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We assessed the prevalence and risk factors for preclinical pulmonary fibrosis (PrePF) in first-degree relatives of patients with FIP and determined the utility of deep learning in detecting PrePF on CT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First-degree relatives of patients with FIP over 40 years of age who believed themselves to be unaffected by pulmonary fibrosis underwent CT scans of the chest. Images were visually reviewed, and a deep learning algorithm was used to quantify lung fibrosis. Genotyping for common idiopathic pulmonary fibrosis risk variants in <jats:italic>MUC5B<\/jats:italic> and <jats:italic>TERT<\/jats:italic> was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>In 494 relatives of patients with FIP from 263 families of patients with FIP, the prevalence of PrePF on visual CT evaluation was 15.6% (95% CI 12.6 to 19.0). Compared with visual CT evaluation, deep learning quantitative CT analysis had 84% sensitivity (95%\u2009CI 0.72 to 0.89) and 86% sensitivity (95%\u2009CI 0.83 to 0.89) for discriminating subjects with visual PrePF diagnosis. Subjects with PrePF were older (65.9, SD 10.1 years) than subjects without fibrosis (55.8 SD 8.7 years), more likely to be male (49% vs 37%), more likely to have smoked (44% vs 27%) and more likely to have the <jats:italic>MUC5B<\/jats:italic> promoter variant rs35705950 (minor allele frequency 0.29 vs 0.21). <jats:italic>MUC5B<\/jats:italic> variant carriers had higher quantitative CT fibrosis scores (mean difference of 0.36%), a difference that remains significant when controlling for age and sex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>PrePF is common in relatives of patients with FIP. Its prevalence increases with age and the presence of a common <jats:italic>MUC5B<\/jats:italic> promoter variant. Quantitative CT analysis can detect these imaging abnormalities.<\/jats:p><\/jats:sec>","DOI":"10.1136\/thoraxjnl-2018-212430","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T00:26:40Z","timestamp":1569544000000},"page":"1131-1139","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":70,"title":["<i>MUC5B<\/i> variant is associated with visually and quantitatively detected preclinical pulmonary fibrosis"],"prefix":"10.1136","volume":"74","author":[{"given":"Susan K","family":"Mathai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Humphries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A","family":"Kropski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy S","family":"Blackwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Powers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avram D","family":"Walts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Markin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Woodward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin K","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P","family":"Steele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"Loyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin I","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasha","family":"Fingerlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana V","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,9,26]]},"reference":[{"key":"2020050723472202000_74.12.1131.1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S54815"},{"key":"2020050723472202000_74.12.1131.2","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1056\/NEJMoa1402584","article-title":"Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis","volume":"370","author":"Richeldi","year":"2014","journal-title":"N Engl J Med Overseas Ed"},{"key":"2020050723472202000_74.12.1131.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402582"},{"key":"2020050723472202000_74.12.1131.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013660"},{"key":"2020050723472202000_74.12.1131.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2609"},{"key":"2020050723472202000_74.12.1131.6","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02115-2015"},{"key":"2020050723472202000_74.12.1131.7","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.trsl.2013.12.006","article-title":"Association between MUC5B and TERT polymorphisms and different interstitial lung disease phenotypes","volume":"163","author":"Wei","year":"2014","journal-title":"Translational Research"},{"key":"2020050723472202000_74.12.1131.8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1216076"},{"key":"2020050723472202000_74.12.1131.9","doi-asserted-by":"publisher","DOI":"10.1378\/chest.127.6.2034"},{"key":"2020050723472202000_74.12.1131.10","doi-asserted-by":"crossref","unstructured":"Diaz de Leon A , Cronkhite JT , Katzenstein A-LA , et al . 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