Article

Long-Term Inhaled Corticosteroids in Preschool Children at High Risk for Asthma

University of California, San Diego, San Diego, California, United States
New England Journal of Medicine (Impact Factor: 54.42). 06/2006; 354(19):1985-97. DOI: 10.1056/NEJMoa051378
Source: PubMed

ABSTRACT It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma.
We randomly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate (at a dose of 88 mug twice daily) or masked placebo for two years, followed by a one-year period without study medication. The primary outcome was the proportion of episode-free days during the observation year.
During the observation year, no significant differences were seen between the two groups in the proportion of episode-free days, the number of exacerbations, or lung function. During the treatment period, as compared with placebo use, use of the inhaled corticosteroid was associated with a greater proportion of episode-free days (P=0.006) and a lower rate of exacerbations (P<0.001) and of supplementary use of controller medication (P<0.001). In the inhaled-corticosteroid group, as compared with the placebo group, the mean increase in height was 1.1 cm less at 24 months (P<0.001), but by the end of the trial, the height increase was 0.7 cm less (P=0.008). During treatment, the inhaled corticosteroid reduced symptoms and exacerbations but slowed growth, albeit temporarily and not progressively.
In preschool children at high risk for asthma, two years of inhaled-corticosteroid therapy did not change the development of asthma symptoms or lung function during a third, treatment-free year. These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued. (ClinicalTrials.gov number, NCT00272441.).

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    • "The clinical implications are wide; it raised the possibility of airway remodelling secondary to airway injury after a chronic cough and the importance of addressing bronchial constriction in addition to inflammation. It may ultimately lead to new therapeutic approaches, bearing in mind that anti-inflammatory treatment has not been shown to modify the natural history of lung function changes in prospective studies (Guilbert 2006). "
    Bronchial Asthma - Emerging Therapeutic Strategies, 02/2012; , ISBN: 978-953-51-0140-6
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    • "The adverse effects of ICS on growth of preschool children have been examined in three recent high-quality trials of ICS treatment administered either as long-term prophylaxis (Guilbert et al., 2006; Murray et al., 2006) or as " on-demand " intermittent therapy for wheezing (Bisgaard et al., 2006). The general conclusion from these studies regarding the effect of ICS on linear growth is that these agents may affect linear growth, although the relevance of these findings with respect to height at a later age is unknown as linear growth rate appears to accelerate after discontinuation of the medication (Guilbert et al., 2006). Along the same lines, height Z-scores of subjects that received 9 months of treatment did not differ at 5 years of age from those on placebo (Murray et al., 2006), and the standing height of children who received 3 years of intermittent therapy was similar to that of controls (Bisgaard et al., 2006). "
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    ABSTRACT: Chronic illness per se, including asthma, may cause retardation of linear growth and this confounding factor is often difficult to separate from the potential stunting effect of inhaled corticosteroids (ICS) on children’s height. It has been proposed that the vast majority of asthmatic children will attain a normal adult height, and that most perceived growth failure is due to pubertal delay. Long-term treatment with ICS has profound effects on bone metabolism and linear growth. These effects are sensitive and specific and may represent an evolutionary adaptation in order to redirect resources during physiologic stress. It appears that any impairment of linear growth velocity in these children is likely to be reversible and of short duration. Although the deceleration of linear growth is widely accepted as amarker of the systemic effects of ICS, recent observational studies have reported that satisfactory growth does not exclude the possibility of adrenal suppression. Various polymorphisms in the glucocorticoid receptor could be related to the susceptibility to glucocorticoid-induced side effects. This chapter presents cutting-edge information of the effects of asthma per se as well as of ICS on linear growth of children and highlights the current knowledge on the interactions between this effect and that on the hypothalamic-pituitary-adrenal axis.
    Handbook of Growth and Growth Monitoring in Health and Disease, 1rst edited by V.R. Preedy, 01/2012: chapter Growth in Asthmatic Children: pages 1755-1762; Springer Science+Business Media.
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    • "The natural history of asthma is still poorly understood [1]. Diagnosis in infants often proves difficult treatment, although well-codified, poses complex practical issues at such an early age [2]. Early childhood wheezing disorders follow different time courses, probably corresponding to different endophenotypes [1] [3] [4]. "
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    ABSTRACT: Background. In recurrent wheezing infants, it is important to identify those likely to remain asthmatic in order to propose appropriate long-term management. Objective. To establish predictive factors for persistent asthma at adolescence in a population of recurrent wheezing infants. Methods. Retrospective study of 227 infants. Inclusion criteria were age under 36 months, a history of at least three wheezing episodes assessed via a doctor-led ISAAC questionnaire and a standardized allergy testing programme. At 13 years, active asthma was assessed by questionnaire. Results. Risk factors for asthma persisting into adolescence were allergic sensitization to multiple airborne allergens (OR 4.6, CI-95% (1.9–11.2) P = 0.001), initial atopic dermatitis (OR 3.4, CI-95% (1.9–6.3) P < 0.001), severe recurrent wheezing (OR 2.3, CI-95% (1.3–4.2) P = 0.007), and hypereosinophilia ≥470/mm3 (OR 2.2, CI-95% (1.07–4.7) P = 0.033). Conclusion. While it is still difficult to predict the long-term course of asthma, atopy remains the major risk factor for persistent asthma.
    07/2011; 2011:493624. DOI:10.5402/2011/493624
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