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, School of Medicine researchers 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 was presented recently at a symposium by J. Perren Cobb, M.D., director of the Center for Critical Illness and Health Engineering.
“This is an important step toward validation of a specific molecular test for diagnosing infection — particularly pneumonia — and predicting patients’ recovery,” Cobb said. “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 that 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 the fourth and seventh days, the expression of the 85 genes was significantly altered in the patients who had developed pneumonia versus those who had not. The modified gene expression occurred some 24-72 hours before clinical symptoms of pneumonia were detected by physicians.
“This suggests 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 said.
Interestingly, the researchers noted that as the health of the patients with pneumonia improved, alterations in the expression of the 85 genes diminished, indicating 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.