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Proteins associated with preserved ratio impaired spirometry

Lindberg, Eva ; Zhou, Xingwu ; Behndig, Annelie F. ; Caidahl, Kenneth ; Egesten, Arne LU ; Engström, Gunnar LU ; Engvall, Jan E. ; Eriksson, Maria J. ; Fall, Tove and Gummesson, Anders , et al. (2025) In ERJ open research 11(3).
Abstract

Background Preserved ratio impaired spirometry (PRISm) is a spirometry pattern of interest regarding incident airflow obstruction and higher mortality risk. We applied a proteomic approach to gain more insight into the biological mechanisms associated with PRISm. Methods From the population-based Swedish Cardiopulmonary Bioimage Study (SCAPIS), participants in the Main (n=4835) and Pilot (n=1054) studies, were included as discovery and replication cohorts. The lower limit of normal (LLN) of post-bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC was defined as the fifth percentile in healthy, never-smoking SCAPIS participants. Participants were subdivided into five... (More)

Background Preserved ratio impaired spirometry (PRISm) is a spirometry pattern of interest regarding incident airflow obstruction and higher mortality risk. We applied a proteomic approach to gain more insight into the biological mechanisms associated with PRISm. Methods From the population-based Swedish Cardiopulmonary Bioimage Study (SCAPIS), participants in the Main (n=4835) and Pilot (n=1054) studies, were included as discovery and replication cohorts. The lower limit of normal (LLN) of post-bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC was defined as the fifth percentile in healthy, never-smoking SCAPIS participants. Participants were subdivided into five groups: reference: FEV1/FVC⩾LLN and FEV1⩾LLN and FVC⩾LLN (n=4084)); mild chronic airflow limitation (CAL): FEV1/FVC<LLN and FEV1⩾LLN (n=278); moderate–severe CAL: FEV1/FVC<LLN and FEV1<LLN (n=170); restrictive spirometric pattern (RSP): FEV1/FVC ⩾LLN and FVC<LLN (n=238); and PRISm: FEV1/FVC⩾LLN and FEV1<LLN (n=238). Proximity extension assays were used to measure 168 proteins. The associations of each standardised protein were assessed with each study group by multiple linear regression models, adjusting for age, sex, body mass index (BMI), smoking, physical activity and study centres, and corrected for multiple testing to control for a false discovery rate of 5%. Results Eight proteins were associated with PRISm and replicated: tumour necrosis factor receptor superfamily member 10A, interleukin-6, paraoxonase 3 (negative association), renin, urokinase plasminogen activator surface receptor (U-PAR), E-selectin, matrix metalloproteinase 7 and chitinase-3-like protein 1. Interleukin-6 and U-PAR were also associated with moderate–severe CAL and E-selectin with RSP. In addition, five other proteins were associated with moderate–severe CAL and three with RSP. Conclusion Protein profile in PRISm differs from other spirometric patterns suggesting specific disease mechanisms.

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type
Contribution to journal
publication status
published
subject
in
ERJ open research
volume
11
issue
3
article number
01045-2024
publisher
European Respiratory Society
external identifiers
  • pmid:40589910
  • scopus:105012028655
ISSN
2312-0541
DOI
10.1183/23120541.01045-2024
language
English
LU publication?
yes
additional info
Publisher Copyright: © The authors 2025.
id
9c0585d4-86c5-4a3f-93ec-8f5520b839c2
date added to LUP
2025-12-19 13:19:50
date last changed
2025-12-20 03:00:03
@article{9c0585d4-86c5-4a3f-93ec-8f5520b839c2,
  abstract     = {{<p>Background Preserved ratio impaired spirometry (PRISm) is a spirometry pattern of interest regarding incident airflow obstruction and higher mortality risk. We applied a proteomic approach to gain more insight into the biological mechanisms associated with PRISm. Methods From the population-based Swedish Cardiopulmonary Bioimage Study (SCAPIS), participants in the Main (n=4835) and Pilot (n=1054) studies, were included as discovery and replication cohorts. The lower limit of normal (LLN) of post-bronchodilator forced expiratory volume in 1 s (FEV<sub>1</sub>), forced vital capacity (FVC) and FEV<sub>1</sub>/FVC was defined as the fifth percentile in healthy, never-smoking SCAPIS participants. Participants were subdivided into five groups: reference: FEV<sub>1</sub>/FVC⩾LLN and FEV<sub>1</sub>⩾LLN and FVC⩾LLN (n=4084)); mild chronic airflow limitation (CAL): FEV<sub>1</sub>/FVC&lt;LLN and FEV<sub>1</sub>⩾LLN (n=278); moderate–severe CAL: FEV<sub>1</sub>/FVC&lt;LLN and FEV<sub>1</sub>&lt;LLN (n=170); restrictive spirometric pattern (RSP): FEV<sub>1</sub>/FVC ⩾LLN and FVC&lt;LLN (n=238); and PRISm: FEV<sub>1</sub>/FVC⩾LLN and FEV<sub>1</sub>&lt;LLN (n=238). Proximity extension assays were used to measure 168 proteins. The associations of each standardised protein were assessed with each study group by multiple linear regression models, adjusting for age, sex, body mass index (BMI), smoking, physical activity and study centres, and corrected for multiple testing to control for a false discovery rate of 5%. Results Eight proteins were associated with PRISm and replicated: tumour necrosis factor receptor superfamily member 10A, interleukin-6, paraoxonase 3 (negative association), renin, urokinase plasminogen activator surface receptor (U-PAR), E-selectin, matrix metalloproteinase 7 and chitinase-3-like protein 1. Interleukin-6 and U-PAR were also associated with moderate–severe CAL and E-selectin with RSP. In addition, five other proteins were associated with moderate–severe CAL and three with RSP. Conclusion Protein profile in PRISm differs from other spirometric patterns suggesting specific disease mechanisms.</p>}},
  author       = {{Lindberg, Eva and Zhou, Xingwu and Behndig, Annelie F. and Caidahl, Kenneth and Egesten, Arne and Engström, Gunnar and Engvall, Jan E. and Eriksson, Maria J. and Fall, Tove and Gummesson, Anders and Hamrefors, Viktor and Janson, Christer and Johnsson, Åse and Lindberg, Anne and Mannila, Maria and Nyström, Fredrik H. and Olin, Anna Carin and Magnus Sköld, C. and Söderberg, Stefan and Tanash, Hanan and Torén, Kjell and Östgren, Carl Johan and Malinovschi, Andrei and Blomberg, Anders}},
  issn         = {{2312-0541}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{European Respiratory Society}},
  series       = {{ERJ open research}},
  title        = {{Proteins associated with preserved ratio impaired spirometry}},
  url          = {{http://dx.doi.org/10.1183/23120541.01045-2024}},
  doi          = {{10.1183/23120541.01045-2024}},
  volume       = {{11}},
  year         = {{2025}},
}