A restructuring of microbiome niche space is associated with Elexacaftor-Tezacaftor-Ivacaftor therapy in the cystic fibrosis lung

Sosinski, Lo M.; H, Christian Martin; Neugebauer, Kerri A.; Ghuneim, Lydia-Ann J.; Guzior, Douglas V.; Castillo-Bahena, A.; Mielke, Jenna A.; Thomas, Ryan M.; McClelland, Marc; Conrad, Doug; Quinn, Robert A.

doi:10.1016/j.jcf.2021.11.003

Cited by 40 publications

(48 citation statements)

References 50 publications

(78 reference statements)

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“…Even the combination lumacaftor/ivacaftor suggests a moderate change in the lung microbiota [ 21 ]. Moreover, a recent study documented the chance of elexacaftor-tezacaftor-ivacaftor in shifting the microbiome and even metabolome in the CF lung [ 22 ]. Although triple combination therapy is a recent combination, its clinical use resulted in a possible reduction in the microbial colonization rate of the airway that we still need entirely to understand.…”

Section: Discussionmentioning

confidence: 99%

Elexacaftor-Tezacaftor-Ivacaftor as a Final Frontier in the Treatment of Cystic Fibrosis: Definition of the Clinical and Microbiological Implications in a Case-Control Study

Migliorisi¹,

Collura²,

Ficili³

et al. 2022

Pharmaceuticals

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The use of modulator drugs that target the cystic fibrosis transmembrane conductance regulator (CFTR) is the final frontier in the treatment of Cystic Fibrosis (CF), a genetic multiorgan disease. F508del is the most common mutation causing defective formation and function of CFTR. Elexacaftor-tezacaftor-ivacaftor is the first triple combination of CFTR modulators. Herein, we report on a one-year case-control study that involved 26 patients with at least one F508del mutation. Patients were assigned to two similar groups, and patients with the worse clinical condition received treatment with the triple combination therapy. The study aimed to define the clinical and especially microbiological implications of treatment administration. The treatment provided significant clinical benefits in terms of respiratory, pancreatic, and sweat function. After one year of therapy, airway infection rates decreased and pulmonary exacerbations were dramatically reduced. Finally, treated patients reported a surprising improvement in their quality of life. The use of triple combination therapy has become essential in most CF people carrying the F508del mutation. Although the clinical and instrumental benefits of treatment are thoroughly known, further investigations are needed to properly define its microbiological respiratory implications and establish the real advantage of life-long treatment with elexacaftor-tezacaftor-ivacaftor.

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Section: Discussionmentioning

confidence: 99%

Elexacaftor-Tezacaftor-Ivacaftor as a Final Frontier in the Treatment of Cystic Fibrosis: Definition of the Clinical and Microbiological Implications in a Case-Control Study

Migliorisi¹,

Collura²,

Ficili³

et al. 2022

Pharmaceuticals

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“…Thus far, few data are available about the effects of ETI on chronic airway infections as well as on CF bacterial community. In this context, one of the most recent studies is that from Sosinski et al [ 78 ] that we previously mentioned. They analysed sputum microbiome and metabolome from CF patients before and after ETI therapy and showed that the treatment was associated with a change of microbiome and metabolome in the airways.…”

Section: Cftr Modulators and Chronic Airway Infections/recurrent Exac...mentioning

confidence: 99%

“…A recent study analysing sputum microbiome and metabolome in a small number of CF patients ( n = 24) before and after ETI therapy showed that this treatment was associated with changes in the airway microbiome and metabolome [ 78 ]. The drug effect was stronger on sputum biochemistry with a decrease in peptides, amino acids and kynurenine metabolism; these findings suggest that ETI therapy and possibly other CFTR modulators [ 77 ] might “reshape microbiome niche space in CF mucus” by decreasing the availability of peptides and amino acids, an effect that could have clinical implications for the treatment of lung infections.…”

Section: Cftr Modulators and Cf Microbiologymentioning

confidence: 99%

CFTR Modulator Therapies: Potential Impact on Airway Infections in Cystic Fibrosis

Saluzzo

Riberi

Messore

et al. 2022

Cells

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Cystic Fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding for the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein, expressed on the apical surface of epithelial cells. CFTR absence/dysfunction results in ion imbalance and airway surface dehydration that severely compromise the CF airway microenvironment, increasing infection susceptibility. Recently, novel therapies aimed at correcting the basic CFTR defect have become available, leading to substantial clinical improvement of CF patients. The restoration or increase of CFTR function affects the airway microenvironment, improving local defence mechanisms. CFTR modulator drugs might therefore affect the development of chronic airway infections and/or improve the status of existing infections in CF. Thus far, however, the full extent of these effects of CFTR-modulators, especially in the long-term remains still unknown. This review aims to provide an overview of current evidence on the potential impact of CFTR modulators on airway infections in CF. Their role in affecting CF microbiology, the susceptibility to infections as well as the potential efficacy of their use in preventing/decreasing the development of chronic lung infections and the recurrent acute exacerbations in CF will be critically analysed.

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“…Work has continued on understanding the complex polymicrobial communities in the CF lung, the impact of treatments on the microbiome and its relationship with disease severity [ 92 , 93 ]. Preliminary studies show that CFTR modulators are associated with modest changes in the CF microbiome [ 94 , 95 ]. ETI treatment is associated with increased population diversity and a reduction in the ratio of pathogens to anaerobes [94] .…”

Section: Microbiologymentioning

confidence: 99%

“…Preliminary studies show that CFTR modulators are associated with modest changes in the CF microbiome [ 94 , 95 ]. ETI treatment is associated with increased population diversity and a reduction in the ratio of pathogens to anaerobes [94] . IVA treatment is associated with a higher density of strict anaerobic bacteria and an increase in richness and diversity [95] .…”

Section: Microbiologymentioning

confidence: 99%

A year in review: Real world evidence, functional monitoring and emerging therapeutics in 2021

Barr

Bihouée²,

Zwitserloot

2022

Journal of Cystic Fibrosis

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A restructuring of microbiome niche space is associated with Elexacaftor-Tezacaftor-Ivacaftor therapy in the cystic fibrosis lung

Cited by 40 publications

References 50 publications

Elexacaftor-Tezacaftor-Ivacaftor as a Final Frontier in the Treatment of Cystic Fibrosis: Definition of the Clinical and Microbiological Implications in a Case-Control Study

Elexacaftor-Tezacaftor-Ivacaftor as a Final Frontier in the Treatment of Cystic Fibrosis: Definition of the Clinical and Microbiological Implications in a Case-Control Study

CFTR Modulator Therapies: Potential Impact on Airway Infections in Cystic Fibrosis

A year in review: Real world evidence, functional monitoring and emerging therapeutics in 2021

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