Different cytokine patterns in BMPR2-mutation positive patients and pulmonary arterial hypertension patients without mutations and their influence on survival

To the editor:
Pulmonary arterial hypertension (PAH) covers a range of life-limiting illnesses that are characterized by increased mean pulmonary artery pressures that, if untreated, lead to right heart failure and death. This is due to remodeling of the small-to-medium sized pulmonary vessels, which obstruct blood flow. PAH can be further categorized into idiopathic PAH (without any identifiable cause, 6th World Symposium class 1.11) and heritable PAH (defined by mutations in specific genes, 6th World Symposium class 1.21), the most common affecting bone morphogenetic protein receptor type II (BMPR2).2,3 It is known that patients who are BMPR2-mutation positive have worse cardiac indexes at presentation and a worse overall outcome compared with PAH without mutations.4 Possessing a BMPR2 mutation also creates a proinflammatory state, through loss of endothelial barrier function5 and loss of antioxidant capability.6 This then begs the question as to whether the mutation-positive groups have different underlying pathogenetic mechanisms and require different biomarkers and treatments, analogous to how patients with epidermal growth factor receptor-mutation-positive non-small cell lung cancer respond to tyrosine kinase inhibition, although the majority of patients with non-small cell lung cancer do not.

We wondered if the broad proinflammatory phenotype seen in idiopathic PAH7 would be different in the heritable PAH subgroup. To answer questions like these, the National Cohort Study of Idiopathic and Heritable PAH (http://www.ipahcohort.com/) was set up in 2014.