New Findings May Have Implications for PH Classification

Researchers have found that patients who have idiopathic pulmonary arterial hypertension (IPAH) with a phenotype characterized by a smoking history and low diffusion capacity for carbon monoxide had little in common with patients with classical IPAH.

Researchers of a new study have published their findings on the characterization of patients with pulmonary hypertension (PH), suggesting that their findings may result in the reclassification of certain forms of PH.

The group compiled data from 2 European PH registries of over 2000 patients with classical idiopathic pulmonary arterial hypertension (IPAH), patients with IPAH and a lung phenotype, and patients with PH resulting from lung disease. They published their findings in The Lancet Respiratory Medicine.

The researchers found that patients who have IPAH with a phenotype characterized by a history of smoking and low diffusion capacity for carbon monoxide (DLCO), an emerging lung phenotype, had little in common with patients with classical IPAH—those without cardiopulmonary comorbidities and a DLCO of 45% or higher of the predicted value—who were predominantly young and otherwise healthy. Commonalities between the 2 groups included precapillary PH, baseline characteristics, treatment response, and survival.

“These findings highlight a problem of the current diagnostic classification of patients with a low DLCO and no or mild parenchymal lung disease, which are classified as IPAH according to current guidelines, when in fact they phenotypically resemble patients with group 3 PH,” wrote the researchers.

Across the registries—COMPERA and ASPIRE—patients with IPAH with a lung phenotype and those with PH shared various features, including age, sex, functional impairment at diagnosis, response to PH treatment, and survival. Risk factors for left heart disease, including hypertension, coronary heart disease, and diabetes, were similar between the 2 groups.

In patients with IPAH and a lung phenotype, DLCO was significantly reduced in both registries, at 30% of the predicted value in COMPERA and 27% of the predicted value in ASPIRE. Meanwhile, DLCO was mildly reduced in patients with classical IPAH.

“As in previous studies, a DLCO of 45% or more or a DLCO of less than 45% of the predicted value discriminated between patients with classical IPAH and patients with IPAH and a lung phenotype,” explained the researchers. “It is unknown whether the low DLCO in patients with IPAH and a lung phenotype is caused by parenchymal abnormalities or by a distinct pulmonary vasculopathy involving the loss of small pulmonary vessels, for which the term vanishing pulmonary capillary syndrome has been proposed. In mice models, prolonged exposure to tobacco smoke causes endothelial cell apoptosis in pulmonary capillaries, which precedes the development of emphysema.”

According to the researchers, the diagnostic classification of older patients, such as the patients with IPAH and a lung phenotype in their study, can be challenging. Most of these patients exhibited normal or near normal status and dynamic lung function parameters. The majority also had a mild degree of parenchymal involvement but severe precapillary PH.

Their findings, say the group, have implications for treatment considerations for these patients with IPAH and a lung phenotype. They explained that there are insufficient data on the safety and efficacy of PAH treatment in these patients, with no pivotal trials of globally approved treatments reporting the DLCO of the study participants. They noted that a recent study found PAH treatments may actually further compromise gas exchange in these patients with a low DLCO.


Hoeper MM, Dwivedi K, Pausch C, et al. Phenotyping of idiopathic pulmonary arterial hypertension: a registry analysis. Lancet Respir Med. Published online June 28, 2022. doi:10.1016/S2213-2600(22)00097-2

Related Videos
Screenshot of Eva Parker, MD, smiling during an interview
Screenshot of Eleonora Lad, MD, PhD, smiling
Related Content
© 2023 MJH Life Sciences
All rights reserved.