High Altitude-Induced Pulmonary Hypertension: Our Scientific Journey to Prove Cold Exposure Is Also an Important Cause

Djuro Kosanovic

https://doi.org/10.1002/pul2.70186 

Abstract

From the earliest days of human existence, people have inhabited some of the most challenging environments on Earth, including high-altitude regions. It is well established that chronic hypoxia, the defining environmental feature of mountainous areas, leads to high altitude-induced pulmonary hypertension (HAPH) in individuals who are not adequately adapted. Yet, despite the apparent presence of another environmental stressor, such as cold, its role in development remained overlooked for decades.

My personal connection to this question began in childhood, when I spent holidays with my grandparents in a mountain village. Even before I understood the science of hypoxia, my mother always reminded me to “dress well because it's a mountain and it's colder there.” For me, the mountains were synonymous with cold. This early association stayed with me, and years later, as I embarked on a research career in pulmonary vascular diseases, I was struck by how little attention had been paid to the effects of cold exposure on pulmonary circulation in the context of HAPH. While working at Justus-Liebig University in Giessen, Germany, I decided to address the childhood experience and address the many remaining gaps in our understanding of the effect of high altitude. The scientific literature offered only a few notable studies conducted in cattle: one by the Grover group and another by Busch et al. [1, 2]. These investigations demonstrated that cold and high altitudes significantly impact the pulmonary vasculature in cattle. However, there was a glaring lack of data on how cold affects humans living at high altitudes.

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