Idiopathic pulmonary arterial hypertension and co-existing lung disease: is this a new phenotype?

Patients classified as idiopathic pulmonary arterial hypertension (defined as Group 1 on European Respiratory Society (ERS)/European Cardiac Society (ESC) criteria) may have evidence of minor co-existing lung disease on thoracic computed tomography. We hypothesised that these idiopathic pulmonary arterial hypertension patients (IPAH _{lung disease} ) are a separate subgroup of idiopathic pulmonary arterial hypertension with different phenotype and outcome compared with idiopathic pulmonary arterial hypertension patients without co-existing lung disease (IPAH _{no lung disease} ). Patients with 'IPAH _{lung disease} ' have been eligible for all clinical trials of Group 1 patients because they have normal clinical examination and normal spirometry but we wondered whether they responded to treatment and had similar survival to patients with 'IPAH _{no lung disease} '. We described the outcome of the cohort of patients with 'IPAH _{no lung disease} ' in a previous paper. Here, we have compared incident 'IPAH _{lung disease} ' patients with 'IPAH _{no lung disease} ' patients diagnosed concurrently in all eight Pulmonary Hypertension centres in the UK and Ireland between 2001-2009. Compared with 'IPAH _{no lung disease} ' (n = 355), 'IPAH _{lung disease} ' patients (n = 137) were older, less obese, predominantly male, more likely to be current/ex-smokers and had lower six-minute walk distance, lower % predicted diffusion capacity for carbon monoxide, lower mean pulmonary arterial pressure and lower pulmonary vascular resistance index. After three months of pulmonary hypertension-targeted treatment, six-minute walk distance improved equally in 'IPAH _{lung disease} ' and 'IPAH _{no lung disease} '. However, survival of 'IPAH _{lung disease} ' was lower than 'IPAH _{no lung disease} ' (one year survival: 72% compared with 93%). This survival was significantly worse in 'IPAH _{lung disease} ' even after adjusting for age, gender, smoking history, comorbidities and haemodynamics. 'IPAH _{lung disease} ' patients had similar short-term improvement in six-minute walk distance with anti-pulmonary arterial hypertension therapy but worse survival compared with 'IPAH _{no lung disease} ' patients. This suggests that 'IPAH _{lung disease} ' are a separate phenotype and should not be lumped with 'IPAH _{no lung disease} ' in clinical trials of Group 1 pulmonary arterial hypertension.