In a prior study, TNF-α, a neutrophil and eosinophil chemoattractant, increased sputum neutrophilia and airway hyperresponsiveness in normal subjects.55 TNF-α also promotes the damaging effects of eosinophilic inflammation on the epithelium.52 Thus, elevations of both IL-13 and TNF-α may suggest a ‘double hit’ in these mepolizumab patients. The gene discussed is TNF; the disease is airway hyperresponsiveness.