Statins Effective in Treating Severe Lung Disease: Study

Statin drugs could serve as an alternative treatment option to treat severe lung diseases caused by surfactant clog, finds a new study.

In a condition like pulmonary alveolar proteinosis, where surfactant clogs up the air sacs in the lungs, statins can be effective, finds a new study. The findings of this stud are published in the journal of Nature Communications.

// 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.

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‘Disruption of cell regulation tends to trigger PAP; statins can, therefore, restore this dysregulation and help the macrophages clear out cholesterol which otherwise could lead to surfactant accumulation’

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."

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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.

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In both human patients and animal models of PAP, statin 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.

Source-Eurekalert

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