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

https://doi.org/10.1016/j.jaci.2004.08.032Get 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 TH2-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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