Immune responses and exacerbations in severe asthma.

Asthma as a clinical entity manifests with a broad spectrum of disease severity. Unlike milder asthma, severe disease is poorly controlled by inhaled corticosteroids, the current standard of care. Transcriptomic data, along with patient characteristics and response to biologics show that though Type 2 (T2) immune response remains an integral feature of asthma, additional molecular and immunologic factors may play important roles in pathogenesis. Mechanisms of T2 development, cellular sources of T2 cytokines and their relationship to additional immune pathways concurrently activated may distinguish several different subphenotypes, and perhaps endotypes of asthma, with differential response to non-specific and targeted anti-inflammatory therapies. Recent data have also associated non-T2 cytokines derived from T cells, particularly IFN-γ, and epithelial mediators with severe asthma. These topics and their relationships to acute asthma exacerbations are discussed in this review.