Asthma, COPD, EVALi and CF Flashcards
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
- COPD (chronic obstructive pulmonary disease)
- pulmonary
- lung
factors contributing to recent pulmonary disease
- EVALI (E-cigarette/Vaping use Associated Lung Injury)
- COVID-19 and potentially long COVID
- Post COVID-19 pulmonary fibrosis
- ARDS (Acute Respiratory Distress Syndrome)
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
- elastic
- gas
- alveoli
- cilia and mucus
Triad of Lung Disease Inducers
genetic, environmental, and medications
Defining Asthma
- Wheezing, coughing, SOB
- ___ of airway
- inflammation and airway ___
- release of ___ mediators
- ___ of airway smooth muscle
- ___ secretion of mucus
- ___ of repiratory mucosa
- narrowing
- hyperreactivity
- inflammatory
- constriction
- excess
- edema
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 ___
- IgE, histamine, LTC4, mast
- contraction, leakage
Pathogenesis of Asthma
Delayed Reaction (2-___ hours)
* ___ bronchoconstriction
* activation of ___ lymphocytes (release of ___, IL-4, ___, and IL-13)
* mucus ___ : Goblet cells
* Cellular infiltration: ___
2-8 hours
* sustained
* TH2 (GM-CSF, IL-4, IL-5, IL-13)
* hypersecretion
* eosinophils
Mast Cell Activation
- IgE is bound to ___
- crosslinking by the antigen leads to mast cell ___
- FcR
- degranulation
IAR
immediate asthmatic response
LAR
late asthmatic response
FEV1
Forced Expiratory Volume
ECP
eosinophil cationic protein
cytotoxic secretory protein & marker of inflammation
PAF
platelet activating factor
hyper-responsiveness
Neutrophil Proteases may activate ___
eosinophils
Periostin
matrix protein that is used as an asthma biomarker
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
- minutes
- bronchoconstriction
- mast, histamine, PAF
- antigen presenting
Introduction to Asthma
Oscillating pressure effect leads to ___
wheezing
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 ___)
- hours
- submucosal edema, hyperresponsiveness
- IL-8, IFN-gamma, eosinophils
- LTB4, PAF, eosinophils
- MBP and ECP
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 ___
- days
- epithelial cell damage, mucus hypersecretion, hyperresponsiveness
- eosinophilopoesis
- IL-5, GM-CSF
- ECP
PAF = hyperresponsiveness
ECP = cytotoxic protein/inflammation
Goblet Cells and Hypersecretion in Asthma
4 factors that could cause goblet cell hyperplasia
- cytokines (TH2)
- bacterial products
- proteinases (neutrophil)
- oxidants (smoking)
Goblet Cells and Hypersecretion in Asthma
What 2 cell components are key in the development of goblet hyperplasia?
What maintains hyperplasia?
- EGFR, CLCA
- Bcl-2
Genetic contribution to Goblet Cell Hyperplasia - R576 polymorphism
- R576 polymorphism in the ___ receptor leads to enhanced response to ___
- ___ binds to dimer of ___ and ___ recpetors
- IL-4a, IL-13
- IL-13, IL-4a, IL-13a1
IL-4a receptor also lets IL-13 bind
Genetic contribution to Goblet Cell Hyperplasia - Q576R polymorphism
- Q576R polymorphism in IL-4a receptors induces ___ to inhaled antigens.
- Mechanism: amino acid change from ___ to ____
- hyperreactivity
- Q (glutamate) to R (Arganine)
Q576 turns into R576 = more goblet cells.
Periostin promotes chronic allergic ___ in
response to ___ cytokines
- inflamation
- TH2
Periostin is an extracellular matrix protein induced by ___ and ___
IL-13, IL-4
Periostin is a ligand for alpha/beta ___ to support adhesion and cell migration
integrins
Airway Remodeling in Asthma
Epithelium - mucous ___ and ___
hyperplasia and hypersecretion
Airway Remodeling in Asthma
Basement membrane
thickening
Airway Remodeling in Asthma
smooth muscle
hypertrophy
Airway Remodeling in Asthma
- allergens trigger ___ (initiators)
- immune cells (amplifiers) - ___ mediated
- ___ and smooth muscle cells in the asthmatic airway wall (effectors)
- epithelium
- TH2
- fibroblasts
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
- adult
- 6th
- allergic
- 85%
- chronically
- bronchitis
emphysema is the destruction of the alveolar wall
COPD vs. Asthma
- onset: often in ___
- linked to specific triggers
- ___ attacks
- childhood
- episodic
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
- barrel
- breathlessness
- CAT
- limitation
- smoking
Remodeling in COPD
- ___ of small airways
- ___inflation of lungs
- alveolar ___
- alveolar wall ___
- mucus ___secretion
- fibrosis
- hyperinflation
- enlargement
- destruction
- hypersecretion
Remodeling in COPD
genetic deficiency of ___ causes emphysema and mucus hypersecretion
a1-anti-trypsin
Asthma vs. COPD - site
Site of disease (COPD): ___, ___, and ___
Site of disease (asthma): ___
COPD: peripheral airways, lung parenchyma, and pulmonary vessels
Asthma: proximal airways
Asthma vs. COPD - cells
COPD: ___, macrophages, and ___
Asthma: ___, macrophages, and ___
COPD: neutrophils, CD8 T cells (TH1)
Asthma: eosinophils, CD4 T cells (TH2)
Asthma vs. COPD - key mediators
COPD: ___, ___ , ___ , and ___
Asthma: ___, ___, and ___
COPD: IL-8, TNF-a, IL-1B, IL-6
Asthma: IL-4, IL-5, IL-13
Asthma utilizes more NO than COPD
Asthma vs. COPD - oxidative stress
Does COPD or Asthma have more oxidative stress?
COPD
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
- elastase, damage
- migration, inflammation, protease
- lung
- height, respiratory
E-cigs and Vaping
Vaping generates an aerosol vapor that can alters indoor air quality and contains toxic
___ and other substance of unknown toxicity
aldehydes
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
- pneumonitis
- innate
- E
- hydrocarbons
- oxidative
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 ___
- alveolar, granulocytes, polymorphonuclear
- NETosis
- infections
Cystic Fibrosis
autosomal ___ , chronic disease that results from the mutation of the ____ gene
recessive, Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis - stats
- usually diagnosed by age __
- 1:___ births in US
- life expectancy: late ___
- 2
- 3200
- 30s
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
- obstructs
- pathogens
- pancreatic
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
- 1480
- ABC
- Cl-
- PKA, R
- airway, pancreatic
Loss of CFTR function in sweat duct epithelium
Loss of CFTR function causes ___ NaCl concentration in sweat
increased
T or F: excessively salty sweat is a sign of cystic fibrosis
True
There is an opposite effect on sodium in the lungs
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 ___
- Na+
- ENaC
- H2O
- ASL, mucus
ASL = airway surface liquid
