Rare pulmonary diseases and pulmonary hypertension

Pulmonary hypertension (PH) is a significant complication of various lung diseases, including rare conditions such as lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). This review explores the pathophysiology, diagnostic challenges, and therapeutic strategies for managing PH in these conditions, emphasizing recent findings and gaps in knowledge.

In LAM, PH primarily results from parenchymal destruction and hypoxic vasoconstriction rather than direct vascular involvement, leading to its reclassification from Group 5 to Group 3 PH. Sirolimus, an mTOR inhibitor, has demonstrated benefits in stabilizing lung function and may indirectly reduce pulmonary pressures, though direct effects remain unproven. In PLCH, PH is often disproportionate to lung function impairment, suggesting a distinct pulmonary vasculopathy. Histopathologic studies reveal extensive vascular remodeling, including features of pulmonary veno-occlusive disease. Case reports suggest potential benefits of PH-specific therapies such as endothelin receptor antagonists and phosphodiesterase-5 inhibitors, but their use requires caution due to the risk of worsening gas exchange.

PH in LAM and PLCH is uncommon but clinically relevant, particularly in advanced disease. While emerging therapies show promise, further research is needed to optimize management and improve patient outcomes.