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

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 (D<inf>LCO</inf>) 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 D<inf>LCO</inf> (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 D<inf>LCO</inf> and emphysema groups (p ≤ 0.01). CT low-attenuation area percentage was not increased in IPAH with low D<inf>LCO</inf> compared to any group. ¹²⁹Xe MRI-derived surface-volume ratio was reduced in IPAH with low versus preserved D<inf>LCO</inf> (p = 0.04). Conclusion: Results are consistent with a loss of pulmonary capillaries in patients with IPAH and low D<inf>LCO</inf> along with destruction of alveolar tissue, likely due to early diffuse emphysema. Key Points: Question A loss of pulmonary capillaries has been suggested in patients with IPAH and low diffusion capacity without clinically significant emphysema on CT. Findings ¹²⁹Xe uptake in red blood cells and lung surface-volume ratio were reduced in IPAH patients with low compared to preserved diffusion capacity. Clinical relevance This 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.