By Phoebe Ingraham Renda
When patients need mechanical ventilation for pneumonia or acute respiratory failure, clinicians often search the lungs for harmful microbes to identify the cause and guide treatment. A fungus called Candida albicans—naturally found in and on the body—frequently shows up in the airways of these critically ill patients. But because it has long been considered a harmless resident rather than a disease-causing one, clinicians typically ignore it. New findings are challenging that notion.
This long-held assumption that Candida in the lungs is an innocent “bystander” needs to be revisited, according to a study led by University of Pittsburgh School of Medicine researchers, published Sept. 21 in Proceedings of the National Academy of Sciences.
In their clinical work, Assistant Professors Georgios Kitsios and William Bain noticed a pattern that kept surfacing. Among patients on life support, C. albicans kept turning up in those with the worst outcomes. That observation posed a fundamental question: “Is this fungus truly a bystander—or is it contributing to lung damage?”
But with no way to answer that question using existing human data, Kitsios, the study’s corresponding author, and his team took their bedside observations into the laboratory.
To their surprise, the fungus showed that it was anything but innocent in the lab. In mouse models, the fungus directly damaged the thin membrane that separates air from blood in the lungs—the same barrier that fails in life-threatening conditions like acute respiratory distress syndrome.
This damage, they found, depended on the fungus’s ability to transform itself from a round yeast form into long, thread-like filaments called hyphae. “Whenever the fungus was able to form hyphae, it caused severe lung injury,” said Kitsios. “When we used a mutant Candida that could not form those hyphae, there was dramatically less lung damage.”
When the team experimentally removed neutrophils, the immune cells that keep the fungus in check, C. albicans grew without restraint, spreading beyond the lungs, and the resulting infection often turned fatal. This finding matters beyond the lab, Kitsios and Bain note, because C. albicans is commonly found in the airways of patients whose immune systems are already weakened, whether by cancer, chemotherapy, organ transplantation or other causes.
Taking their laboratory findings back to the bedside, the team confirmed these clinical associations in two independent cohorts, one from UPMC and the other from the University of Washington in Seattle, totaling more than 600 research participants. In both cohorts, patients with C. albicans in their airways had worse lung function, spent more time on ventilators and were more likely to die, with the most severe outcomes occurring in patients who harbored both the fungus and bacterial pathogens simultaneously.
These findings, Kitsios said, suggest that C. albicans is not the innocent bystander clinicians have long assumed it to be. Instead, it may be actively injuring the lungs of critically ill patients. But he is careful to note that the study does not mean clinicians should start treating every patient who has the fungus in their lungs.
“Not every patient with Candida in their airways is being harmed by it,” said Kitsios. “We need more nuanced tools to characterize both the fungus and the patient to understand who is vulnerable and who would benefit from targeted antifungal treatment. That’s where we want to take this work next.”