WS8.1 The role of second-generation sequencing in describing the fungal microbiota in the adult cystic fibrosis (CF) airway and its correlation with clinical phenotype

The lung mycobiome in the next-generation sequencing era

“…Most diseases that have been studied, including CF, asthma, lung transplant, and COPD, have been associated with decreases in fungal diversity. 10,11,9,14 Across these diseases, lower fungal diversity is correlated with lower respiratory function. The reduced diversity may be caused by an overgrowth of a single fungal species, or by the loss of rare species that comes with a reduction in overall fungal abundance.…”

“…Harrison et al found that over 82% of the species identified by sequencing were not found by culture-based methods which detected fungi in only 27% of the sputum samples from 55 CF patients compared to a 90% detection rate by sequencing. 14 Willger and colleagues sought to compare sputum from 6 CF patients before and after antimicrobial therapy and found that the fungal communities were relatively stable. 16 Similarly, a study of 89 sputum samples from 28 CF patients showed that the fungal communities were stable through clinical exacerbation and treatment.…”

The utility of the basophil activation test in differentiating asthmatic subjects with and without allergic bronchopulmonary aspergillosis

“…can be isolated in sputum culture in more than half of the patients with CF of whom up to one‐fourth can have persistent colonisation 31 . Further, the fungal load in CF is higher than that in non‐CF bronchiectasis 32 . These differences could have resulted in constant immune activation and higher basophil sensitisation in CF.…”

Fungi in Cystic Fibrosis and Non–Cystic Fibrosis Bronchiectasis

“…Few studies of bronchiectasis outside of asthma and CF have systematically examined the role of fungi, and the study of the mycobiomic contribution to the total microbiome of lung disease, still in its infancy, has to date only investigated CF. [18][19][20] In general, pathogenesis of bronchiectasis due to fungal infection seems to occur when the host has a significant airway clearance defect allowing endobronchial fungal growth (i.e., localized airway infection) and a genetic predisposition to immune deviation toward a Th2-dominated response, a feature common to severe atopic asthma and CF. 21…”

“…[70][71][72][73] The finding of a complex microbiota containing bacterial, fungal, and viral elements supports the polymicrobial origin and nature of bronchiectasis in CF in which dysfunctional CFTR linked to chronic inflammation is paramount and in which exacerbations or accelerated disease progression may be due to bacterial, fungal, or viral infection. [18][19][20]74,75 Although fungi have not yet been specifically investigated with respect to early onset of CF bronchiectasis, it is notable that the Australian AREST CF consortium recently noted that recovery of Af in bronchoalveolar lavage fluid of children with CF younger than 2 years (13% of their birth cohort) was an independent predictor of lower spirometric pulmonary function at ages 4 to 8 years. 76 In older CF patients, the persistent recovery of Af has been specifically linked to more severe bronchiectasis on HRCT, suggesting a unique contribution to inflammatory remodeling by Af colonization.…”