PT  - JOURNAL ARTICLE
AU  - Susan K Mathai
AU  - Stephen Humphries
AU  - Jonathan A Kropski
AU  - Timothy S Blackwell
AU  - Julia Powers
AU  - Avram D Walts
AU  - Cheryl Markin
AU  - Julia Woodward
AU  - Jonathan H Chung
AU  - Kevin K Brown
AU  - Mark P Steele
AU  - James E Loyd
AU  - Marvin I Schwarz
AU  - Tasha Fingerlin
AU  - Ivana V Yang
AU  - David A Lynch
AU  - David A Schwartz
TI  - <em>MUC5B</em> variant is associated with visually and quantitatively detected preclinical pulmonary fibrosis
AID  - 10.1136/thoraxjnl-2018-212430
DP  - 2019 Dec 01
TA  - Thorax
PG  - 1131--1139
VI  - 74
IP  - 12
4099  - http://thorax.bmj.com/content/74/12/1131.short
4100  - http://thorax.bmj.com/content/74/12/1131.full
SO  - Thorax2019 Dec 01; 74
AB  - Background Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis. 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.Methods 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 MUC5B and TERT was performed.Findings 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% CI 0.72 to 0.89) and 86% sensitivity (95% CI 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 MUC5B promoter variant rs35705950 (minor allele frequency 0.29 vs 0.21). MUC5B variant carriers had higher quantitative CT fibrosis scores (mean difference of 0.36%), a difference that remains significant when controlling for age and sex.Interpretation PrePF is common in relatives of patients with FIP. Its prevalence increases with age and the presence of a common MUC5B promoter variant. Quantitative CT analysis can detect these imaging abnormalities.