Smoking Cigarettes Pathophysiology

Tobacco smoke is a toxic mix of more than 7,000 chemicals and compounds

Pathophysiology of Cigarette Smoking on Medium Sized Airways, Small Airways and Alveoli
Ashley Davidoff
  • Tobacco smoke contains chemicals in the form of
    • particulate substances and
    • gases.
  • Smoking causes increased cellularity of both
    • Alveolar macrophages
      • smoking influences the phenotype of pulmonary macrophages, resulting in
        • more undifferentiated immature monocyte-like macrophages with a
          • reduction in the mature AM surface markers needed for
            • phagocytosis,
            • efferocytosis,
            • cell–cell and cell to matrix interaction
          • The increase in the immature macrophages seen in smokers may be due to the influx of monocyte-derived cells from the peripheral blood, with the additional increase due to AM proliferation within the lung.38
    • Neutrophils
  • may be explained by chemotactic factors generated in the lung
  • Resulting in release of
    • proteases
      • from macrophages and neutrophils
      • smoke evokes an inflammatory cell reaction and that these cells release proteases that overwhelm the antiproteolytic defenses of the lower respiratory tract,
        • Proteinase/anti-proteinase imbalance and tissue destruction
          one of the causes of smoking-related lung damage is through the imbalance of proteolytic enzymes (proteinases)
        • Smoking  tips the balance of proteinase/anti-proteinase release from AMs, contributing to cell death alongside inadequate repair, with elastolysis and connective tissue destruction, all of which are involved in the pathology of emphysema.
    • cytotoxic,
    • mutagenic and
    • proinflammatory substances contained in cigarettes
    • Surfactant
      • smoking is associated with reduced surfactant phospholipids
    • fibrotic factors
b) Inhaled cigarette smoke and other irritants activate epithelial cells and macrophages to release chemotactic factors that attract inflammatory cells to the lungs, including CCL2, which acts on CCR2 to attract monocytes, CXC-chemokine ligand (CXCL)1 and CXCL8, which act on CCR2 to attract neutrophils and monocytes (which differentiate into macrophages in the lungs) and CXCL9, CXCL10 and CXCL11, which act on CXCR3 to attract Th1 cells (T cell helper) and type 1 cytotoxic T-cells (Tc1 cells). These cells, together with macrophages and epithelial cells, release proteases, such as matrix metalloproteinase (MMP)9, which cause elastin degradation and emphysema. Neutrophil elastase also causes mucus hypersecretion. Epithelial cells and macrophages release transforming growth factor (TGF)-β, which stimulates fibroblast proliferation, resulting in fibrosis in the small airways.
Revised from an article Barnes P , Mechanisms in COPD compared with asthma Semantic Scholar

T helper type 1 (Th1) cells are a lineage of CD4+ effector T cell that promotes cell-mediated immune responses and is required for host defense against intracellular viral and bacterial pathogens. Th1 cells secrete IFN-gamma, IL-2, IL-10, and TNF-alpha/beta.


pigmented “smoker’s macrophages” in respiratory bronchioles and neighbouring alveoli, containing granular, yellow-brown cytoplasmic pigments


Cell Mediated Immunity Wiki

Barnes P , Mechanisms in COPD compared with asthma  semantic Scholar

Benjamin, R MD, MBA VADM, USPHS, Surgeon GeneralExposure to Tobacco Smoke Causes Immediate Damage: A Report of the Surgeon General

Bohadana A et al   Mechanisms of chronic airway obstruction in smokers Respiratory Medicine Volume 98, Issue 2, February 2004, Pages 139-151


Smoking Related Lung Diseases