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Tumour necrosis factor α in refractory asthma: new insight
  1. S A Nachman
  1. Assistant Professor on Clinical Medicine, Columbia University/Harlem Hospital Center, New York, NY, USA; san14{at}

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The authors showed that monocytes from 10 patients with refractory asthma expressed significantly higher levels of TNF-α receptor 1, TNF-α converting enzyme, and membrane bound TNF-α than monocytes from 10 normal controls or from 10 patients with mild to moderate asthma.

They also investigated the effect of 10 weeks of treatment with etanercept, a soluble TNF-α receptor antagonist, on 10 patients with refractory asthma in a randomised, double blind, placebo controlled, crossover study. Compared with placebo, etanercept significantly reduced peripheral blood monocyte expression of membrane bound TNF-α, increased the concentration of methacholine required to decrease forced expiratory volume in 1 second (FEV1) by 20%, and improved asthma quality of life scores. Furthermore, treatment significantly improved post bronchodilator FEV1 and decreased the total symptoms score and mean sputum histamine concentration. There was no significant difference between groups in any of the other airway inflammatory markers studied (exhaled nitric oxide concentrations, sputum eosinophilic cationic protein, interleukin 8, or cysteinyl leukotriene concentrations).

The study concluded that the TNF-α axis is upregulated in peripheral blood monocytes of patients with refractory asthma. Although not powered to detect effects on airway inflammatory markers, the significant reduction in sputum histamine but not in other markers suggests that the effect of etanercept is primarily directly on smooth muscle and mast cells. Further investigations are needed to confirm this.