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Infection Dynamics of Aspergillus fumigatus in Adults with Cystic Fibrosis (CF)

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Abstract

Objective

Aspergillus fumigatus (A. fumigatus) has emerged as a significant pathogen in patients with cystic fibrosis (CF) and currently is within the top five isolated organisms reported in several international CF patient registries. A. fumigatus has been attributed to disease progression, although its role remains controversial. There is a paucity of reports on its infection dynamics, it was the aim of this study to examine time to first laboratory reports of A. fumigatus acquisition and to correlate this with patient gender and cystic fibrosis transmembrane conductance regulator (CFTR) mutation type.

Methods

One hundred adult (≥ 18 years) CF patients were examined (50 females, 50 males; mean age 24.6 years ± 6.25 (SD), median age 24 years; maximum age 76 years). CFTR mutation groups consisted (i) F508del/F508del homozygous (n = 45), (ii) F508del/other heterozygous (n = 45) and (iii) others (n = 10). CFTR mutation type, patient gender, presence/absence of A. fumigatus and time (months) to first isolation of A. fumigatus were examined.

Results

Microbiological data was examined from 100 patients from birth to present (31/12/2021), equating to 2455 patient years. A. fumigatus was isolated from 66/100 (66%) adult CF patients; (i) F508del/F508del homozygous (82%; 37/45), (ii) F508del/other heterozygous (56%; 25/45) and (iii) others (40%; 4/10). Within the F508del/other heterozygous group, 14 mutations were noted on the second allele, with R560T and R117H collectively accounting for 36% of the second mutations. Four unique allele/allele mutations were noted in the Other Mutations category. There was a trend to a higher A. fumigatus acquisition in F508del/F508del homozygous patients than with F508del/other patients (p = 0.0529). Of the 66 patients who were positive for A. fumigatus, 35(53%) were male and 31(47%) were female. The median and mean time to first isolation of A. fumigatus in all A. fumigatus-positive patients was 119.5 months and 128 months, respectively, shortest time was 12 months, longest time 288 months. There was a statistical significance in time-to-first isolation in relation to CFTR mutation group (p = 0.0272), whereby F508del homozygous individuals had their first isolation of A. fumigatus at 116.8 ± 7.9 months (mean ± standard error of the mean (SEM)) and F508del heterozygous patients had their first isolate of A. fumigatus at 150.4 months ± 13.7 months (mean ± SEM), approximately 2.75 years after their F508del homozygous peers. There was no significant difference (p = 0.12) in time to first acquisiton between males and females, whereby males had their first A. fumigatus isolate at 118 ± 9.4 months, whereas females had their first A. fumigatus isolate at 140 ± 10.8 months. The highest rate of first A. fumigatus isolation was from 4 years until 16 years and by the age of 16 years, approximately 85% of A. fumigatus-positive patients had recorded their first A. fumigatus isolate.

Conclusion

To minimise the risk of first acquisition of A. fumigatus, it is important that infection prevention educational messaging is delivered in the paediatric clinic, to enhance health literacy around A. fumigatus acquisition.

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Authors and Affiliations

  1. Laboratory for Disinfection and Pathogen Elimination Studies, Northern Ireland Public Health Laboratory, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AD, Northern Ireland, UK

    John E. Moore & Beverley C. Millar

  2. Northern Ireland Regional Adult Cystic Fibrosis Centre, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, Northern Ireland, UK

    John E. Moore, Jacqueline C. Rendall & Beverley C. Millar

  3. School of Medicine, Dentistry and Biomedical Sciences, The Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK

    John E. Moore & Beverley C. Millar

  4. School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, UK

    John E. Moore & Beverley C. Millar

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  1. John E. Moore
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  2. Jacqueline C. Rendall
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Contributions

CRediT authorship contribution statement; BCM: Conceptualization; formal analysis; methodology; roles/writing—original draft; writing—review and editing; JCR: Writing—review and editing; JEM: Conceptualization; formal analysis; methodology; roles/writing—original draft; writing—review and editing.

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Correspondence to John E. Moore.

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The authors declare that the research was conducted in the absence of any commercial, financial or other relationships that could be construed as a potential conflict of interest.

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This study did not have any involvement or interaction with human or animal subjects.

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Moore, J.E., Rendall, J.C. & Millar, B.C. Infection Dynamics of Aspergillus fumigatus in Adults with Cystic Fibrosis (CF). Mycopathologia 188, 699–704 (2023). https://doi.org/10.1007/s11046-023-00725-1

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