Idiopathic PAH rethink needed after ‘distinct’ form identified


By Emma Wilkinson

18 Jul 2022

Some forms of pulmonary hypertension should be reclassified say researchers who identified a group of patients with a disease phenotype that seems to be linked to excessive smoking.

It follows emerging evidence that while idiopathic pulmonary arterial hypertension (IPAH) was traditionally found in young otherwise healthy individuals, it is increasingly being diagnosed in older patients with co-morbidities.

Now analysis of data from two European pulmonary hypertension registries (COMEPRA and ASPIRE) has shown a group of patients who meet the diagnostic criteria for IPAH but who have a distinct “presumably smoking-related” form of pulmonary hypertension accompanied by a low diffusion capacity for carbon monoxide.

These patients resemble those who have pulmonary hypertension due to lung disease and have very little in common with patients presenting with classical IPAH, the researchers from Germany and the UK reported in The Lancet Respiratory Medicine.

Patients diagnosed with IPAH who have “a lung phenotype” share many features with those with pulmonary hypertension associated with lung disease including sex and age distribution, functional impairment at diagnosis, response to pulmonary hypertension medications, and survival, the analysis showed.

In all, the study looked at 313 patients with classical IPAH, 407 patients with IPAH and a lung phenotype, and 1285 patients with pulmonary hypertension due to lung disease.

Compared with patients with classical IPAH, patients with IPAH and a lung phenotype were older with a median age of around 70 years more often male. 

All patients were smokers with a median tobacco exposure of 40 pack years in one registry and 30 pack years in the other.

Forced vital capacity and forced expiratory volume were mostly normal but the diffusion capacity for carbon monoxide was severely reduced and the patients were more hypoxaemic than patients with a classical phenotype, they reported.

The findings highlight a problem of the current diagnostic classification, the researchers noted, in that those with a low diffusion capacity for carbon monoxide and no or mild parenchymal lung disease are classified as IPAH according to current guidelines but in reality they phenotypically resemble patients with group 3 pulmonary hypertension. 

“These observations challenge the current diagnostic classification of pulmonary hypertension, and we propose to add a phenotypic component to the classification of unexplained pre-capillary pulmonary hypertension taking into account smoking history, DLCO, chest CT findings, and risk factors for left heart disease,” they said.

More data is also needed on the safety and efficacy of treatments for pulmonary arterial hypertension in this group, they added.

“Future clinical trials on PAH should collect and report data on smoking status and DLCO of their participants. 

“Finally, our observations support the hypothesis that there is a distinct smoking-related pulmonary vasculopathy, which needs to be further investigated.” 

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