These inhibitors reverse corticosteroid insensitivity by increasing HDAC2 activity and improve airway inflammation by modulating endoplasmic reticulum stress.[83,84] Dual PI3Kδ/γ inhibitors such as TG100-115 and IPI-145 are being evaluated in clinical trials for the treatment of asthma and chronic obstructive pulmonary disease (COPD), showing positive results.[85,86] In a study of asthmatic mice,[87] toluene diisocyanate produced elevated NET levels induced through the p38 and ERK signaling pathways, promoting elevated IL-8 levels. This evidence concerns the gene MAPK14 and chronic obstructive pulmonary disease.