L10.1 COPD Flashcards
3 components of COPD
- Emphysema
- Soft tissues destroyed → leaving holes
- Loss of elastic recoil
- Bronchiolitis
- Thick fibrous airway inflamed
- Chronic bronchitis
- Excessive mucus secretion
How does maternal smoking relate to offspring COPD?
- Maternal smoking → IUGR → small lungs
Relationship b/w smoking and lung cancer
- Smoking → lose lung function
- Lung function begins to fall → disability (already lost more than half of lung function) → death
What is the FEV1/FVC ratio for?
- Measure of lung health → lower = worse
Why do COPD patients have increased fear and anxiety?
- Breathlessness in the same brain region as fear and anxiety
- COPD patients → don’t want to live longer
Structure reinforcing small airways to keep it opened
- Elastin fibres surrounding alveoli
- Expiration → fibres squeeze alevoli and force air out
- Keeps small airway open even under tremendous pressure
- Smaller airways have no cartilage to keep it open
Structures compromised in COPD → hyperinflation of the lungs due to loss of recoil function
How do macrophages function differently in COPD
- Macrophages accumulates in lungs and function changes in COPD
- Cannot clear viruses/bacteria properly → but remains pro-inflammatory
Cigarettes effect on lungs
- IL8/IP10 stimluated by cigarettes → release oxidants/cytokines → structural changes
- Mucus gland hypertrophy
- Fibrosis/septal detachment
- Emphysema
Problems with emphysema treatments
- Trials aim to slow/reverse emphysema BUT are long and benefit is very hard to show
Problems with bronchiolitis treatment
- Difficult to treat inflammation without increasing infection risk.
- Macrophages immune response damaged in COPD, increased susceptibilty to infections.
Problems with bronchitis treatment
- Bacteria grow in mucus in deep areas → worsen disease
Treatment of COPD
- Vaccination recommended for all COPD patients
- But poor response → due to compromised immune system
- Lung vol reduction surgery
- Improves patients quality of life → but decreases survivability
- Bronchodilators (LABA, LAMA, combo)
- Steroids (work poorly, increase pneumonia risk)
- Xanthines and PDE4 blockers (poor efficacy)
- Macrolides (deafness, CVS risk)
- NAC (borderline efficacy)
Summary of drug treatments
Triple Therapy
LAMA + uLABA + GCS
Cholingeric treatment
- 50% of Ach comes from inflammed tissue and not from N (non-neuronal Ach)
- ↑Ach produced in COPD lungs→ ∴cholingeric treatment is effective
- Want to block M3. R in SM
- Avoid blocking R in the heart (M2. R)
- BUT nearly impossible to make a purely selective M3 blockage
COPD and decrease in muscle strength
- COPD → leads to weak muscles (due to lack of exercise → skeletal muscle wastage)
- Especially selective for muscles responsible for mobility
- Treatment = Myo-mediation → from physiotherapy + pharmacology
- Myostatin usually blocks muscle growth
- Able to block myostatin to promote muscle growth
- Myostatin usually blocks muscle growth
Mech of decreasing muscle strength in COPD
- S26 proteasome → recycles proteins into AA
- Activated by E1-3 ligases (usually repressed by IGF-1 but is repressed in COPD)
- TNF/IL6/IL1 → activates S26 proteosome
- Repressed MyoD function
Smoking’s effect on gram negative bacteria
- Smoking impairs macrophage phagocytosis of gram negative bacteria
Serum Amyloid A’s relationship with COPD
- Serum amyloid A (SAA) ↑ with COPD
- Made by macrophage
- Deposited into lungs → pro-inflammatory (makes inflam chronic)
Inflammation resolution
- Epithelial cells converted into lipoxins (req 5LO and 15LO)
- 15LO from inflam; 5LO made from inflam mediators
- Activate ALX R. → mediates strong resolution process
- COPD → R swapped in conformation → lipoxin becomes pro-inflam instead
Lung cancer’s association with COPD
- Lung cancer has poor response to treatment
- Shared susceptibility of COPD and lung cancer
- Smoke is mutagenic → induce permanent field changes → somatic mutations
