Mild parenchymal lung disease and/or low diffusion capacity impacts survival and treatment response in patients diagnosed with idiopathic pulmonary arterial hypertension
Robert A. Lewis, A. A. Roger Thompson, Catherine Billings, Athanasios Charalampopoulos, Charlie Elliot, Neil Hamilton, Catherine Hill, Judith Hurdman, Smitha Rajaram, Ian Sabroe, Andy Swift, David G. Kiely, Robin Condliffe
Abstract
There are limited published data defining survival and treatment response in patients with mild lung disease and/or reduced gas transfer who fulfil diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH). Patients diagnosed with IPAH between 2001 and 2019 were identified in the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) registry. Using prespecified criteria based on computed tomography (CT) imaging and spirometry, patients with a diagnosis of IPAH and no lung disease were termed IPAH no-LD (n=303), and those with minor/mild emphysema or fibrosis were described as IPAH mild-LD (n=190). Survival was significantly better in IPAH no-LD than in IPAH mild-LD (1- and 5-year survival 95% and 70% versus 78% and 22%, respectively; p<0.0001). In the combined group of IPAH no-LD and IPAH mild-LD , independent predictors of higher mortality were increasing age, lower diffusing capacity of the lung for carbon monoxide ( D LCO ), lower exercise capacity and a diagnosis of IPAH mild-LD (all p<0.05). Exercise capacity and quality of life improved (both p<0.0001) following treatment in patients with IPAH no-LD , but not IPAH mild-LD . A proportion of patients with IPAH no-LD had a D LCO <45%; these patients had poorer survival than patients with D LCO ≥45%, although they demonstrated improved exercise capacity following treatment. The presence of even mild parenchymal lung disease in patients who would be classified as IPAH according to current recommendations has a significant adverse effect on outcomes. This phenotype can be identified using lung function testing and clinical CT reports. Patients with IPAH, no lung disease and severely reduced D LCO may represent a further distinct phenotype. These data suggest that randomised controlled trials of targeted therapies in patients with these phenotypes are required.