Pulmonary Arterial Hypertension (PAH)

People Panel A_2x4_Rare DiseasesBackground

Idiopathic and heritable pulmonary arterial hypertension (PAH) are rare diseases (incidence 2-4/million per year) that occur in early middle age with a female gender bias (F:M, 2.3:1). The condition is characterised by narrowing and obliteration of small pulmonary arteries in the lung leading to increased pulmonary vascular resistance and severe pulmonary hypertension, leading to extreme breathlessness, even at rest. The condition severely limits life expectancy (3 year mortality 40%) with patients ultimately dying from right heart failure. While treatment can relieve some of the symptoms of PAH, the only currently known method for extending life in patients is lung transplantation.

A genetic basis to PAH was first suggested by the observation that the disease occasionally occurred in families. In 2000 researchers identified mutations in a particular gene, called BMPR2, in the majority of these families. This discovery accelerated our understanding of the disease and has offered new avenues to develop treatments. It was subsequently found that mutations in BMPR2 also cause disease in patients with sporadic forms of the disease in whom there is no previous family history. Over the last few years additional uncommon mutations have been identified in PAH patients in genes that are related to the BMPR2 gene. Based on these observations it is likely that the majority of PAH is caused by genetic mutations, although additional environmental factors are often required for the disease to manifest.

All patients in the UK are managed at one of seven National Pulmonary Hypertension Centres and as such the study aims to recruit every PAH patient in the UK, with power being increased by additional samples from collaborating institutes in Europe.

The discovery of the range of genetic mutations underlying PAH will provide a more complete picture of the cause of this disease and identify rational targets for new drugs. It will also pave the way towards prevention strategies for this disease and of the prediction of prognosis based on a genetic classification of PAH.

Centres at which PAH is recruiting:

Cambridge University Hospitals NHS Foundation Trust
Great Ormond Street Hospital for Children NHS Foundation Trust 
Golden Jubilee National Hospital, Glasgow
Imperial College Healthcare NHS Trust, London
Newcastle upon Tyne NHS Foundation Trust
NHS Greater Glasgow and Clyde
Papworth Hospital NHS Foundation Trust
, Cambridgeshire
Royal Brompton & Harefield NHS Foundation Trust
Royal Free Hospital NHS Foundation Trust
, London
Royal United Hospital Bath
Sheffield Teaching Hospitals NHS Foundation Trust

Lead:
Professor Nick Morrell

If you feel your NHS site would be suitable to recruit for PAH please get in contact with the PAH Study Coordinator Jennifer Martin