Evolving Histopathologic and Clinical Profiles in Idiopathic Pulmonary Arterial Hypertension

Idiopathic pulmonary arterial hypertension (IPAH) was originally defined as a rapidly progressive disease predominantly affecting young women without comorbidities. The hallmark histopathologic feature of this condition was the plexiform lesion, a complex, lumen-obliterating structure in small pulmonary arteries.

Over time, the clinical understanding of IPAH has evolved, with the condition now being associated with older patients, more males, and a higher prevalence of comorbidities. Additionally, many patients diagnosed with IPAH have a low diffusing capacity of the lungs for carbon monoxide (Dlco), which correlates with worse outcomes despite normal spirometry and minimal emphysema.

Historically, the understanding of IPAH's histopathology was based on lung specimens from autopsies or lung transplants in younger patients with PPH. However, in recent years, fewer autopsies and transplants have been performed on older patients with comorbidities, creating a gap in knowledge about the current histopathologic features of IPAH. There is uncertainty whether plexiform lesions continue to be the predominant characteristic in modern cases or if the vascular phenotype has shifted along with the changing clinical demographics of patients diagnosed with IPAH. To address this, the researchers aimed to examine lung histopathology in patients with IPAH and to correlate these findings with their clinical characteristics.

In a study published in CHEST, researchers reviewed histopathology samples from 50 patients with IPAH diagnosed between 1996 and 2018. These samples came from lung biopsies, transplants, or autopsies, and the clinical data were obtained from the Amsterdam University Medical Center’s Pulmonary Hypertension Biobank. The histopathologic assessments focused on the presence of plexiform vasculopathy and other vascular abnormalities. Notably, plexiform vasculopathy was observed in 52% of the cases, while the remaining 48% showed nonplexiform vasculopathy. Among those with nonplexiform vasculopathy, 3 patients had pulmonary veno-occlusive disease (PVOD), indicating variability in the underlying vascular pathology.

The findings suggest that a significant proportion of modern IPAH cases may not exhibit the classic plexiform vasculopathy seen in earlier descriptions of the disease. This indicates that the vascular phenotype of IPAH may have shifted, possibly in response to the changing clinical profiles of patients.

These results underscore the importance of further research to understand the full spectrum of histopathologic features in IPAH and their implications for diagnosis and treatment in different patient populations.

Reference

Nossent EJ , Smits JA, Seegers C, et al. Clinical correlates of a nonplexiform vasculopathy in patients with a diagnosis of idiopathic pulmonary arterial hypertension. CHEST. 2024;166(1)190-200. doi:https://doi.org/10.1016/j.chest.2024.02.046