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Brief Reports Indian Pediatrics 2002; 39:1017-1021 |
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Circulating Adhesion Molecule Levels in Childhood Asthma |
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Mucosal inflammation is a feature of asthma, with the evidence of tissue eosinophilia, mast cell and T-lymphocyte activation(1). The importance of leukocyte endothelial adhesion molecules which mediate the migration of leukocytes to the inflammation area in various chronic diseases, has been established in recent years(2). Accumulating evidence suggests that these molecules play an important role in the pathophysiology of asthma and other allergic disorders. In the present study, sE-selectin, soluble intercellular adhesion molecule-I (sICAM-1) and soluble vascular cell adhesion molecule-I (sVCAM-1) levels in serum samples of children with asthma and healthy controls were evaluated to determine whether adhesion molecule levels showed any difference between asthmatic and healthy children and whether these levels changed with atopic status or disease activity. Subjects and Methods The study population consisted of 30 patients with mild persistent asthma, followed up at University of Ankara, Department of Pediatric Immunology-Allergy with a median age of 6 years (range 2-12 y) and 10 healthy controls with a median age of 7 years (range 2-14 y). The diagnosis of asthma was based on International Pediatric Asthma Consensus Group Reports(3). The asthmatic children population consisted of three groups: acute asthmatics, atopic stable asthmatics and nonatopic stable asthmatics(Table I). The first group consisted of 10 children with acute asthma, admitted to the hospital within 24 hours from the onset of their symptoms. The clinical examination of the patients revealed wheezing, tachypnea and prolonged expiration time in addition to decreased values of peak expiratory flow rate (PEFR) (when available; in patients where a complete compliance was achieved, ł 5 years) during asthma attack. No signs of bacterial infection were detected on admission during physical examination or in blood counts and chest X-rays. Children who had already received systemic steroid for the presenting exacerbation of asthma before coming to hospital were not included in the study. Table I- Patient Characteristics in the Four Study Groups
* Fluticasone dipropionate 125-250 µg/day The second and the third group of patients consisted of stable atopic and stable nonatopic asthmatic children. Stable asthma was defined on the basis of lack of clinical symptoms such as wheezing, tachypnea, and prolonged expiration time in addition to PEFR greater than 80% of predicted in patients who were able to undergo the evaluation. None of the patients with stable asthma (atopic/nonatopic) had experienced acute exacerbation during the preceding month and none had clinical signs of infection. An informed consent was obtained from parents prior to recruitment. Table II- Serum sICAM-1, sVCAM-1 and sE-selectin Levels (mean ± SD) in Asthmatic and Healthy Children
* Significantly different ( P < 0.05) from the other three groups
Measurement of serum sICAM-1, sVCAM-1 and sE-selectin Serum levels of sICAM-1, sVCAM-1 and sE-selectin were measured by commercially available ELISA kits (sE-Selectin; Bender Med Systems, BMS 205, Vienna, Austria; sICAM-1: Biosource Int., KHS5402, California, USA; sVCAM-1: Biosource Int., Cytoscreen, KHT0602, California, USA) following manufacturers instructions. The lower limit of detection sensitivity was 0.04 ng/mL for sICAM-1, 0.5 ng/mL for sVCAM-1 and 1.6 ng/mL for sE-selectin. The distribution of sICAM-1, sVCAM-1 and sE-selectin values were controlled by the Kolmogorov-Smirnov testing method and their statistical significance was analyzed by the ANOVA and Duncan test. The results were considered statistically significant at P < 0.05. Results Table II summarizes the serum levels of sE-selectin, sICAM-1 and sVCAM-1 for each patient group. Sera collected during asthma attacks had significantly higher sE-selectin levels than that of stable atopic asthmatics, nonatopic asthmatics or healthy controls ( P < 0.05). No difference in sE-selectin levels between the atopic and nonatopic stable asthmatics was observed. There was no correlation between sE-selectin levels and inhaler corticosteroid (ICS) dosage or duration in patients who were on inhaler steroid treatment. Mean serum sICAM-1 and sVCAM-1 levels of acute asthmatic children were found to be higher than that of stable atopic and stable nonatopic asthmatics and healthy children, but the differences were not statistically significant (P > 0.05). However, 7 out of 10 patients with acute asthma were receiving ICS (125-250 µg fluticasone dipropionate) and their sICAM-1 levels correlated negatively with dosage and duration of treatment ( r = 0.64, P < 0.05, r = 0.65, P < 0.05) (r = –0.64, P < 0.05; r = 0.65, P < 0.05) respectively. No difference was observed between stable atopic and stable nonatopic asthmatics for sICAM-1 and sVCAM-1 levels. Discussion Adhesion molecules may play a pivotal role in inflammatory process associated with asthma(1,4). Previous studies, conducted in adult asthma patients, have shown that sICAM-1 and sE-selectin levels increased in sera obtained during an asthmatic exacerbation(5,6,7). In a study performed by Laan et al.(8) on pediatric patients, no difference in sICAM-1 and sE-selectin levels were found among children with stable atopic asthma, stable nonatopic asthma, atopic dermatitis and healthy children. Oymar et al(9) measured serum sICAM-1, sE-selectin, sL-selectin, sVCAM-1 levels in pediatric asthma patients (15 acute asthma, 24 stable asthma) and found that sICAM-1 levels increased in acute asthmatics compared to stable asthmatics and the control group. sE-selectin and sVCAM-1, levels were not found to be significantly raised in any of the asthma groups in this study. In a recent study, El-Sawy et al.(10) found elevated levels of sICAM-1 in children with acute asthma. The results of the present study agree with those of the other authors who reported increased levels of serum sE-selectin in acute asthmatic adult subjects compared to stable asthmatics(5,6,7) but differ from Oymar et al.(9) who did not find significant elevation in sE-selectin levels in acute asthmatic children. This fact may be attributed to the difference in timing of sE-selectin sampling; which was assessed within 24 hours from the onset of the symptoms while no time period was given in Oymar’s study(9). E-selectin has a much shorter bioactivity compared to ICAM-1 with peak expression reached at 2-4 hours and decline to basal levels occuring by 24 hours(1). In our study the slight increase in sICAM-1 and sVCAM-1 levels during asthma exacerbation when compared to stable asthmatics and healthy subjects, was not statistically significant. This discrepancy with the results of other studies(9,10), in sICAM-1 levels may be related to the supressor effect of ICS treatment on ICAM-1 release or expression, since our correlation analyses revealed a negative relationship between sICAM-1 and ICS treatment (dosage and duration) in acute asthmatic patients. Thus the effect of ICS therapy on levels of sICAM-1 observed in the present study, revealed the necessity of further studies on a larger scale to determine whether or not ICAM-1 level measurements are useful in assessing the efficacy of long-term ICS therapy. In summary, the reason why the increased sICAM-1 level in acute asthmatic patients compared to stable atopic, nonatopic and healthy children were found to be statistically insignificant, has been attributed to the administration of ICS. sE-selectin levels were found to be elevated during asthma attacks in mild persistent asthma. Therefore sE-selectin and sICAM-1 seem to be promising serological markers for showing disease activity. However further studies are required to clarify the function and utility of soluble adhesion molecules in the management of asthmatic children. Contributors: FD collected the data, helped in the analysis and drafted the manuscript. AI designed the study and helped in the preparation of the manuscript. YE analyzed the data. EB did the critical review of the manuscript. FD shall act as guarantor for the study. Funding: None. Competing interests: None stated.
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