PAD-4-deficient mouse neutrophils fail to release NETs in response to LPS and TNF stimulation.[99] Simvastatin inhibits NETosis neutrophilic inflammation and AHR by reducing PAD-4 expression in a mouse model of severe asthma.[100] In addition, H3cit has been suggested as a possible novel and specific biomarker for this process.[101] The clinical relevance of increased serum H3cit to the mechanism of asthma progression and risk of exacerbation remains to be determined, and no effective biological agents are available. The gene discussed is TNF; the disease is asthma.