Risk factors for respiratory Aspergillus fumigatus in German Cystic Fibrosis patients and impact on lung function

Abstract

Airway inflammation and chronic lung infections in cystic fibrosis (CF) patients are mostly caused by bacteria, e.g. Pseudomonas aeruginosa (PA). The role of fungi in the CF lung is still not well elucidated, but evidence for a harmful and complex role is getting stronger. The most common filamentous fungus in CF is Aspergillus fumigatus (AF). Age and continuous antibiotic treatment have been discussed as risk factors for AF colonisation but did not differentiate between transient and persistent AF colonisation. Also, the impact of co-colonisation of PA and AF on lung function is still under investigation. Data from patients with CF registered in the German Cystic Fibrosis Registry database in 2016 and 2017 were retrospectively analysed, involving descriptive and multivariate analysis to assess risk factors for transient or persistent AF colonisation. Age represented an independent risk factor for persistent AF colonisation. Prevalence was low in children less than ten years, highest in the middle age and getting lower in higher age (≥ 50 years). Continuous antibiotic lung treatment was significantly associated with AF prevalence in all age groups. CF patients with chronic PA infection had a lower lung function (FEV1%predicted), which was not influenced by an additional AF colonisation. AF colonisation without chronic PA infection, however, was significantly associated with a lower function, too. Older age up to 49 years and continuous antibiotic use were found to be the main risk factors for AF permanent colonisation. AF might be associated with decrease of lung function if not disguised by chronic PA infection.

Coil embolisation for massive haemoptysis in cystic fibrosis

“…The role of fungi in the CF lung is still not well elucidated, but evidence of a harmful and complex role is getting stronger. 42 …”

Fungal Infection and Inflammation in Cystic Fibrosis

“…Scedosporium has also been identified in airway samples from pwCF [ 19 , 22 , 32 , 33 , 34 ]. Recent German registry data noted that Scedosporium was one of the more common fungi isolated from pwCF (1.9% of pwCF in 2017 registry) [ 22 ]. Scedosporium has been found in approximately 3% of pwCF in the United States and, similar to Aspergillus , has been associated with older age, inhaled antibiotic use, and increased IV antibiotic episodes [ 32 ].…”

“…Scedosporium has been found in approximately 3% of pwCF in the United States and, similar to Aspergillus , has been associated with older age, inhaled antibiotic use, and increased IV antibiotic episodes [ 32 ]. Yeast including Candida albicans are also detected with estimated prevalence of 50–75%, although laboratory reporting of yeast varies [ 19 , 22 ]. Other fungal pathogens that may have clinical consequences in CF include Rasamsonia argillacea complex, Trichosporon mycotoxinovorans , and Exophiala dermatitidis ; however, the rarity of these organisms leads to difficulty interpreting observed clinical correlations [ 35 , 36 , 37 , 38 ].…”

“…Transient detection of fungus with subclinical airway changes, fungal bronchitis, sensitization to fungal proteins, and allergic bronchopulmonary aspergillosis (ABPA) have all been described, yet clear consensus guidelines have yet to be determined [ 15 , 17 ]. Studies have shown an association with worse clinical outcomes in some individuals with fungi, but whether fungi are independent contributors to poor outcomes or a reflection of a diseased airway is not clear [ 20 , 21 , 22 ].…”

CF Fungal Disease in the Age of CFTR Modulators

“…Age, inhaled corticosteroids and antibiotic use (macrolide and inhaled antibiotics) have been identified as risk factors for Aspergillus colonisation. Although causality is unproven, it is hypothesised that earlier aggressive use of inhaled antibiotics as antimicrobial prophylaxis could potentially predispose to increased fungal colonisation rates [4,4] The clinical significance of Aspergillus fumigatus in CF depends on the host's immunological response.…”