Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment.
BACKGROUND
Anti-IgE, omalizumab, inhibits the allergen response in patients with asthma. This has not been directly related to changes in inflammatory conditions. We hypothesized that anti-IgE exerts its effects by reducing airway inflammation. To that end, the effect of anti-IgE on allergen-induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a randomized, double-blind, placebo-controlled study.


METHODS
Allergen challenge followed by a bronchoscopy at 24 h was performed at baseline and after 12 weeks of treatment with anti-IgE or placebo. Provocative concentration that causes a 20% fall in forced expiratory volume in 1 s (PC(20)) methacholine and induced sputum was performed at baseline, 8 and 12 weeks of treatment. Changes in the early and late responses to allergen, PC(20), inflammatory cells in biopsies and sputum were assessed.


RESULTS
Both the early and late asthmatic responses were suppressed to 15.3% and 4.7% following anti-IgE treatment as compared with placebo (P < 0.002). This was paralleled by a decrease in eosinophil counts in sputum (4-0.5%) and postallergen biopsies (15-2 cells/0.1 mm(2)) (P < 0.03). Furthermore, biopsy IgE+ cells were significantly reduced between both the groups, whereas high-affinity IgE receptor and CD4+ cells were decreased within the anti-IgE group. There were no significant differences for PC(20) methacholine.


CONCLUSIONS
The response to inhaled allergen in asthma is diminished by anti-IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE-bearing cells postallergen without changing PC(20) methacholine. This suggests that the benefits of anti-IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE-bearing cells.
van Rensen
E L J
EL
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Evertse
C E
CE
van Schadewijk
W A A M
WA
van Wijngaarden
S
S
Ayre
G
G
Mauad
T
T
Hiemstra
P S
PS
Sterk
P J
PJ
Rabe
K F
KF
D000293:Adolescent; D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation; D008297:Male; D000069444:Omalizumab; D017455:Receptors, IgE / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult
D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017455:Receptors, IgE; D000069444:Omalizumab; D007073:Immunoglobulin E