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Lungs and COPD (Inflammation (Structural (Epithelial (TGF-b (Fibrosis),…

- - - - Release inflammatory mediators
        
        TNF-a --> NF-kB
        
        NLRP3
      - Secrete elastolytic enzymes, including matrix metalloproteinases (MMPs) 2, 9, and 12
        
        Increase in elastase activity --> breaks down elastin --> ephysema
      - Reduced phagocytic uptake of bacteria
    - - Secrete serine proteases, including neutrophil elastase, cathepsin G, and proteinase-3, as well as MMP-8 and MMP-9
        
        Alveolar destruction and mucus secretion
  - - - CD4+
      - CD8+
        
        Apoptosis alveolar cells
  - - - Produce inflammatory mediators, including TNF-a, IL-1b, IL-6, GM-CSF, and CXCL8 (IL-8)
      - TGF-b
        
        Fibrosis
      - EGFR
        
        Mucus hypersecretion
- - - - Increased acetylation of histones in the promoter region of pro‑inflammatory genes
      - Increased acetylation Nrf2 --> decreased AOX
      - Decreased SIRT1 (HDAC)
    - - Accumulation of dysfunctional proteins
        
        Apoptosis and inflammation
    - - Increased mTOR
    - - Increased mitochondrial ROS
    - - Excessive differentiation due to oxidative stress and damage
    - - Immunosenescence
    - - Double-stranded breaks
      - Microsatellite instability
- - - - BPD
  - - - Glutathione S-transferase
        
        polymorphism on this gene causes airflow limitation
        
        strongly expressed in alveoli, alveolar macrophages and bronchioles
        
        metabolises various toxic substances.
      - Alpha-1 antitrypsin
        
        mutation in the SERPINA1 gene causes a deficiency
        
        inhibits serine proteases
        
        causes degradation of lung tissue --> emphysema
      - SOD3
        
        encodes superoxide dismutase
        
        chronic inflammation
        
        scavenger of superoxide
- - - - Inflammation of mucosa, submucosa and glandular tissue
      - Hypertrophy and hyperplasia of mucous glands and ciliary dysfunction
        
        Hypersecretion mucus
      - Epithelial-cell hyperplasia