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Proteins associated with preserved ratio impaired spirometry.

Eva Lindberg1, Xingwu Zhou1,2,3, Annelie F Behndig4

  • 1Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

ERJ Open Research
|July 1, 2025
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Summary

Preserved ratio impaired spirometry (PRISm) involves distinct biological mechanisms, identified through a proteomic analysis. This study reveals specific protein profiles associated with PRISm, differentiating it from other spirometric patterns.

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Area of Science:

  • Pulmonary Medicine
  • Proteomics
  • Biomarker Discovery

Background:

  • Preserved ratio impaired spirometry (PRISm) is a spirometric pattern linked to increased mortality and incident airflow obstruction.
  • Understanding the underlying biological mechanisms of PRISm is crucial for targeted interventions.

Purpose of the Study:

  • To investigate the proteomic differences associated with PRISm using a large-scale population-based study.
  • To identify specific proteins that characterize PRISm and potentially indicate distinct disease pathways.

Main Methods:

  • Utilized data from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) as discovery and replication cohorts.
  • Defined spirometric patterns including PRISm based on post-bronchodilator FEV1, FVC, and FEV1/FVC relative to the lower limit of normal (LLN).
  • Employed proximity extension assays to measure 168 proteins and analyzed associations with spirometric patterns using multiple linear regression, adjusting for covariates and controlling for false discovery rate.

Main Results:

  • Eight proteins were significantly associated with PRISm and replicated across cohorts, including IL-6, U-PAR, and E-selectin.
  • Interleukin-6 and U-PAR also showed associations with moderate-severe chronic airflow limitation (CAL).
  • E-selectin was associated with the restrictive spirometric pattern (RSP), and other proteins were linked to moderate-severe CAL and RSP.

Conclusions:

  • The proteomic profile in PRISm is distinct from other spirometric patterns.
  • These findings suggest unique underlying disease mechanisms for PRISm.
  • Protein biomarkers may aid in understanding and potentially managing PRISm.