Does the presence of thrombophilia increase the risk of developing idiopathic pulmonary fibrosis?

Lead Research Organisation: University of Nottingham
Department Name: School of Life Sciences


The cut surface of the lung resembles a bath sponge ? with numerous tiny air sacs being supplied with air by larger airways. Each air sac is surrounded by a lattice-work structure of small blood vessels which remove the oxygen from the air sac and transport it on around the body. Idiopathic pulmonary fibrosis (IPF) is a disease in which the walls of the air sacs become thickened and distorted, and the close relationship between the air sac and the blood vessels destroyed. As a consequence the lungs become stiff and inefficient and people with IPF develop an annoying and persistent cough, and marked shortness of breath on exertion. The average life expectancy of a person with idiopathic pulmonary fibrosis is less than 3 years and people die about 7 years prematurely. There are about 4500 new cases of idiopathic pulmonary fibrosis each year in the UK, and this number is increasing rapidly for reasons that are not known. At present there are no treatments which improve the outlook for people with idiopathic pulmonary fibrosis, in terms of either survival or symptom control.

About 20% of the UK population have an increased tendency to clot (thrombophilia) as a consequence of either inherited or acquired defects in the clotting cascade. On the basis of evidence from laboratory experiments, epidemiological studies and one small trial we believe that these people might be at increased risk of developing IPF and once they get it might have a worse outlook. In our study we will look for the presence of thrombophilia in 250 people with IPF collected from 9 hospital centres in the Trent region of the UK and compare these people to 250 members of the public without IPF recruited from general practice. We will also follow-up our people with IPF to determine their outcome.

If our study shows that our hypothesis is correct then the next step is a simple trial of anticoagulation in this patient group. The drugs to do this are currently available in the UK and used to treat other conditions, such as deep vein thrombosis. The development of this trial would offer the hope of some benefit from medical intervention for this patient group for the first time.

Technical Summary

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown aetiology. Current estimates suggest that there are about 4500 new cases of IPF each year in the UK and the median survival from diagnosis is about 3 years. There has been a marked and progressive increase in the incidence of IPF since the early 1980s. There are no treatments which have been shown to reduce the mortality or morbidity associated with IPF.

There is evidence from in vitro and ex vivo experiments, one small clinical trial of warfarin, circumstantial pathological evidence and observational data that activation of the clotting cascade might be an important risk factor for idiopathic pulmonary fibrosis. Since approximately 20% of the general population have an increased tendency to clot (thrombophilia) as a result of a combination of inherited and acquired defects in the clotting cascade our new hypothesis is that thrombophilia represents a risk factor for IPF and may also be associated with a worse outcome in these patients.

Our proposed study is a case-control study of incident cases of IPF in the East-midlands (n=250) and general population controls (n=250). Cases will be recruited from 9 hospital centres within the Trent region of the UK and our controls will be sampled from 10 general practices which are part of the UK General Practice Research Network sample at random from our geographical area.

We will compare the odds of having thrombophilia between cases and controls and look for evidence of interaction between thrombophilia and other environmental risk factors for IPF (occupation and smoking). Our study has 90% power to detect an odds ratio of 2.0 or greater assuming a thrombophilia prevalence in the general population of 20%. In addition we will follow our cases of IPF to determine whether the presence of thrombophilia is associated with a worse survival. For this analysis we have assumed that 20% of our cases will have a clotting abnormality and that the median survival in people with normal clotting is 3 years and so with a sample size of 250 people with IPF we will have 90% power to detect a hazard ratio of 1.8 or greater

If our results confirm an association between thrombophilia and IPF the next step will be to conduct a large scale trial of anticoagulation with warfarin in this patient group to determine whether this is an effective treatment for IPF.
Description Editor in Chief Thorax
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact As Editor-in-Chief of Thorax (the official journal of the British Thoracic Society and 4th highest Respiratory Journal) we have completely revised the instructions for authors to emphasise scientific rigour with explicit guidelines for research of many disciplines.
Description British Lung Foundation Travel Fellowship
Amount £750 (GBP)
Organisation British Lung Foundation (BLF) 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2010 
End 09/2010
Title TLFS database 
Description Database of all cases and controls recruited for the study and all information collected (including results of thrombophilia screen) 
Type Of Material Database/Collection of Data/Biological Samples 
Provided To Others? No  
Impact Extensive database of incidenct cases of IPF in the Trent region.