Sputum and bronchial submucosal IL-13 expression in asthma and eosinophilic bronchitis

doi:10.1016/j.jaci.2004.08.032

Journal of Allergy and Clinical Immunology

Volume 114, Issue 5, November 2004, Pages 1106-1109

https://doi.org/10.1016/j.jaci.2004.08.032 Get rights and content

Background

Nonasthmatic eosinophilic bronchitis is a condition characterized by the presence of eosinophilic airway inflammation in the absence of airflow obstruction or airway hyperresponsiveness. In asthma, the T_H2-type cytokine IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness. Whether the expression of IL-13 is different between these 2 conditions is unknown.

Objective

We sought to investigate whether IL-13 expression is increased in asthma compared with eosinophilic bronchitis.

Methods

Sputum samples from subjects with mild asthma (n = 30) and eosinophilic bronchitis (n = 15) and normal controls (n = 16) were dialyzed, and IL-13 concentration was measured by ELISA. In a subgroup of these patients, IL-13 protein expression in bronchial biopsies was assessed by immunohistochemistry.

Results

The concentration of sputum IL-13 was higher in patients with mild asthma than in normal controls (P = .03) and in patients with eosinophilic bronchitis (P = .03). The median (interquartile range) number of IL-13⁺ cells/mm² submucosa was significantly higher in asthma 4 (8) than eosinophilic bronchitis 1.7 (1.9) and normal controls 0.5 (1.1; P = .004). Eighty-three percent of the cells expressing IL-13 in the submucosa were eosinophils, and 8% were mast cells. The median (interquartile range) proportion of eosinophils that expressed IL-13 was higher in the subjects with asthma, 16 (10)%, than those with eosinophilic bronchitis, 7 (3)% (P = .02).

Conclusion

The increased expression of IL-13 in asthma compared with eosinophilic bronchitis supports the concept that IL-13 may play a critical role in the pathophysiology of asthma.

Section snippets

Subjects

Patients with eosinophilic bronchitis, patients with asthma, and healthy volunteers were recruited from respiratory clinics and from staff at Glenfield Hospital. Subjects with asthma (n = 30) gave a suggestive history and had objective evidence of variable airflow obstruction as indicated by one or more of the following: (1) methacholine airway hyperresponsiveness (PC₂₀ FEV₁ < 8 mg/mL), (2) >15% improvement in FEV₁ 10 minutes after 200 μg inhaled salbutamol, or (3) peak expiratory flow (>20%

Results

The mucolytic dithiothreitol affected recovery of IL-13 by using both commercial ELISA kits (Caltag-Medsystems and R&D). The percentage recovery (coefficient of variation) of standards spiked with dithiothreitol compared with standards without dithiothreitol was similar with both assays: 38% (14%) and 36% (29%) for the Caltag-Medsystems and R&D ELISA, respectively. The Caltag-Medsytems ELISA was more sensitive and therefore was further validated. The recovery of IL-13 standard after dialysis

Discussion

This is the first study to fully validate the measurement of IL-13 in induced sputum. In addition, this study has made two important and novel observations. First, we have shown that the expression of IL-13 protein in the bronchial submucosa and the sputum concentration of IL-13 were increased in asthma compared with eosinophilic bronchitis, supporting the concept that IL-13 plays a critical role in the pathophysiology of asthma. Second, we identified that most of the cells in the bronchial

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: Supported by a grant from Asthma UK and Cambridge Antibody Technology. Dr Brightling is supported by a DoH Clinician Scientist Award.

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Mechanisms of asthma and allergic inflammationSputum and bronchial submucosal IL-13 expression in asthma and eosinophilic bronchitis

Background

Objective

Methods

Results

Conclusion

Section snippets

Subjects

Results

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Eosinophils in asthma and other allergic diseases

Br Med Bull

Th-2 cytokines in allergic disease

Br Med Bull

Mast-cell infiltration of airway smooth muscle in asthma

N Engl J Med

Comparison of airway immunopathology of eosinophilic bronchitis and asthma

Thorax

Interleukin-4 and -13 expression is co-localized to mast cells within the airway smooth muscle in asthma

Clin Exp Allergy

Histamine and methacholine inhalation tests: a laboratory tidal breathing protocol

The use of induced sputum to investigate airway inflammation

Thorax

Mechanisms of asthma and allergic inflammation
Sputum and bronchial submucosal IL-13 expression in asthma and eosinophilic bronchitis