Evidence of a Role of Tumor Necrosis Factor {alpha} in Refractory Asthma

doi:10.1056/NEJMoa050580

Volume 354:697-708		February 16, 2006		Number 7

Evidence of a Role of Tumor Necrosis Factor ${alpha}$ in Refractory Asthma

Mike A. Berry, M.R.C.P., Beverley Hargadon, R.G.N., Maria Shelley, R.G.N., B.A., Debbie Parker, B.Sc., Dominick E. Shaw, M.R.C.P., Ruth H. Green, M.D., M.R.C.P., Peter Bradding, D.M., F.R.C.P., Christopher E. Brightling, Ph.D., M.R.C.P., Andrew J. Wardlaw, Ph.D., F.R.C.P., and Ian D. Pavord, D.M., F.R.C.P.

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ABSTRACT

Background The development of tumor necrosis factor ${alpha}$ (TNF- ${alpha}$ )antagonists has made it feasible to investigate the role ofthis cytokine in refractory asthma.

Methods We measured markers of TNF- ${alpha}$ activity on peripheral-bloodmonocytes in 10 patients with refractory asthma, 10 patientswith mild-to-moderate asthma, and 10 control subjects. We alsoinvestigated the effects of treatment with the soluble TNF- ${alpha}$ receptor etanercept (25 mg twice weekly) in the patients withrefractory asthma in a placebo-controlled, double-blind, crossoverpilot study.

Results As compared with patients with mild-to-moderate asthmaand controls, patients with refractory asthma had increasedexpression of membrane-bound TNF- ${alpha}$ , TNF- ${alpha}$ receptor 1, and TNF- ${alpha}$ –convertingenzyme by peripheral-blood monocytes. In the clinical trial,as compared with placebo, 10 weeks of treatment with etanerceptwas associated with a significant increase in the concentrationof methacholine required to provoke a 20 percent decrease inthe forced expiratory volume in one second (FEV₁) (mean differencein doubling concentration changes between etanercept and placebo,3.5; 95 percent confidence interval, 0.07 to 7.0; P=0.05), animprovement in the asthma-related quality-of-life score (by0.85 point; 95 percent confidence interval, 0.16 to 1.54 ona 7-point scale; P=0.02), and a 0.32-liter increase in post-bronchodilatorFEV₁ (95 percent confidence interval, 0.08 to 0.55; P=0.01).

Conclusions Patients with refractory asthma have evidence ofup-regulation of the TNF- ${alpha}$ axis. (ClinicalTrials.gov number,NCT00276029 [ClinicalTrials.gov] .)

Source Information

From the Institute for Lung Health, University Hospital of Leicester National Health Service Trust, Glenfield Hospital, Leicester, United Kingdom.

Address reprint requests to Prof. Pavord at the Institute for Lung Health, University Hospital of Leicester National Health Service Trust, Glenfield Hospital, Groby Rd., Leicester LE3 9QP, United Kingdom, or at ian.pavord{at}uhl-tr.nhs.uk.

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Tumor Necrosis Factor ${alpha}$ in Refractory Asthma
Oliveri C., Polosa R., Berry M. A., Pavord I. D.
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N Engl J Med 2006; 354:2074-2075, May 11, 2006. Correspondence

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