PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Unraveling cystic fibrosis puzzle, taking it personally matters

Researchers find a clue to disease's damage while fighting private struggle

2015-03-23
(Press-News.org) In the genetic disorder cystic fibrosis (CF), the most severe symptoms are recurring episodes of lung inflammation and bacterial infection (known as "exacerbations") that happen from one to three times a year and cause ever-increasing amounts of lung damage through the course of a CF patient's life. While it is well understood that CF lung problems are ultimately due to bacterial infections encouraged by a CF patient's abnormally thick mucus, medical science has been unable to define specific causes that trigger the periodic flare-ups.

In a recent article in the Journal of Clinical Microbiology, lead author Joshua Stokell, a post-doctoral researcher in biology, and a team from University of North Carolina at Charlotte describe an unusual, single-patient study and an important finding that may point to an immediate cause of CF exacerbations. The study found sudden growth of a specific bacterium, Burkholderia multivorans, preceded periods of acute illness. While Burkholderia has been known as a common pathogen in the lungs of CF patients, it is far less abundant than another pathogen, Pseudomonas aeruginosa, whose populations did not show significant changes prior to the life-threatening episodes.

Stokell's co-authors on the paper are UNC Charlotte biologist Todd Steck and UNC Charlotte bioinformaticians Anthony Fodor, Malcolm Zapata, Raad Gharaibeh and Timothy Hamp.

Stokell and his colleagues were able to implicate Burkholderia thanks to a detailed genomic and metagenomic analysis of a unique, extensive collection of lung sputum samples taken twice-weekly over a three-year period.

"This study represents the most intensive sampling of a single CF patient to date," the article notes. "Our study was based upon the assumption that a detectable shift in the bacterial community precedes a pulmonary exacerbation. Testing our assumption required a longitudinal study to reveal the relationship between disease progression, occurrence of a pulmonary exacerbation and various components of a bacterial community, such as the change in diversity, richness, or the abundance of specific members of the microbiota."

"Most studies that you look at collect one pre-exacerbation sample, one during exacerbation and one during periods of stability," Stokell noted. "With that kind of study, it's hard to get an idea of how changes are occurring because those are more like cross-sectional analyses. Our focus was to look at how these changes are occurring generally, and in order to get some sort of baseline information we have to check changes frequently over time."

In discussing the work, Stokell is somewhat shy about mentioning that the unusually extensive sampling and analysis was only possible because of the willing contribution of an unusually cooperative patient: himself.

Because Stokell was both the researcher and the study subject, the team had unparalleled access to the subject's life history and medical records, providing critical context. "We have all kinds of patient background information," Stokell noted, "so we can associate the changes in bacteria with the occurrence of an exacerbation and also with when antibiotics are administered."

Chronic diseases like CF are often daunting puzzles that require an extraordinary amount of research effort to understand -- the long-term interaction between the human body's dynamic systems and the disease can be extremely complex, even when there's a relatively simple initiating cause, such as a genetic defect. Consequently, researchers studying such diseases need an extra amount of commitment and passion to struggle with the intricate complexities involved.

In Stokell's case, the commitment and passion came naturally because the disease is personal. UNC Charlotte biologist Todd Steck, whose lab Stokell now works in was Stokell's mentor, both in college and in graduate school. Steck observed that the experience of having cystic fibrosis played an important role in both developing Stokell's initial general interest in biology and in leading him to the line of research that he is now pursuing.

As a masters student at UNC Charlotte, Stokell took a class in bioinformatics from Anthony Fodor (also an author on the current paper), where students had to come up with projects involving metagenomic analysis of bacterial populations. Stokell recognized that this might be important research area relevant to his own disease, so he chose lung bacteria in cystic fibrosis, with himself as a research subject. Once engaged, he found that the interaction between CF and the human microbiome is difficult to unravel, but his personal connection to the disease kept him motivated.

The current study still does not answer all the questions raised by Stokell's class project, though he has now done both metagenomic analysis (which allows cataloging the full range of bacterial populations by finding variants of the 16S rRNA gene) and whole-genome sequencing (on a small group of bacterial varieties) on three year's worth of steady sampling. In addition to identifying Burkholderia as a key pathogen, the team found that richness and diversity of bacterial communities decreased over time, while the overall abundance of bacteria increased, perhaps due to ongoing antibiotic treatment and the steady progress of the disease. However, those changes are not associated with the disease's damaging flare-ups.

"There were no changes in the metagenomic sequencing and the relative abundance of bacterial communities that were specifically associated with the occurrence of exacerbation," Stokell said. "Nothing that occurred within two weeks prior to the exacerbation indicated this is what is causing the individual to become ill.

"We did see treatment effects for richness and diversity - we saw those decreases during antibiotic treatment. And over a three-year period, bacteria continued to increase in abundance. But when we looked at specific pathogens, Burkholderia was the one that showed an increase in abundance prior to exacerbation. So we can speculate that that was the initiator of the exacerbation," he said.

The next step, the researchers say, is to do further study on a larger group of patients. Stokell and Steck have received grants from NIH and the Cystic Fibrosis Foundation that will allow them to do that. If findings in a larger sample support the pattern Stokell has found in himself, treatment of Burkholderia specifically may be an important target in managing the damaging effects of the disease.

Though significant research problems undoubtedly lie ahead, the real challenge for Stokell perhaps is the personal one he faces in the progress of his own disease. Though he has struggled all his life to maintain his health, at age 35 Stokell is now in late stage lung disease and will need a lung transplant sometime in the near future.

"I'm being considered for a double-lung transplant at Duke University Medical Center," Stokell said, explaining that this entails not just a complex operation but also three-months of pre-operation preparation and six months of recovery on-site, not to mention expensive medications he will be required to take for the rest of his life. And, unfortunately, the difficulty of his situation is not limited to surviving until the transplant and enduring the medical realities.

"Undergoing a transplant is not only difficult because of the surgery, the associated monetary costs are quite high," he explained. "Typically, individuals in my situation are required to raise money prior to the surgery."

To raise the funds for transplant-related expenses, Stokell will be working with the Children's Organ Transplant Association (COTA), a 501(c)3 not-for-profit organization that receives donations to assist with transplant-related expenses. The goal for the COTA campaign in honor of Josh is $75,000.

With the cost of a transplant often exceeding $500,000, many transplant families are unable to shoulder the financial burden of such a procedure. The organization's priority is to ensure that a transplant does not financially devastate a family. One hundred percent of all funds raised are used for patients' transplant-related expenses.

"My hope is that I can spread the word about my need for a transplant and the financial needs I have associated with it," Stokell explained. "My transplant pulmonologist is guessing that I won't need a transplant for six months. However, because of the unpredictable nature of this disease at such a late-stage, that time could be quickly reduced or hopefully, extended."

INFORMATION:

Anyone interested in making secure credit card donation can do so online through a website COTA has established: http://www.COTAforJoshuaS.com. Donations may also be mailed to the Children's Organ Transplant Association, 2501 West COTA Drive, Bloomington, Indiana, 47403. Checks or money orders should be made payable to COTA, with "In Honor of Joshua S" written on the memo line of the check. Fundraising proceeds will benefit COTA in honor of Stokell to assist with transplant-related expenses.

Sources: Joshua Stokell, jrstokel@uncc.edu
Todd Steck, 704-687-8534, t.steck@uncc.edu



ELSE PRESS RELEASES FROM THIS DATE:

Global water use may outstrip supply by mid-century

2015-03-23
DURHAM, N.C. -- Population growth could cause global demand for water to outpace supply by mid-century if current levels of consumption continue. But it wouldn't be the first time this has happened, a Duke University study finds. Using a delayed-feedback mathematical model that analyzes historic data to help project future trends, the researchers identified a regularly recurring pattern of global water use in recent centuries. Periods of increased demand for water -- often coinciding with population growth or other major demographic and social changes -- were followed ...

Report reveals alarming lack of water, sanitation and hygiene in health care facilities

2015-03-23
The World Health Organization and UNICEF have commissioned the first comprehensive, multi-country analysis on water, sanitation and hygiene (WaSH) services in health care facilities, calling for global action to push toward 100 percent coverage of these services through new policies, collaboration, monitoring and training. The report, released March 17, evaluated available WaSH data from 66,101 health-care facilities in 54 low- and middle-income countries and found that 38 percent of those facilities lack an improved water source, 19 percent lack improved sanitation, ...

Quantum cause and effect

2015-03-23
Does taking a drug and then getting better mean that the drug made you better? Did that tax cut really stimulate the economy or did it recover on its own? The problem of answering such questions - of inferring causal relationships from correlations - reaches across the sciences, and beyond. Normally, correlation by itself does not imply causation. But new research from Perimeter and the Institute for Quantum Computing (IQC) has found that in the case of quantum variables, it sometimes can. The new work, just published in Nature Physics, is the result of a collaboration ...

New insights into survival outcomes of Asian Americans diagnosed with cancer

2015-03-23
Numerous studies have documented racial differences in deaths from cancer among non-Hispanic whites and African Americans, but little has been known about survival outcomes for Asian Americans who have been diagnosed with cancer, until now. A new study from Quoc-Dien Trinh, MD and colleagues at Brigham and Women's Hospital (BWH) examined cancer patients in eight different Asian American subgroups and found their cancer-specific mortality (CSM) was substantially lower than that of non-Hispanic white patients. The findings are published in the March 20 issue of the Journal ...

Better debugger

2015-03-23
Integer overflows are one of the most common bugs in computer programs -- not only causing programs to crash but, even worse, potentially offering points of attack for malicious hackers. Computer scientists have devised a battery of techniques to identify them, but all have drawbacks. This month, at the Association for Computing Machinery's International Conference on Architectural Support for Programming Languages and Operating Systems, researchers from MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL) will present a new algorithm for identifying ...

Discovery could yield more efficient portable electronics, solar cells

2015-03-23
MADISON, Wis. -- By figuring out how to precisely order the molecules that make up what scientists call organic glass -- the materials at the heart of some electronic displays, light-emitting diodes and solar cells -- a team of chemists from the University of Wisconsin-Madison has set the stage for more efficient and sturdier portable electronic devices and possibly a new generation of solar cells based on organic materials. Writing this week (March 23, 2015) in the Proceedings of the National Academy of Sciences (PNAS), a team led by UW-Madison chemistry Professor Mark ...

Wandering Jupiter accounts for our unusual solar system

2015-03-23
Jupiter may have swept through the early solar system like a wrecking ball, destroying a first generation of inner planets before retreating into its current orbit, according to a new study published March 23 in Proceedings of the National Academy of Sciences. The findings help explain why our solar system is so different from the hundreds of other planetary systems that astronomers have discovered in recent years. "Now that we can look at our own solar system in the context of all these other planetary systems, one of the most interesting features is the absence of planets ...

'Most attractive' male birds don't have the best genes

2015-03-23
'Attractive' male birds that mate with many females aren't passing on the best genes to their offspring, according to new UCL research which found promiscuity in male birds leads to small, genetic faults in the species' genome. Although minor, these genetic flaws may limit how well future generations can adapt to changing environments. The study, published this week in Proceedings of the National Academy of Sciences and funded by the European Research Council, shows for the first time the power of sexual selection - where some individuals are better at securing mates ...

Comparing the genomes of the leprosy bacteria

2015-03-23
Leprosy is a chronic infection of the skin, peripheral nerves, eyes and mucosa of the upper respiratory tract, affecting over a quarter million people worldwide. Its symptoms can be gruesome and devastating, as the bacteria reduce sensitivity in the body, resulting in skin lesions, nerve damage and disabilities. Until recently, leprosy was attributed to a single bacterium, Mycobacterium leprae; we now suspect that its close relative, Mycobacterium lepromatosis, might cause a rare but severe form of leprosy. Scientists at École Polytechnique Fe?de?rale de Lausanne (EPFL) ...

Study: Western forests decimated by pine beetles not more likely to burn

2015-03-23
Western U.S. forests killed by the mountain pine beetle epidemic are no more at risk to burn than healthy Western forests, according to new findings by the University of Colorado Boulder that fly in the face of both public perception and policy. The CU-Boulder study authors looked at the three peak years of Western wildfires since 2002, using maps produced by federal land management agencies. The researchers superimposed maps of areas burned in the West in 2006, 2007 and 2012 on maps of areas identified as infested by mountain pine beetles. The area of forests burned ...

LAST 30 PRESS RELEASES:

Development of a global innovative drug in eye drop form for treating dry age-related macular degeneration

Scientists unlock secrets behind flowering of the king of fruits

Texas A&M researchers illuminate the mysteries of icy ocean worlds

Prosthetic material could help reduce infections from intravenous catheters

Can the heart heal itself? New study says it can

Microscopic discovery in cancer cells could have a big impact

Rice researchers take ‘significant leap forward’ with quantum simulation of molecular electron transfer

Breakthrough new material brings affordable, sustainable future within grasp

How everyday activities inside your home can generate energy

Inequality weakens local governance and public satisfaction, study finds

Uncovering key molecular factors behind malaria’s deadliest strain

UC Davis researchers help decode the cause of aggressive breast cancer in women of color

Researchers discovered replication hubs for human norovirus

SNU researchers develop the world’s most sensitive flexible strain sensor

Tiny, wireless antennas use light to monitor cellular communication

Neutrality has played a pivotal, but under-examined, role in international relations, new research shows

Study reveals right whales live 130 years — or more

Researchers reveal how human eyelashes promote water drainage

Pollinators most vulnerable to rising global temperatures are flies, study shows

DFG to fund eight new research units

Modern AI systems have achieved Turing's vision, but not exactly how he hoped

Quantum walk computing unlocks new potential in quantum science and technology

Construction materials and household items are a part of a long-term carbon sink called the “technosphere”

First demonstration of quantum teleportation over busy Internet cables

Disparities and gaps in breast cancer screening for women ages 40 to 49

US tobacco 21 policies and potential mortality reductions by state

AI-driven approach reveals hidden hazards of chemical mixtures in rivers

Older age linked to increased complications after breast reconstruction

ESA and NASA satellites deliver first joint picture of Greenland Ice Sheet melting

Early detection model for pancreatic necrosis improves patient outcomes

[Press-News.org] Unraveling cystic fibrosis puzzle, taking it personally matters
Researchers find a clue to disease's damage while fighting private struggle