CRITICAL CARE
The Tipping Point
Could the complement immune system be responsible for pulmonary hypertension?
Most patients don’ t feel symptoms of pulmonary hypertension until it’ s too late: Widespread, potentially irreversible changes to the entire cardiopulmonary system are already well underway. Some patients respond well to treatment. Others rapidly decline. There is no cure. With nearly $ 14 million in funding from the National Institutes of Health, an international team of researchers is investigating a potential root culprit: the destructive potential of the innate immune system.
At first glance, pulmonary hypertension looks pretty simple. It’ s an increase in blood pressure in the lungs.
A lot of things can trigger it. Genetics, infection, drugs, tumors, metabolic dysfunction. It’ s a complication of disease. It can occur idiopathically. It affects all ages, from newborns to the very old. It takes many forms.
But the mechanics are the same: some insult causes the pulmonary artery to constrict. The subsequent rise in pressure damages the vessels and hampers gas exchange, leading to hypoxia, which further damages the artery. Those insults trigger inflammation, and that’ s where things seem to go awry.
Inflammation stiffens and thickens the artery, ramping up the pressure, creating an environment so hostile and diseased it warps cells’ genetic expression at the molecular level. It doesn’ t just affect the cardiopulmonary system. It seems to fundamentally rebuild the system. Often, the changes are irreversible( 1).
Theoretically, you should be able to reverse the process, or at least stop it from progressing, by relaxing the pulmonary artery. Indeed, dozens of vasodilators have been tried, and some of them, in some situations, can slow the cycle down.
Just as often, though, they don’ t. And when they don’ t, there’ s not much else.
THE VICIOUS CYCLE
In many ways, pulmonary hypertension, or PH, is still poorly understood. Still, few people in the world can claim to have done as much to understand it as pediatric critical care specialist Kurt Stenmark, MD. His work has been supported for 45 years by the longest continuously funded program project grant in the Division of Lung Diseases of the NIH. He helped found and has led the Division of Critical Care at Children’ s Hospital Colorado since 1987. He’ s led the Cardiovascular Pulmonary Research Lab at the neighboring University of Colorado School of Medicine— the CVP for short— since 2005, growing a team of more than 30 of the world’ s foremost pulmonary hypertension researchers. He’ s
10 | CHILDREN’ S HOSPITAL COLORADO