Proteins associated with preserved ratio impaired spirometry

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.

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/FVC1≥LLN (n=278); moderate-severe CAL: FEV₁/FVC11/FVC ≥LLN and FVC1/FVC≥LLN and FEV₁

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.

Protein profile in PRISm differs from other spirometric patterns suggesting specific disease mechanisms.