Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma

When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 mu g bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV1) greater than or equal to 70% predicted; EIB greater than or equal to 20% fall in FEV1 from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were rerandomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV1 from baseline) and methacholine challenge using a dosimetric technique (expressed as PD20) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV1 being reduced from 34.1% to 9.9% for 100 mu g FP bid, and from 35.9% to 7.6% for 250 mu g FP bid (P <0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD20 methacholine improved significantly during the first 6 weeks as compared to placebo (P <0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 mu g FP bid, 1.6 dose steps; 250 mu g FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment. (C) 2000 Wiley-Liss, Inc

PELICAN: A quality of life instrument for childhood asthma: Study Protocol of two Randomized Controlled Trials in Primary and Specialized Care in the Netherlands

Contains fulltext : 108946.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Asthma is one of the major chronic health problems in children in the Netherlands. The Pelican is a paediatric asthma-related quality of life instrument for children with asthma from 6-11 years old, which is suitable for clinical practice in primary and specialized care. Based on this instrument, we developed a self-management treatment to improve asthma-related quality of life. The Pelican intervention will be investigated in different health care settings. Results of intervention studies are often extrapolated to other health care settings than originally investigated. Because of differences in organization, disease severity, patient characteristics and care provision between health care settings, extrapolating research results could lead to unnecessary health costs without the desired health care achievements. Therefore, interventions have to be investigated in different health care settings when possible. This study is an example of an intervention study in different health care settings. In this article, we will present the study protocol of the Pelican study in primary and specialized care. METHOD/DESIGN: This study consists of two randomized controlled trials to assess the effectiveness of the Pelican intervention in primary and specialized care. The trial in primary care is a multilevel design with 170 children with asthma in 16 general practices. All children in one general practices are allocated to the same treatment group. The trial in specialized care is a multicentre trial with 100 children with asthma. Children in one outpatient clinic are randomly allocated to the intervention or usual care group. In both trials, children will visit the care provider four times during a follow-up of nine months. This study is registered and ethically approved. DISCUSSION: This article describes the study protocol of the Pelican study in different health care settings. If the Pelican intervention proves to be effective and efficient, implementation in primary and specialized care for paediatric asthma in the Netherlands will be recommended. TRIAL REGISTRATION: This study is registered by clinicaltrial.gov (NCT01109745)