Urinary eosinophil protein X in children with atopic asthma: A useful marker of antiinflammatory treatment,☆☆,,★★

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Abstract

BACKGROUND: Bronchial asthma is associated with elevated serum levels of eosinophil products, such as eosinophil protein X (EPX), but the occurrence in urine of this substance in patients with asthma has not previously been studied. OBJECTIVE: This study was performed to clarify whether increased amounts of eosinophil granulocyte proteins in urine and serum reflect ongoing asthmatic inflammation and whether decreasing values reflect successful treatment. METHODS: Twelve children with a median age of 12.5 years who had mild or moderate atopic asthma were studied for 3 months. At the time of inclusion in the study, treatment with inhaled budesonide was initiated. Nine children of the same age without atopic disease served as control subjects. Levels of EPX, eosinophil cationic protein (ECP), and myeloperoxidase in serum and in urine (urinary EPX) were determined at inclusion and then after 3 months of treatment. Spirometry was performed on the same occasions. RESULTS: At the time of inclusion, urinary EPX and serum ECP were significantly higher in children with atopic asthma than in the control subjects (mean, 116.4 vs 43.0 μg/mmol creatinine [p = 0.004] and 37.0 vs 14.8 μg/L [p = 0.004]). In the asthma group urinary EPX, as well as serum ECP, decreased significantly after 3 months of treatment with budesonide (116.4 to 68.4 μg/mmol creatinine [p = 0.005] and 37.0 to 24.0 μg/L [p = 0.04]). At the same time, peak expiratory flow values increased significantly in the children with asthma (76.0% to 87.8% of predicted value [p = 0.005]) but not in the control subjects (87.0% to 90.1%). In the asthma group the levels of myeloperoxidase were similar to those in the control group, both at inclusion and after 3 months. CONCLUSION: Increased urinary EPX and serum ECP levels seem to reflect active atopic asthma, whereas decreased levels after antiinflammatory treatment probably reflect normalization of airway inflammation, and indirectly, improved lung function. (J Allergy Clin Immunol 1996;97:1179-87.)

Section snippets

Study design

The children were seen at two visits, 3 months apart. The visits included a detailed medical history and a thorough physical examination. The samples and tests were performed in the following order: urine, blood sample, spirometry, and skin prick test (SPT). The SPT was performed only at visit 1.

The study was approved by the Ethics Committee of the Medical Faculty, University of Göteborg.

Subjects

Twenty-one children were included: 12 had atopic asthma, and nine without atopy served as control subjects.

Leukocytes, CRP, and total IgE

In the asthma group eosinophil counts were significantly higher than in the control group, both at inclusion and after 3 months (p < 0.05 and p < 0.01, respectively). Other white blood cell counts were similar in both groups. CRP was not greater than 10 mg/L in any patient. Total IgE was significantly higher than that in the control group. No difference was observed between visits 1 and 2 regarding white blood cell counts, CRP, or total IgE (Table III).

Urinary EPX, sECP, sEPX, and sMPO

At inclusion, urinary EPX was

DISCUSSION

The eosinophil-derived proteins MBP and ECP may damage the respiratory epithelium through their cytotoxic effects.6 EPX is not cytotoxic to respiratory epithelium but has neurotoxic and biochemical properties similar to those of ECP.4, 7 Previous studies have shown a correlation between the levels of ECP in serum and BAL fluid in patients with asthma.8, 9, 16 These findings suggest that eosinophil granulocyte proteins in serum may indirectly reflect ongoing airway inflammation. One aim of this

Acknowledgements

We thank Mrs. Agneta Wyholt, RN, for her expert help.

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    From the Departments of aPaediatrics and b Virology, University of Göteborg; and cPharmacia Diagnostics AB, Uppsala, Sweden.

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    Supported by grants from the First of May Flower Annual Campaign for Children’s Health, the Gothenburg Society of Medicine, the Swedish Society of Medicine, the Swedish Heart Lung Foundation, the Gothenburg Masonic Order Orphanage Foundation, and the Research Fund of the Children’s Clinics, Gothenburg.

    Reprint requests: Sigurdur Kristjánsson, MD, PhD, Department of Paediatrics, University of Göteborg, Östra University Hospital, S-416 85 Göteborg, Sweden.

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