Study Identifies Genes Linked to Rapid Lung Function Decline
Scientists have identified several genes associated with rapid lung function decline in former and current smokers that might help identify people who are most at risk of developing smoking-related conditions like chronic obstructive pulmonary disorder (COPD).
These genes could also improve future clinical trials by helping to identify patients who are more likely to benefit from experimental treatments, according to investigators.
Their findings were reported in the study “Bronchial gene expression signature associated with rate of subsequent FEV1 decline in individuals with and at risk of COPD,” published in the journal Thorax.
Although smoking can cause COPD, not all smokers develop the condition. Furthermore, although current treatments can ease COPD symptoms, they cannot stop its progression. Therefore, knowing who is most likely to develop the disease could prove vital to treating it at an early stage, when treatment is more likely to have greater effect.
Based on past research that had identified COPD-related changes in how often proteins were made from certain genes — a process known as gene expression — researchers at Boston University School of Medicine tracked gene expression changes in 134 active and former smokers as their lung function declined over a mean of nearly 6.5 years.
Examining cells taken from smokers’ airways, the investigators identified a total of 171 genes whose activity was altered and associated with a rapid lung function decline, as measured by forced expiratory volume in one second (FEV1). FEV1 is a lung function parameter that measures the total amount of air a person is able to exhale in one second after a deep breath.
The researchers found the same general gene expression signature in an independent dataset of biopsies taken from the airways of COPD patients.
In particular, they observed that many genes whose expression increased with worsening FEV1 were related to mucin, a component of mucus, which builds up in the airways of people with COPD.
Many of these genes were also regulated by XBP1, a transcription factor that is known to control the activity of many genes involved in cellular stress responses. A transcription factor is a protein that is able to control the activity of a specific gene or group of genes.
“Our discovery that airway genes change before a rapid decline in lung function should give patients with COPD a lot of hope,” Katrina Steiling, MD, the study’s senior co-author, said in a press release.
“A test like this could help doctors identify people at risk for COPD before they get it, and help scientists find new treatments to stop the disease before it gets worse,” she added.
Beyond the genetic findings, the study also showed that a less invasive sampling of cells taken from the patients’ airways can provide useful information on more profound changes taking place deeper in the lungs.
“Because the changes in the airways are similar to those that occur deep inside the lung, testing the cells in the airways can be used to detect diseases deep within the lungs,” said Marc Lenburg, PhD, senior co-author of the study.
These discoveries also carry important implications for future clinical research, said Elizabeth Becker, PhD, one of the study’s co-authors.
“Being able to identify people most at risk for worsening lung function might also make clinical trials of COPD fighting medications easier, by enriching the trials testing new medications for people most likely to benefit from them,” she said.