Proteins associated with preserved ratio impaired spirometry

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.