Clinical characteristics of people with cystic fibrosis and frequent fungal infection

Abstract

Background: Individuals with cystic fibrosis (CF) and fungal airway infection may present with fungal bronchitis, allergic bronchopulmonary aspergillosis (ABPA) or may appear unaffected despite fungal detection. We sought to characterize people with CF with frequent detection of fungi from airway samples and determine clinical outcomes.Methods: This retrospective study included individuals with CF with ≥4 lower airway cultures over a 2-year baseline period and ≥2 years of follow-up. We defined two groups: ≤1 positive fungus culture (rare) or ≥2 positive cultures during baseline (frequent). Clinical characteristics and outcomes were determined.Results: Between 2004 and 2016, 294 individuals met inclusion with 62% classified as rare and 38% as frequent fungi during baseline. Median follow-up was 6 years (range: 2-9 years). Aspergillus fumigatus was the most common fungal species detected. Individuals with frequent fungi were older (13.7 vs. 11.7 years, p = .02) and more likely to have Stenotrophomonas maltophilia (35% vs. 17%, p < .001) at baseline, but did not differ in lung function or ABPA diagnosis. During follow-up, those with frequent fungi were more likely to have chronic Pseudomonas aeruginosa and S. maltophilia. Individuals with ABPA and frequent fungi had the highest rates of co-infection and co-morbidities, and a trend towards more rapid lung function decline.Discussion: Fungal infection in CF was associated with frequent P. aeruginosa and S. maltophilia co-infection even in those without ABPA. Individuals with frequent fungi and ABPA had worse outcomes, highlighting the potential contribution of fungi to CF pulmonary disease.

Identification of a system for hydroxamate xenosiderophore-mediated iron transport in Burkholderia cenocepacia

“…As B. cenocepacia and other Bcc members have been increasingly observed in polymicrobial respiratory tract infections in CF patients [58,59], the ability of these organisms to use hydroxamate siderophores to pirate iron may provide B. cencocepacia with a similar advantage during infection, depending on the presence of co-infecting hydroxamate siderophore producers such as Achromobacter xylosoxidans (alcaligin), Aspergillus fumigatus and Aspergillus nidulans (TAF, ferricrocin, ferrichrome) and more rarely Bordetella bronchiseptica (alcaligin), Fusarium (TAF, ferricrocin), Penicillium (TAF, ferrichrome) and Rhodotorula (rhodotorulic acid) spp. [56,[60][61][62][63][64][65][66].…”

Infection, Allergy, and Inflammation: The Role of Aspergillus fumigatus in Cystic Fibrosis

“…In a retrospective, single-center study, our group compared clinical characteristics and outcomes in people with CF with frequent fungal positive cultures (most commonly Af) to those with no or rare fungi [ 58 ]. Individuals with frequent fungal positive cultures were more likely to have Stenotrophomonas maltophilia co-infection and Pseudomonas aeruginosa co-infection but were not more likely to have ABPA or lower lung function (culture positivity for Af is not a required criteria for a diagnosis of ABPA).…”

“…When comparing those with rare fungal infection to those with frequent infection, there was no difference detected in lung function decline. Those with both ABPA and frequent fungal infection had a more clinically (but not statistically) significant decline in lung functions as well as a higher incidence of CF-related diabetes (CFRD) in comparison to those without ABPA and compared to those with ABPA but rare fungal positive cultures [ 58 ].…”

“…Co-infection with specific bacterial infections and the presence of other clinical characteristics are associated with the Af infection in pwCF. Multiple studies have found associations with P. aeruginosa and S. maltophilia and Af acquisition, showing that in many instances, pwCF isolate these Gram-negative organisms prior to Af detection [ 58 , 79 , 80 , 81 ]. In particular, P. aeruginosa has been implicated as having some role in Af infection, yet the exact mechanism is unknown.…”

A case‐control study of the effects of Aspergillus clinical phenotypes on pulmonary functions in patients with cystic fibrosis

“…Aspergillus species (spp.) are the most common filamentous fungi in CF airways, with prevalence rates of up to 78% 2 . Moreover, Reece et al reported that Aspergillus fumigatus was likely more prevalent in early CF disease than was currently reported due to proving that molecular methods were superior in detecting A. fumigatus in pwCF sputum 3 .…”