Fungal Infection and Inflammation in Cystic Fibrosis

Abstract

Fungi are frequently recovered from lower airway samples from people with cystic fibrosis (CF), yet the role of fungi in the progression of lung disease is debated. Recent studies suggest worsening clinical outcomes associated with airway fungal detection, although most studies to date are retrospective or observational. The presence of fungi can elicit a T helper cell type 2 (Th-2) mediated inflammatory reaction known as allergic bronchopulmonary aspergillosis (ABPA), particularly in those with a genetic atopic predisposition. In this review, we discuss the epidemiology of fungal infections in people with CF, risk factors associated with development of fungal infections, and microbiologic approaches for isolation and identification of fungi. We review the spectrum of fungal disease presentations, clinical outcomes after isolation of fungi from airway samples, and the importance of considering airway co-infections. Finally, we discuss the association between fungi and airway inflammation highlighting gaps in knowledge and future research questions that may further elucidate the role of fungus in lung disease progression.

Exploring the Cystic Fibrosis Lung Microbiome: Making the Most of a Sticky Situation

“…Viral infections are associated with poorer response to treatment, greater deterioration in lung function, and reduced time to next PEx [ 67 ]. Fungi, particularly Aspergillus and Candida spp, are frequently recovered from sputum in pwCF but their role in pathogenesis remains unclear [ 68 ].…”

Culture-dependent evaluation of the respiratory microbiome in children with cystic fibrosis

“…Simultaneously, P. aeruginosa exerts an inhibitory effect on these microorganisms through siderophores and iron uptake from Aspergillus spp. However, fungi have mechanisms to avoid the inhibitory effect of the bacteria [18,19]. In our study, the frequency rate of Aspergillus spp., in combination with P. aeruginosa was 20.41 % and statistically significantly higher than in the group without the bacteria (χ 2 = 20.952; p ˂ 0.001).…”

“…The significance of oropharyngeal swabs was equivalent to sputum and BALF; however, they were compromised by oral flora. Literature data supports that swabs from the posterior pharyngeal wall poorly reflect the microbial composition of the lungs [2,19,20]. BALF is the deepest and the most accurate sample but is invasive and requires general anaesthesia, especially in children.…”

“…The role of fungi in pulmonary pathology under the dysfunction of CFTR remains questionable. However, some data shows that moulds in airways are also linked with poor clinical outcomes [17][18][19]. There was Aspergillus spp.…”

Biologic drugs in treating allergic bronchopulmonary aspergillosis in patients with cystic fibrosis: a systematic review

“…This inflammatory pathway is significantly enhanced in CFTR knockout mice, probably due to impaired channel calcium function in CD3+ T-cells induced by defective CFTR [ 60 , 61 ]. In patients with CF, impaired mucociliary clearance and thick mucus make these individuals more susceptible than patients with asthma to fungal colonisations/infections and then inflammatory/allergic responses [ 62 ]. The lung microbiome also plays a role in fungal colonisation through bacterial and fungal interactions.…”