More diversity in airway fungi tied to healthier lungs, CFTR modulators
Like bacteria, fungi lose in richness and diversity with CF progression
Communities of fungi in the airways can be more diverse in cystic fibrosis (CF) patients with better lung function and those using medications known as CFTR modulators, a study found.
“As CF lung disease progresses, bacterial richness and diversity are known to decrease, concomitant with increased absolute and relative abundance of CF pathogens,” its researchers wrote. Likewise, in this work, “we observed lower fungal diversity in more advanced lung disease.”
The study, “Distinct community structures of the fungal microbiome and respiratory health in adults with cystic fibrosis,” was published in the Journal of Cystic Fibrosis.
249 different groups of fungi identified in sputum samples
In CF patients, mutations in the CFTR gene result in mucus so thick it can clog the airways and provide a ground for germs to thrive, making infections more likely and harder to clear.
More is known about the bacteria that grow in the lungs of CF patients than is known about fungi. Earlier work has suggested that most CF patients have communities of fungi in their airways, yet the fungi may come and go in waves of activity.
A research team in the U.S. set out to gain a better understanding of fungi communities in CF patients’ lungs, and how they relate to clinical characteristics such as lung function.
Their study included 66 adults (34 women and 32 men; median age of 29) being followed at University of Pennsylvania’s CF center in 2017.
Almost half of these patients carried two copies of F508del, the most common CF-causing mutation. More than one-third (36.4%) were being treated with the CFTR modulators Kalydeco (ivacaftor) or Orkambi (ivacaftor/lumacaftor). Seven (10.6%) were taking anti-fungal medications.
Patients’ median percent predicted forced expiratory volume in one second (FEV1%), a measure of lung health, was 57.5%. Normal values are considered an FEV1 of at least 80% predicted value.
Researchers looked for fungi present in samples of sputum, or phlegm, collected from these patients. At the time of sampling, more than half were experiencing a respiratory exacerbation, or flare of lung symptoms.
A total of 249 different fungi groups, or taxa, were identified. The most abundant were fungi of the Candida genus. Other taxa present in high amounts in some samples were Apiotrichum, Trichosporon, and Scedosporium. The yeast Saccharomyces cerevisiae was also common.
“Candida species are rarely implicated as the cause of acute lower respiratory [airway] infections and are present in the oral cavity of healthy and diseased individuals,” the researchers wrote. “It is plausible that the Candida recovered in the sputum could represent contamination from passage through the mouth during sampling.”
Nine CF patients (13.6%) had a history of Aspergillus fumigatus. Aspergillus species were detected in more than half (56%) of the samples, but mostly at low levels.
Modulator use linked with greater diversity, antibiotic tied to poorer diversity
CF patients with higher FEV1% — that is, better lung function — had greater alpha diversity. Alpha diversity is a measure of the degree of diversity, or number of different taxa, in a single sample.
Greater alpha diversity also was found in CF patients using CFTR modulator therapies, while chronic use of azithromycin, an oral antibiotic CF treatment, linked with lower alpha diversity.
“Greater bacterial richness and alpha diversity have been reported in CFTR modulators, but fungal diversity has not been previously described to our knowledge,” the researchers wrote. “CFTR modulators are known to exhibit antimicrobial properties, but the direct mechanism of how improved CFTR function alters the microbiome remains unknown.”
The microbiome refers to the community of germs that live in a particular environment.
Differences were evident in fungi communities of samples taken from CF patients experiencing an exacerbation compared with those with clinically stable disease. These differences remained after researchers adjusted for age, sex, and lung function.
Specifically, the dominant fungi in 51.6% of stable patients was Candida albicans, while Candida dubliniensis was the abundant group in those with acute exacerbations. A “higher C. dubliniensis/C. albicans [ratio] was associated with pulmonary exacerbation state whereas a lower ratio was associated with stable state,” the researchers wrote.
“The differences in the fungal community structure of CF sputa influenced by C. albicans and C. dubliniensis in pulmonary exacerbation states and high respiratory symptom burden requires further investigation to determine whether fungi may contribute,” the scientists added.
They also called for further studies into the “associations between azithromycin, CFTR modulation, and lung function with fungal richness and diversity” in CF airways.
Of note, this study was conducted before 2019, when Trikafta (elexacaftor/tezacaftor/ivacaftor), a next-generation CFTR modulator, first became available.
Preliminary work has suggested that Trikafta may help clear A. fumigatus from the lungs and prevent severe infections in children and adults with CF.