From the artery to the interstitium: deconstructing the T Box

What is it about?

In this study, we describe the Spanish experience with PAH associated with TBX4 variants. All patients had a reduction in diffusion capacity, reflecting the involvement of alveolo-capillar barrier. Apart from this, we observe a wide spectrum of clinical phenotypes, probably due to a different genetic and pathological background.

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Photo by Sangharsh Lohakare on Unsplash

Photo by Sangharsh Lohakare on Unsplash

Why is it important?

This wide phenotype spectrum of TBX4 variants forces us to an individualized approach of each patient. One might consider these patients as group 3 PH due to lung parenchymal involvement. However, this is a dangerous simplification that might lead to misdiagnosis and inappropriate treatment. Some findings run against this explanation. Firstly, there is no correlation between Pulmonary Vascular Resistance and DLCO. Moreover, patients had a favourable response to PAH-targeted and a low risk situation can be achieved. It is important to keep in mind that TBX4 mutations might lead to isolated vasculopathy, typical PAH phenotype (group 1). The most reasonable approach is contextualizing PH severity using a comprehensive evaluation. It is important to elucidate the predominant profile: hemodynamic vs. respiratory. The spectrum of both vasculopathy and parenchymal lung disease is probably a continuum in TBX4 carriers PH. Whether these patients have PAH and lung disease due to TBX4 mutations vs. PH to parenchyma lung disease remains a dilemma. We recommend early referral to an expert center for a comprehensive evaluation to reach an accurate diagnosis. Furthermore, PAH therapy should be considered when PH cannot be easily explained by a mild form of lung disease.

Perspectives