Klin Padiatr 2023; 235(02): 130-131
DOI: 10.1055/s-0043-1761569
Abstracts | GPP
17. März 2023
V-02 | Kurzvorträge
10:30 – 12:00 SH 0.101

Effects of Elexacaftor/Tezacaftor/Ivacaftor on Sputum Viscoelastic Properties, Airway Infection and Inflammation in Patients with Cystic Fibrosis

Simon Graeber
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
7   Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Deutschland
,
Annalisa Addante
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
,
MIrjam Völler
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
,
Laura Schaupp
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
,
Kerstin Fentker
2   Max-Delbrueck-Centrum fuer Molekulare Medizin in der Helmholtz-Gemeinschaft, Proteomics Platform, Berlin, Deutschland
3   Freie Universitaet Berlin, Institute for Chemistry and Biochemistry, Berlin, Deutschland
,
Markus Bardua
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
,
Aditi Kuppe
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
,
Julia Duerr
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
,
Linus Piehler
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
,
Jobst Röhmel
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
,
Stephanie Thee
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
7   Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Deutschland
,
Marieluise Kirchner
2   Max-Delbrueck-Centrum fuer Molekulare Medizin in der Helmholtz-Gemeinschaft, Proteomics Platform, Berlin, Deutschland
,
Matthias Ziehm
2   Max-Delbrueck-Centrum fuer Molekulare Medizin in der Helmholtz-Gemeinschaft, Proteomics Platform, Berlin, Deutschland
,
Daniel Lauster
3   Freie Universitaet Berlin, Institute for Chemistry and Biochemistry, Berlin, Deutschland
,
Rainer Haag
3   Freie Universitaet Berlin, Institute for Chemistry and Biochemistry, Berlin, Deutschland
,
Michael Gradzielski
4   Technische Universitaet Berlin, Stranski-Laboratorium für Physikalische und Theoretische Chemie, Institut für Chemie, Berlin, Deutschland
,
Mirjam Stahl
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
7   Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Deutschland
,
Philipp Mertins
2   Max-Delbrueck-Centrum fuer Molekulare Medizin in der Helmholtz-Gemeinschaft, Proteomics Platform, Berlin, Deutschland
,
Sebastien Boutin
5   Heidelberg University, Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg, Deutschland
8   University of Heidelberg, Translational Lung Research Center (TLRC), Heidelberg, Deutschland
,
MarcusA. Mall
1   Charite – Universitaetsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Deutschland
6   German Center for Lung Research (DZL), associated partner site, Berlin, Deutschland
7   Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Deutschland
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Background We recently demonstrated that the triple combination CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves lung ventilation and airway mucus plugging determined by multiple-breath washout and magnetic resonance imaging in CF patients with at least one F508del allele. However, effects of ELX/TEZ/IVA on viscoelastic properties of airway mucus, chronic airway infection and inflammation have not been studied. The aim of this study was, therefore, to determine the effects of ELX/TEZ/IVA on airway mucus rheology, microbiome and inflammation in CF patients with one or two F508del alleles aged 12 years and older.

Methods In this prospective observational study, we assessed sputum rheology, the microbiome, inflammation markers and proteome before and 8 to 16 weeks after initiation of ELX/TEZ/IVA.

Results In total, 59 patients with CF and at least one F508del allele and 10 healthy controls were enrolled in this study. ELX/TEZ/IVA improved the elastic modulus (G’; -6.3 Pa; IQR, -17.9 to 1.2; P<0.01) and viscous modulus (G''; -1.6 Pa; IQR, -3.6 to 0.5; P<0.05) of CF sputum. Further, ELX/TEZ/IVA improved the microbiome α-diversity (0.6; IQR, 0.0 to 1.2; P<0.001) and decreased the relative abundance of Pseudomonas aeruginosa in CF sputum. ELX/TEZ/IVA also reduced IL-8 (-11.7 ng/ml, IQR, -36.5 to 11.2; P<0.05) and free NE activity (-27.5 µg/ml, IQR, -64.5 to -3.5; P<0.001), and shifted the CF sputum proteome towards healthy.

Conclusions Our data demonstrate that ELX/TEZ/IVA improves sputum viscoelastic properties, chronic airway infection and inflammation in CF patients with at least one F508del allele, however, without reaching levels close to healthy.



Publication History

Article published online:
09 March 2023

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