Another later small double-blind placebo-controlled study on the use of etanercept (a biologic medical product that interferes with TNF pathways) in severe refractory asthma confirmed that the therapy led to improvements in quality of life, lung function, and bronchial hyperresponsiveness; the authors did not find a significant change in sputum inflammatory cells, but reported a marked reduction in sputum histamine concentration: this not only suggests that etanercept inhibited primary mast cell activation, but also that MC-derived TNF-α plays a critical role in asthma pathophysiology [102]. This evidence concerns the gene TNF and asthma.