Fungal Pathogens in CF Airways: Leave or Treat?

Abstract

Chronic airway infection plays an essential role in the progress of cystic fibrosis (CF) lung disease. In the past decades, mainly bacterial pathogens, such as Pseudomonas aeruginosa, have been the focus of researchers and clinicians. However, fungi are frequently detected in CF airways and there is an increasing body of evidence that fungal pathogens might play a role in CF lung disease. Several studies have shown an association of fungi, particularly Aspergillus fumigatus and Candida albicans, with the course of lung disease in CF patients. Mechanistically, in vitro and in vivo studies suggest that an impaired immune response to fungal pathogens in CF airways renders them more susceptible to fungi. However, it remains elusive whether fungi are actively involved in CF lung disease pathologies or whether they rather reflect a dysregulated airway colonization and act as microbial bystanders. A key issue for dissecting the role of fungi in CF lung disease is the distinction of dynamic fungal-host interaction entities, namely colonization, sensitization or infection. This review summarizes key findings on pathophysiological mechanisms and the clinical impact of fungi in CF lung disease.

Pseudomonas aeruginosaeradication therapy and risk of acquiringAspergillusin young children with cystic fibrosis

“…Since no diagnostic threshold for infection with Aspergillus in BAL cultures has been determined and as its pathogenetic role is yet to be fully established, 22 for this study we adopted a conservative approach and accepted any growth of Aspergillus in BAL fluid as indicating acquisition without asserting this was infection. As described previously, BAL and OP specimens were plated onto selective and non-selective media for counting and identifying respiratory pathogens by standard microbiological techniques.…”

Aspergillus fumigatus complex: A new problem in a challenging pathogen, azole resistance

“…KF'deki enfeksiyonun kronik polimikrobiyal doğasından ötürü, mantarların patogenezdeki rolünün kanıtlanması zorlaşmaktadır. Yine de, mantar izolasyonunun hastalığa katkısını gösteren kanıtlar gittikçe artmaktadır (6,(18)(19)(20) .…”

Fungal Respiratory Infections in Cystic Fibrosis (CF): Recent Progress and Future Research Agenda

“…Fungal diagnostic criteria in CF patients [6,9,12,13] 3. Antifungal therapy in CF patients [7,9,[14][15][16][17] 4. Aspergillus, Exophiala and Pneumocystis in CF patients [8][9][10][11] 5.…”

“…The investigative team recommended a standardized protocol with the use of four culture media to facilitate the growth of Aspergillus species and yeasts, and slow-growing molds with a 16-day incubation period [13]. Hector et al [14] also write critically about the unsolved issues around fungal colonization, sensitization or invasion of CF airways. Additionally, the authors provide an impressive schematic about the recognition of fungal pathogens by various receptors on the innate immune cells.…”

“…Although the authors' main focus is on A. fumigatus, C. albicans, E. dermatitidis and P. jirovecii, they also examine the role of other fungi as well as bacteria from the culture-independent microbiome studies. The co-colonization of CF lungs by bacteria especially Pseudomonas aeruginosa and Staphylococcus aureus is evaluated for its likely impact on fungi in CF lungs [14]. The triazole antifungals are metabolized variably and sub-optimally in CF patients, and the resultant pharmacokinetics derangements could complicate treatment and even lead to the emergence of antifungal resistance.…”