Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene chips used to distinguish ventilator-associated pneumonia from underlying critical illness

14.02.2008
Early, more accurate detection on the horizon

Critically ill patients who need a ventilator to breathe face a high risk of pneumonia. The lung infection, however, is exceedingly difficult to diagnose because a patient's underlying condition often skews laboratory test results and masks pneumonia's symptoms – a reality that can delay appropriate antibiotic treatment.

Using gene chip technology, scientists at Washington University School of Medicine in St. Louis demonstrate for the first time they can distinguish pneumonia associated with ventilator use from other serious illnesses. The research, published Feb. 13 in the journal Public Library of Science One, suggests that the method may lead to early, more accurate detection and treatment of ventilator-associated pneumonia.

The team analyzed patterns of expression in more than 8,000 genes as patients on mechanical ventilators developed and recovered from pneumonia. They found changes in the activity of 85 genes could pinpoint early activation of the immune system in response to pneumonia, typically several days before clinical signs of the infection developed. By adding computational tools to their genomic analysis, the researchers also showed they could objectively monitor patients' recovery by graphing changes over time, creating a tool they called the "riboleukogram."

"This is an important step toward the development of a specific molecular test for diagnosing infection – in particular pneumonia – and predicting patients' recovery," says J. Perren Cobb, M.D., director of Washington University's Center for Critical Illness and Health Engineering and an intensivist at Barnes-Jewish Hospital. "If we could determine which patients are destined to develop pneumonia based on early changes in the activity of genes that regulate immune response, we could give them antibiotics sooner, with the hope that we might be able to prevent or curtail the infection."

As one of the more common and deadly hospital-acquired infections, ventilator-associated pneumonia has recently become a target for both quality improvement and patient safety efforts. Up to 30 percent of patients on a ventilator develop pneumonia, statistics show, increasing length of stay and the risk of death while adding thousands of dollars to each patient's hospital bill. The breathing tube is inserted into patients' lungs, bypassing the body's natural protective mechanisms that normally filter out harmful bacteria. The air that is pumped through the tube also must be humidified, which creates a breeding ground for microorganisms.

Scientists have tried unsuccessfully for years to identify a single marker or a suite of markers that could diagnose infection in ICUs. While both fever and an elevated white blood cell count often indicate an infection in healthy individuals, the same symptoms are widespread in ICU patients, where they are linked to a range of underlying conditions, including trauma, shock, organ failure and surgical complications. Diagnosis of infection is even more complicated in patients on a ventilator because they are sedated and the breathing tube prevents them from talking.

The current study took Cobb and his Washington University colleagues from the laboratory bench to patients' bedsides as they refined their method to diagnose pneumonia. Initially, they used the gene chip technology in mice to identify 219 genes whose patterns of expression could distinguish pneumonia from widespread inflammation, another common condition in intensive care units that involves systemic activation of the immune system. The patterns of gene expression in mice also could differentiate between gram-negative bacteria (Pseudomonas), a common type responsible for ventilator-associated pneumonia, and gram-positive bacteria (Streptococcus), which is a frequent cause of pneumonia in a community setting.

The researchers then moved to the ICU to determine whether the activity of the equivalent human genes could differentiate between pneumonia and inflammation in patients breathing with the assistance of ventilators. They narrowed their focus to 11 of 20 patients who developed pneumonia more than two days after having a breathing tube inserted. These patients had blood samples drawn at 48-hour intervals to determine whether changes in gene expression could monitor patients' response to treatment and their recovery. Most of the patients developed pneumonia within three to six days of being on a ventilator. None of them died.

The researchers used microarray analysis to study gene expression patterns in infection-fighting white blood cells contained in the blood samples. They found alterations in the activity of 85 genes some 24 to 72 hours before diagnosis of pneumonia by the physician attending in the ICU.

"This suggests that we could start patients on antibiotics earlier, say at the first change in these genomic vital signs, and we likely could significantly improve their ability to recover from pneumonia," Cobb says.

Many of the genes identified by the research team regulate specialized immune cells known as neutrophils. These cells dramatically increase in number as bacteria invade the body. "We found genes that control neutrophil activation were turned on, and that is consistent with someone developing a bacterial infection," Cobb explains. "We did not find neutrophil genes being activated in patients who did not have infection, even though they had fevers and high white blood cell counts."

Other genes of interest regulated messenger proteins called chemokines, which send signals recruiting immune cells to fight off infection.

The scientists confirmed the ability of their genomic analysis to diagnose infection and monitor recovery in a second small group of seven patients on mechanical ventilators, two of whom developed pneumonia. As the patients healed, alterations in the expression of the 85 genes diminished, indicating that they had returned to a healthy state.

"Dr. Cobb's work represents an important step forward in developing an objective way to diagnose ventilator associated-pneumonia in intensive care units and predict patients' recovery," says Sarah Dunsmore, Ph.D., who oversees sepsis grants at the National Institute of General Medical Sciences, which partially funded the study. "This innovative approach has the potential to benefit patients, through earlier diagnosis and treatment, and to help hospitals better control outbreaks of pneumonia in patients on ventilator support."

Cobb says he and his team now plan to evaluate the clinical usefulness of the genetic analysis in a larger, independent group of patients with ventilator-associated pneumonia.

Caroline Arbanas | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>