Mod 11 Asthma Cascade

Question 1

What are 3 types of Asthma Cascade?

Answer 1

1. Allergic Eosinophilic
2. Non-allergic Eosinophilic
3. T2 Independent pathways

Question 2

What are Basphils?

Answer 2

WBC that defend your body against pathogens, allergens, and parasite

Question 3

During the Allergic Eosinophilic, what order can you expect the pathway to follow from a introduction of a stimulus? (5)

Answer 3

1. Dendritic Cells (DC) present cells and starts immune response in allergic asthma
2. DC takes up and migrates harmful pathogen to lymphoid tissue (lymph nodes, spleen, tonsils, mucous membranes)
3. IgE and B cells activates naïve T cells (thymus cells)
4. When activated, the release of inflammatory mediators is called degranulation
5. Mass cell degranulation releases histamines, prostaglandins, leukotrienes, kinins, serotonin and serine proteases

Question 4

What are 3 antigens in a allergic reaction?

Answer 4

Allergens, cytokines, and fungi

Question 5

What are cytokines?

Answer 5

Think of them as chemical messengers that tell cells how to behave.

• Your cells release cytokines when there’s a threat

Question 6

What is Thymic Stromal Lymphopoietin (TSLP)?

Answer 6

An epithelial cell derived cytokine

Question 7

What kind of cytokines produce a allergic response?

Answer 7

• Type 2 cytokines,
• interleukin-4 (IL-4), IL-5 and IL-13

Question 8

What kind of reactions are produced by cytokines

Answer 8

An allergic response that promotes

• Airway eosinophilia
• Mucus overproduction
• Bronchial hyperresponsiveness
• and immunoglobulin E (IgE) synthesis

Question 9

What engages types 2 inflammation in basophils?

• what secondary affect is produced?

Answer 9

IL-33 and IL-25

• A secondary affect is a increase basophil activation and migratory potential
• Stimulates extra kill response basically

Question 10

What are naive T cells?

Answer 10

stem cells that spend maturation phase in thymus and move into the lymphatic/blood system where they sit until activation

• Are equipped to kill but inactivated
• Respond to pathogen that immune system hasn’t encountered

Question 11

How are IgE and B cell synthesized and stimulated?

Answer 11

T helper 2 (TH2) cell activation leads to increase cytokine production (IL4, IL5, and IL13) which induce IgE and B cells.

• Signals from both IL-4 and IL-13 and ligation of CD40 are needed

Question 12

What is Cluster of Differentiation 40 (CD40)?

Answer 12

CD antigens are a group of cell surface markers that can be used to identify different stages of B cell development or activation

Question 13

Where do IgE antibodies reside?

• what do they do?

Answer 13

Present on mast cell surfaces.

• When activated, the release of inflammatory mediators is called degranulation

Question 14

What is released during mass cell degranulation?

Answer 14

histamines, prostaglandins, leukotrienes, kinins, serotonin and serine proteases are released

Question 15

What are Histamines Cells?

Answer 15

A signaling chemical to send messages between cells.

• Increases the permeability of capillaries to WBCs and some proteins, so they can fight pathogens in infected tissues
• Antihistamines reduce or block histamines. They do not relieve every symptom

Question 16

What are Prostaglandin cells?

Answer 16

Group of lipids that control inflammation, blood flow and formation of blood clots

Question 17

What are Leukotrienes Cells?

Answer 17

They are lipid mediators that are vital in acute and chronic inflammation and allergic diseases.

• Are rapidly synthesized and released ONLY when needed
• They bind G-protein-coupled receptors (there are different types), which mediates inflammatory processes

Question 18

What do Kinin cells do?

Answer 18

Stimulate glandular secretion, increase vascular permeability and stimulate sensory nerves to produce upper airway symptoms (nasal congestion, rhinorrhea, nasal/throat irritation)

Question 19

What is the role of Serotonin in asthma?

Answer 19

critical factor to recruit inflammatory cells and prime TH2 responses by activation of bone marrow-derived dendritic cells

Question 20

Role of Serine proteases in asthma?

Answer 20

Activate PAR2 (a G-protein-coupled receptor), which mediates inflammatory processes

Question 21

What are Allergic Asthma Drugs?

Answer 21

Mast Cell Stabilizers

• Stabilize membranes of mast cells by blocking a calcium channel that is essential for mast cell degranulation

Anti-Leukotriene Drugs (LTRAs = Leukotriene Receptor Antagonists)

• Long-term asthma control. Shut down leukotriene effects or stop your body from producing them

Anti-IgEs

• Binding of the antibody of IgE molecules and reduces high-affinity receptors on effector cells

Biologics

• Injectable meds that target different molecules to prevent cascade and ends in “–umab” (ex. Omalizumab targets the C3 epitope on IgE)

Question 22

What do Mast Cell Stabilizers drugs do?

Answer 22

Stabilize membranes of mast cells by blocking a calcium channel that is essential for mast cell degranulation

Question 23

What do Anti-Leukotriene Drugs (LTRAs = Leukotriene Receptor Antagonists) do?

Answer 23

Long-term asthma control.

• Shut down leukotriene effects or stop your body from producing them

Question 24

What is the trigger for non allergic asthma?

Answer 24

Any type of cell can be triggered (i.e stressed out) and start this process:

• Cold or dry air, heat, humidity, exercise, bacterial or viral infections, cigarette smoke, perfume, stress, negative emotions, air pollution

Question 25

What is non allergic asthma characterized by?

Answer 25

symptomatic airway inflammation characterized by eosinophils in the airways

Note that Interleukins still plan a role here!
IL-5 is essential for eosinophil maturation in the bone marrow, release into the blood, activation and survival
IL-5 only acts on eosinophils and basophils
ILC2 = Group 2 Innate Lymphoid Cells
Belong to lymphoid lineage
Lack B or T cell receptors
ILC2s produce a large amount of IL-5 and IL-13 in response to cytokines such as IL-25, IL-33 and TSLP (Thymic Stromal Lymphopoietin  an epithelial cell-derived cytokine), leading to inflammation

Question 26

What is Type 2 independent asthma characterized by?

Answer 26

Triggers, such as viruses, smoke, etc, leads to increased production of TSLP (Thymic Stromal Lymphopoietin  an epithelial cell-derived cytokine)
Asthmatic lung fibroblasts promote type 2 immune responses via stress response dependent thymic stromal lymphopoietic secretions
Fibroblasts are the most abundant cell in the connective tissue
With mast cell degranulation and mediator release, neighboring fibroblasts can be activated, causing collagen production
Collagen deposition in the airways was linked with asthma severity
Excessive collagen deposits and increased airway stiffening leads to airway remodeling
IL-6 presence can be used as an indicator for asthma  encourages IL-4 production in naïve T cells
Goblet cell degranulation (epithelial mucus secretion) may cause airway obstruction in asthma exacerbations. Chronic degranulation can leads to chronic airway narrowing in severe asthma

Question 27

GOLD pharm for Bronchodilation

Answer 27

Regular and PRN SABA or SAMA  ↑FEV1
Combo SABA and SAMA is best
LABAs and LAMAs  ↑lung function, ↓SOB, ↑health status and ↓ exacerbations
LAMA better than LABA
LAMA + LABA best
Spiriva  better pulmonary rehab
Theophylline  Small bronchodilator effect and show modest symptom benefit

Question 28

GOLD pharm for anti inflammatories

Answer 28

ICS + LABA = more effective  ↑ lung function and ↓ exacerbations
ICS  ↑ risk of pneumonia
Triple therapy = LABA + LAMA + ICS and works BEST
PDE4 inhibitors (Phosphodiesterase 4 inhibitors)  ↑ lung function and ↓ exacerbations for severe to very severe
Roflumilast (AKA Daxas)
Antibiotics
Azithromycin and erythromycin long-term  ↓ exacerbations over 1 year
Associated with ↑ bacterial resistance and hearing issues
Blood eosinophil counts predict the effect of ICS (High eosinophil levels is >=3%)
Eosinophils contribute to inflammation that promotes airway obstruction

Question 29

Mast Cell Stabilizers (AKA Chromones) drugs?

Answer 29

Intal/Cromolyn Sodium/Sodium Cromoglycate
Nedocromil sodium

Question 30

Anti IgE drugs?

Answer 30

Omalizumab/Xolair
SubQ Injection

Question 31

Anti-IL5 and Anti-IL5R drugs?

Answer 31

Mepolizumab
Reslizumab
Benralizumab

Question 32

What does the combined effect of mast cell degranulation end with?

Answer 32

The combined effects of histamine, leukotrienes, and prostaglandins lead to smooth muscle contraction in the bronchioles, resulting in bronchoconstriction.

1. Histamines initially dilating vessels and causing smooth muscle contraction in the airways (dilates than constricts)
2. Leukotrienes and prostaglandin = inflammation (amped further by cytokines)
3. End results in increased mucous production and airway obstruction via bronchoconstriction

Question 33

Allergic Eosinophilic Asthma:

1. Trigger?
2. Mechanism
3. Characteristics?
4. Treatment?

Answer 33

Allergic Eosinophilic Asthma:

1. Trigger: Allergens such as pollen, pet dander, mold, or dust mites.
2. Mechanism: This type of asthma is driven by an allergic response. When exposed to specific allergens, the immune system in individuals with allergic eosinophilic asthma produces immunoglobulin E (IgE) antibodies.

Mast cells, which contain granules with inflammatory mediators, including eosinophils, are activated upon subsequent exposure to the allergen.

3. Characteristics: Eosinophils play a significant role in the inflammatory response, and increased levels of eosinophils are often found in the airways.
4. This subtype is often responsive to corticosteroid treatments.

Question 34

What are immunoglobulins (IgE)?

Answer 34

A antibody proteins that your immune system makes to fight germs, such as viruses and bacteria.

Question 35

What are eosinophils?

Answer 35

a type of white blood cell associated with allergic reactions.

Question 36

Non-Allergic Asthma:

1. Trigger
2. Mechanism
3. Characteristics:
4. Treatment?

Answer 36

Non-Allergic Asthma:

1. Trigger: Non-allergic factors such as respiratory infections, exercise, cold air, or stress.
2. Mechanism: Non-allergic asthma is not primarily driven by an allergic response. Instead, it may be triggered by factors like irritants, infections, or physical exertion.

The inflammation in the airways is less likely to involve IgE antibodies and may be more associated with other immune responses or irritant-induced inflammation.

3. Characteristics: Eosinophils may or may not be prominent in the airways.
4. Non-allergic asthma may have a different response to treatment compared to allergic asthma, and corticosteroids may be less effective in some cases.

Question 37

Type 2 Independent Asthma:

1. Mechanism
2. Characteristics

Answer 37

Type 2 Independent Asthma:

1. Mechanism: This subtype of asthma is not primarily driven by the classic Type 2 inflammatory pathway, which involves the activation of certain immune cells (such as eosinophils) and the release of specific cytokines. Instead, T2 independent asthma may involve different inflammatory pathways or mechanisms not associated with the classical Type 2 response.
2. Characteristics: The inflammation in T2 independent asthma may not be as responsive to corticosteroids targeting the Type 2 pathway. It represents a more heterogeneous group, and understanding its specific mechanisms is an area of ongoing research.

Question 38

Initial Gold Treatment chart

Answer 38

Gold and mmrc details

Question 39

Generally, describe a typical event timeline for the asthma cascade

edit

• need to break up the parts into separate cards

Answer 39

1. Trigger Exposure (allergens and irritants)
2. Immune Response (exaggerated immune response in the airways. AKA activation of immune cells, particularly mast cells and eosinophils.)
3. Release of Mediators (Immune cells release chemical mediators, including histamine and leukotrienes, which contribute to inflammation and bronchoconstriction.)
4. Airway Inflammation (Inflammatory cells infiltrate the airway walls, leading to swelling and increased production of mucus. The inflammation narrows the airways, making it difficult for air to pass through.)
5. Bronchoconstriction (Smooth muscle contraction in the airway walls, triggered by mediators like histamine and leukotrienes, leads to bronchoconstriction, further reducing airflow.)
6. Increased Mucus Production (Goblet cells in the airway lining produce excess mucus, contributing to airway obstruction and coughing.)
7. Airway Hyperresponsiveness (Airways become hypersensitive leading to exaggerated responses and further bronchoconstriction)
8. Symptoms (The combination of inflammation, bronchoconstriction, and mucus production results in asthma symptoms)

Question 40

What are general symptoms of asthma?

Answer 40

The combination of inflammation, bronchoconstriction, and mucus production results in asthma symptoms, including coughing, wheezing, shortness of breath, and chest tightness.