In cystic fibrosis (CF) therapy, the recent approval of CF-transmembrane conductance
regulator (CFTR) channel modulators is considered to be the major breakthrough.
However, the current first-line approach based mainly on pulmonary function to
measure effects of the novel therapy, tested by forced expiratory volumes in one
second (FEV1), provides restricted sensitivity to detect early structural damages.
Accordingly, there is a need for new sensitive surrogate parameters. Most interestingly,
these should quantify inflammation that precedes a decline of pulmonary function. We
present a novel method assessing inflammatory markers in the upper airways’ epithelial
lining fluid (ELF) obtained by nasal lavage (NL). In contrast to broncho-alveolar lavage, ELF
sampling by NL is an attractive method due to its limited invasiveness which allows
repeated analyses, even performed in a home-based setting. In a longitudinal cohort
study (ClinicalTrials.gov, Identifier: NCT02311140), we assessed changes of inflammatory
mediators in 259 serially obtained nasal lavages taken up to every second day before and
during therapy with ivacaftor from ten CF patients carrying a G551D mutation. Patients
were trained to sample NL-fluid at home, to immediately freeze and transfer chilled
secretions to centers. Neutrophil Elastase, Interleukins IL-1b, IL-6 and IL-8 in NL were
quantified. During 8-12 weeks of ivacaftor-treatment, median values of IL-1b and IL-6
significantly declined 2.29-fold (2.97!1.30 pg/mL), and 1.13-fold (6.48!5.72 pg/mL),
respectively. In parallel, sweat tests and pulmonary function improved considerably. This
is the first study assessing changes of airway inflammation on a day-to-day basis in CF patients receiving a newly administered CFTR-modulator therapy. It proves a decline of
airway inflammation during ivacaftor-therapy.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84293 |
| Date | 24 March 2023 |
| Creators | Mainz, Jochen G., Arnold, Christin, Wittstock, Kara, Hipler, Uta-Christina, Lehmann, Thomas, Zagoya, Carlos, Duckstein, Franziska, Ellemunter, Helmut, Hentschel, Julia |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1664-3224, 642180 |
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