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

Abstract

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.