Pulmonary Venous Vasculopathy in Connective Tissue Disease‐Associated Pulmonary Arterial Hypertension With Reduced Diffusion Capacity for Carbon Monoxide

ABSTRACT Connective tissue disease‐associated pulmonary arterial hypertension (CTD‐PAH) has a poorer prognosis than idiopathic PAH, potentially attributable to pulmonary veno‐occlusive disease (PVOD)‐like involvement. The diffusing capacity for carbon monoxide (DLco) may reflect small pulmonary venous obliteration. Whether severely reduced DLco reflects the severity of venous remodelling in CTD‐PAH remains incompletely characterised, particularly with quantitative morphometric assessment. Thus, we evaluated the association of reduced DLco with clinical characteristics and venous vasculopathy in patients with CTD‐PAH. We retrospectively reviewed patients with CTD‐PAH without interstitial pneumonia. Patients were categorised into two groups based on %DLco (< 45%: severely reduced DLco or ≥ 45%: non‐severely reduced DLco). Clinical characteristics and survival rates were compared. Histopathological characteristics of the pulmonary vasculature were analysed in eight autopsy cases. Of the 86 patients (mean age, 49.2 ± 16.8 years), 25 (29.1%) were classified into the severely reduced DLco group. They were older, showed a higher prevalence of systemic sclerosis, and exhibited lower arterial oxygen saturation and mean pulmonary arterial pressure compared with the other group. The severely reduced DLco group had a worse survival in unadjusted analysis ( p = 0.048). Histopathological analysis revealed that the severity of small pulmonary venous stenosis was inversely correlated with %DLco ( R 2 = 0.537, p = 0.039; 95% CI, −0.69 to −0.03). Patients with CTD‐PAH and a severely reduced DLco demonstrated a poorer prognosis than those without. Reduced DLco was associated with the severity of small pulmonary venous stenosis, consistent with a PVOD‐like venous remodelling spectrum in CTD‐PAH. DLco may serve as a clinically accessible marker of venous involvement within the PVOD‐like spectrum of CTD‐PAH.