Asthma - Dr. Monteil Flashcards
Asthma patients normally have what kind of cough?
Nocturnal cough
What cells predominate in asthma?
Eosinophils and TH2 cells
What cytokines are DIRECTLY released due to epithelial injury?
IL-25, IL-33, TSLP. They stimulate other cytokines to be released by stimulation of mast cells (mast cells also release chemotaxic factors) and other innate cells.
Activation of mast cells leads to an IL-4 rich environment.
TSLP stimulates DC cells and lead to TH2 differentiation.
Mast cells are usually close to what structures?
Small blood vessels.
How do eosinophils cause epithelial damage?
Mast cells release chemotaxic factors which recruits eosinophils. These eosinophils are activated and occupy the subepithelial space and get into the epithelium, where they cause damage.
IL-13 is responsible for what?
Goblet cell hyperplasia and increased production of mucous.
Endotype: Type 2 vs Non-type 2
Type 2: High IgE, Eosinophilia, High FeNO, Glucocorticoid sensitive
Non-type 2: Neutrophil, Pauci-Inflammatory, Less responsive to glucocorticoid Rx
Immunotherapy does what?
Immunotherapy decreases the production of TH2 cells and increases the presence of TH1 cells.
Treg cells are increased and the production of IL-4, IL-5, IL-13 is decreased. Treg cells secrete inhibitory cytokines such as IL10, which decreases TH2 responses and IgE production.
There is a decrease in the amount of B cells that are producing IgE. They stop making IgE and start making other kinds of antibodies such as IgG4.
Anaphylaxis
Low blood pressure, angioedema, & airway obstruction can be fatal (e.g. allergies to nuts, insect venom)
Asthma
Reversible airway obstruction occurs in the bronchi
Rhinitis
Discharge, sneezing, & nasal obstruction often coexist with allergic conjunctivitis
Urticaria
Itchy edema of the cutaneous tissues is short lived. Lesion is identical to that induced by skin-prick testing.
Angioedema
Short-lived, non-itchy edema of the subcutaneous tissues occurs. Some forms, such as lip-swelling, may be manifestations of food allergy.
Atopic Eczema
Chronic, itchy inflammation of the skin occurs. Some cases are caused by food allergy
Definition of Allergen
Allergens are substances that trigger allergic reactions in susceptible individuals
Characteristics:
Small particles or low-molecular weight glycoyslated substances with high solubility that penetrate body after being inhaled, eaten or administered
How are mast cells and basophils activated?
By cross-linking of high affinity IgE receptors on their surfaces. This occurs when allergen simultaneously engages two or more allergen-specific IgE molecules attached to these receptors.
What 3 biologic responses result from mast cell activation?
- Secretion of preformed granules (e.g. histamine) by exocytosis (degranulation)
- De novo synthesis and secretion of lipid mediators, e.g. leukotriene production from membrane phospholipid
- Synthesis and secretion of cytokines e.g. IL4, IL5, IL6, IL13 and TNF
What does histamine do?
Vasodilation and increased vascular permeability, especially of capacitance vessels.
Histamine induces the production of smooth muscle relaxants, nitric oxide and prostacyclin by vascular endothelial cells
What mediates bronchial smooth muscle constriction?
Prostaglandin D2, leukotrienes, and platelet activating factor.
These mediators also increase intestinal smooth muscle hypermotility.
What does tryptase do?
Cytokines and some of the other mast cell granule constituents such as tryptase are important in important in mediating inflammatory responses and tissue damage and possibly repair by fibrosis.
How do eosinophils cause damage?
By releasing lytic enzymes can cause tissue damage.
IgE, mast cells and eosinophils are important components of man’s defense response against parasites
What drug should be used for the immediate management of anaphylaxis?
Epinephrine. It causes bronchodilation and vasoconstriction, and it does this in a few minutes.
What does diphenhyramine do?
It is an anti-histamine and will compete with any residual histamine, released from mast cells and basophils, for histamine receptors.
Early phase vs. Late phase
Early phase response following mast cell degranulation is caused by preformed mediators such as histamine and de novo mediators such as leukotrienes. In our patient, the consequent
Late phase responses are thought to be mediated by inflammatory cells that come to the affected areas several hours after the initial stimulus. These cells are encouraged to these sites by chemotactic factor released in the first phase of response and by cytokines also released by the mast cells. The inflammatory cells themselves release mediators that induce a recrudescence of symptoms.
