Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2025
Change in pulmonary pathogens 3 years after elexacaftor/tezacaftor/ivacaftor: an observational study in the Danish cystic fibrosis cohort.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Bendixen Maria Pals, Jeppesen Majbritt, Irazoki Oihane, Jensen Camilla Bjørn, Wang Mikala, Petersen Janne, Katzenstein Terese Lea, Pressler Tacjana, Skov Marianne, Olesen Hanne Vebert, Jensen-Fangel Søren, Qvist Tavs, Johansen Helle Krogh, TransformCF Study Group
Аннотация
OBJECTIVES: Cystic fibrosis (CF) is a severe autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The resulting dysfunction of the CFTR chloride channel leads to dehydrated mucus, reduced mucociliary clearance, and pulmonary infections. Introduction of the CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI) has revolutionized the treatment of people with CF (pwCF). ETI changes mucus composition, volume, and viscosity and improves lung function and life expectancy. Long-term ETI impact on CF pulmonary pathogens is an important clinical question. We investigated changes in airway sputum sampling, changes in CF pathogen prevalence, and changes in infection status in pwCF before and after ETI initiation.
METHODS: We conducted a national cohort study of airway pathogens from 5 years before to 3 years after ETI initiation in 282 Danish pwCF above 12 years of age. Samples comprised expectorates, nasopharyngeal aspirates, and bronchoalveolar lavages. A generalized linear mixed effects model and Wilcoxon signed-rank tests were employed in the analysis of data from the Danish CF Registry.
RESULTS: During the 8-year study period, 19,739 airway samples were cultured. Sampling decreased from 10 to 6 samples per person per year after ETI initiation. We observed a significant reduction in the average percentage of airway cultures with growth of Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus spp., and Stenotrophomonas maltophilia in the years after ETI initiation. Despite this, 18% of the cohort had growth of P. aeruginosa in >50% of their samples in the third year after ETI.
CONCLUSION: Our work underscores the positive effect of ETI on CF airway microbiology as a significant and sustained reduction of key CF airway pathogens at a population level during 3 years of follow-up. However, most pwCF remained culture positive 3 years after ETI. We emphasize the importance of continued close microbial monitoring and optimization of airway sampling procedures and microbial diagnostic methods.
METHODS: We conducted a national cohort study of airway pathogens from 5 years before to 3 years after ETI initiation in 282 Danish pwCF above 12 years of age. Samples comprised expectorates, nasopharyngeal aspirates, and bronchoalveolar lavages. A generalized linear mixed effects model and Wilcoxon signed-rank tests were employed in the analysis of data from the Danish CF Registry.
RESULTS: During the 8-year study period, 19,739 airway samples were cultured. Sampling decreased from 10 to 6 samples per person per year after ETI initiation. We observed a significant reduction in the average percentage of airway cultures with growth of Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus spp., and Stenotrophomonas maltophilia in the years after ETI initiation. Despite this, 18% of the cohort had growth of P. aeruginosa in >50% of their samples in the third year after ETI.
CONCLUSION: Our work underscores the positive effect of ETI on CF airway microbiology as a significant and sustained reduction of key CF airway pathogens at a population level during 3 years of follow-up. However, most pwCF remained culture positive 3 years after ETI. We emphasize the importance of continued close microbial monitoring and optimization of airway sampling procedures and microbial diagnostic methods.