Asthma, COPD, EVALi and CF

Question 1

Factors Contributing to Growing Pulmonary Drug Market in the US

• growing prevalence of ___
• advantages of the ___ route as an alternative to oral and parenteral
• rising incidence of ___ disease across the world

Answer 1

• COPD (chronic obstructive pulmonary disease)
• pulmonary
• lung

Question 2

factors contributing to recent pulmonary disease

Answer 2

• EVALI (E-cigarette/Vaping use Associated Lung Injury)
• COVID-19 and potentially long COVID
• Post COVID-19 pulmonary fibrosis
• ARDS (Acute Respiratory Distress Syndrome)

Question 3

4 Hallmarks of a Normal Functioning of the Lung
1. ____ - expand/deflate
2. ___ exchange - O2 intake and CO2 exhaled
3. ___ - site of gas exhange
4. ____ and ___ - clean lungs from dust and microbes

Answer 3

• elastic
• gas
• alveoli
• cilia and mucus

Question 4

Triad of Lung Disease Inducers

Answer 4

genetic, environmental, and medications

Question 5

Defining Asthma

• Wheezing, coughing, SOB
• ___ of airway
• inflammation and airway ___
• release of ___ mediators
• ___ of airway smooth muscle
• ___ secretion of mucus
• ___ of repiratory mucosa

Answer 5

• narrowing
• hyperreactivity
• inflammatory
• constriction
• excess
• edema

Question 6

Pathogenesis of Asthma

Early Reaction - Immediate Bronchoconstriction
* antigen binding to ___ antibodies triggers release of ___, tryptase, ___, LTD4, and prostaglandins from ___ cells
* Bronchial smooth muscle ___ and vascular ___

Answer 6

• IgE, histamine, LTC4, mast
• contraction, leakage

Question 7

Pathogenesis of Asthma

Delayed Reaction (2-___ hours)
* ___ bronchoconstriction
* activation of ___ lymphocytes (release of ___, IL-4, ___, and IL-13)
* mucus ___ : Goblet cells
* Cellular infiltration: ___

Answer 7

2-8 hours
* sustained
* TH2 (GM-CSF, IL-4, IL-5, IL-13)
* hypersecretion
* eosinophils

Question 8

Mast Cell Activation

• IgE is bound to ___
• crosslinking by the antigen leads to mast cell ___

Answer 8

• FcR
• degranulation

Question 9

IAR

Answer 9

immediate asthmatic response

Question 10

LAR

Answer 10

late asthmatic response

Question 11

FEV1

Answer 11

Forced Expiratory Volume

Question 12

ECP

Answer 12

eosinophil cationic protein

cytotoxic secretory protein & marker of inflammation

Question 13

PAF

Answer 13

platelet activating factor

hyper-responsiveness

Question 14

Neutrophil Proteases may activate ___

Answer 14

eosinophils

Question 15

Periostin

Answer 15

matrix protein that is used as an asthma biomarker

Question 16

Phases of Asthma - IAR

Time: ___
Action: ___
Mechanism:
1. antigen triggers ___ cell to release mediators ( ___, PGD2, LTC4, LTD4, LTB4, and ___). These mediators play key roll in bronchoconstriction and activating immune cells in LAR.
2. antigen also triggers ___ cells which activate lymphocytes which play key roll in LAR and chronic asthma

Answer 16

• minutes
• bronchoconstriction
• mast, histamine, PAF
• antigen presenting

Question 17

Introduction to Asthma

Oscillating pressure effect leads to ___

Answer 17

wheezing

Question 18

Phases of Asthma - LAR

Time: ___
Action: ___
Mechanism:
1. Lymphocytes release ___, IL-4, and ___ to activate neutrophils, ___, and macrophages (respectfully)
2. mast cell mediators, ___ and ___, cause neutrophils, ___, and macrophages to release more mediators (PAF, LTC4, ___, and ___)

Answer 18

• hours
• submucosal edema, hyperresponsiveness
• IL-8, IFN-gamma, eosinophils
• LTB4, PAF, eosinophils
• MBP and ECP

Question 19

Phases of Asthma - Chronic Asthma

Time: ___
Action: ___
Mechanism:
1. lympocytes cause ___. More eosinophils means more mediators
2. lympocytes also release ___ and ___, which further increase eosinophil response
3. Both eosinophils and lymphocytes release PAF, LTC4, MBP, cytokines, and ___

Answer 19

• days
• epithelial cell damage, mucus hypersecretion, hyperresponsiveness
• eosinophilopoesis
• IL-5, GM-CSF
• ECP

PAF = hyperresponsiveness
ECP = cytotoxic protein/inflammation

Question 20

Goblet Cells and Hypersecretion in Asthma

4 factors that could cause goblet cell hyperplasia

Answer 20

1. cytokines (TH2)
2. bacterial products
3. proteinases (neutrophil)
4. oxidants (smoking)

Question 21

Goblet Cells and Hypersecretion in Asthma

What 2 cell components are key in the development of goblet hyperplasia?

What maintains hyperplasia?

Answer 21

• EGFR, CLCA
• Bcl-2

Question 22

Genetic contribution to Goblet Cell Hyperplasia - R576 polymorphism

• R576 polymorphism in the ___ receptor leads to enhanced response to ___
• ___ binds to dimer of ___ and ___ recpetors

Answer 22

• IL-4a, IL-13
• IL-13, IL-4a, IL-13a1

IL-4a receptor also lets IL-13 bind

Question 23

Genetic contribution to Goblet Cell Hyperplasia - Q576R polymorphism

• Q576R polymorphism in IL-4a receptors induces ___ to inhaled antigens.
• Mechanism: amino acid change from ___ to ____

Answer 23

• hyperreactivity
• Q (glutamate) to R (Arganine)

Q576 turns into R576 = more goblet cells.

Question 24

Periostin promotes chronic allergic ___ in
response to ___ cytokines

Answer 24

• inflamation
• TH2

Question 25

Periostin is an extracellular matrix protein induced by ___ and ___

Answer 25

IL-13, IL-4

Question 26

Periostin is a ligand for alpha/beta ___ to support adhesion and cell migration

Answer 26

integrins

Question 27

# Airway Remodeling in Asthma Epithelium - mucous ___ and ___

Answer 27

hyperplasia and hypersecretion

Question 28

# Airway Remodeling in Asthma Basement membrane

Answer 28

thickening

Question 29

# Airway Remodeling in Asthma smooth muscle

Answer 29

hypertrophy

Question 30

# Airway Remodeling in Asthma 1. allergens trigger ___ (initiators) 2. immune cells (amplifiers) - ___ mediated 3. ___ and smooth muscle cells in the asthmatic airway wall (effectors)

Answer 30

* epithelium * TH2 * fibroblasts

Question 31

# COPD vs. Asthma COPD * onset: late ___ hood * ___ leading cause of death in the US * Not linked to ___ response * ___ are smokers * ___ symptomatic * emphysema and chronic ___ IRREVERSIBLE

Answer 31

* adult * 6th * allergic * 85% * chronically * bronchitis | emphysema is the destruction of the alveolar wall

Question 32

# COPD vs. Asthma * onset: often in ___ * linked to specific triggers * ___ attacks

Answer 32

* childhood * episodic

Question 33

# COPD symptoms and assessment * chronic cough, sputum, dyspnea and ___ chest * ___ score related to everyday activities * ___ (COPD assessment test) considers mucus, chest tightness, sleep, breathlessness, etc * degree of airflow ___ * comorbidities - ___, diabetes, cardiovascular, respiratory infections, and cancer

Answer 33

* barrel * breathlessness * CAT * limitation * smoking

Question 34

# Remodeling in COPD * ___ of small airways * ___inflation of lungs * alveolar ___ * alveolar wall ___ * mucus ___secretion

Answer 34

* fibrosis * hyperinflation * enlargement * destruction * hypersecretion

Question 35

# Remodeling in COPD genetic deficiency of ___ causes emphysema and mucus hypersecretion

Answer 35

a1-anti-trypsin

Question 36

# Asthma vs. COPD - site Site of disease (COPD): ___, ___, and ___ Site of disease (asthma): ___

Answer 36

COPD: peripheral airways, lung parenchyma, and pulmonary vessels Asthma: proximal airways

Question 37

# Asthma vs. COPD - cells COPD: ___, macrophages, and ___ Asthma: ___, macrophages, and ___

Answer 37

COPD: neutrophils, CD8 T cells (TH1) Asthma: eosinophils, CD4 T cells (TH2)

Question 38

# Asthma vs. COPD - key mediators COPD: ___, ___ , ___ , and ___ Asthma: ___, ___, and ___

Answer 38

COPD: IL-8, TNF-a, IL-1B, IL-6 Asthma: IL-4, IL-5, IL-13 | Asthma utilizes more NO than COPD

Question 39

# Asthma vs. COPD - oxidative stress Does COPD or Asthma have more oxidative stress?

Answer 39

COPD

Question 40

# Genetic deficiency of a1-anti-trypsin * a1-anti-trypsin inhibits neutrophil ___ and limits lung tissue ___ * deficiency causes increased neutrophil ___ and damage via ___ and ___ activity * ZZ allele results in disadvantageous ___ function * PI-MZ allele result in increased ___ and ___ function

Answer 40

* elastase, damage * migration, inflammation, protease * lung * height, respiratory

Question 41

# E-cigs and Vaping Vaping generates an aerosol vapor that can alters indoor air quality and contains toxic ___ and other substance of unknown toxicity

Answer 41

aldehydes

Question 42

# E-cigarette/Vaping product use associated lung injury (EVALI) * sterile exogenous ___ like reaction. * ___ immune response * vitamin ___ acetate * ___carbons in counterfeit vaping products * many of these compounds are involved in ___ stress and inflammatory responses in the lung

Answer 42

* pneumonitis * innate * E * hydrocarbons * oxidative

Question 43

# E-cigarette/Vaping product use associated lung injury (EVALI) * first responders: airway epithelial cells, ___ macrophages (AMs), and ___/neutrophils or ___ cells (PMNs) * ___ is initiated to trap particles/pathogens but adverse effect is tissue ___. * Dyregulated netosis leads to increased susceptibilty to ___

Answer 43

* alveolar, granulocytes, polymorphonuclear * NETosis * infections

Question 44

# Cystic Fibrosis autosomal ___ , chronic disease that results from the mutation of the ____ gene

Answer 44

recessive, Cystic Fibrosis Transmembrane Conductance Regulator

Question 45

# Cystic Fibrosis - stats * usually diagnosed by age __ * 1:___ births in US * life expectancy: late ___

Answer 45

* 2 * 3200 * 30s

Question 46

# Cystic Fibrosis CF patients secrete extremely viscous mucus that: * ___ airflow to the lungs * harbors ___ leading to lung infections * obstructs the ___ duct that interferes with digestion

Answer 46

* obstructs * pathogens * pancreatic

Question 47

# Cystic Fibrosis Transmembrane Conductance Regulator * ___ amino acid protein * an ___ transporter * functions as a ___ channel * gated by ___ phosphorylation or ___ domain * CFTRs are expressed in: ___, sweat, and ___ duct epithelium

Answer 47

* 1480 * ABC * Cl- * PKA, R * airway, pancreatic

Question 48

# Loss of CFTR function in sweat duct epithelium Loss of CFTR function causes ___ NaCl concentration in sweat

Answer 48

increased

Question 49

T or F: excessively salty sweat is a sign of cystic fibrosis

Answer 49

True | There is an opposite effect on sodium in the lungs

Question 50

# Loss of CFTR function in airway epithelium CFTR function inhibits ENaC-mediated ___ influx. CFTR dysfunction causes: * increased ___ activities * increased ___ uptake into epithelial cells dehydration of ___ causes thickening of ___

Answer 50

* Na+ * ENaC * H2O * ASL, mucus | ASL = airway surface liquid