New Aspects in the Immunopathology of Severe Asthma

Abstract

Severe asthma afflicts only a small portion of the population of asthmatics; however, due to the severity of the disease, treatment of these patients generates disproportionately high costs, which account for as much as spent for treatment of all other asthmatics. This issue gains even more importance since currently available medications are often not sufficient to treat or even dampen the inflammatory response in the airways of severe asthmatics. Whereas mild-to-moderate asthma is characterized by reversibility of airway obstruction, severe asthma frequently includes a degree of fixed airflow limitation and corticosteroid refractoriness. In contrast to mild-to-moderate asthma, the inflammatory response in the airways appears to be much more complex including neutrophils as the dominating leukocyte subpopulation. A plethora of neutrophilderived mediators and enzymes appears to perpetuate or aggravate the inflammatory response and its pathophysiologic consequences by forming several positive feedback loops. Although neutrophil infiltration into the airways is a common feature of acute asthma exacerbations, these cells are observed in the airways of severe asthmatics in the absence of bacterial infections. Since the identification of T helper 17 (TH17) cells in airway infiltrates of severe asthmatics, TH17 cells are also implicated in the immunopathology of the disease. By secreting interleukin 17A TH17 cells are able to induce the airway epithelial cell production of IL-8, the most potent chemoattractant for neutrophils. However, understanding the role of these cells within the context of the immunopathology of severe asthma is just in the fledging stages. This review aims at summarizing the actual knowledge on the immunopathologic mechanisms underlying this disease. Keywords: Asthma, allergy, neutrophils, HNE, T17 cells, IL-17