Proteins associated with preserved ratio impaired spirometry.

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.