New findings on fungal asthma

A multi-organization team identifies 19 genetic variants related to susceptibility and damage risk

Kelsey Kaustinen
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LONDON—In February, researchers from the National Aspergillosis Centre in Manchester, U.K., in partnership with Genestack, presented research at the Obstructive Airway Diseases International Symposium in Belgium on the discovery of a genetic cause for fungal asthma. The team shared information on 19 genetic alterations in asthma patients that render them more susceptible to the effects of fungus than others. Most patients involved had more than one genetic alteration. Specifically, these variants are tied to an increased risk of damage to the lining cells of the lung airways, as well as an inability to rapidly kill the Aspergillus fungus.
“Understanding complex disorders such as allergic fungal asthma requires a different scientific approach from the study of diseases with single gene defects. The collaboration with Genestack has allowed us to ask complex questions and given us the power to select the right genetic variations to direct biological experiments that can give us important answers,” said Dr. Paul Bowyer, a senior researcher in the Manchester Fungal Infection Group (MFIG), who supervised the work.
“Genestack worked closely with researchers from Manchester to develop several applications within our platform that allowed them to distill terabytes of raw genomic sequence down to a few causal mutations,” Misha Kapushesky, CEO of Genestack, explained in a news release. “We are happy to report also that these applications are available for current and future Genestack clients.”
At present, it is estimated that some 300 million people worldwide suffer from asthma, with six million to 15 million of those affected by fungal asthma. Many individuals with atopy—which is defined by the American Academy of Allergy, Asthma and Immunology as “the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma and atopic dermatitis”—suffer from severe asthma and chronic rhinitis, some of which is due to fungal allergy. While most patients benefit from antifungal therapy, modern diagnostic methods in many parts of the world, including for fungal asthma.
“Unraveling the causes of fungal asthma will lead to much better and precise diagnostics, probably genetic tests. Long-term studies will better define what genetic factors are associated with better or worse asthma control and complications,” commented Prof. David Denning, director of the National Aspergillosis Centre at the University Hospital of South Manchester. Denning presented the team's data at the Obstructive Airway Diseases International Symposium.
This is not the only work for these organizations in fungal asthma, just the latest. This past December, a team led by Denning announced the publication of the first clinical guidelines for chronic fungal lung infections, describing the features of the disease and comprehensive treatment recommendations. Chronic pulmonary aspergillosis (CPA) is an ongoing issue for patients whose lungs are already comprised; some 80 percent of sufferers die from CPA within five years without diagnosis and long-term antifungal treatment. These guidelines are the result of a two-year collaboration between the European Respiratory Society and the European Society of Clinical Microbiology and Infectious Diseases.
In more recent news, two MFIG researchers published a paper in Nature Communications generating new diagnostics for the visualization of fungal infections. The work focuses on the pathogen Aspergillus fumigatus, which is a common cause of fungal pneumonia and invasive pulmonary aspergillosis (IPA). The paper notes that “Current diagnostic approaches for IPA rely on histological analysis, cultures from bronchoalveolar lavage fluid and sampling peripheral blood. These methods are fraught with problems of upper airway contamination and diagnostic delays, by which time the disease may have progressed or been treated empirically with inappropriate drugs.”
Their approach, by comparison, looks at fluorescence. As noted in the abstract, “Fluorescent antimicrobial peptides are promising structures for in situ, real-time imaging of fungal infection. Here we report a fluorogenic probe to image Aspergillus fumigatus directly in human pulmonary tissue. We have developed a fluorogenic Trp-BODIPY amino acid with a spacer-free C-C linkage between Trp and a BODIPY fluorogen, which shows remarkable fluorescence enhancement in hydrophobic microenvironments. The incorporation of our fluorogenic amino acid in short antimicrobial peptides does not impair their selectivity for fungal cells, and enables rapid and direct fungal imaging without any washing steps. We have optimized the stability of our probes in human samples to perform multi-photon imaging of A. fumigatus in ex-vivo human tissue.”

Kelsey Kaustinen

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