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      Adrenal Function Improves in Asthmatic Children on Inhaled Steroids: A Longitudinal Study

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          Abstract

          Background/Aims: Asthmatic children on long-term treatment with inhaled corticosteroids (ICS) may exhibit mild adrenal suppression. We aimed to test the hypothesis that baseline adrenal function of some asthmatic children might be lower than that of others and that this difference might be accentuated by ICS therapy. Methods: A low-dose Synacthen test was performed in 41 prepubertal asthmatic children placed on long-term inhaled budesonide (400 µg/day) prior to the onset of ICS treatment, 6 and 12 months later. Five children withdrew before the 6- and another 2 before the 12-month follow-up. Results: Low adrenal function was demonstrated in 4 children (9.8%) upon recruitment and in another 8 at the 6-month evaluation (22.2%). Adrenal function normalized in the aforementioned 4 children at the 6-month evaluation, while 6 (17.6%) exhibited suppressed adrenal function at the 12-month evaluation. Three of these patients had also exhibited adrenal suppression at the 6-month visit. A significant improvement in peak cortisol values from baseline to the 6- and 12-month evaluation (95% confidence intervals: –283.9 to –69.0 and –239.8 to –50.8, respectively) was evident when children with suppressed adrenal response at the second or third evaluation were excluded. Conclusions: In many asthmatic children, adrenal response improves on long-term ICS. The expected adrenal suppression of certain patients on maintenance ICS appears to constitute a separate phenomenon.

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          Most cited references 22

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          Long-term effects of budesonide or nedocromil in children with asthma. The Childhood Asthma Management Program Research Group.

          Antiinflammatory therapies, such as inhaled corticosteroids or nedocromil, are recommended for children with asthma, although there is limited information on their long-term use. We randomly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide (311 children), 8 mg of nedocromil (312 children), or placebo (418 children) twice daily. We treated the participants for four to six years. All children used albuterol for asthma symptoms. There was no significant difference between either treatment and placebo in the primary outcome, the degree of change in the forced expiratory volume in one second (FEV1, expressed as a percentage of the predicted value) after the administration of a bronchodilator. As compared with the children assigned to placebo, the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV1 to forced vital capacity (FVC, expressed as a percentage) before the administration of a bronchodilator (decline in FEV1:FVC, 0.2 percent vs. 1.8 percent). The children given budesonide also had lower airway responsiveness to methacholine, fewer hospitalizations (2.5 vs. 4.4 per 100 person-years), fewer urgent visits to a caregiver (12 vs. 22 per 100 person-years), greater reduction in the need for albuterol for symptoms, fewer courses of prednisone, and a smaller percentage of days on which additional asthma medications were needed. As compared with placebo, nedocromil significantly reduced urgent care visits (16 vs. 22 per 100 person-years) and courses of prednisone. The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group (22.7 vs. 23.8 cm, P=0.005); this difference was evident mostly within the first year. The height increase was similar in the nedocromil and placebo groups. In children with mild-to-moderate asthma, neither budesonide nor nedocromil is better than placebo in terms of lung function, but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil. The side effects of budesonide are limited to a small, transient reduction in growth velocity.
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            Stress Hormones, Th1/Th2 patterns, Pro/Anti-inflammatory Cytokines and Susceptibility to Disease

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              Effect of long-term treatment with inhaled budesonide on adult height in children with asthma.

              Short-term studies have shown that inhaled corticosteroids may reduce the growth of children with asthma. However, the effect of long-term treatment on adult height is uncertain. We conducted a prospective study in children with asthma to examine the effect of long-term treatment with inhaled budesonide on adult height. We report on 211 children who have attained adult height: 142 budesonide-treated children with asthma, 18 control patients with asthma who have never received inhaled corticosteroids, and 51 healthy siblings of patients in the budesonide group, who also served as controls. The children in the budesonide group attained adult height after a mean of 9.2 years of budesonide treatment (range, 3 to 13) at a mean daily dose of 412 microg (range, 110 to 877). The mean cumulative dose of budesonide was 1.35 g (range, 0.41 to 3.99). The mean differences between the measured and target adult heights were +0.3 cm (95 percent confidence interval, -0.6 to + 1.2) for the budesonide-treated children, -0.2 cm (95 percent confidence interval, -2.4 to +2.1) for the control children with asthma, and +0.9 cm (95 percent confidence interval, -0.4 to +2.2) for the healthy siblings. The adult height depended significantly (P<0.001) on the child's height before budesonide treatment. Although growth rates were significantly reduced during the first years of budesonide treatment, these changes in growth rate were not significantly associated with adult height. Children with asthma who have received long-term treatment with budesonide attain normal adult height.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                2006
                August 2006
                08 August 2006
                : 13
                : 1
                : 56-62
                Affiliations
                aDepartment of Allergy and Pneumonology, P. Penteli Children’s Hospital, Penteli, bThird Department of Pediatrics, Attikon Hospital, and cFirst Department of Pediatrics, Aghia Sophia Children’s Hospital, Athens University Medical School, Athens, and dRespiratory Unit, Department of Pediatrics, University of Patras, Patras, Greece
                Article
                94645 Neuroimmunomodulation 2006;13:56–62
                10.1159/000094645
                16864985
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, Tables: 4, References: 31, Pages: 7
                Categories
                Original Paper

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