A droplet of exhaled breath may lose some of its disease clues before a breath test is even finished. Researchers at the University of Notre Dame have found that evaporation can strip biomarkers from tiny droplets during collection, a discovery that points to a practical source of error in tests designed to monitor lung disease.
The work matters because chronic obstructive pulmonary disease, or COPD, makes breathing harder over time and is the third leading cause of death worldwide. Diagnosing and tracking it can involve uncomfortable blood tests or costly imaging, such as CT scans. COPD flare-ups can also arrive without warning and worsen quickly. Exhaled breath condensate testing, known as EBC, offers a less invasive option: a small, portable device cools a person's breath into liquid, which can then be checked for biomarkers—substances that signal what is happening in the body.
EBC has been proposed as a way to diagnose disease since the 1970s, but repeated tests have often produced inconsistent results. Researchers have commonly treated those differences as biological variation, making it seem hard to standardize the test. Jingcheng Ma, an assistant professor in Notre Dame's Department of Aerospace and Mechanical Engineering, led a team that instead examined what happens as breath changes from gas to liquid and as the collected droplets sit and evaporate.
The research, published in Nano Letters, used a fluorescence measurement platform built by Ma's group to observe how substances move in individual droplets. The team studied two processes: co-condensation, or how much of a target substance enters droplets as they form, and evaporation, which can carry that substance back into the air. The researchers created a mathematical model of biomarker loss in a single droplet, then extended it to the group of droplets that would collect on a real condenser surface.
Tests designed to mimic patient sample collection varied breath duration, pauses between breaths and total collection time. The team found that droplet size strongly affected whether meaningful losses occurred. Pauses between breaths were linked to greater losses from evaporation. The researchers also identified room temperature, humidity and the temperature of the collection plate as factors to investigate further.
That gives clinicians and device designers something specific to measure and control, rather than treating every inconsistent result as a difference between patients. Ma said better measurement standards could support reliable testing not only for people with COPD, but also for people with diabetes and preterm infants. The approach could be especially useful where portable equipment offers a more accessible alternative to blood draws or imaging, though the findings do not yet make EBC a ready replacement for existing diagnosis methods.
Amio Ritwik, a doctoral student in Ma's Interfacial Thermofluids Laboratory and lead author of the paper, called the work a first step toward identifying sources of error. Further study will need to separate the effects of the different collection conditions. For now, the team's results suggest that a breath test's reliability may depend not just on what a patient exhales, but also on what happens to each tiny droplet along the way.