Toxins from mold found growing on nuts or corn can weaken the airways’ self-clearing mechanisms and immunity, opening the door for respiratory diseases and exacerbating existing ones, suggests a study in Nature Scientific Reports published this month from otolaryngology researchers at thePerelman School of Medicine at the University of Pennsylvania.

Poisonous and cancer-causing, aflatoxins are a type of mycotoxins produced by certain fungi (Aspergillus flavus, for example) growing on and in certain foods. Overall, 25 percent of the world’s food crops are contaminated with these molds, though exposure often occurs via contaminated dust inhaled during food processing. They are known to cause allergic fungal rhinosinusitis and bronchopulmonary aspergillosis, two infections that can be treated with antifungal medications and surgery, if needed. However, the downstream effects of aflatoxins on the airway passage is less studied and understood.

In laboratory imaging experiments with human upper airway cells, researchers showed that acute exposure to aflatoxins slowed down and impaired key defense mechanisms in the airways, including mucosal ciliary clearance (MCC) and ciliary beat frequency (CBF). Cilia are tiny, hair-like structures that line the airways and clean out dust and dirt.

The results suggest that aflatoxins enhance the pathogenicity of the fungi and possibly other co-infecting pathogens, such as bacteria.

“With these defenses impaired, it may create a window of opportunity for the infection, and potentially a domino effect,” said lead author Robert J. Lee, PhD an assistant professor in the departments of Otorhinolaryngology: Head and Neck Surgery and Physiology at Penn.  

Added senior author Noam A. Cohen, MD, PhD, an associate professor of Otorhinolaryngology at Penn: “Patients may become more susceptible to upper respiratory infections and chronic rhinosinusitis (CRS) that can ‘seed’ lower respiratory infections, especially in those with a compromised immune system. It can also exacerbate the more severe lung diseases, such as cystic fibrosis or chronic obstructive pulmonary disease.”

In immunocompromised individuals (chemotherapy patients, for example) or poorly controlled diabetics, upper airway Aspergillus infections can invade the mucosa and underlying tissue and become lethal, so it is particularly critical to understand its interactions with the airway epithelium.  A better understanding of the complex pathogenesis of the fungal infection could lead to novel therapies and improve outcomes for these airway diseases, the authors wrote.  

The Penn researchers found that the fungal toxins activate protein kinase C (PKC), which decreases ciliary beat frequency and thus decreases MCC. That increased kinase activity presents a potential treatment opportunity, they said.

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