A Call for a Better PoPH Risk Assessment Model, and Treatment Direction

This serendipitous encounter, initially sparked by a single patient, began my profound and enduring interest in pulmonary vascular disease, particularly pulmonary hypertension. Learning from this, my career has been shaped, to a large extent, by clinical observation, translational research, and collaboration with peers, all driven by a curiosity to understand the complex mechanisms of pulmonary vascular disease. This journey underscores the value of curiosity-driven research, demonstrating how unexpected clinical encounters can profoundly influence a medical career, hopefully leading to advancements in understanding and treating pulmonary hypertension. You could easily say that pentazocine hooked me.

My journey into studying nitric oxide (NO) bioavailability developed as I explored the role of nitrite ions. The traditional view that nitrite was merely an inactive byproduct of NO oxidation was a perspective I sought to challenge. As I continued my research at Papworth and Addenbrooke's Hospitals under Professor Higenbottam, I hypothesized that nitrite ions could be a source of NO bioactivity.

Pfizer initiated their Phase III trial of sildenafil for the treatment of PAH (SUPER study), which later led to the publication of the results [4] and the approval of sildenafil (20 mg, three times a day) in 2006 for the management of PAH. This period marked a pivotal moment in the medical history of treating PAH. I witnessed firsthand how this development transformed the landscape of treatment options for patients suffering from this severe condition.

In 1979, during my cardiology fellowship, a 16-year-old with primary pulmonary hypertension (PPH), a rare and severe condition at that time, spurred my research. There was limited literature then. My pediatric cardiology colleagues, who were experienced in dealing with pulmonary hypertension linked to congenital heart diseases, introduced me to vasoreactivity testing, a method involving the administration of oxygen and tolazoline to assess operability. Tolazoline administration resulted in a significant decrease in pulmonary artery (PA) pressure, suggesting potential therapeutic responsiveness, though diuretics were the only treatment for pulmonary hypertension and right heart failure at that time. This prompted my search for a viable solution.