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

Andrew J Peacock; Yi Ling; Martin K Johnson; David G Kiely; Robin Condliffe; Charlie A Elliot; J Simon R Gibbs; Luke S Howard; Joanna Pepke-Zaba; Karen K K Sheares; Paul A Corris; Andrew J Fisher; James L Lordan; Sean Gaine; J Gerry Coghlan; S John Wort; Michael A Gatzoulis

doi:10.1177/2045894020914851

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

Pulm Circ. 2020 Mar 30;10(1):2045894020914851. doi: 10.1177/2045894020914851. eCollection 2020 Jan-Mar.

Authors

Andrew J Peacock¹, Yi Ling¹, Martin K Johnson¹, David G Kiely², Robin Condliffe², Charlie A Elliot², J Simon R Gibbs³, Luke S Howard³, Joanna Pepke-Zaba⁴, Karen K K Sheares⁴, Paul A Corris⁵, Andrew J Fisher⁵, James L Lordan⁵, Sean Gaine⁶, J Gerry Coghlan⁷, S John Wort⁸, Michael A Gatzoulis⁸

Affiliations

¹ Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, UK.
² Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.
³ National Heart and Lung Institute, Imperial College London and Hammersmith Hospital, London, UK.
⁴ Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, UK.
⁵ Northern Pulmonary Vascular Unit, Freeman Hospital, Newcastle, UK.
⁶ National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland.
⁷ Pulmonary Hypertension Unit, Royal Free Hospital, London, UK.
⁸ Royal Brompton Pulmonary Hypertension and Adult Congenital Heart Centre, London, UK.

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.

Keywords: idiopathic pulmonary arterial hypertension (IPAH); lung disease; survival; treatment response.