6.19 - COPD: Clinical Trial of a Novel Drug Flashcards
1
Q
What is the affected site in asthma vs COPD?
A
- asthma - lung and small airways (not alveoli), airway hyper-responsiveness (narrowing), increased mucus
- COPD - airways and lung, very little AHR, increased mucus
2
Q
What are the inflammatory cells involved in asthma vs COPD?
A
- asthma - eosinophils, mast cells, Th2 lymphocytes
- COPD - neutrophils, macrophages, Tc1 lymphocytes
3
Q
What are the mediators involved in asthma vs COPD?
A
- asthma - IL-4, IL-5, cysLTs
- COPD - TNFa, IL-8, LTB4
4
Q
What is the treatment for asthma vs COPD?
A
- asthma - bronchodilators and corticosteroids used
- COPD - not used
5
Q
Is airway obstruction in asthma or COPD more reversible?
A
Asthma
6
Q
What is it called when you have both asthma and COPD?
A
- wheezy bronchitis
- 10%
7
Q
What is the background of asthma pathology?
A
- bronchoconstriction and mucus
- thicker muscle walls and mucus plug in airway lumen
- bronchoconstriction causes epithelium thrown into folds (folded walls)
8
Q
What are three features of COPD?
A
- chronic bronchitis
- chronic bronchiolitis - small airways disease
- emphysema
9
Q
What is the background of COPD pathology? - Chronic bronchitis
A
- chronic bronchitis affecting the bronchi
- mucus hypersecretion due to increased goblet cells and hyperplasia (bigger)
- cilia cannot move as well and there is less of them = causes mucus build up
- main bronchus = extrapulmonary
- smaller diameter airway = intrapulmonary
10
Q
What is the background of COPD pathology? - Chronic bronchiolitis (small airways disease)
A
- chronic bronchiolitis - small airways disease
- COPD patients/smokers get fibrosis in airway which narrows lumen –> small airway obstruction (bronchioles)
- leads to wheezy patients
11
Q
What is the background of COPD pathology? - Emphysema
A
- emphysema - lung destruction
- gross pathology of lung - black and holey due to parenchyma destruction (alveoli and acini) –> structure loss
- blacker on CT scan due to more air due to structural loss = lung elasticity is lost (can take deep breath in but not out)
12
Q
What happens to alveolar attachments in COPD?
A
- normal - airway held open by alveolar attachments
- COPD - alveolar attachments degrade, making alveoli collapse more = more airway obstruction
13
Q
What is the pathophysiology of COPD?
A
- occurs due to the absence of epithelial folding, bronchoconstriction is not prevalent
- main mechanisms are chronic inflammation and mucous hypersecretion (hypertrophy of goblet cells and submucosal glands)
- COPD includes chronic bronchitis, small airways disease and emphysema
- proteases (e.g. neutrophil elastase, matrix metalloproteinase) > antiproteases
14
Q
What are the two types of emphysema?
A
- centrolobular - smoking-related, happens in bronchi
- panacinar - happens more distally in acinar tissue
15
Q
What is the pathophysiology of emphysema?
A
- alveolar destruction associated with proteases degrading lung tissue
- peribronchial inflammation and fibrosis causes bronchiole lumen to decrease - epithelial cells exposed to cigarette smoke and produce TGF-beta leading to fibroblast activation
- macrophages produce MCP-1 which has autocrine/paracrine effects and recruits more macrophages - produce neutrophil chemotactic factors (CXCL8 and LTB4)
- neutrophils secrete proteases (neutrophil elastase & MMPs) to cause alveolar destruction and degeneration of alveolar attachments - reduced elasticity and capacity to hold bronchioles open
- activation of cytotoxic CD8 lymphocytes
