Loss of pulmonary capillaries in idiopathic pulmonary arterial hypertension with low diffusion capacity is accompanied by early diffuse emphysema detected by 129Xe MRI

Abstract

Objectives Recent studies suggest the existence of an idiopathic pulmonary arterial hypertension (IPAH) phenotype affecting mostly patients with a smoking history, characterised by low diffusion capacity for carbon monoxide (DLCO) without clinically significant emphysema. This study’s objective was to test the hypothesis of a loss of pulmonary capillaries as an underlying mechanism by comparison to other patient groups with and without pulmonary hypertension (PH). Materials and methods Between March 2019 and June 2023, patients of four groups were recruited for this observational study: IPAH with preserved (1) and low DLCO (2), combined pulmonary fibrosis and emphysema with PH (3), and emphysema without PH (4). Patients underwent clinical CT and 129Xe MRI including dissolved-phase imaging yielding the ratio of 129Xe in red blood cells and membrane tissues (RBC-M), chemical shift saturation recovery for determining RBC fraction η and diffusion-weighted imaging yielding surface-volume ratio. Kruskal–Wallis tests were used for statistical analysis. Results Twenty-nine participants were recruited, of which 22 (age 64 ± 10, 11 male, 5/5/7/5 for the individual groups) could be included in the analysis. RBC-M and η were reduced in IPAH with low versus preserved DLCO and emphysema groups (p ≤ 0.01). CT low-attenuation area percentage was not increased in IPAH with low DLCO compared to any group. 129Xe MRI-derived surface-volume ratio was reduced in IPAH with low versus preserved DLCO (p = 0.04). Conclusion Results are consistent with a loss of pulmonary capillaries in patients with IPAH and low DLCO along with destruction of alveolar tissue, likely due to early diffuse emphysema. Key Points QuestionA loss of pulmonary capillaries has been suggested in patients with IPAH and low diffusion capacity without clinically significant emphysema on CT. Findings129Xe uptake in red blood cells and lung surface-volume ratio were reduced in IPAH patients with low compared to preserved diffusion capacity. Clinical relevanceThis study furthers the understanding of the underlying pathological mechanisms in IPAH with low diffusion capacity, providing evidence that loss of pulmonary capillaries is accompanied by alveolar tissue destruction despite near-normal CT.