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Effect of low-dose theophylline plus beclometasone on lung function in smokers with asthma: a pilot study

M. Spears¹, I. Donnelly², L. Jolly², M. Brannigan¹, K. Ito³, C. McSharry², J. Lafferty¹, R. Chaudhuri¹, G. Braganza¹, I. M. Adcock³, P. J. Barnes³, S. Wood, ⁴ and N. C. Thomson¹

¹ Respiratory Medicine, ² Immunology, ⁴ General Practice, Faculty of Medicine, University of Glasgow, Glasgow, and ³ National Heart and Lung Institute, Imperial College, London, UK.

CORRESPONDENCE: N. C. Thomson, Respiratory Medicine Section, Division of Immunology, Infection and Inflammation, Faculty of Medicine, University of Glasgow and Gartnavel General Hospital, Glasgow, G12 OYN, UK. Fax: 44 1412113464. E-mail: n.c.thomson{at}clinmed.gla.ac.uk

Keywords: Asthma, corticosteroid insensitivity, histone deacetylase, smoking, theophylline

Received: October 20, 2008
Accepted January 7, 2009

Smoking is common in asthma and is associated with worse asthma control and a reduced therapeutic response to corticosteroids. The present authors hypothesised that treating smokers with asthma with low-dose theophylline added to inhaled corticosteroids would enhance steroid sensitivity and thereby improve lung function and symptoms.

In a double-blind, parallel group exploratory trial, 68 asthmatic smokers were randomised to one of three treatments for 4 weeks: inhaled beclometasone (200 µg·day^–1), theophylline (400 mg·day^–1) or both treatments combined. Outcome measures included change in lung function and Asthma Control Questionnaire (ACQ) scores.

At 4 weeks, theophylline added to inhaled beclometasone produced an improvement in peak expiratory flow (39.9 L·min^–1, 95% confidence intervals (CI) 10.9–68.8) and ACQ score (-0.47, 95% CI -0.91– -0.04) and a borderline improvement in pre-bronchodilator forced expiratory volume in one second (mean difference 165 mL, 95% CI -13–342) relative to inhaled corticosteroid alone. Theophylline alone improved the ACQ score (-0.55, 95% CI -0.99– -0.11), but not lung function.

In the present pilot study, the combination of low-dose theophylline and inhaled beclometasone produced improvements in both lung function and symptoms in a group of smokers with asthma. Larger trials are required to extend and confirm these findings.

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