Non-type 2 inflammation in severe asthma is propelled by neutrophil cytoplasts and maintained by defective resolution.

Asthma is a highly prevalent heterogeneous inflammatory disorder of the airways. Not all patients respond to anti-inflammatory treatment with corticosteroids, leading to significant morbidity in severe asthma. Much attention has been paid to defining the cellular and molecular mechanisms of type 2 inflammation that are operative in asthma. Development of targeted therapies for pathologic type 2 inflammation is opening a new approach to asthma treatment; however, not all asthmatics have type 2 airway inflammation, especially those with severe corticosteroid-refractory asthma. Much less is known about non-type 2 immunological mechanisms in asthma. In health, inflammation triggers resolution mechanisms that control immune (type 1 and type 2) responses and enable the restoration of tissue homeostasis. The resolution response is comprised of cellular and molecular events, including production of specialized pro-resolving mediators (SPMs). SPMs halt leukocyte recruitment, promote macrophage efferocytosis, and restore epithelial barrier integrity, all of which are critical to resolution of inflammation in the lungs. Here, we review recent insights into the disruption of these homeostatic mechanisms and their contributions to non-type 2 inflammation in severe asthma immunopathogenesis.