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Dose‐responses over time to inhaled fluticasone propionate treatment of exercise‐ and methacholine‐induced bronchoconstriction in children with asthma
Author(s) -
Hofstra Winfried B.,
Neijens Herman J.,
Duiverman Eric J.,
Kouwenberg Jan M.,
Mulder Paul G.H.,
Kuethe Maarten C.,
Sterk Peter J.
Publication year - 2000
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/(sici)1099-0496(200006)29:6<415::aid-ppul1>3.0.co;2-7
Subject(s) - medicine , fluticasone propionate , methacholine , bronchoconstriction , asthma , placebo , fluticasone , bronchial hyperresponsiveness , anesthesia , corticosteroid , exercise induced asthma , bronchodilator , respiratory disease , lung , alternative medicine , pathology
Abstract 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 μg 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 (FEV 1 ) ≥70% predicted; EIB ≥20% fall in FEV 1 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 re‐randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV 1 from baseline) and methacholine challenge using a dosimetric technique (expressed as PD 20 ) 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 FEV 1 being reduced from 34.1% to 9.9% for 100 μg FP bid, and from 35.9% to 7.6% for 250 μg FP bid ( P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD 20 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 μg FP bid, 1.6 dose steps; 250 μg 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. Pediatr Pulmonol. 2000; 29:415–423. © 2000 Wiley‐Liss, Inc.