Published ahead of print on June 1, 2004, doi:10.1164/rccm.200312-1651OC
American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 583-593, (2004)
© 2004 American Thoracic Society
Effects of Treatment with Anti-immunoglobulin E Antibody Omalizumab on Airway Inflammation in Allergic Asthma
Ratko Djukanovi ,
Susan J. Wilson,
Monica Kraft,
Nizar N. Jarjour,
Mark Steel,
K. Fan Chung,
Weibin Bao,
Angel Fowler-Taylor,
John Matthews,
William W. Busse,
Stephen T. Holgate and
John V. Fahy
University of Southampton, Southampton; Imperial College, London; Novartis Horsham Research Centre, Horsham, United Kingdom; National Jewish Center, Denver, Colorado; University of Wisconsin Hospital and Clinics, Madison, Wisconsin; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey; and University of California, San Francisco, San Francisco, California
Correspondence and requests for reprints should be addressed to Ratko Djukanovi, M.D., F.R.C.P., Respiratory Cell and Molecular Biology, Division of Infection, Inflammation, and Repair, Level D, Centre Block, Mail Point 810, University of Southampton, Southampton SO16 6YD, UK. E-mail: rd1{at}soton.ac.uk
IgE plays an important role in allergic asthma. We hypothesized that reducing IgE in the airway mucosa would reduce airway inflammation. Forty-five patients with mild to moderate persistent asthma with sputum eosinophilia of 2% or more were treated with humanized monoclonal antibody against IgE (omalizumab) (n = 22) or placebo (n = 23) for 16 weeks. Outcomes included inflammatory cells in induced sputum and bronchial biopsies, and methacholine responsiveness. Treatment with omalizumab resulted in marked reduction of serum IgE and a reduction of IgE+ cells in the airway mucosa. The mean percentage sputum eosinophil count decreased significantly (p < 0.001) from 6.6 to 1.7% in the omalizumab group, a reduction significantly (p = 0.05) greater than with placebo (8.5 to 7.0%). This was associated with a significant reduction in tissue eosinophils; cells positive for the high-affinity Fc receptor for IgE; CD3+, CD4+, and CD8+ T lymphocytes; B lymphocytes; and cells staining for interleukin-4, but not with improvement in airway hyperresponsiveness to methacholine. This study shows antiinflammatory effects of omalizumab treatment and provides clues for mechanisms whereby omalizumab reduces asthma exacerbations and other asthma outcomes in more severe asthma. The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma.
Key Words: eosinophils • high-affinity Fc receptor for IgE, Fc RI • interleukin-4
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Copyright © 2004 American Thoracic Society
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