Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pitt team first to profile genes in acutely ill idiopathic pulmonary fibrosis patients

08.07.2009
The first findings from a one-of-a-kind, patient-driven effort to provide lung tissue for research might help doctors predict when patients with idiopathic pulmonary fibrosis (IPF) are becoming dangerously ill and also could point the way to interventions that could sustain them until life-saving transplants can be performed.

According to senior author Naftali Kaminski, M.D., associate professor of medicine, computational biology and pathology, and director of the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases at the University of Pittsburgh School of Medicine and UPMC, the research published today in the American Journal of Respiratory and Critical Care Medicine addresses a dilemma in IPF care that currently is unsolved.

"Approximately 10 percent of patients develop an acute phase that in most cases is lethal," Dr. Kaminski explained. "There has been very little understanding of the molecular basis of this syndrome, but because of the dedication of our patients and their families, we are getting closer to some answers."

For most patients, the lung-scarring disease progresses gradually and lung function slowly deteriorates. But there is neither a cure nor effective treatment, so median survival is about three years. For unknown reasons, some IPF patients experience rapid declines that cause diffuse damage of the lung alveoli, the tiny sacs where the exchange of oxygen and carbon dioxide occurs.

To better understand the molecular mechanisms of disease exacerbation or, as Dr. Kaminski puts it, acceleration, the researchers compared the gene activity profile of the lungs of eight IPF patients whose disease was dramatically worsening when they died with those of 23 stable IPF patients and 15 people with healthy lungs.

In the first analysis of its kind, "gene activity patterns were found to be more similar among all IPF patients compared to healthy people," said lead author Kazuhisa Konishi, M.D., a visiting postdoctoral fellow in Dr. Kaminski's lab who performed the gene profiling. "But nearly 600 genes were differentially expressed between IPF patients who had accelerated disease and those who were stable."

There was no evidence that infection or inflammation was the cause of disease acceleration, he noted. Instead, there were indications that the cells of the alveolar epithelium, which is the tissue that covers the surface of the air sacs, were rapidly dying.

"That could mean that drugs that are used to protect the epithelium in other illnesses, such as cancer, might help IPF patients survive an exacerbation," said study co-author Kevin Gibson, M.D., associate professor in the Division of Pulmonary, Allergy and Critical Care Medicine at Pitt School of Medicine and medical director of the Simmons Center. "If we can keep them alive, there's a chance they could get a life-saving lung transplant."

To test whether the changes in the lungs could be revealed in the blood, the Pitt investigators contacted Dr. Kaminski's longtime collaborator, Dong Soon Kim, M.D., a renowned IPF researcher at Asan Medical Center and the University of Ulsan in Seoul, South Korea, who has been at the forefront of studying the acceleration syndrome. With her help, they found that levels of a protein called alpha-defensin were particularly high in the blood of patients experiencing an exacerbation. If the findings are verified with more research, which is underway, the proteins could be the first biomarker blood tests that doctors could track to identify patients at risk for sudden deterioration of lung function.

"This work opens an important window into the mystery of why patients with lung fibrosis suddenly decompensate and how to identify these patients for more aggressive therapies," said Mark T. Gladwin, M.D., chief of Pitt's Division of Pulmonary, Allergy and Critical Care Medicine. "Our current research efforts in the division focus on the development of novel therapeutics that will target the molecular pathways identified by our basic science laboratories."

If not for the altruism of IPF patients, the research and its promising results would not have been possible, Dr. Kaminski noted. The IPF tissue samples used for the study were collected through the Simmons Center's warm autopsy program, which is the only one for lungs in the world.

Several years ago, an IPF patient told Kathleen Lindell, Ph.D, R.N., the Simmons Center nurse, a quality of life researcher and a study co-author, that he wanted to aid research efforts by donating his lungs to science after death. In response, she developed the warm autopsy program.

"The tissue has to be collected within six hours of death, so it demands a great deal of flexibility and commitment on the part of caregivers and family," Dr. Lindell said. "The gene components of the lung cells degrade very quickly, so without the warm autopsy protocol, we couldn't have done the activity profiling that was the foundation of this research."

Other study authors include Thomas J. Richards, Ph.D., Yingze Zhang, Ph.D., Simmons Center; Rajiv Dhir, M.D., Michelle Bisceglia, and Samuel A. Yousem, M.D., Department of Pathology; Sebastien Gilbert, M.D., Department of Thoracic Surgery, all from the Pitt School of Medicine; and Jing Woo Song, Asan Medical Center, University of Ulsan, Seoul, South Korea.

The research was funded by the National Institutes of Health and by the Dorothy P. and Richard P. Simmons Endowed Chair for Interstitial Lung Diseases.

As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see www.medschool.pitt.edu.

Anita Srikameswaran | EurekAlert!
Further information:
http://www.upmc.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>