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Characterisation of airway inflammation and proteomes associated with cystic fibrosis-related diabetes

Diemer, Stefanie LU ; Chowdhury, Sounak LU ; Sahl, Cecilia LU orcid ; Happonen, Lotta LU and Påhlman, Lisa LU orcid (2025) In ERJ Open Research 11(6).
Abstract
Background: Cystic fibrosis (CF)-related diabetes (CFRD) is the most common extrapulmonary complication in CF. CFRD is associated with low lung function, but the underlying mechanisms are poorly understood. The aim of the present study was to compare airway inflammation and the airway proteome in people with CF (pwCF) with and without CFRD.

Methods: Sputum samples from pwCF were analysed for neutrophil elastase (NE) activity with a chromogenic assay, inflammatory cytokines using Meso Scale and bacterial load via quantitative PCR of the 16S rRNA gene. The sputum proteome was characterised by liquid chromatography-mass spectrometry.

Results: 33 pwCF were included in the study, of which 55% had CFRD. The CFRD group had... (More)
Background: Cystic fibrosis (CF)-related diabetes (CFRD) is the most common extrapulmonary complication in CF. CFRD is associated with low lung function, but the underlying mechanisms are poorly understood. The aim of the present study was to compare airway inflammation and the airway proteome in people with CF (pwCF) with and without CFRD.

Methods: Sputum samples from pwCF were analysed for neutrophil elastase (NE) activity with a chromogenic assay, inflammatory cytokines using Meso Scale and bacterial load via quantitative PCR of the 16S rRNA gene. The sputum proteome was characterised by liquid chromatography-mass spectrometry.

Results: 33 pwCF were included in the study, of which 55% had CFRD. The CFRD group had significantly lower lung function and higher sputum levels of NE, interleukin (IL)-8 and IL-1β, whereas IL-6 levels were lower compared to pwCF without CFRD. Proteome analysis identified 27 sputum proteins linked to CFRD, mainly involved in neutrophil degranulation. Given that lung function could be a possible confounding factor, we matched pwCF with and without CFRD based on lung function. In these lung function-matched cohorts, IL-8 and IL-6 levels did not differ significantly, but IL-1β showed a trend towards higher levels in the CFRD group. 10 CFRD-associated proteins were significantly more abundant in the CFRD group, including prothymosin α, which plays a role in diabetes and insulin release.

Conclusion: CFRD is associated with lower lung function, increased sputum levels of NE, IL-8 and IL-1β, and specific protein profiles. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
ERJ Open Research
volume
11
issue
6
article number
00290-2025
publisher
European Respiratory Society
external identifiers
  • pmid:41220822
ISSN
2312-0541
DOI
10.1183/23120541.00290-2025
language
English
LU publication?
yes
id
a64d975e-3e01-4c57-8799-0cc1ca6f2414
date added to LUP
2025-11-21 14:28:42
date last changed
2025-11-22 03:00:04
@article{a64d975e-3e01-4c57-8799-0cc1ca6f2414,
  abstract     = {{Background: Cystic fibrosis (CF)-related diabetes (CFRD) is the most common extrapulmonary complication in CF. CFRD is associated with low lung function, but the underlying mechanisms are poorly understood. The aim of the present study was to compare airway inflammation and the airway proteome in people with CF (pwCF) with and without CFRD.<br/><br/>Methods: Sputum samples from pwCF were analysed for neutrophil elastase (NE) activity with a chromogenic assay, inflammatory cytokines using Meso Scale and bacterial load via quantitative PCR of the 16S rRNA gene. The sputum proteome was characterised by liquid chromatography-mass spectrometry.<br/><br/>Results: 33 pwCF were included in the study, of which 55% had CFRD. The CFRD group had significantly lower lung function and higher sputum levels of NE, interleukin (IL)-8 and IL-1β, whereas IL-6 levels were lower compared to pwCF without CFRD. Proteome analysis identified 27 sputum proteins linked to CFRD, mainly involved in neutrophil degranulation. Given that lung function could be a possible confounding factor, we matched pwCF with and without CFRD based on lung function. In these lung function-matched cohorts, IL-8 and IL-6 levels did not differ significantly, but IL-1β showed a trend towards higher levels in the CFRD group. 10 CFRD-associated proteins were significantly more abundant in the CFRD group, including prothymosin α, which plays a role in diabetes and insulin release.<br/><br/>Conclusion: CFRD is associated with lower lung function, increased sputum levels of NE, IL-8 and IL-1β, and specific protein profiles.}},
  author       = {{Diemer, Stefanie and Chowdhury, Sounak and Sahl, Cecilia and Happonen, Lotta and Påhlman, Lisa}},
  issn         = {{2312-0541}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{European Respiratory Society}},
  series       = {{ERJ Open Research}},
  title        = {{Characterisation of airway inflammation and proteomes associated with cystic fibrosis-related diabetes}},
  url          = {{http://dx.doi.org/10.1183/23120541.00290-2025}},
  doi          = {{10.1183/23120541.00290-2025}},
  volume       = {{11}},
  year         = {{2025}},
}