Pathobiology of Human Disease: Asthma

Asthma is an obstructive pulmonary disease affecting children and adults with increasing prevalence. The pathophysiology of asthma is complex, with both genes and the environment playing important roles. Inflammation is a key process, and interaction among the three T helper (Th) lymphocyte subsets, Th1, Th2, and Th17, as well as other inflammatory cells (mast cells, eosinophils, and neutrophils) and host parenchyma leads to cLinical symptoms. Airway wall remodeLing also contributes to cLinical symptoms and involves airway smooth muscle, angiogenesis, extracellular matrix, mucous cells, and epitheLium. Certain histological features that are seen in endobronchial biopsies of patients with asthma include submucosal eosinophiLia, prominent airway smooth muscle, thickening of the basement membrane, and goblet cell hyperplasia. Although there are defined cLinical asthma phenotypes and tissue asthma phenotypes, there is imperfect correlation between histological features and cLinical phenotype. Although biopsy is used in the research setting, it is impractical to biopsy asthma patients to confirm the diagnosis, and therefore, besides a purely cLinical diagnosis based on symptoms, there are biomarkers, such as exhaled nitric oxide and inflammation in sputum, which can be used to help diagnose and monitor the disease. Asthma therapy can be classified as short-term controllers for acute exacerbation, for example, short-acting beta-2-receptor agonists, or long-term controllers, such as corticosteroids. New adjunct therapies include biologics targeting specific types of cells and bronchial thermoplasty, a procedure to ablate the airway smooth muscle. Mouse models of asthma have mostly focused on isolating the roles of the different types of inflammation and how the inflammation relates to airway remodeLing in the setting of different environmental exposures.