Virtual symposium by the iPVD Consortium: Infection series – fungi

Date: November 29, 2023

Beyond parasites and viruses: Fungi & PH (moderator introduction)
Dr. Sharilyn Almodovar (Texas Tech University, USA)

Pulmonary paracoccidioidomycosis-induced pulmonary hypertension
Dr. Alexandre Todorovic Fabro (University of São Paulo, Brazil)

Summary:

• Fungi can cause significant lung infections and may lead to pulmonary hypertension (PH)—particularly in immunocompromised persons. These fungi include black mold, Aspergillus fumigatus, Cryptococcus, Pneumocystis, and Histoplasma.
• Dr. Fabro at the University of São Paulo studies pulmonary paracoccidioidomycosis (PCM)—a fungal infection endemic to Latin America—and its link to PH.
• Many PCM patients showed vascular remodeling even at sites distant from granulomas. Historic research identified PH and cor pulmonale in PCM patients, but clinical guidelines under-recognize this association. Review of 5,000 PCM cases showed that of those who had echocardiography, 50% had evidence of elevated right ventricular pressure (suggesting PH), independent of COPD or smoking status.
• Experimental rat models of PCM resulted in high-density lung granulomas and significantly increased right ventricular pressures. Detailed tissue analysis revealed: 1) vascular remodeling and adventitial thickening, especially in small vessels; 2) Collagen deposition in vessel walls; and 3) Evidence of myofibroblast activation within the vessel adventitia.
• Human lung biopsies mirrored experimental findings: extensive vessel wall remodeling and collagen deposition.
• These data suggest a potential mechanism by which PCM may promote PH: myofibroblast activation leading to collagen buildup and vascular stiffening, elevating pulmonary arterial pressure, which in turn provokes further vascular damage and contributes to PH progression.