Exam 2 Asthma, COPD, EVALi and CF

Question 1

Why are pulmonary drugs on the market growing?

Answer 1

1. a growing prevalence of chronic obstructive pulmonary disease (COPD)
2. the potential advantages of the pulmonary route as an alternative to oral and parenteral delivery methods
3. rising incidence of lung disease → due to pollutants, irritants

Question 2

What is a new pulmonary disease that is emerging?

Answer 2

E-cigarette/vaping product use Associated Lung Injury (EVALI)

Question 3

What is the normal function of the lungs?

Answer 3

1. has elastic property → can expand/deflate
2. gas exchange in which O2 in being taken in and CO2 is being exhaled
3. site of exchange are at the alveoli (around 480 million)
4. cilia and mucus clean the lungs from dust and microbes

Question 4

What is the triad of inducers?

Answer 4

genetic, medications, environmental

Question 5

What is the definition of asthma?

Answer 5

1. wheezing, coughing, shortness of breath
2. narrowing of the airway
3. inflammation and airway hyperreactivity
4. release of inflammatory mediators
5. constriction of airway smooth muscle
6. excess secretion of mucus
7. edema of respiratory mucosa

Question 6

What is the wheezing mechanism?

Answer 6

normal airway → slightly narrowing of airway, velocity increases while pressure decreases → greater narrowing, velocity decreases while pressure increases → alteration of slight and great narrowing (flutter)

Question 7

What is the difference between a normal airway, an asthmatic airway, and an asthmatic airway during attack?

Answer 7

normal airway → relaxed smooth muscles, walls are not inflamed or thickened
asthmatic airway → relaxed smooth muscles, walls are inflamed and thickened
asthmatic airway during attack → tightened smooth muscles, wall inflamed and thickened, air trapped in alveoli

Question 8

What happens during the early reaction (immediate bronchoconstriction)?

Answer 8

1. antigen binding to IgE antibodies triggers release of histamine, tryptase, LTC4, LTD4, and prostaglandins from mast cells
2. bronchial smooth muscle contraction and vascular leakage

Question 9

What happens during a delayed reaction (2-8 hours)?

Answer 9

1. sustained bronchoconstriction
2. activation of TH2 lymphocytes → release of GM-CSF, IL-4, IL-5, IL-13
3. mucus hypersecretion → goblet cells
4. cellular infiltration → eosinophils

Question 10

How are mast cells activated?

Answer 10

1. IgE is bound to FcR

2. crosslinking by the antigen leads to mast cell degranulation

Question 11

What are some terms and phrases regarding asthma?

Answer 11

1. IAR → immediate asthmatic response
2. LAR → late asthmatic response
3. FEV1 → forced expiratory volume
4. ECP → eosinophil cationic protein (a cytotoxic secretory protein and marker of inflammation)
5. PAF → platelet activating factor (hyper-responsiveness)
6. neutrophil proteases → may activate eosinophils
7. periostin → matrix protein that is used as an asthma biomarker

Question 12

What are the different phases of asthma?

Answer 12

1. immediate asthma response → minutes and characterized by bronchoconstriction
2. late asthma response → hours and characterized by submucosal edema, hyperresponsiveness
3. chronic asthma → days and characterized by epithelial cell damage, mucus hypersecretion, hyperresponsiveness

Question 13

Which phase of asthma is ECP and PAF associated with?

Answer 13

late asthma response and chronic asthma

Question 14

How are cytokines produced in asthma?

Answer 14

allergen activates TH2 cells that activate/produce cytokines which then induce goblet cells along with bacterial products, proteinases, and oxidants to lead to the hypersecretion of mucus

Question 15

What proteins on goblet cells lead to the development of hyperplasia?

Answer 15

EGFR and CLCA

Question 16

What protein on goblet cells maintain hyperplasia?

Answer 16

Bcl-2

Question 17

What is an example of the genetic contribution to goblet cell hyperplasia?

Answer 17

1. the R576 polymorphism in the IL-4alpha receptor mediates enhanced response to IL-13 in a mouse model
2. IL-13 binds to a dimer of the IL-4alpha and IL-13alpha1 receptors
3. overrepresented in African Americans that are homozygous for R576 in IL-4alpha
4. the Q576R polymorphism in the IL-4alpha receptor induces hyperreactivity to inhaled antigens in a mouse model

Q576R → change from Q to R

Question 18

What receptors are upregulated in asthma?

Answer 18

IL-13alpha1, IL-4alpha, and the IL-13alpha2 receptors are increased in asthma patients compared to controls

Question 19

Why is IL-13 a key hub in asthma?

Answer 19

can lead to a number of effects with the activation of different cells:

1. macrophages
2. fibroblasts → fibrosis
3. goblet cells → mucus hypersecretion
4. steroid resistance
5. airway epithelium releases eotaxin which influences eosinophils
6. B lymphocytes and mast cells through IgE

Question 20

What are the targets for treating asthma?

Answer 20

IL-13 and IgE

Question 21

How do we know that IL-13 and IgE are targets for treating asthma?

Answer 21

stains of a transgenic mouse model shows overexpression of IL-13 and IgE that shows pulmonary fibrosis

Question 22

Where does IgE act on regarding IL-13?

Answer 22

IgE can act both upstream and downstream of IL-13