Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 1;210(9):1155-1158.
doi: 10.1164/rccm.202406-1128RL.

Elexacaftor/Tezacaftor/Ivacaftor Markedly Reduces Aspergillus fumigatus in Cystic Fibrosis

Sarah J Morgan  1 , David P Nichols  2 , Windy Ni  1 , Gina Hong  3 , Stephen J Salipante  4 , George M Solomon  5 , Steven M Rowe  2   5 , John P Clancy  3 , Robert A Cramer  6 , Pradeep K Singh  1
Affiliations

Elexacaftor/Tezacaftor/Ivacaftor Markedly Reduces Aspergillus fumigatus in Cystic Fibrosis

Sarah J Morgan et al. Am J Respir Crit Care Med. .
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Negative controls, specificity, and dynamic range of Aspergillus fumigatus (Af) droplet-digital PCR (ddPCR) assays. (A) Internal transcribed spacer (ITS) ddPCR results for water (n = 26), water that had been DNA-extracted (extraction) (n = 20), sputum from people with cystic fibrosis deemed Af negative by University of Washington’s clinical lab who also had no Af detected in the 2 years before and after the examined sample (Af-neg sputum) (n = 14), and cultures of ∼2 × 106 conidia/ml of A. niger (n = 3), A. flavis (n = 3), or Af (n = 11). Circles represent independent assays, and red lines indicate conidia/ml added to the reaction. ND = ddPCR results considered negative. (B) ITS ddPCR detection using (left) indicated concentrations of cultured lab isolates of Af conidia from 10 replicate extractions and quantifications, and (right) 18 sputum samples yielding 1–2 colonies (i.e., >∼40 colonies/ml) and 17 yielding <3 colonies (i.e., <∼40 colonies/ml) of Af growth after plating ∼50 μl of sputum by University of Washington’s clinical lab.
Figure 2.
Figure 2.
Aspergillus fumigatus (Af) detection and density decreased within a month of starting elexacaftor/tezacaftor/ivacaftor (ETI). (A) Proportion of PROMISE participants with internal transcribed spacer (ITS) droplet-digital PCR (ddPCR)-positive sputum, including those missing samples at one or more   visits; P < 0.0001 pre-ETI versus all other time points by chi-square. Analyses eliminating participants with missing data showed similar trends (not shown); n indicates number of subjects providing sputum at each time point. (B) Proportion of registry-recorded Af-positive sputum cultures during indicated time periods in the 22 study participants who had two or fewer registry-recorded fungal cultures in the two 2-year periods before and the 2-year period after starting ETI. Five participants had only negative cultures reported. Data from individuals are linked by lines. Red lines indicate the mean; P < 0.002 for post-ETI compared with both pre-ETI periods by mixed model. (C) ITS ddPCR results for 32 baseline ITS-positive participants. Points represent samples; lines connect samples from each participant. Black solid circles indicate participants with any Af+ cultures, and gray open circles indicate participants with no Af+ cultures reported in registry records in the 2 years before ETI. Red line indicates the geometric mean. P < 0.003 for comparison of 1 month, 1 year, and 2 years post-ETI time points to baseline using mixed model on log-transformed data; n indicates number of subjects providing sputum at each time point. (D) Results of ITS (left), Stenotrophomonas maltophilia (center), and Pseudomonas aeruginosa (right) ddPCR before and after 1 month of ETI. Points represent samples; lines connect samples from each participant. Only baseline ddPCR-positive participants are shown. Red lines indicate the geometric mean. There was no significant difference (P = 0.362) in the proportion of baseline S. maltophilia–positive participants becoming ddPCR negative at 1 month versus the proportion becoming Af negative. The proportion of baseline P. aeruginosa–positive participants becoming ddPCR negative at 1 month was significantly lower (P < 0.0001) than that for Af by Fisher’s exact test. ND = not detected.
See this image and copyright information in PMC

References

    1. Poore TS, Zemanick ET. Infection, allergy, and inflammation: the role of Aspergillus fumigatus in cystic fibrosis. Microorganisms . 2023;11:2013. - PMC - PubMed
    1. Chesnay A, Bailly É, Cosson L, Flament T, Desoubeaux G. Advent of elexacaftor/tezacaftor/ivacaftor for cystic fibrosis treatment: what consequences on Aspergillus-related diseases? Preliminary insights. J Cyst Fibros . 2022;21:1084–1085. - PubMed
    1. Nichols DP, Morgan SJ, Skalland M, Vo AT, Van Dalfsen JM, Singh SB, et al. PROMISE-Micro Study Group Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist. J Clin Invest . 2023;133:e167957. - PMC - PubMed
    1. Schaupp L, Addante A, Völler M, Fentker K, Kuppe A, Bardua M, et al. Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on sputum viscoelastic properties, airway infection and inflammation in patients with cystic fibrosis. Eur Respir J . 2023;62:2202153. - PubMed
    1. Morgan S, Cramer R, Vesely E, Ni W, Hong G, Salipante S, et al. Sputum density of Aspergillus fumigatus markedly declines after treatment with elexacaftor-tezacaftor-ivacaftor [abstract] J Cyst Fibros . 2023;22:S34–S35.

LinkOut - more resources