0
Original Research: COPD |

Treatment Effects of Low-Dose Theophylline Combined With an Inhaled Corticosteroid in COPD

Paul A. Ford, PhD; Andrew L. Durham, PhD; Richard E. K. Russell, PhD; Fabiana Gordon, PhD; Ian M. Adcock, PhD; Peter J. Barnes, DM, FCCP
Author and Funding Information

From the Airway Disease Section (Drs Ford, Durham, Russell, Adcock, and Barnes), National Heart and Lung Institute, and the Statistical Advisory Service (Dr Gordon), Imperial College, London, England.

Correspondence to: Paul Ford, PhD, Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, England; e-mail: p.ford@imperial.ac.uk


Funding/Support: This work was supported by the Medical Research Council UK and by an unrestricted educational grant from Mitsubishi-Tanabe Pharma (Japan).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(6):1338-1344. doi:10.1378/chest.09-2363
Text Size: A A A
Published online

Background:  Inhaled corticosteroids (ICS) have proved disappointing at reducing airway inflammation in COPD. However, previous studies indicate that low doses of theophylline enhance the activity of a key corticosteroid-associated corepressor protein, histone deacetylase (HDAC)2, which is reduced in COPD. This may account, at least in part, for the relative corticosteroid resistance. Thus, combination therapy with an ICS and low-dose theophylline may be of benefit in the treatment of COPD.

Methods:  To test the hypothesis that ICS and theophylline have a greater therapeutic effect than theophylline alone, 30 patients with COPD were treated with placebo theophylline capsules and either inhaled fluticasone propionate (FP) (500 μg bid) or inhaled placebo for 4 weeks in a double-dummy, randomized, double-blind, parallel study. After a 2-week washout, patients were given active theophylline capsules (plasma level of 8.8-12.4 mg/L).

Results:  In an across-arm comparison, combination treatment with FP and theophylline did not reduce total sputum neutrophils but significantly reduced total sputum eosinophils (P < .05). Additional across-arm comparisons suggest a further reduction in percentage sputum neutrophils and sputum chemokine (C-X-C motif) ligand 8/IL-8 (P < .05). Furthermore, within-arm observational data also demonstrated increases in forced midexpiratory flow rate and FEV1% predicted (P < .05) following combination treatment only. In an open-label study, low-dose theophylline when added to inhaled FP increased total HDAC activity in peripheral blood monocytes ninefold (P < .01) compared with FP alone from the same patients with COPD.

Conclusions:  Combination therapy with an inhaled corticosteroid and low-dose theophylline may attenuate airway inflammation in patients with COPD.

Trial registration:  clinicaltrials.gov; Identifier NCT00241631

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543