{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:06:49Z","timestamp":1779210409388,"version":"3.51.4"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":59,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["R01HL125280"],"award-info":[{"award-number":["R01HL125280"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["P30DK065988"],"award-info":[{"award-number":["P30DK065988"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["P01HL164320"],"award-info":[{"award-number":["P01HL164320"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["Button19G0"],"award-info":[{"award-number":["Button19G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006501","name":"Cystic Fibrosis Foundation Therapeutics","doi-asserted-by":"crossref","award":["Button07XX0"],"award-info":[{"award-number":["Button07XX0"]}],"id":[{"id":"10.13039\/100006501","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>Airway mucus clearance from the lungs occurs by 2 widely recognized mechanisms: cilia-mediated clearance and high-velocity airflow-mediated cough clearance. However, a potentially important third mechanism of mucus clearance, referred to as cilia-independent gas\u2013liquid transport (GLT), was proposed based on in vitro model systems to occur during normal tidal breathing but has largely been overlooked. We conducted in vitro and in vivo studies to investigate the role of tidal breathing airflow rates in mucus clearance. An in vitro airway culture bead-tracking model demonstrated airflow-dependent mucus transport at tidal breathing flow rates. As with other modes of mucus clearance, GLT was critically dependent on mucus concentration. In vivo studies in cilial beat-deficient mice demonstrated that GLT-mediated mucus clearance occurs during tidal breathing in the absence of cough, and the rate of GLT mucus clearance was dependent on breathing frequency and body orientation. These studies demonstrated that GLT is a third mechanism of mucus clearance and likely represents a significant mode of clearance in persons with cilial dysfunction. These findings indicate that increasing breathing rates through exercise, using mucus rehydrating agents or mucolytics, or combining these approaches may restore clinically and physiologically meaningful airway clearance in these patients.<\/jats:p>","DOI":"10.1172\/jci182984","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:00:53Z","timestamp":1773763253000},"source":"Crossref","is-referenced-by-count":0,"title":["Cilia-independent gas\u2013liquid transport, a third mechanism mediating airway mucus clearance"],"prefix":"10.1172","volume":"136","author":[{"given":"Siddharth K.","family":"Shenoy","sequence":"first","affiliation":[{"name":"Marsico Lung Institute,"},{"name":"Department of Biomedical Engineering, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Gutay","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute,"},{"name":"Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Brown","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute,"},{"name":"Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Troy D.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kane","family":"Banner","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute,"},{"name":"Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nico","family":"Olegario","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute,"},{"name":"Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Griffin","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute,"},{"name":"Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry P.","family":"Goodell","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan","family":"Yoder","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Lalush","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine, Johns Hopkins University Medical School, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard C.","family":"Boucher","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara R.","family":"Grubb","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8623-0576","authenticated-orcid":true,"given":"Brian","family":"Button","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute,"},{"name":"Department of Biomedical Engineering, and"},{"name":"Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1968.24.3.373"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/137.3.726"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1965.03090240094043"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3233\/bir-1989-26407"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1977.03630210060019"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3233\/bir-1989-26406"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201412-2230OC"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2010.0823"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1990.69.5.1670"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1986.60.3.901"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9290(78)90011-8"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1987.62.3.959"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(70)90094-0"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1136\/thx.18.1.54"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.07521210"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1378\/chest.95.3.658"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/0025-5564(73)90073-4"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1378\/chest.98.3.608"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2174\/1874306401812010001"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4081\/monaldi.2010.299"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505832200"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201304-0733OC"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00001.2009"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3109\/01902148709064320"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73469"},{"key":"B26"},{"issue":"s36","key":"B27","article-title":"Airflow-mediated mucus transport: a novel form of clearance","volume":"48","author":"Shenoy","year":"2013","journal-title":"Pediatr Pulmonol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0668.2009.00619.x"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.009817"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00004.2021"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1126\/science.1223012"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1907962"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1378\/chest.129.1.118"},{"key":"B34"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00616-2025"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811787115"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2003755"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201802-0245OC"},{"key":"B39"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-969151"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00239.2023"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0328OC"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0417OC"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0118OC"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00015.2016"},{"issue":"6","key":"B46","first-page":"684","article-title":"Dose regimens, variability, and complications associated with using repeat-bolus dosing to extend a surgical plane of anesthesia in laboratory mice","volume":"53","author":"Jaber","year":"2014","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aeg222"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2014.1189"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9290(75)90023-8"},{"issue":"5","key":"B50","first-page":"999","article-title":"Morphometry of the human lung: the state of the art after two decades","volume":"15","author":"Weibel","year":"1979","journal-title":"Bull Eur Physiopathol Respir"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1986.60.3.908"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087681"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1987.135.4.831"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-015-0408-1"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31967"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-10"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00011814"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1979.120.4.739"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.physio.2006.07.005"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1191\/1479972306cd097rs"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009720"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1977.43.1.46"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1980.49.3.506"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02652-2017"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043891"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2018.04.003"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(23)00226-6"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201804-0734OC"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-79"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3109\/01902149509050835"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-861-7:183"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01297-2018"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/54\/5\/013"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/182984\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:17:51Z","timestamp":1779207471000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/182984"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":73,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,3,17]]},"published-print":{"date-parts":[[2026,5,15]]}},"alternative-id":["10.1172\/JCI182984"],"URL":"https:\/\/doi.org\/10.1172\/jci182984","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]},"article-number":"e182984"}}