Evidence of a Role of Tumor Necrosis Factor α in Refractory Asthma

• Published in: The New England journal of medicine Vol. 354; no. 7; pp. 697 - 708
• Main Authors: Berry, Mike A, Hargadon, Beverley, Shelley, Maria, Parker, Debbie, Shaw, Dominick E, Green, Ruth H, Bradding, Peter, Brightling, Christopher E, Wardlaw, Andrew J, Pavord, Ian D
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 16.02.2006
• Subjects: ADAM Proteins - biosynthesis; ADAM17 Protein; Adolescent; Adult; Aged; Asthma - drug therapy; Asthma - metabolism; Asthma - physiopathology; Biomarkers - metabolism; Bronchial Hyperreactivity - drug therapy; Bronchial Hyperreactivity - metabolism; Case-Control Studies; Cross-Over Studies; Double-Blind Method; Etanercept; Female; Forced Expiratory Volume - drug effects; Humans; Immunoglobulin G - therapeutic use; Immunologic Factors - therapeutic use; Male; Methacholine Chloride; Middle Aged; Monocytes - metabolism; Pilot Projects; Receptors, Tumor Necrosis Factor - therapeutic use; Receptors, Tumor Necrosis Factor, Type I - biosynthesis; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa050580

Patients with severe asthma are distinct from patients with milder forms of the disease. Peripheral-blood monocytes from patients with severe asthma were shown to have enhanced expression of markers associated with tumor necrosis factor α (TNF-α). In a pilot, placebo-controlled, crossover study, the TNF-α receptor–binding agent etanercept improved airway responsiveness and asthma-related quality of life. TNF-α may have a role in refractory asthma. In a pilot study, the TNF-α receptor–binding agent etanercept improved airway responsiveness and asthma-related quality of life. TNF-α may have a role in refractory asthma. The rates of death and complications are high among patients with refractory asthma and account for a disproportionate amount of the health resource burden attributed to asthma. 1 Treatment options are limited for these patients. The airway abnormality in refractory asthma differs from that in mild-to-moderate asthma in having a more heterogeneous pattern of inflammatory response, 2 with greater involvement of neutrophils 3 and the distal lung 4 and increased airway remodeling. 5 Tumor necrosis factor α (TNF-α) is a pleiotropic inflammatory cytokine expressed in increased amounts by mast cells 6 and present in increased concentrations in bronchoalveolar fluid from the airways of patients with asthma. . . .