What do cystic fibrosis patients and factory workers in microwave popcorn plants have in common? The answer, according to Katrine Whiteson, a postdoctoral researcher from San Diego State Univeristy, is a molecule known as 2,3-butanedione (diacetyl). Cystic fibrosis patients have higher concentrations of diacetyl in their lungs than healthy adults, and diacetyl is a toxic lung-damaging agent.
The motivation behind Whiteson’s study was the mystery of what is different about cystic fibrosis patients’ lungs during times of symptom flare-ups, or exacerbations, compared to periods of relatively calm symptoms. At the doctor’s office, cystic fibrosis patients inhale vaporized salts to induce coughing so that they can produce a mucus sample. When the mucus is cultured to identify microbes, there is no difference in microbes between calm and exacerbated periods. This makes it nearly impossible to help warn patients when an exacerbation is imminent so that they can ward off future lung damage by taking antibiotics.
Knowing that something must be different, Whiteson and colleagues at San Diego State University and the University of California, Irvine, turned their attention to the gases produced by cystic fibrosis patients during breathing. Comparing the gases from healthy individuals, the researchers found a significant >7-fold increase in the levels of diacetyl in the cystic fibrosis patients. This increase was reduced 10-fold by the administration of antibiotics. It was theorized that Streptococcus species in the mouth produce diacetyl during fermentation to avoid lethal acidification, leading to harmful effects of other microbes that exist in the lungs; for example, lung microbe P. aeruginosa increases production of exotoxin and phenazine and improves biofilm formation when exposed to diacetyl, found another study from Cornell University.
Although the study used only a small number of patients and volunteers, future validation may lead to technology that can detect the presence of diacetyl in the breath of cystic fibrosis patients. Detection would then indicate that patients are about to experience a flare-up of symptoms and should take antibiotics to prevent it. “If you had a device to detect these metabolites, you’d know, ‘Oh, it’s time to take antibiotics again,'” said Whiteson. This technology is not merely a dream, either: Whiteson is working with Metabolomx to develop a microchip that detects diacetyl and other indicators of cystic fibrosis exacerbations. “It’s a constant battle going on,” said Whiteson, indicating that a microchip would not be the end-all for helping cystic fibrosis patients. “There’s not just one thing that keeps you healthy.”
The work was published last month in The ISME Journal Multidisciplinary Journal of Microbial Ecology and was accompanied by a study from Cornell University that describes the effects of diacetyl of P. aeruginosa.