Nav: Home

Taking a pill can effectively treat brutal lung disease

August 07, 2018

CINCINNATI - Researchers report in Nature Communications they figured out why air sacs in the lungs clog up with a thick substance called surfactant in a brutal disease called Pulmonary Alveolar Proteinosis (PAP), and they show taking cholesterol-busting pills called statins can effectively treat the disease.

That's good news for people with PAP because at present the current standard treatment is something called a whole lung lavage. Essentially, it involves flushing patient lungs to clear out the gunk--a procedure so invasive it requires putting people under general anesthesia. Furthermore, the procedure has to be repeated every time the lungs clog up, which translates into some pretty serious quality of life issues for patients.

Researchers at Cincinnati Children's Hospital Medical Center found out the culprit is cholesterol. Led by Bruce Trapnell, MD, director of the Translational Pulmonary Science Center, the team found out years ago that PAP is linked to disruption of cell regulation by a molecule called granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF is crucial for the development of fully mature macrophage cells in the lungs, which are needed to clear away used surfactant--a substance important to lung function--so that people can breathe.

In their new study of PAP patients and mouse models of the disease, the researchers uncovered a more precise reason that disruption of cell regulation by GM-CSF triggers PAP. It's because cell dysregulation reduces the ability of macrophages to process and clear out cholesterol, allowing its levels to build up. This contributes to the accumulation of surfactant that causes PAP and hinders breathing, according to study authors.

"Showing that the pathogenic driver of the disease is disruption of cholesterol homeostasis in these patients will change thinking in the PAP field," explains Trapnell. "Now that we know cholesterol in macrophages is a target for therapeutic development, repurposing statins is a pretty straight forward pharmacological approach for treating people with PAP."

Clinical Trial Planned

The findings are expected to lead to a clinical trial to test statin therapy in larger numbers of people suffering from PAP, said Trapnell. The current study tested statin therapy in two adult patients and in genetically engineered mouse models of PAP.

In both human patients and animal models of PAP, stain therapy was associated with improved cholesterol balance in pulmonary macrophage cells and allowed surfactant to be cleared from lung air sacs. This improved respiratory function in the adult patients and in the laboratory models. Those tests were the result of earlier experiments on mouse pulmonary macrophages and cells donated from patients.
-end-
First author on the study is Cormac McCarthy, MD, PhD, and a Rare Lung Diseases Consortium Scholar in the Translational Pulmonary Science Center at Cincinnati Children's.

Funding support for the study came in part from the National Institutes of Health/National Heart, Lung, and Blood Institute (R01085453, HL118161, HL136543), and a National Center for Advancing Translational Science grant through the National Heart, Lung, and Blood Institute (HL127672).

About Cincinnati Children's

Cincinnati Children's Hospital Medical Center ranks second in the nation among all Honor Roll hospitals in U.S. News and World Report's 2018-2019 Best Children's Hospitals ranking. In addition, Cincinnati Children's ranks first in the pediatric specialties of cancer and gastroenterology/GI surgery care, and among the top five pediatric hospitals in nine of 10 specialties. Founded in 1883, Cincinnati Children's vision is to be the leader in improving child health, through patient care, research and education.

Cincinnati Children's Hospital Medical Center

Related Cholesterol Articles:

Cholesterol -- a key player at the lung surface
Cholesterol, a naturally occurring compound at the lung surface, has been shown to have a clear effect on the properties of this nanoscale film that covers the inside of our lungs.
Does boosting 'good' cholesterol really improve your health?
A new review addresses the mysteries behind 'good' HDL cholesterol and why boosting its levels does not necessarily provide protection from cardiovascular risk for patients.
Researchers zero-in on cholesterol's role in cells
For the first time, by using a path-breaking optical imaging technique to pinpoint cholesterol's location and movement within the cell membrane, chemists at the University of Illinois at Chicago have made the surprising finding that cholesterol is a signaling molecule that transmits messages across the cell membrane.
Cholesterol important for signal transmission in cells
Cholesterol can bind important molecules into pairs, enabling human cells to react to external signals.
Raising 'good cholesterol' not as effective as lowering 'bad cholesterol'
Low and very high levels of HDL, or 'good cholesterol' are associated with a higher risk of dying from heart disease, cancer and other causes, according to a study today in the Journal of the American College of Cardiology.
New gene for familial high cholesterol
New research from Denmark reveals the gene that explains one quarter of all familial hypercholesterolemia with very high blood cholesterol.
No need to fast before a cholesterol test
New research from Denmark, Canada and the US involving more than 300,000 individuals suggests that patients do not need to check their cholesterol levels on an empty stomach.
Cyclodextrin dissolves away cholesterol crystals
Cyclodextrin has been shown in mice to dissolve cholesterol crystals and prevent plaque formation.
New vaccine could prevent high cholesterol
A new cholesterol-lowering vaccine leads to reductions in 'bad' LDL cholesterol in mice and macaques, according to research published in Vaccine.
Enriched broccoli reduces cholesterol
Including a new broccoli variety in the diet reduces blood LDL-cholesterol levels by around 6 percent, according to the results of human trials led by the Institute of Food Research.

Related Cholesterol Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...