Fig. 2. Inflammatory pathway and therapeutic approach for the management of NERD. Various exogenous factors, such as viruses, bacteria, and environmental factors, can initiate epithelial injury and release of alarmins, IL33, IL25, and TSLP. These elevated levels of alarmins and cytokines from epithelial cells induce type 2 inflammatory responses by activating mast cells and ILC2 which are capable of activating eosinophils. Activated mast cells and eosinophils release various cytokines and chemokines that can induce mucosal inflammation and bronchoconstriction. The increased burden of platelet-associated leukocytes in NERD can further enhance the production of cysLTs, PGD2, and TXA2.

NERD, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease; IL, interleukin; TSLP, thymic stromal lymphopoietin; ILC2, innate lymphoid type-2 cell; cysLT, cysteinyl leukotriene; PGD2, prostaglandin D2; TXA2, thromboxane A2; TGF, transforming growth factor; DPP10, dipeptidyl peptidase 10; SPD, surfactant protein D; LT, leukotriene; PG, prostaglandin; TX, thromboxane; INF, interferon.