The pathogenesis of asthma involves genetic and environmental factors that contribute to chronic airway inflammation. Several genes coding for proteins (IL-33, ST2 receptor, ADAM33) have been proposed but their function is not elucidated. Histopathology of asthma is characterized by bronchial infiltration of inflammatory cells and airway remodeling. More frequent in severe asthma, remodeling includes epithelial injury, basement membrane thickening, subepithelial fibrosis and bronchial smooth muscle layer thickening. Multiple cell types such as dendritic cells, TH2 cells, B cells, mast cell, eosinophils, epithelial cells and bronchial smooth cells, are involved in airway inflammation. Mediators produced by these inflammatory and immune cells associate antibodies (IgE), cytokines (IL-4, IL-5, IL-13, IL-9, TSLP), chemokines and proteases. The cell type or the mediator that may orchestrate this complex inflammatory process is not identified. Studying the links between pathophysiologic mechanisms (endotype) and disease characteristics (phenotype) is a priority research area to validate therapeutic targets in asthma.
In COPD, alpha-1 antitrypsin deficiency is a rare genetic disorder associated with early-onset emphysema. In most patients, tobacco components trigger directly airway inflammation and are responsible for irreversible lung damages. Cigarette smoke stimulates macrophages and epithelial cells leading to release of chemokines that attract inflammatory cells (neutrophils, monocytes, TH1 cells, cytotoxic T cells) to the lungs. Epithelial cells, macrophages and other inflammatory cells produce proteases (neutrophil elastase, MMP9) resulting in mucus hypersecretion, elastin degradation and emphysema. Epithelial cells and macrophages also release fibrotic mediator (TGF??) that induces fibroblast proliferation, leading to peribronchiolar fibrosis. Lung parenchyma destruction, bronchial remodeling and vascular dysfunction drive the development of pulmonary hypertension that is associated with poor prognosis.