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 hyperresponsiveness to methacholine in mild to moderate asthma.

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

“…It has been shown that 16-week omalizumab therapy significantly reduces the number of IgE--positive and FceRI-positive cells in the bronchial submucosa [8]. As noted by Lin et al [13], this inhibition of FceRI expression on basophils can be seen after seven days from omalizumab administration, and as MacGlashan et al [14] demonstrated, three months following the commencement of treatment, the inhibition effect is 96%.…”

“…An important role in this phenomenon is played by Th2-lymphocytes and by IL-4 and IL-13 produced by Th2-lymphocytes [6]. Omalizumab was confirmed to reduce the amount of IL-4 [8] and IL-13 [9] positive cells and B lymphocytes in bronchial tissue [8].…”

Improving the diagnosis of eosinophilic asthma

“…Cross-linking of IgE molecules causes the release of mediators (histamine, arachidonic acid metabolites) and cytokines (tumor necrosis factor alpha, IL-4, and IL-5) which are responsible for the immediate and latephase allergic response, and the associated influx of eosinophils in the airway [48]. Several studies have found an association between serum IgE levels and airway eosinophilia in asthma, and treatment with anti-IgE has been shown to be associated with a significant reduction in tissue eosinophils [49]. However, despite these findings, the use of IgE as a biomarker for eosinophilic inflammation is not recommendable.…”

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

“…For instance, anti-immunoglobulin E [4] or antiinterleukin (IL)-5 [5] therapy greatly diminish multiple features of inflammation without altering hyperresponsiveness in asthma. Conversely, anti-tumour necrosis factor (TNF)-a treatment was shown to be associated with reduction of AHR without changing the markers of airway inflammation (except for a decrease in histamine concentrations in sputum supernatant), suggesting that the benefit of the treatment is derived primarily by an effect on ASM and mast cells [6].…”