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.