LPS preparations from multiple bacterial species were tested for capacity to engage the non-canonical inflammasome in epithelial cells, and publicly available human asthma datasets were analyzed for airway expression of caspase-4 and gasdermin D.<h4>Results</h4>Intracellular LPS activated caspase-4-dependent pyroptotic signaling, resulting in gasdermin D cleavage, IL-33 release, and MAPK-dependent transcriptional responses. The gene discussed is CASP4; the disease is asthma.