Gene chips accurately detect pneumonia in ICU patients on ventilators

November 14, 2008

Nov. 17, 2008 -- Even seasoned doctors have a difficult time diagnosing pneumonia in hospitalized patients breathing with the assistance of a ventilator. That's because a patient's underlying illness often skews laboratory test results and masks pneumonia's symptoms.

Now, researchers at Washington University School of Medicine in St. Louis report they have validated the use of gene chip technology to rapidly and accurately detect pneumonia associated with ventilator use in hospitalized patients. While more testing is needed among larger patient groups, their work suggests gene chips may lead to early, more accurate diagnosis and treatment of ventilator-associated pneumonia, one of the most common and deadly hospital-acquired infections in the United States.

The research will be presented by J. Perren Cobb, M.D., director of Washington University's Center for Critical Illness and Health Engineering on Monday, Nov. 17 at the sixth annual Symposium on the Functional Genomics of Critical Illness and Injury. The symposium is a prelude to the Inaugural Meeting of the U.S. Critical Illness and Injury Trials Group, led by Cobb, on Nov. 18 and 19. Both meetings are at the National Institutes of Health in Bethesda, Maryland.

"This is an important step towards validation of a specific molecular test for diagnosing infection - particularly pneumonia - and predicting patients' recovery," says Cobb. "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 could prevent or curtail the infection."

Cobb and his team first analyzed patterns of expression in more than 8,000 genes in a small patient cohort at Barnes-Jewish Hospital, where Cobb specializes in the care of critical illness and injury. The researchers used the gene chips to study gene expression patterns in infection-fighting white blood cells obtained from blood samples drawn every 48 hours. The team found changes in the activity of 85 genes could pinpoint the early activation of the immune system in response to pneumonia, typically several days before clinical symptoms developed. By adding computational tools to their genomic analysis, the researchers also showed they could objectively monitor patients' recovery by graphing changes over time, using a tool they developed called a "riboleukogram."

The researchers then evaluated the 85-gene riboleukogram in 158 ICU patients on ventilators as part of a large-scale collaborative research program funded by the National Institute of General Medical Sciences. The technology accurately identified the 52 patients who developed pneumonia in the days following the insertion of their breathing tubes.

The riboleukograms looked similar in all patients in the first several days after the breathing tubes had been inserted. But between days 4-7, the expression of the 85 genes was significantly altered in the patients who had developed pneumonia vs. those who had not. The modified gene expression occurred some 24 to 72 hours before clinical symptoms of pneumonia were detected by physicians in the ICU.

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

Interestingly, the researchers noted that as the health of the patients with pneumonia improved, alterations in the expression of the 85 genes diminished, indicated they had returned to a healthy state. Thus, Cobb and colleagues suggest that riboleukogram technology can be used to quantify immune health and disease, acting as an EKG for the immune system.
-end-
Editor's note: The Inaugural meeting of the U.S. Critical Illness and Injury Trials Group, Nov. 18-19, National Institutes of Health, Bethesda, MD, will bring together for the first time physicians, nurses, research scientists and others in critical illness and injury specialties to advocate for clinical research. The Group will develop a cooperative clinical research framework and clinical protocols that evaluate different approaches to caring for critically ill patients nationwide.

The research is funded by the National Institutes of Health and the Barnes-Jewish Hospital Foundation.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Washington University School of Medicine

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.