Secondary prevention of asthma by the use of Inhaled Fluticasone propionate in Wheezy INfants (IFWIN): double-blind, randomised, controlled study.
ABSTRACT Wheezing and asthma often begins in early childhood, but it is difficult to predict whether or not a wheezy infant will develop asthma. Some researchers suggest that treatment with inhaled corticosteroids at the first signs of wheezing in childhood could prevent the development of asthma later in life. However, other investigators have reported that although such treatment could help control symptoms, the benefits can disappear within months of stopping treatment. We tested our hypothesis that to prevent loss of lung function and worsening asthma later in childhood, anti-inflammatory treatment needs to be started early in life.
We did a randomised, double-blind, controlled study of inhaled fluticasone propionate 100 mug twice daily in young children who were followed prospectively and randomised after either one prolonged (>1 month) or two medically confirmed wheezy episodes. The dose of study drug was reduced every 3 months to the minimum needed. If the symptoms were not under control by 3 months, open-label fluticasone propionate 100 mug twice daily was added to the treatment. Children were followed-up to 5 years of age, at which point we gave their parents or guardians questionnaires, and measured the children's lung function (specific airways resistance [sR(aw)], forced expiratory volume in 1s [FEV1]) and airway reactivity (eucapnic voluntary hyperventilation [EVH] challenge). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN86717853.
We followed 1073 children prospectively, of whom 333 were eligible, and 200 of these began treatment (130 male, median age 1.2 years [range 0.5-4.9]; 101 placebo, 99 treatment); 173 (85 treatment, 88 placebo) completed the follow-up at age five years. The groups did not differ significantly in the proportion of children with current wheeze, physician-diagnosed asthma or use of asthma medication, lung function, or airway reactivity (percentage change in FEV1, adjusted mean for placebo 5.5% [95% CI -2.5 to 13.4]) vs for treatment 5.0% [-2.2 to 12.2], p=0.87). There were no differences in the results after adjustment for open-label fluticasone propionate, nor between the two groups in the time before the open-label drug was added (estimated hazard ratio 1.12 [95% CI 0.73-1.73], p=0.60), or the proportion needing the open-label drug (43 [42.57%] placebo, 41 [41.41%] treatment).
The early use of inhaled fluticasone propionate for wheezing in preschool children had no effect on the natural history of asthma or wheeze later in childhood, and did not prevent lung function decline or reduce airway reactivity.
- SourceAvailable from: Kostas N Priftis
Chapter: Growth in Asthmatic Children[Show abstract] [Hide abstract]
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.
- [Show abstract] [Hide abstract]
ABSTRACT: Beneficial effects of anti-inflammatory therapy such as fluticasone propionate (FP) and montelukast (Mk) have been demonstrated in preschool children with asthma. However, comparative studies are lacking in this age group. Therefore, we conducted a study to evaluate and compare the effect of FP and Mk in preschool children with asthma-like symptoms. In this multicenter, randomized, placebo-controlled, double-blind, double-dummy trial, children aged 2-6 years with asthma-like symptoms were included. In total, 63 children were randomly allocated to receive FP (25), Mk (18) or placebo (20) for 3 months. The primary outcome was the daily symptom score (wheeze, cough, shortness of breath) as recorded by caregivers in a symptom diary card. Secondary endpoints were rescue medication free days, blood eosinophils and lung function (interrupter technique and forced oscillation technique (FOT)). During the 3 months study period, symptoms improved in all 3 groups, with a statistically significant difference between FP and placebo in favor of the FP group (p=0.021). A significant reduction in circulating eosinophils after 3 months of treatment was found in the Mk group only (p=0.008), which was significantly different from the change found in the placebo group (p=0.045). With the exception of frequency dependence (measured by FOT), which showed a difference between FP and Mk after 3 months of treatment in favor of the FP group (p=0.048), no differences in lung function within or between groups were found. In spite of a lack of power, our results suggest that FP has a beneficial effect on symptoms and Mk on blood eosinophil level as compared to placebo. Except for a difference in one lung function parameter after 3 months between FP and Mk in favor of the FP group, this study revealed no differences between FP and Mk.Pulmonary Pharmacology & Therapeutics 10/2008; 21(5):798-804. DOI:10.1016/j.pupt.2008.06.004 · 2.57 Impact Factor
Article: Pathogenesis of asthma.[Show abstract] [Hide abstract]
ABSTRACT: While asthma is considered an inflammatory disorder of the conducting airways, it is becoming increasingly apparent that the disease is heterogeneous with respect to immunopathology, clinical phenotypes, response to therapies, and natural history. Once considered purely an allergic disorder dominated by Th2-type lymphocytes, IgE, mast cells, eosinophils, macrophages, and cytokines, the disease also involves local epithelial, mesenchymal, vascular and neurologic events that are involved in directing the Th2 phenotype to the lung and through aberrant injury-repair mechanisms to remodeling of the airway wall. Structural cells provide the necessary "soil" upon which the "seeds" of the inflammatory response are able to take root and maintain a chronic phenotype and upon which are superimposed acute and subacute episodes usually driven by environmental factors such as exposure to allergens, microorganisms, pollutants or caused by inadequate antiinflammatory treatment. Greater consideration of additional immunologic and inflammatory pathways are revealing new ways of intervening in the prevention and treatment of the disease. Thus increased focus on environmental factors beyond allergic exposure (such as virus infection, air pollution, and diet) are identifying targets in structural as well as immune and inflammatory cells at which to direct new interventions.Clinical & Experimental Allergy 07/2008; 38(6):872-97. DOI:10.1111/j.1365-2222.2008.02971.x · 4.32 Impact Factor