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 (<i>IPAH _{lung disease}</i> ) 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 (<i>IPAH _{no lung disease}</i> ). Patients with '<i>IPAH _{lung disease}</i> ' 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 '<i>IPAH _{no lung disease}</i> '. We described the outcome of the cohort of patients with '<i>IPAH _{no lung disease}</i> ' in a previous paper. Here, we have compared incident '<i>IPAH _{lung disease}</i> ' patients with '<i>IPAH _{no lung disease}</i> ' patients diagnosed concurrently in all eight Pulmonary Hypertension centres in the UK and Ireland between 2001-2009. Compared with '<i>IPAH _{no lung disease}</i> ' (<i>n</i> = 355), '<i>IPAH _{lung disease}</i> ' patients (<i>n</i> = 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 '<i>IPAH _{lung disease}</i> ' and '<i>IPAH _{no lung disease}</i> '. However, survival of '<i>IPAH _{lung disease}</i> ' was lower than '<i>IPAH _{no lung disease}</i> ' (one year survival: 72% compared with 93%). This survival was significantly worse in '<i>IPAH _{lung disease}</i> ' even after adjusting for age, gender, smoking history, comorbidities and haemodynamics. '<i>IPAH _{lung disease}</i> ' patients had similar short-term improvement in six-minute walk distance with anti-pulmonary arterial hypertension therapy but worse survival compared with '<i>IPAH _{no lung disease}</i> ' patients. This suggests that '<i>IPAH _{lung disease}</i> ' are a separate phenotype and should not be lumped with '<i>IPAH _{no lung disease}</i> ' in clinical trials of Group 1 pulmonary arterial hypertension.