Cystic fibrosis is a disease that causes very thick mucus secretions to build up within the lungs, which in turn, leads to inflammation and chronic lung infections. The disease can reduce the life expectancy of those afflicted to about 40 years, with death primarily due to lung failure.
A team of researchers at the Center for Nanomedicine at the Wilmer Eye Institute, part of Johns Hopkins University School of Medicine has been studying mucus in the lungs of cystic fibrosis patients. Their primary goal was to design inhalable therapeutic nanoparticles that cross the cystic fibrosis mucus barrier in the lung, to help restore normal function.
But the work recently led the researchers to the unexpected discovery that mucus appears to change as the disease progresses. They found that the mobility of these nanoparticles could vary widely in mucus from different patients. They will describe their findings this week during The Society of Rheology's 87th Annual Meeting, being held Oct. 11-15, 2015, in Baltimore, Md. Rheology is the branch of physics that deals with the deformation and flow of matter.
"At the time of our discovery, we didn't have a great explanation for this finding," said Gregg Duncan, a postdoctoral fellow. "So, we set out to figure out what caused the differences and whether or not it was related to cystic fibrosis lung disease severity."
They explored these differences by using a technique called "multiple particle tracking," which allowed them to take videos of nanoparticle movement within cystic fibrosis mucus, using a fluorescent microscope.
That enabled the researchers to interpret "the speed at which nanoparticles move in cystic fibrosis mucus, to relate it to the mucus gel's properties on extremely short length scales from micrometers (one millionth of a meter) to nanometers (one billionth of a meter)," explained Duncan.
Prior studies of cystic fibrosis mucus were somewhat limited in their ability to characterize micro- to nano-scale properties. "Changes of these length scales in cystic fibrosis mucus may dictate how pathogens spread in the lung and the ability of immune cells to fight infection," Duncan said. "Our findings suggest that the micro- and nano-scale properties in cystic fibrosis mucus change in patients as their disease progresses."
In terms of applications for their findings, there are currently no available biomarkers that reliably predict pulmonary exacerbations, a drastic decline in lung health. That knowledge would help to better manage cystic fibrosis patient care. "Our hope is that this approach will provide more insights into the cystic fibrosis lung microenvironment that are important to maintaining proper lung function," said Duncan.
The next step for the team will be to expand their studies "to larger patient populations, to assess whether our measurement can be used as a biomarker in cystic fibrosis, to determine the risks of pulmonary exacerbation," said Duncan.