Effects of adding either a leukotriene receptor antagonist or low-dose theophylline to a low or medium dose of inhaled corticosteroid in patients with persistent asthma

Owen J. Dempsey, Stephen J. Fowler, Andrew Wilson, Gwen Kennedy, Brian J. Lipworth (Lead / Corresponding author)

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Abstract

Study objectives: To evaluate the effect of adding zafirlukast or low-dose theophylline to a beclomethasone dipropionate (BDP) extra-fine hydrofluoroalkane aerosol on bronchial hyperresponsiveness as the primary outcome variable.

Methods: Twenty-four patients with mild-to-moderate asthma were studied using a randomized crossover design with the following three treatment blocks: (1) beclomethasone, 100 μg/d, alone for the first 2 weeks followed by 400 μg/d alone for the next 2 weeks; (2) beclomethasone, 100 μg/d, followed by 400 μg/d, with the addition of zafirlukast, 20 mg bid; (3) beclomethasone, 100 μg/d, followed by 400 μg/d, with the addition of theophylline, 200 to 300 mg bid. Measurements were made after 2 and 4 weeks of each treatment and at pretreatment baseline.

Results: The mean trough plasma theophylline concentration was 6.7 mg/L, coinciding with the anti-inflammatory target range (ie, 5 to 10 mg/L). The provocative dose of methacholine causing a 20% fall in FEV1 (as doubling dose difference from baseline) was significantly (p < 0.05) greater with beclomethasone, 100 μg, plus zafirlukast (1.1 doubling dose) but not with beclomethasone, 100 μg, plus theophylline (0.7 doubling dose) compared to beclomethasone, 100 μg alone (0.4 doubling dose), but not compared to beclomethasone, 400 μg alone (1.1 doubling dose). There were also significant (p < 0.05) differences between beclomethasone, 100 μg, plus zafirlukast (but not BDP, 100 μg, plus theophylline) vs beclomethasone, 100 μg, alone in terms of nitric oxide level, midexpiratory phase of forced expiratory flow, and peak expiratory flow. There were no further significant improvements observed with the addition of zafirlukast or theophylline to beclomethasone, 400 μg.

Conclusions: A leukotriene receptor antagonist, but not low-dose theophylline, conferred significant additive anti-inflammatory effects to therapy with a low-dose inhaled corticosteroid but not to that with a medium dose of an inhaled corticosteroid. Thus, optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step, which is in keeping with current guidelines.

Original languageEnglish
Pages (from-to)151-159
Number of pages9
JournalChest
Volume122
Issue number1
DOIs
Publication statusPublished - Jul 2002

Fingerprint

Leukotriene Antagonists
Beclomethasone
Theophylline
Adrenal Cortex Hormones
Asthma
HFA 134a
Anti-Inflammatory Agents
Methacholine Chloride
Aerosols
Cross-Over Studies
Nitric Oxide

Keywords

  • Airway hyperresponsiveness
  • Asthma
  • Beclomethasone
  • Theophylline
  • Zafirlukast

Cite this

@article{0ee17ec65e554fecbd3ceb71cea7eb6a,
title = "Effects of adding either a leukotriene receptor antagonist or low-dose theophylline to a low or medium dose of inhaled corticosteroid in patients with persistent asthma",
abstract = "Study objectives: To evaluate the effect of adding zafirlukast or low-dose theophylline to a beclomethasone dipropionate (BDP) extra-fine hydrofluoroalkane aerosol on bronchial hyperresponsiveness as the primary outcome variable.Methods: Twenty-four patients with mild-to-moderate asthma were studied using a randomized crossover design with the following three treatment blocks: (1) beclomethasone, 100 μg/d, alone for the first 2 weeks followed by 400 μg/d alone for the next 2 weeks; (2) beclomethasone, 100 μg/d, followed by 400 μg/d, with the addition of zafirlukast, 20 mg bid; (3) beclomethasone, 100 μg/d, followed by 400 μg/d, with the addition of theophylline, 200 to 300 mg bid. Measurements were made after 2 and 4 weeks of each treatment and at pretreatment baseline.Results: The mean trough plasma theophylline concentration was 6.7 mg/L, coinciding with the anti-inflammatory target range (ie, 5 to 10 mg/L). The provocative dose of methacholine causing a 20{\%} fall in FEV1 (as doubling dose difference from baseline) was significantly (p < 0.05) greater with beclomethasone, 100 μg, plus zafirlukast (1.1 doubling dose) but not with beclomethasone, 100 μg, plus theophylline (0.7 doubling dose) compared to beclomethasone, 100 μg alone (0.4 doubling dose), but not compared to beclomethasone, 400 μg alone (1.1 doubling dose). There were also significant (p < 0.05) differences between beclomethasone, 100 μg, plus zafirlukast (but not BDP, 100 μg, plus theophylline) vs beclomethasone, 100 μg, alone in terms of nitric oxide level, midexpiratory phase of forced expiratory flow, and peak expiratory flow. There were no further significant improvements observed with the addition of zafirlukast or theophylline to beclomethasone, 400 μg.Conclusions: A leukotriene receptor antagonist, but not low-dose theophylline, conferred significant additive anti-inflammatory effects to therapy with a low-dose inhaled corticosteroid but not to that with a medium dose of an inhaled corticosteroid. Thus, optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step, which is in keeping with current guidelines.",
keywords = "Airway hyperresponsiveness, Asthma, Beclomethasone, Theophylline, Zafirlukast",
author = "Dempsey, {Owen J.} and Fowler, {Stephen J.} and Andrew Wilson and Gwen Kennedy and Lipworth, {Brian J.}",
year = "2002",
month = "7",
doi = "10.1378/chest.122.1.151",
language = "English",
volume = "122",
pages = "151--159",
journal = "Chest",
issn = "0012-3692",
publisher = "Elsevier",
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TY - JOUR

T1 - Effects of adding either a leukotriene receptor antagonist or low-dose theophylline to a low or medium dose of inhaled corticosteroid in patients with persistent asthma

AU - Dempsey, Owen J.

AU - Fowler, Stephen J.

AU - Wilson, Andrew

AU - Kennedy, Gwen

AU - Lipworth, Brian J.

PY - 2002/7

Y1 - 2002/7

N2 - Study objectives: To evaluate the effect of adding zafirlukast or low-dose theophylline to a beclomethasone dipropionate (BDP) extra-fine hydrofluoroalkane aerosol on bronchial hyperresponsiveness as the primary outcome variable.Methods: Twenty-four patients with mild-to-moderate asthma were studied using a randomized crossover design with the following three treatment blocks: (1) beclomethasone, 100 μg/d, alone for the first 2 weeks followed by 400 μg/d alone for the next 2 weeks; (2) beclomethasone, 100 μg/d, followed by 400 μg/d, with the addition of zafirlukast, 20 mg bid; (3) beclomethasone, 100 μg/d, followed by 400 μg/d, with the addition of theophylline, 200 to 300 mg bid. Measurements were made after 2 and 4 weeks of each treatment and at pretreatment baseline.Results: The mean trough plasma theophylline concentration was 6.7 mg/L, coinciding with the anti-inflammatory target range (ie, 5 to 10 mg/L). The provocative dose of methacholine causing a 20% fall in FEV1 (as doubling dose difference from baseline) was significantly (p < 0.05) greater with beclomethasone, 100 μg, plus zafirlukast (1.1 doubling dose) but not with beclomethasone, 100 μg, plus theophylline (0.7 doubling dose) compared to beclomethasone, 100 μg alone (0.4 doubling dose), but not compared to beclomethasone, 400 μg alone (1.1 doubling dose). There were also significant (p < 0.05) differences between beclomethasone, 100 μg, plus zafirlukast (but not BDP, 100 μg, plus theophylline) vs beclomethasone, 100 μg, alone in terms of nitric oxide level, midexpiratory phase of forced expiratory flow, and peak expiratory flow. There were no further significant improvements observed with the addition of zafirlukast or theophylline to beclomethasone, 400 μg.Conclusions: A leukotriene receptor antagonist, but not low-dose theophylline, conferred significant additive anti-inflammatory effects to therapy with a low-dose inhaled corticosteroid but not to that with a medium dose of an inhaled corticosteroid. Thus, optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step, which is in keeping with current guidelines.

AB - Study objectives: To evaluate the effect of adding zafirlukast or low-dose theophylline to a beclomethasone dipropionate (BDP) extra-fine hydrofluoroalkane aerosol on bronchial hyperresponsiveness as the primary outcome variable.Methods: Twenty-four patients with mild-to-moderate asthma were studied using a randomized crossover design with the following three treatment blocks: (1) beclomethasone, 100 μg/d, alone for the first 2 weeks followed by 400 μg/d alone for the next 2 weeks; (2) beclomethasone, 100 μg/d, followed by 400 μg/d, with the addition of zafirlukast, 20 mg bid; (3) beclomethasone, 100 μg/d, followed by 400 μg/d, with the addition of theophylline, 200 to 300 mg bid. Measurements were made after 2 and 4 weeks of each treatment and at pretreatment baseline.Results: The mean trough plasma theophylline concentration was 6.7 mg/L, coinciding with the anti-inflammatory target range (ie, 5 to 10 mg/L). The provocative dose of methacholine causing a 20% fall in FEV1 (as doubling dose difference from baseline) was significantly (p < 0.05) greater with beclomethasone, 100 μg, plus zafirlukast (1.1 doubling dose) but not with beclomethasone, 100 μg, plus theophylline (0.7 doubling dose) compared to beclomethasone, 100 μg alone (0.4 doubling dose), but not compared to beclomethasone, 400 μg alone (1.1 doubling dose). There were also significant (p < 0.05) differences between beclomethasone, 100 μg, plus zafirlukast (but not BDP, 100 μg, plus theophylline) vs beclomethasone, 100 μg, alone in terms of nitric oxide level, midexpiratory phase of forced expiratory flow, and peak expiratory flow. There were no further significant improvements observed with the addition of zafirlukast or theophylline to beclomethasone, 400 μg.Conclusions: A leukotriene receptor antagonist, but not low-dose theophylline, conferred significant additive anti-inflammatory effects to therapy with a low-dose inhaled corticosteroid but not to that with a medium dose of an inhaled corticosteroid. Thus, optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step, which is in keeping with current guidelines.

KW - Airway hyperresponsiveness

KW - Asthma

KW - Beclomethasone

KW - Theophylline

KW - Zafirlukast

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U2 - 10.1378/chest.122.1.151

DO - 10.1378/chest.122.1.151

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JO - Chest

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