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TWICS - Theophylline with Inhaled CorticoSteroids

Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease affecting approximately 3 million people in the UK.  It is the fifth leading cause of death in the UK and costs the NHS approximately £1 billion annually.  Exacerbations of COPD are associated with accelerated rate of lung function decline, reduced physical activity, reduced quality of life, increased mortality and increased risk of other illnesses such as acute myocardial infarction and stroke.    Usual treatment for COPD is inhaled corticosteroids.  Previous small studies showed that giving patients theophylline at a low dose can increase the sensitivity of their airway to the effects of inhaled corticosteroids – and thus make the inhaled corticosteroids work better. 

In the TWICS study, we aimed to determine whether adding low dose oral theophylline to inhaled corticosteroid therapy in patients with COPD reduces the risk of exacerbation, is cost effective to the NHS, improves quality of life and lung function and reduces mortality.  To do this, we compared the effects of low dose theophylline against the effects of a placebo ‘dummy treatment’, which looks like the genuine medicine but contains no active ingredient.

We invited people with COPD to take part in our study.  Those who agreed were allocated to receive low-dose theophylline or placebo for 12 months.  Half of the participants in the study took low-dose theophylline and half of the participants took placebo.  We followed study participants up after 6 and 12 months to find out how they are getting on and whether they have had any exacerbations of their COPD.    

Between January 2014 and August 2017, 1567 people with COPD took part in TWICS: half took low-dose theophylline for up to a year and half took dummy placebo tablets. People were recruited in 121 hospitals and GP practices around the UK, from Inverness in the North to Truro in the South. 

We counted how many flare-ups each person had over the twelve month period they were in the TWICS study for.  The people taking the dummy placebo tablets had an average of 2.23 flare ups a year and the people taking low dose theophylline had an average of 2.24 flare ups a year.  The number of people reporting possible side effects was similar for low-dose theophylline and dummy placebo groups.  We also showed that low-dose theophylline had no overall beneficial effect on lung capacity, episodes of pneumonia, quality of life or NHS costs.  We did notice that low-dose theophylline reduced the number of people admitted to hospital with a flare up of COPD. However, this was for a small (1-2%) group of people admitted 3 or more times a year to hospital. Further work is needed to sort out whether this is a real effect or a chance finding

The overall conclusion of TWICS is that low-dose theophylline has no beneficial effect when given to people with COPD.  This might be because low-dose theophylline has no effect at all, or the number of people who benefitted from low-dose theophylline is balanced by the number of people who did worse whilst taking low-dose theophylline.   The results of the study have been published

We are grateful to everyone who took part in the TWICS study.  Thanks to their help, TWICS was a great success and has provided a very strong result for the NHS to act on.  We are now running another study for people who have COPD.  In this new study, we are using a different drug – a beta-blocker called bisoprolol.  Please do get in touch if you would like to know about this new study, which is called the BICS study.  You can contact the study office on 01224 438178 or email


General Data Protection Regulation (GDPR) 
Participant Information

University of Aberdeen/NHS Grampian is the sponsor for this study based in the United Kingdom. We will be using information from you and your medical records in order to undertake this study and will act as the data controller for this study. This means that we are responsible for looking after your information and using it properly. University of Aberdeen/NHS Grampian will keep identifiable information about you at least 15 years after the study has finished. 

Your rights to access, change or move your information are limited, as we need to manage your information in specific ways in order for the research to be reliable and accurate. If you withdraw from the study, we will keep the information about you that we have already obtained. To safeguard your rights, we will use the minimum personally-identifiable information possible.

You can find out more about how we use your information



The Health Services Research Unit is funded by the Chief Scientists Office of the Scottish Government Health and Social Care Directorates