L10.1 COPD

Question 1

3 components of COPD

Answer 1

• Emphysema
  
  • Soft tissues destroyed → leaving holes
  • Loss of elastic recoil
• Bronchiolitis
  
  • Thick fibrous airway inflamed
• Chronic bronchitis
  
  • Excessive mucus secretion

Question 2

How does maternal smoking relate to offspring COPD?

Answer 2

• Maternal smoking → IUGR → small lungs

Question 3

Relationship b/w smoking and lung cancer

Answer 3

• Smoking → lose lung function
• Lung function begins to fall → disability (already lost more than half of lung function) → death

Question 4

What is the FEV1/FVC ratio for?

Answer 4

• Measure of lung health → lower = worse

Question 5

Why do COPD patients have increased fear and anxiety?

Answer 5

• Breathlessness in the same brain region as fear and anxiety
  
  • COPD patients → don’t want to live longer

Question 6

Structure reinforcing small airways to keep it opened

Answer 6

• 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

Question 7

How do macrophages function differently in COPD

Answer 7

• Macrophages accumulates in lungs and function changes in COPD
  
  • Cannot clear viruses/bacteria properly → but remains pro-inflammatory

Question 8

Cigarettes effect on lungs

Answer 8

• IL8/IP10 stimluated by cigarettes → release oxidants/cytokines → structural changes
  
  • Mucus gland hypertrophy
  • Fibrosis/septal detachment
  • Emphysema

Question 9

Problems with emphysema treatments

Answer 9

• Trials aim to slow/reverse emphysema BUT are long and benefit is very hard to show

Question 10

Problems with bronchiolitis treatment

Answer 10

• Difficult to treat inflammation without increasing infection risk.
  
  • Macrophages immune response damaged in COPD, increased susceptibilty to infections.

Question 11

Problems with bronchitis treatment

Answer 11

• Bacteria grow in mucus in deep areas → worsen disease

Question 12

Treatment of COPD

Answer 12

• 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)

Question 13

Summary of drug treatments

Answer 13

Question 14

Triple Therapy

Answer 14

LAMA + uLABA + GCS

Question 15

Cholingeric treatment

Answer 15

• 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

Question 16

COPD and decrease in muscle strength

Answer 16

• 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

Question 17

Mech of decreasing muscle strength in COPD

Answer 17

• 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

Question 18

Smoking’s effect on gram negative bacteria

Answer 18

• Smoking impairs macrophage phagocytosis of gram negative bacteria

Question 19

Serum Amyloid A’s relationship with COPD

Answer 19

• Serum amyloid A (SAA) ↑ with COPD
  
  • Made by macrophage
  • Deposited into lungs → pro-inflammatory (makes inflam chronic)

Question 20

Inflammation resolution

Answer 20

• 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

Question 21

Lung cancer’s association with COPD

Answer 21

• Lung cancer has poor response to treatment
• Shared susceptibility of COPD and lung cancer
• Smoke is mutagenic → induce permanent field changes → somatic mutations