Asthma

Abstract

Asthma is a common pathology caused by intermittent bronchial obstruction. It is a syndrome with multiple etiologies, but dominated by the role of an allergic reaction. The incidence of asthma increased considerably during the second half of the ^20th century. Allergic asthma involves the polarization of CD4 T lymphocytes of the " TH2 " type. These cells produce cytokines : IL-4, IL-5 ; IL-13, in particular, which recruit and activate eosinophils and induce the production of IgE isotype antibodies responsible for the release of bronchonstrictor mediators by mast cells, basophils and eosinophils. The characteristics of the dendritic cells in contact with the bronchial epithelium and the lumen where the initiating antigens are found also play a key role, under the effect of alarmines excreted by the stimulated epithelial cells. In addition, activation of specialized respiratory epithelial cells by IL-5 and IL-13 leads to excessive mucus secretion, which obstructs the bronchial airways. Other cytokines (ECP, MCP) released by eosinophils contribute to sub-epithelial fibrosis and basement membrane thickening, which contribute to the chronic nature of bronchoconstriction. Alongside TH2, innate lymphoid cells of the 2 type also contribute to this pathophysiology.

A recent advance concerns the characterization of allergens. These may act through their protease properties, which can activate alarmins (see above). Alongside known notions of genetic risk factors, the role of the environment has been clearly highlighted by epidemiological studies of cohorts of children. It has been shown that children raised for the first five years of their lives on farms with animals and subjected to numerous antigenic stimuli from the microbial environment had a lower risk of developing allergy, and asthma in particular. This phenomenon suggests an early organization of immune responses linked to the conditions of activation of innate immunity at the level of the respiratory tree. This finding has potential applications in terms of preventive measures. In this context, early respiratory viral infections are also a risk factor.

All this data has led to the development of new therapies for chronic and severe asthma, based on the use of bioreactive inhibitors of cytokines with a proven pathological role : IL-4, IL-5, IL-13 in addition to IgE. The results obtained are convincing, but still far from perfect control of this disabling disease. Other avenues (neutralization of alarmines, etc.) are also being evaluated.