{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T09:54:13Z","timestamp":1773482053177,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,12]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Post-tuberculosis (TB) lung disease (PTLD) affects approximately 50% of persons with pulmonary TB. We recently discovered whole blood transcriptional signatures associated with PTLD. We examined whether a minimum gene signature predicts PTLD as a clinically useful biomarker.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We prospectively enrolled 301 treatment na\u00efve adults with newly diagnosed pulmonary TB (PTB) (cohort A). We collected whole blood at 0 and 6-month visits, isolated RNA, and measured a modified MTB Host Response (HR) signature (mHR) based on expression of DUSP3, GBP5, and TMBIM6. We recorded spirometry at 6 (n=216) and 12 months (n=210) after treatment initiation and examined the association of the mHR score with PTLD and Mtb aerosolization. We recruited household contacts of cohort A to compare mHR score with non-PTB participants (cohort B).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>mHR was associated with TB (p=4.15e-66) when compared to HHCs, treatment response (p=1.07e-53), and characteristics including CD4 count (p=0.003), bacillary load (p=3.02e-05), lung cavities (p=1.59e-04), and lung quadrants involved (p=3.87e-06). The mHR score was not associated with Mtb aerosolization. In total, 105 (50%) participants had PTLD at 12 months including 61 with restriction, 26 with obstruction, and 18 with mixed obstruction and restriction. Baseline mHR was associated with obstructive PTLD at both 6 (p=0.003) and 12 months (p=0.012) in bivariate and multivariate analyses. The mHR score was not associated with restrictive lung disease.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>Baseline mHR was associated with obstructive PTLD at 6 and 12 months and may have applications in targeting treatment and prognostication.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.11.26348051","type":"posted-content","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:17Z","timestamp":1773360017000},"source":"Crossref","is-referenced-by-count":0,"title":["A whole-blood transcriptional signature associated with obstructive post-tuberculosis lung disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9840-2977","authenticated-orcid":false,"given":"Renee E.","family":"Newby","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5809-0419","authenticated-orcid":false,"given":"Lucy","family":"Kijaro","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Diseases Research, Kenya Medical Research Institute, Nairobi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1481-7065","authenticated-orcid":false,"given":"Kimberly A.","family":"Dill-McFarland","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5067-0788","authenticated-orcid":false,"given":"Lilian N.","family":"Njagi","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Diseases Research, Kenya Medical Research Institute, Nairobi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4495-2957","authenticated-orcid":false,"given":"Wilfred B.","family":"Murithi","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Diseases Research, Kenya Medical Research Institute, Nairobi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zipporah","family":"Mwongera","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Diseases Research, Kenya Medical Research Institute, Nairobi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moeko","family":"Agata","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8740-2351","authenticated-orcid":false,"given":"Jodi","family":"Byers","sequence":"additional","affiliation":[{"name":"Department of Global Health, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6965-2626","authenticated-orcid":false,"given":"Glenna J.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9416-0686","authenticated-orcid":false,"given":"Kevin P.","family":"Fennelly","sequence":"additional","affiliation":[{"name":"Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2266-8349","authenticated-orcid":false,"given":"Videlis","family":"Nduba","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Diseases Research, Kenya Medical Research Institute, Nairobi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5680-9074","authenticated-orcid":false,"given":"David J.","family":"Horne","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2742-5976","authenticated-orcid":false,"given":"Jerry S.","family":"Zifodya","sequence":"additional","affiliation":[{"name":"Department of Medicine, Tulane University School of Medicine, New Orleans, LA. 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