A very interesting article by Prof. Werner Seeger recounts the discovery and development of inhaled prostanoids for pulmonary hypertension at the Giessen Pulmonary Hypertension center (Germany) in the late 1980s-1990s (§). Initially researching acute lung injury/Acute Respiratory Distress Syndrome (ARDS), researchers at Giessen observed that while intravenous vasodilators worsened ventilation/perfusion mismatch, aerosolized prostacyclin (PGI2) reduced pulmonary artery pressure while improving oxygenation.
In 1993, Marliese K., a 56-year-old woman with severe CREST syndrome-associated pulmonary arterial hypertension (CREST is a milder, localized form of scleroderma, an autoimmune disease causing tissue hardening that can lead to pulmonary arterial hypertension), became the first patient to inhale iloprost using a new nebulizer device developed at Giessen. iloprost was marketed in Germany as Ilomedin® for intravenous infusion in Winiwarter-Buerger disease. Marliese, who was in a low cardiac output state due to a failing right heart, with prominent jugular veins and severe peripheral edema had previously been referred for lung transplant, recovered impressively, showed dramatic improvement (pulmonary artery pressure dropped from 75 to 50 mmHg, cardiac output increased from 2.7 to 4.5 L/min), and lived another 10 years on this regimen.
This pioneering work led to phase III trials, worldwide approval of inhaled iloprost for World Health Organisation (WHO) Group 1 pulmonary hypertension (published in New England Journal of Medicine (NEJM 2002), and later development of inhaled treprostinil, establishing inhaled prostanoids as a cornerstone therapy for pulmonary hypertension.
Footnotes
(§) The establishment of the pulmonary hypertension center in Giessen was initiated in the late 1980s and further developed over the following decades by the founding team of Friedrich Grimminger, Ardeschir Ghofrani, Ralph Schermuly, and Werner Seeger.
Citation
W. Seeger, “ The Discovery of Inhaled Prostanoids for Pulmonary Hypertension,” Pulmonary Circulation 15 (2025): 1-4. https://doi.org/10.1002/pul2.70192.