeNO)
What are biomarkers and treatment markers of eosinophilic asthma?
Biomarkers and treatment markers of eosinophilic asthma: IL-4, IL-5, IL-9, IL-13, PGD2, Cys-LTs, MBP, ECP, EPO and TGF-beta
What are biomarkers and treatment markers of non-eosinophilic asthma?
Biomarkers and treatment markers of non-eosinophilic asthma: IL-8, IL-17, IL-22, MMP-9, neutrophil-elastase, LTB4, TNF-alfa, ROS and IFN-gamma
What are clinical phenotypes of eosinophilic asthma?
Allergy and eosinophilic inflammation
What are clinical phenotypes of non-eosinophilic asthma?
Neutrophilic inflammation and paucigranulocytic inflammation
What clinical phenotype is present in both eosinophilic asthma and non-eosinophilic asthma?
Airway hyperresponsiveness and remodeling
What cells are involved in non-eosinophilic asthma?
Cells involved in non-eosinophilic asthma: Epithelium, Th17, Neutrophil, ILC3, TH1, NK/NKT
What cells are involved in eosinophilic asthma?
Cells involved in eosinophilic asthma: Epithelium, eosinophil, Th2, mast cell and ILC2
Is eosinophilic early onset or late onset?
Eosinophilic is early onset
Is non-eosinophilic early onset or late onset?
Non-eosinophilic is late onset
What are treatments of asthma?
- Antihistamines
- Bronchodilators: β2 receptor agonists
- (Inhaled) corticosteroids
- Leukotriene inhibitors (LABA)
- New kids on the block: (expensive) biologicals!
Asthma can be subdivided in T2/Th2 and non-T2/Th2 asthma. What are essential elements of T2 asthma?
Eosinophilia, Th2 cells and ILC2 cells
What are the effector cytokines that can be found in T2/Th2-asthma?
TSLP, IL-33, IL-25,(T2 innate cytokines produced by the epithelial cells) IL-4, IL-5, IL-9, IL-13 (produced by Th2 and ILC2 cells).
What happened with the therapeutic application of the monoclonal anti-IgE antibody Omaluzimab?
With this treatment, there was still a seasonal effect, but the amount of excerbations was significantly less than the control group.
What is the effect of therapeutic anti-IgE?
The effect of therapeutic anti-IgE: anti-IgE prevents mast cells from acquiring cell-surface IgE. Mast cell cannot be activated through Fc-epsilon-RI and downregulates its cell-surface expression
What is the effect of experimental anti-IgE?
The effect of experimental anti-IgE: anti-IgE cross-links IgE bound to Fc-epsilon-RI and activates mast-cell deregulation. Inflammatory response
In what group of asthma patients were T2 applied?
A small group of severe (uncontrolled) asthma
What types of biologicals are there?
Anti-IgE, anti-IL-4 receptor, anti-IL-5, IL-5 receptor antagonist, anti-TSLP, anti-IL-33/ST2 and DP2 receptor antagonist (acts on ILC2).
What types of biologicals are FDA approved?
Anti-IgE , anti-IL-5, anti-IL-5R and anti-IL-4R
How effective are biologicals as treatment for asthma?
- All reduced annual exacerbation rate and hospitalization
- Benralizumab (anti-IL-5R), dupilumab (anti-IL-4R) and reslizumab (anti-IL-5) reduce daily dose of oral corticosteroids
- All effect asthma control, Quality of Life and FEV1 slightly to moderately
However, the cost-effectiveness per quality adjusted life year is above willingness to pay threshold
Why is asthma more prevelant in Western countries and urban centres of developing countries?
Because of the change in lifestyle:
•Rural –> Urban (Economic drive)
•Slow food –> Fast Food
•Physical labor –> sitting professions
•Outdoors –> Indoors Housing: isolation, central heating, less humid
•Health care: prevent/treat infections diseases
(improved sanitation)
Huge differences between urban and rural in the immune system detected by mass cytometry (based on 40 markers).
What is Strachan’s hygiene hypothesis?
Strachan’s hygiene hypothesis: children have less hay fever because they are exposed to germs from older siblings.
