Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma

Ratko Djukanović, 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, John V. Fahy

Research output: Contribution to journalArticle

472 Citations (Scopus)

Abstract

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 hyper-responsiveness to methacholine in mild to moderate asthma.

Original languageEnglish (US)
Pages (from-to)583-893
Number of pages311
JournalAmerican journal of respiratory and critical care medicine
Volume170
Issue number6
DOIs
StatePublished - Sep 15 2004
Externally publishedYes

Fingerprint

Immunoglobulin E
Asthma
Inflammation
Methacholine Chloride
Antibodies
Sputum
Eosinophils
Therapeutics
Respiratory Hypersensitivity
Mucous Membrane
Placebos
Antibodies, Monoclonal, Humanized
Fc Receptors
Eosinophilia
Omalizumab
Interleukin-4
B-Lymphocytes
Anti-Inflammatory Agents
Staining and Labeling
T-Lymphocytes

Keywords

  • Eosinophils
  • High-affinity Fc receptor for IgE, FcεRI
  • Interleukin-4

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. / Djukanović, Ratko; Wilson, Susan J.; Kraft, Monica; Jarjour, Nizar N.; Steel, Mark; Chung, K. Fan; Bao, Weibin; Fowler-Taylor, Angel; Matthews, John; Busse, William W.; Holgate, Stephen T.; Fahy, John V.

In: American journal of respiratory and critical care medicine, Vol. 170, No. 6, 15.09.2004, p. 583-893.

Research output: Contribution to journalArticle

Djukanović, R, Wilson, SJ, Kraft, M, Jarjour, NN, Steel, M, Chung, KF, Bao, W, Fowler-Taylor, A, Matthews, J, Busse, WW, Holgate, ST & Fahy, JV 2004, 'Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma', American journal of respiratory and critical care medicine, vol. 170, no. 6, pp. 583-893. https://doi.org/10.1164/rccm.200312-1651OC
Djukanović, Ratko ; Wilson, Susan J. ; Kraft, Monica ; Jarjour, Nizar N. ; Steel, Mark ; Chung, K. Fan ; Bao, Weibin ; Fowler-Taylor, Angel ; Matthews, John ; Busse, William W. ; Holgate, Stephen T. ; Fahy, John V. / Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. In: American journal of respiratory and critical care medicine. 2004 ; Vol. 170, No. 6. pp. 583-893.
@article{a09e24fd29b8457eaf6ad88dff7a2f50,
title = "Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma",
abstract = "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 hyper-responsiveness to methacholine in mild to moderate asthma.",
keywords = "Eosinophils, High-affinity Fc receptor for IgE, FcεRI, Interleukin-4",
author = "Ratko Djukanović and Wilson, {Susan J.} and Monica Kraft and Jarjour, {Nizar N.} and Mark Steel and Chung, {K. Fan} and Weibin Bao and Angel Fowler-Taylor and John Matthews and Busse, {William W.} and Holgate, {Stephen T.} and Fahy, {John V.}",
year = "2004",
month = "9",
day = "15",
doi = "10.1164/rccm.200312-1651OC",
language = "English (US)",
volume = "170",
pages = "583--893",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "6",

}

TY - JOUR

T1 - Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma

AU - Djukanović, Ratko

AU - Wilson, Susan J.

AU - Kraft, Monica

AU - Jarjour, Nizar N.

AU - Steel, Mark

AU - Chung, K. Fan

AU - Bao, Weibin

AU - Fowler-Taylor, Angel

AU - Matthews, John

AU - Busse, William W.

AU - Holgate, Stephen T.

AU - Fahy, John V.

PY - 2004/9/15

Y1 - 2004/9/15

N2 - 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 hyper-responsiveness to methacholine in mild to moderate asthma.

AB - 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 hyper-responsiveness to methacholine in mild to moderate asthma.

KW - Eosinophils

KW - High-affinity Fc receptor for IgE, FcεRI

KW - Interleukin-4

UR - http://www.scopus.com/inward/record.url?scp=4444232912&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444232912&partnerID=8YFLogxK

U2 - 10.1164/rccm.200312-1651OC

DO - 10.1164/rccm.200312-1651OC

M3 - Article

C2 - 15172898

AN - SCOPUS:4444232912

VL - 170

SP - 583

EP - 893

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 6

ER -