Mild parenchymal lung disease and/or low diffusion capacity impacts survival and treatment response in patients diagnosed with idiopathic pulmonary arterial hypertension

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 2001–19 were identified in the ASPIRE registry. Using pre-specified criteria based on CT imaging and spirometry, patients with a diagnosis of IPAH and no lung disease were termed IPAHno-LD (n=303), and those with minor-mild emphysema or fibrosis were described as IPAHmild-LD (n=190).

Survival was significantly better in IPAHno-LD than in IPAHmild-LD (1 and 5-year survival 95% and 70% versus 78% and 22% respectively, p<0.0001). In the combined group of IPAHno-LD and IPAHmild-LD, independent predictors of higher mortality were increasing age, lower DLCO, lower exercise capacity and a diagnosis of IPAHmild-LD (p all <0.05). Exercise capacity and quality of life improved (p both <0.0001) following treatment in patients with IPAHno-LD but not IPAHmild-LD. A proportion of patients with IPAHno-LD had a DLCO <45%; these patients had poorer survival than patients with DLCO ≥45% although 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 DLCO may represent a further distinct phenotype. These data suggest that RCTs of targeted therapies in patients with these phenotypes are required.