The myriad challenges of respiratory fungal infection in cystic fibrosis

Abstract

Fungal infection in cystic fibrosis (CF) is a recognized challenge, with many areas requiring further investigation. Consensus definitions exist for allergic bronchopulmonary aspergillus in CF, but the full scope of clinically relevant non-allergic fungal disease in CF-asymptomatic colonization, transient or chronic infection localized to endobronchial mucus plugs or airway tissue, and invasive disease-is yet to be clearly defined. Recent advances in mycological culture and non-culture identification have expanded the list of both potential pathogens and community commensals in the lower respiratory tract. Here we aim to outline the current understanding of fungal presence in the CF respiratory tract, risk factors for acquiring fungi, host-pathogen interactions that influence the role of fungi from bystander to pathogen, advances in the diagnostic approaches to isolating and identifying fungi in CF respiratory samples, challenges of classifying clinical phenotypes of CF patients with fungi, and current treatment approaches. Development and validation of biomarkers characteristic of different fungal clinical phenotypes, and controlled trials of antifungal agents in well-characterized target populations, remain central challenges to surmount and goals to be achieved.

Inhaled antibiotic use is associated with Scedosporium/Lomentospora species isolation in cystic fibrosis

“…The impact of fungi in the CF airway, specifically Scedosporium/Lomentospora , is not yet known and requires rigorous investigation . Parize et al did not detect an association between Scedosporium apiospermum complex serologic status with lung function; however, the association between culture positivity was not evaluated .…”

“…Despite this, little is known about the characteristics associated with isolation of Scedosporium spp from CF sputum. Furthermore, there is poor understanding of the clinical implications of its detection in the airway, with the exception of its role after CF lung transplantation . Case reports and series have described improved outcomes with antifungal therapy in CF patients chronically colonized with S. apiospermum complex .…”

Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches

“…Fungi are commonly found in patients with CF, and Aspergillus fumigatus is the most frequently isolated, with sputum samples found positive in 16% of children and adolescents [ 3 ] and up to 58% when also including older patients [ 4 ]. The use of specific fungal diagnostic protocols consisting of selective media for fungi and molecular methods has significantly increased Aspergillus detection in recent years [ 5 ]. In a recent study, Reece et al [ 6 ] demonstrated that an extended incubation period and the use of quantitative polymerase chain reaction (qPCR) increased the detection of A. fumigatus in sputum samples from 16 to 52% of patients compared to the routine culture method.…”

“…Colonization of the airways can be suspected when Aspergillus is cultured in two or more samples over a year in patients without new respiratory symptoms and no specific fungal IgG in serum [ 5 , 7 ]. In younger children, data are unclear and colonization prevalence may be underestimated because this age group rarely produce a sputum and microbiological results rely on cough swabs.…”

“…In CF, the main predisposing factor for colonization and eventually infection is impaired muco-ciliary clearance due to the dysfunction of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) that leads to a decrease in airway-surface liquid pH resulting in reduced antimicrobial activity and increased mucus viscosity [ 5 ].…”