For lung transplant recipients, increased levels of iron in the tissue are a risk factor for life-threatening fungal infections, according to a study published in Science Translational Medicine.
Researchers at Stanford (Calif.) University School of Medicine aimed to discover why lung transplant patients are more vulnerable to Aspergillus fumigatus, a fungus known to cause disease in patients with an immunodeficiency.
"People rarely think about how a change in the patient’s body tissues might make it better ground for invasion," said Mark Nicolls, MD, lead study author.
One in three lung transplant recipients develop Aspergillus-related diseases, which include severe asthma and lower respiratory infections. These respiratory infections are often fatal.
Although all lung transplant recipients carry these risks, not all lung transplants result in Aspergillus infections. In cases of infection, something causes the organism to behave differently, said Joe Hsu, MD, lead study author. The study identified iron as a critical factor in these infections. "Iron is like fertilizer for the Aspergillus," Dr. Nicolls said.
Dr. Hsu aimed to identify what triggered Aspergillus to invade tissue. By studying the pathogen in mice, Dr. Hsu found the transplanted tissue bled and accrued high levels of iron. When he biopsied human transplant patients, Dr. Hsu found the same iron distribution, with higher levels in the transplanted tissue than in the host.
After introducing Aspergillus, Dr. Hsu found the elevated iron initiated the pathogen's invasion into the tissue. The invasion progressed deeper into the tissue as Dr. Hsu observed higher levels of iron present.
Infection can be prevented by depriving the Aspergillus organism of iron, the study authors suggested. The mold does not invade the tissue without iron to fuel it. When the mice in the study were injected with an iron-reducing chemical, the depth of invasion decreased.
Dr. Hsu's next step is to study this treatment approach in humans. Since high iron levels are characteristic of other pulmonary diseases, Dr. Hsu estimates this methodology could be applied throughout the pulmonary care field.