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We applied a proteomic approach to gain more insight into the biological mechanisms associated with PRISm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2005s (FEV<jats:sub>1<\/jats:sub>), forced vital capacity (FVC) and FEV<jats:sub>1<\/jats:sub>\/FVC was defined as the fifth percentile in healthy, never-smoking SCAPIS participants. Participants were subdivided into five groups: reference: FEV<jats:sub>1<\/jats:sub>\/FVC\u2265LLN and FEV<jats:sub>1<\/jats:sub>\u2265LLN and FVC\u2265LLN (n=4084)); mild chronic airflow limitation (CAL): FEV<jats:sub>1<\/jats:sub>\/FVC&lt;LLN and FEV<jats:sub>1<\/jats:sub>\u2265LLN (n=278); moderate\u2013severe CAL: FEV<jats:sub>1<\/jats:sub>\/FVC&lt;LLN and FEV<jats:sub>1<\/jats:sub>&lt;LLN (n=170); restrictive spirometric pattern (RSP): FEV<jats:sub>1<\/jats:sub>\/FVC\u2009\u2265LLN and FVC&lt;LLN (n=238); and PRISm: FEV<jats:sub>1<\/jats:sub>\/FVC\u2265LLN and FEV<jats:sub>1<\/jats:sub>&lt;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%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2013severe CAL and E-selectin with RSP. In addition, five other proteins were associated with moderate\u2013severe CAL and three with RSP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Protein profile in PRISm differs from other spirometric patterns suggesting specific disease mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1183\/23120541.01045-2024","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T11:45:20Z","timestamp":1738323920000},"page":"01045-2024","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Proteins associated with preserved ratio impaired spirometry"],"prefix":"10.1183","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-4510","authenticated-orcid":false,"given":"Eva","family":"Lindberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelie F.","family":"Behndig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Caidahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Egesten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-9152","authenticated-orcid":false,"given":"Gunnar","family":"Engstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5716-5098","authenticated-orcid":false,"given":"Jan E.","family":"Engvall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tove","family":"Fall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Gummesson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8475-0866","authenticated-orcid":false,"given":"Viktor","family":"Hamrefors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5093-6980","authenticated-orcid":false,"given":"Christer","family":"Janson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5se","family":"Johnsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3292-7471","authenticated-orcid":false,"given":"Anne","family":"Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mannila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik H.","family":"Nystr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6674-9020","authenticated-orcid":false,"given":"Anna-Carin","family":"Olin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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