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Reduced D\n                      <jats:sub>LCO<\/jats:sub>\n                      with normal spirometry is a common finding that is incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      To assess determinants of isolated, reduced D\n                      <jats:sub>LCO<\/jats:sub>\n                      in an unselected population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The Swedish CArdioPulmonary bioImage Study (SCAPIS) is a multicentre population-based study of adults aged 50\u201364\u00a0years. The 5th percentile of D\n                      <jats:sub>LCO<\/jats:sub>\n                      in healthy never smokers was used as the lower limit of normal (LLN). Using multivariable analysis, we studied factors associated with D\n                      <jats:sub>LCO<\/jats:sub>\n                      \u2009&lt;\u2009LLN in 24 261 subjects with normal spirometry, defined as FEV1, FVC and FEV1\/FVC\u2009&gt;\u2009LLN. Emphysema and interstitial lung abnormalities (ILA) were assessed through computed tomography, physical activity through accelerometry and other factors through questionnaires.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Isolated D\n                      <jats:sub>LCO<\/jats:sub>\n                      \u2009&lt;\u2009LLN (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091 472) was independently associated with emphysema (odds ratio and 95% confidence interval: 2.6 (2.2, 3.2)), lung disease other than asthma or COPD (1.8 (1.2, 2.8)), exertional chest pain (1.6 (1.3, 2.1)), smoking (per-10-pack-years) (1.6 (1.4, 1.9)), ILA (1.4 (1.2, 1.7)), breathing problems (1.4 (1.1, 1.8)), male sex (1.3 (1.1, 1.6)) and coughing (1.2 (1.1, 1.5)). D\n                      <jats:sub>LCO<\/jats:sub>\n                      \u2009&lt;\u2009LLN was less likely if subjects were older, had asthma or had higher BMI, haemoglobin, FVC or physical activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Isolated, reduced D\n                      <jats:sub>LCO<\/jats:sub>\n                      in a large middle-aged population cohort is associated with numerous previously known factors, including emphysema, ILA, smoking and self-reported lung disease. However, several symptoms, including exertional chest pain, breathing problems and coughing, are also independently associated with isolated reduced D\n                      <jats:sub>LCO<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12890-026-04662-9","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:54:14Z","timestamp":1788184454000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isolated, reduced diffusing capacity for carbon monoxide in the population \u2013 relations to symptoms, smoking and comorbidities"],"prefix":"10.1186","volume":"26","author":[{"given":"Viktor","family":"Hamrefors","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Westerbergh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelie","family":"Behndig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Blomberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Brandberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Carl\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Egesten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Ekbom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6ssur Ingi","family":"Emilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Fr\u00f8lich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludger","family":"Grote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christer","family":"Janson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Karimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Moberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Lennart","family":"Persson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Pesonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Sk\u00f6ld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"S\u00f6rensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan","family":"Tanash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjell","family":"Tor\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lowie","family":"Vanfleteren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Wollmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Malinovschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"4662_CR1","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1183\/09031936.05.00034905","volume":"26","author":"N Macintyre","year":"2005","unstructured":"Macintyre N, Crapo RO, Viegi G, et al. 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The study adhered to the Declaration of Helsinki and all participants provided written informed consent.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"JB reports leadership position within the Swedish Society of Radiology, and stocks in AstraZeneca and Novo Nordisk. AE reports consulting fees from Arcede Pharma and BioCyst. \u00d6IE reports honoraria for lectures from MSD, AstraZeneca and Boehringer Ingelheim, payment for expert testimony from MSD, and participation on advisory boards for MSD, AstraZeneca and Boehringer Ingelheim, not related to this manuscript. LG reports shared ownership of a patent on pharmacological therapy in sleep apnea licensed to Desitin GMBH, payment for participation in speakers bureau from Lundbeck, Resmed and AstraZeneca, payment for participation on advisory board for Onera, as well as being Chair of the Swedish Sleep Apnea Registry (SESAR), the national working group on sleep apnea in adults and the ERS-CRC for the European Sleep Apnea Database (ESADA). VH reports support for this manuscript from the Swedish Heart Lung Foundation, Sk\u00e5ne University Hospital Funds, and the governmental funding of clinical research within the Swedish National Health Service. HLP reports consulting fees from the Swedish Medical Products Agency, personal payments for lectures and presentations from AstraZeneca AB, and personal payments from GlaxoSmithKline AB for participation on advisory boards. IP reports consulting fees and payment for lectures from Boehringer Ingelheim. LEGW reports grants from the Swedish Heart Lung Foundation, the Kamprad foundation, Vinnova, AstraZeneca and the Swedish Government and county council (ALF grant ALFGBG-824371), payment for lectures from AstraZeneca, Chiesi, Grifols, GSK, Pulmonx, and Novartis, support for meeting attendance from Menarin Foundation, and participation on advisory board for AstraZeneca.The rest of the authors declare no conflicts of interest relating to this manuscript.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"387"}}