Proteins associated with preserved ratio impaired spirometry (PRISm)

<bold>Background:</bold> Individuals with lung function impairment, despite a preserved FEV1/FVC ratio, comprise a heterogenous group. We studied proteins associated with different types of lung function impairment, with a specific focus on PRISm. <bold>Methods:</bold> From the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS), participants in Main (n=4,835) and Pilot (n=1,054) studies, were included as discovery and replication cohorts. Lower limit of normal (LLN) was defined as 5th percentile in healthy SCAPIS participants. Individuals were sub-divided into four groups based on postbronchodilator spirometry; Group 0 (reference): FEV1/FVC>LLN & FEV1>LNN & FVC>LLN (n=4,084); Group 1: FEV1/FVC<LLN & FEV1<LLN (n=170); Group 2: FEV1/FVC<LLN & FEV1>LLN (n=278) and Group 3 (PRISm): FEV1/FVC>=LLN & FEV1<LLN (n=238). Restrictive spirometric pattern (RSP) was defined as FEV1/FVC ≥LLN & FVC<LLN (n=238). Proximity extension assays were used to measure 168 proteins. Associations of each protein were assessed with each study group by linear regression models, adjusting for age, sex, BMI, smoking, physical activity, study centers, and corrected for multiple testing. <bold>Results:</bold> Eight proteins were associated with PRISm and replicated (Tumor necrosis factor receptor superfamily member 10A, Interleukin-6 (IL-6), S-paraoxonase, Renin, urokinase plasminogen activator surface receptor (U.PAR), E-selectin (SELE), Matrix metalloproteinase-7, Chitinase-3-like protein 1). IL-6 and U.PAR were also associated with Group 1 and SELE with RSP. In addition, 6 other proteins were associated with Group 1 and 3 with RSP. <bold>Conclusion:</bold> The protein profile in PRISm differed from both chronic airflow limitation and RSP suggesting specific disease mechanisms.