BACKGROUND: The development of tumor necrosis factor alpha (TNF-alpha) antagonists has made it feasible to investigate the role of this cytokine in refractory asthma. METHODS: We measured markers of TNF-alpha activity on peripheral-blood monocytes in 10 patients with refractory asthma, 10 patients with mild-to-moderate asthma, and 10 control subjects. We also investigated the effects of treatment with the soluble TNF-alpha receptor etanercept (25 mg twice weekly) in the patients with refractory asthma in aplacebo-controlled, double-blind, crossover pilot study. RESULTS: As compared with patients with mild-to-moderate asthma and controls, patients with refractory asthma had increased expression of membrane-bound TNF-alpha, TNF-alpha receptor 1, and TNF-alpha-converting enzyme by peripheral-blood monocytes. In the clinical trial, as compared with placebo, 10 weeks of treatment with etanercept was associated with a significant increase in the concentration of methacholine required to provoke a 20 percent decrease in the forced expiratory volume in one second (FEV1) (mean difference in doubling concentration changes between etanercept and placebo, 3.5; 95 percent confidence interval, 0.07 to 7.0; P=0.05), an improvement in the asthma-related quality-of-life score (by 0.85 point; 95 percent confidence interval, 0.16 to 1.54 on a 7-point scale; P=0.02), and a 0.32-liter increase in post-bronchodilator FEV1 (95 percent confidence interval, 0.08 to 0.55; P=0.01). CONCLUSIONS:Patients with refractory asthma have evidence of up-regulation of the TNF-alpha axis. (ClinicalTrials.gov number, NCT00276029.). Copyright 2006 Massachusetts Medical Society.
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BACKGROUND: The development of tumor necrosis factor alpha (TNF-alpha) antagonists has made it feasible to investigate the role of this cytokine in refractory asthma. METHODS: We measured markers of TNF-alpha activity on peripheral-blood monocytes in 10 patients with refractory asthma, 10 patients with mild-to-moderate asthma, and 10 control subjects. We also investigated the effects of treatment with the soluble TNF-alpha receptor etanercept (25 mg twice weekly) in the patients with refractory asthma in a placebo-controlled, double-blind, crossover pilot study. RESULTS: As compared with patients with mild-to-moderate asthma and controls, patients with refractory asthma had increased expression of membrane-bound TNF-alpha, TNF-alpha receptor 1, and TNF-alpha-converting enzyme by peripheral-blood monocytes. In the clinical trial, as compared with placebo, 10 weeks of treatment with etanercept was associated with a significant increase in the concentration of methacholine required to provoke a 20 percent decrease in the forced expiratory volume in one second (FEV1) (mean difference in doubling concentration changes between etanercept and placebo, 3.5; 95 percent confidence interval, 0.07 to 7.0; P=0.05), an improvement in the asthma-related quality-of-life score (by 0.85 point; 95 percent confidence interval, 0.16 to 1.54 on a 7-point scale; P=0.02), and a 0.32-liter increase in post-bronchodilator FEV1 (95 percent confidence interval, 0.08 to 0.55; P=0.01). CONCLUSIONS:Patients with refractory asthma have evidence of up-regulation of the TNF-alpha axis. (ClinicalTrials.gov number, NCT00276029.). Copyright 2006 Massachusetts Medical Society.
Authors: Alejandro A Pezzulo; Rosarie A Tudas; Carley G Stewart; Luis G Vargas Buonfiglio; Brian D Lindsay; Peter J Taft; Nicholas D Gansemer; Joseph Zabner Journal: J Clin Invest Date: 2019-01-14 Impact factor: 14.808
Authors: L Dejager; K Dendoncker; M Eggermont; J Souffriau; F Van Hauwermeiren; M Willart; E Van Wonterghem; T Naessens; M Ballegeer; S Vandevyver; H Hammad; B Lambrecht; K De Bosscher; J Grooten; C Libert Journal: Mucosal Immunol Date: 2015-03-11 Impact factor: 7.313
Authors: S S An; T R Bai; J H T Bates; J L Black; R H Brown; V Brusasco; P Chitano; L Deng; M Dowell; D H Eidelman; B Fabry; N J Fairbank; L E Ford; J J Fredberg; W T Gerthoffer; S H Gilbert; R Gosens; S J Gunst; A J Halayko; R H Ingram; C G Irvin; A L James; L J Janssen; G G King; D A Knight; A M Lauzon; O J Lakser; M S Ludwig; K R Lutchen; G N Maksym; J G Martin; T Mauad; B E McParland; S M Mijailovich; H W Mitchell; R W Mitchell; W Mitzner; T M Murphy; P D Paré; R Pellegrino; M J Sanderson; R R Schellenberg; C Y Seow; P S P Silveira; P G Smith; J Solway; N L Stephens; P J Sterk; A G Stewart; D D Tang; R S Tepper; T Tran; L Wang Journal: Eur Respir J Date: 2007-05 Impact factor: 16.671