Breakthrough Blood Test Could Predict Rapid Lung Decline

A rapid decline in lung function is linked to the development of chronic obstructive pulmonary disease (COPD) hospitalizations and increased mortality. The challenge is that accurately tracking this decline using longitudinal spirometry measurements is often difficult in clinical settings.

A collaboration between physicians at the University of California Davis School of Medicine, Vanderbilt University Medical Center, Brigham and Women's Hospital and the Northwestern University Feinberg School of Medicine, with support from the National Institutes of Health, looked to change that.

Their study, published on Aug. 1, 2024, on the American Journal of Respiratory and Critical Care Medicine website looked to define whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality.

Ravi Kalhan, M.D.

“Loss of lung function on a year-over-year basis is associated with poor respiratory health outcomes, but we do not have a good way to easily figure out if a patient is on a steep trajectory of lung function decline,” said Ravi Kalhan, M.D., professor of pulmonary medicine at Northwestern and a co-author of the study. “If we had an easy-to-implement clinical tool, like a blood test, that captured someone’s lung function trajectory at a single time point, it would enable earlier interventions which might, in the long run, improve lung health.”

The researchers conducted a population-based cohort study involving lung health data from 2,470 adults aged 18-30, who were part of a 30-year cardiovascular health study. At the 25-year point, the team analyzed thousands of proteins from blood samples collected from this cohort, ultimately identifying 32 proteins that most effectively predicted rapid declines in lung function. These 32 proteins were then combined into a score to assess an individual’s likelihood of requiring medical treatment for or succumbing to a lung condition or severe respiratory event.

“Protein aptamers associated with an accelerated decline trajectory were identified with multivariable logistic regression followed by LASSO regression,” the authors wrote. “The proteomic respiratory susceptibility score was derived based on these circulating proteins and applied to the UK Biobank and COPDGene studies to examine associations with future respiratory morbidity and mortality.”

From the data, the researchers created a preclinical blood test to identify adults most likely to develop severe respiratory conditions, including COPD.

Adults with higher scores demonstrated a 17% increased likelihood of needing hospitalization for respiratory illnesses, an 84% greater risk of developing COPD, and at least an 81% higher chance of dying from respiratory diseases like COPD or pneumonia. Additionally, these individuals had a 10% increased probability of experiencing respiratory exacerbations, such as cough, mucus production, or shortness of breath, that necessitated treatment.

James P. Kiley, Ph.D., director of the Division of Lung Diseases at NIH’s National Heart, Lung, and Blood Institute, noted the test is not ready to be used in practice, but is a good start to what the scientists hoped to accomplish.

“It consolidates insights from decades of breathing tests and medical evaluations into a single tool that has the potential to identify patients at risk for severe disease and complications,” he said, adding more study would need to be done in the future in clinical trials before being considered for approval by the FDA.