UAMS Innovations Aid $12 Million Asthma Study

UAMS’ Richard Kurten, Ph.D., in his laboratory with living lung samples kept in the incubator pictured, has increased the lung samples’ lifespan from about a week to six weeks, opening the door to new asthma research.

Aug. 23, 2013 | Living human lungs donated to the University of Arkansas for Medical Sciences (UAMS) are helping a multi-center team of researchers begin testing potential breakthrough asthma treatments as part of a 5-year, $11.9 million study funded by the National Institutes of Health (NIH).

The large study was made possible in part due to innovations in the processing and preservation of the lungs by UAMS’ Richard Kurten, Ph.D., a cell biologist who credits the UAMS Translational Research Institute’s support for enabling his participation in the study.

Kurten has helped open the door to exciting new research opportunities by extending the lifespan of donated lungs. Remarkably, they behave as if they were in a living person during experiments – even when the lung has been divided into hundreds of tissue samples.

“We’re just getting this off the ground, but I think we’re going to see some exciting new discoveries, and it wouldn’t have happened without the Translational Research Institute’s support,” Kurten said.

Based at the Lung Cell Biology Laboratory at the Arkansas Children’s Hospital Research Institute, Kurten works closely with the study’s principal investigator, Reynold Panettieri Jr., M.D., at the University of Pennsylvania School of Medicine in Philadelphia.

“Dr. Kurten has become an invaluable collaborator on this project,” Panettieri said. “His novel lung processing techniques will translate to more research opportunities, more efficient research, and a greater likelihood of discoveries that have a real impact on asthma.”

Other collaborating institutions are Johns Hopkins Bloomberg School of Public Health in Baltimore; the University of Maryland in Baltimore; Kimmel Cancer Center at Thomas Jefferson University in Philadelphia; and the University of South Florida in Tampa.

When he first began working with the lungs three years ago, Kurten said the tissue could be kept viable for about a week. His innovations have significantly expanded that timeframe so that incubated lung samples today are viable for experiments up to six weeks. He can also freeze them and store them for a year, then thaw them and perform experiments. In addition, he has increased the number of lung slice samples available for study from 200 to 600 with the potential for up to 2,000.

“That’s the core tool, and my real contribution has been to refine this system,” said Kurten, who expanded the tissue’s lifespan by reducing tissue trauma and oxidative damage during preparation, and by enhancing its nutrient transfer during incubation. With the possible exception of the liver, no other donated human organ offers such potential for study.

With the lung system in place, researchers have a rare platform for a much bigger series of projects testing new and existing asthma medications and to better understanding the cellular mechanisms involved in relaxing and opening constricted airway muscles.

Kurten foresees some exciting studies involving bitter compounds (known for giving beer and tonic water their characteristic taste), which researchers recently learned act as bronchodilators.

As asthma’s societal burden has grown, finding novel approaches to studying, treating and preventing the incurable disease has received greater national priority.

Asthma affects 17.7 percent of children and adults in the United States, according to the Centers for Disease Control and Prevention. In 2009 the disease was responsible for 3,388 deaths, nearly half a million hospitalizations and 1.9 million emergency department visits. It costs the U.S. $56 billion a year, and asthma prevalence has grown by 15 percent in the past decade.

Honoring Donors

The lungs are collected from living donors as potential transplants but are made available for research if there is no immediate need or they are excluded for other reasons. Kurten honors these gifts to science by ensuring that he and other researchers get the most out of every lung.

Knowing that a lung donation can arrive at any time, Kurten keeps a cot and sleeping bag in his small office. “They usually come at night on holiday weekends,” he said. Processing takes about six hours and must be done immediately, but he can grab a few winks during certain phases.

The lungs are inflated and filled with agarose (derived from kelp). After the tissue hardens, cores are made and cut into tiny slices, to allow examination of the airways under a microscope. Kurten was able to triple the number of viable slices thanks to his improvements in lung processing and tissue storage.

Kurten said the Translational Research Institute helped secure UAMS’ portion of the NIH award – $353,130 over five years – by funding a $98,724 pilot study for the preliminary evaluation of lung tissue responses to medications. In addition, the institute paid for travel in January 2011 that helped cement a collaborative relationship with Panettieri. Kurten spent six days working in Panettieri’s laboratory comparing their approaches and standardizing their procedures.

In a note to the Translational Research Institute in January 2011 following Kurten’s visit, Panettieri predicted a fruitful partnership: “This was an extraordinarily productive interaction that will undoubtedly lead to further collaboration, joint publications and funding opportunities,” he wrote.

“It’s about teamwork,” said Kurten, who has also embraced new collaborations using the lung tissue that will help advance knowledge of asthma and other diseases. For example, UAMS’ Daniel E. Voth, Ph.D., who is studying Coxiella burnetii, a bacterial pathogen that causes human Q fever, was in need of the macrophages that were being washed out of the lung airways along with mucous during processing. He learned of Kurten’s work through the Translational Research Institute, which encourages and facilitates research collaboration and efficiency. Kurten and Voth have three published studies as a result of their joint efforts, and Voth has earned additional NIH funding.

The Translational Research Institute also supported the recruitment of asthma researcher and allergist/immunologist Joshua Kennedy, M.D., by awarding him two years of salary support and research funding through the institute’s KL2 Scholar Career Development Award. Kennedy, a UAMS alumnus, is analyzing the role of rhinoviruses – cold viruses – in asthma.

“We are now taking these samples and infecting them with rhinoviruses to try to better mimic what happens in asthma,” Kurten said. “He’ll couple that with collecting samples from kids he sees in clinic who are having an asthma attack.”

In addition, Kurten’s clinical collaborator, Stacie Jones, M.D., co-director of the Lung Cell Biology Laboratory and chief of Pediatric Allergy and Immunology, will study the role allergies play in asthma.

Curtis Lowery, M.D., director of the Translational Research Institute, said the collaborations are a perfect example of how the NIH wants research to be conducted across the country.

“Dr. Kurten and the other researchers and institutions involved are demonstrating how essential collaboration is to advancing science toward real results that will benefit society,” Lowery said.

The Translational Research Institute’s mission is to help accelerate research that will improve the health and health care of people in Arkansas and across the country. It was established with major funding from the National Institutes of Health (NIH) in 2009 and is one of 60 NIH Clinical and Translational Science Award (CTSA) recipients. The institute’s funding from NIH flows through the National Center for Advancing Translational Sciences (NCATS).