HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Phillips, K Articles by Tattersfield, A E Search for Related Content PubMed PubMed Citation Articles by Phillips, K Articles by Tattersfield, A E

Use of sequential quadrupling dose regimens to study efficacy of inhaled corticosteroids in asthma

Division of Respiratory Medicine, University of Nottingham, City Hospital, Nottingham NG5 1PB, UK

Correspondence to:
Correspondence to:
Dr K Phillips
Division of Respiratory Medicine, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK; dr\|[lowbar]\|kate\|[lowbar]\|phillips{at}hotmail.com

Background: Inhaled corticosteroids are widely used to treat asthma. There is a need to be able to compare different inhaled corticosteroids and different doses of an inhaled corticosteroid to determine potency and dose equivalence, but measuring efficacy in a dose related manner is difficult because of their slow onset of action. There is uncertainty about the role of sequential dosing regimens and the best end point for such studies. We have explored the use of sequential quadrupling dose regimens and a range of end points to assess the response to budesonide in subjects with asthma.

Methods: 21 subjects with mild asthma, aged 18–65, took part in a randomised three way crossover study comparing two sequential and one non-sequential regimen, separated by at least 3 weeks. The sequential regimens consisted of increasing doses of inhaled budesonide (100, 400 1600 µg/day) with each dose being given for 1 or 2 weeks; the non-sequential regimen consisted of 1600 µg/day for 2 weeks with end points measured after 1 and 2 weeks. The end points studied included the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD₂₀AMP), lung function, symptoms, and bronchodilator use.

Results: There was a dose related increase in PD₂₀AMP with both sequential dose regimens. The increase in PD₂₀AMP ranged from 1.49 doubling doses (DD) following the lowest dose (100 µg/day) to 3.1 DD following the highest dose (1600 µg/day) in the 1 week sequential regimen and from 1.98 to 4.03 DD in the 2 week sequential regimen; standard deviations (SD) for the changes in PD₂₀AMP ranged from 1.3 to 2.6 DD. Changes in forced expiratory volume in 1 second (FEV₁) and morning peak expiratory flow rate (PEFR) were dose related but small and more variable (maximum change in FEV₁ = 148 ml, SD 228 ml), while changes in evening PEFR, symptoms, and bronchodilator use were small and not dose related. Change in PD₂₀AMP after budesonide 1600 µg did not differ significantly between regimens.

Conclusion: Combining PD₂₀AMP measurements with a sequential regimen of three quadrupling doses of an inhaled corticosteroid given for 1 or 2 weeks provides clear dose-response curves for comparative studies. PD₂₀AMP is a more sensitive end point for this purpose than FEV₁, PEFR, symptoms, or relief inhaler use.

Keywords: asthma; inhaled corticosteroid; bronchial responsiveness

This article has been cited by other articles:

				K Phillips, J Oborne, S Lewis, T W Harrison, and A E Tattersfield Time course of action of two inhaled corticosteroids, fluticasone propionate and budesonide Thorax, January 1, 2004; 59(1): 26 - 30. [Abstract] [Full Text] [PDF]