{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:13:01Z","timestamp":1753884781490,"version":"3.41.2"},"reference-count":75,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["NIH K08 HL135433","NIH PPG HL051670","NIH PPG HL091842","NIH R01 HL136813"],"award-info":[{"award-number":["NIH K08 HL135433","NIH PPG HL051670","NIH PPG HL091842","NIH R01 HL136813"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["ABOU20A0\u2010KB","STOLTZ16XX0","STOLTZ19R0"],"award-info":[{"award-number":["ABOU20A0\u2010KB","STOLTZ16XX0","STOLTZ19R0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In cystic fibrosis (CF), the loss of cystic fibrosis transmembrane conductance regulator (CFTR) mediated Cl<jats:sup>\u2212\u00a0<\/jats:sup>and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>\u00a0secretion across the epithelium acidifies the airway surface liquid (ASL). Acidic ASL alters two key host defense mechanisms: Rapid ASL bacterial killing and mucociliary transport (MCT). Aerosolized tromethamine (Tham) increases ASL pH and restores the ability of ASL to rapidly kill bacteria in CF pigs. In CF pigs, clearance of insufflated microdisks is interrupted due to abnormal mucus causing microdisks to abruptly recoil. Aerosolizing a reducing agent to break disulfide bonds that link mucins improves MCT. Here, we are interested in restoring MCT in CF by aerosolizing Tham, a buffer with a pH of 8.4. Because Tham is hypertonic to serum, we use an acidified formulation as a control. We measure MCT by tracking the caudal movement of individual tantalum microdisks with serial chest computed tomography scans. Alkaline Tham improves microdisk clearance to within the range of that seen in non\u2010CF pigs. It also partially reverses MCT defects, including reduced microdisk recoil and elapse time until they start moving after methacholine stimulation in CF pig airways. The effect is not due to hypertonicity, as it is not seen with acidified Tham or hypertonic saline. This finding indicates acidic ASL impairs CF MCT and suggests that alkalinization of ASL pH with inhaled Tham may improve CF airway disease.<\/jats:p>","DOI":"10.14814\/phy2.15340","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T07:00:45Z","timestamp":1662620445000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tromethamine improves mucociliary clearance in cystic fibrosis pigs"],"prefix":"10.14814","volume":"10","author":[{"given":"Jamison J.","family":"Ash","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Pappajohn Biomedical Institute Roy J and Lucille A Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brieanna M.","family":"Hilkin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Pappajohn Biomedical Institute Roy J and Lucille A Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas D.","family":"Gansemer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Pappajohn Biomedical Institute Roy J and Lucille A Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric A.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Radiology Roy J and Lucille A Carver College of Medicine University of Iowa  Iowa City Iowa USA"},{"name":"Roy J Carver, Department of Biomedical Engineering University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9606-1339","authenticated-orcid":false,"given":"Joseph","family":"Zabner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Pappajohn Biomedical Institute Roy J and Lucille A Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0893-9015","authenticated-orcid":false,"given":"David A.","family":"Stoltz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Pappajohn Biomedical Institute Roy J and Lucille A Carver College of Medicine University of Iowa  Iowa City Iowa USA"},{"name":"Roy J Carver, Department of Biomedical Engineering University of Iowa  Iowa City Iowa USA"},{"name":"Department of Molecular Physiology and Biophysics Roy J and Lucille A Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4525-0217","authenticated-orcid":false,"given":"Mahmoud H.","family":"Abou Alaiwa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Pappajohn Biomedical Institute Roy J and Lucille A Carver College of Medicine University of Iowa  Iowa City Iowa USA"},{"name":"Roy J Carver, Department of Biomedical Engineering University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,8]]},"reference":[{"key":"e_1_2_10_2_1","article-title":"Repurposing tromethamine as inhaled therapy to treat CF airway disease","volume":"1","author":"Abou Alaiwa M. H.","year":"2016","journal-title":"JCI Insight"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_1","DOI":"10.1073\/pnas.1422091112"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_1","DOI":"10.1164\/rccm.201109-1666OC"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_1","DOI":"10.1136\/thx.2009.125831"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_1","DOI":"10.1172\/JCI60429"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_1","DOI":"10.1378\/chest.114.1.171"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_1","DOI":"10.1016\/j.jaerosci.2016.01.016"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_1","DOI":"10.1164\/rccm.201404-0670OC"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_1","DOI":"10.1097\/00005537-199903000-00010"},{"doi-asserted-by":"publisher","key":"e_1_2_10_11_1","DOI":"10.1164\/rccm.202102-0451OC"},{"doi-asserted-by":"publisher","key":"e_1_2_10_12_1","DOI":"10.1007\/BF00545225"},{"doi-asserted-by":"publisher","key":"e_1_2_10_13_1","DOI":"10.1164\/rccm.201906-1227OC"},{"doi-asserted-by":"publisher","key":"e_1_2_10_14_1","DOI":"10.1101\/cshperspect.a009720"},{"doi-asserted-by":"publisher","key":"e_1_2_10_15_1","DOI":"10.1046\/j.1469-7580.2000.19730361.x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_16_1","DOI":"10.1152\/ajplung.00143.2012"},{"doi-asserted-by":"publisher","key":"e_1_2_10_17_1","DOI":"10.4187\/respcare.01753"},{"doi-asserted-by":"publisher","key":"e_1_2_10_18_1","DOI":"10.1183\/09031936.97.10112449"},{"doi-asserted-by":"publisher","key":"e_1_2_10_19_1","DOI":"10.1056\/NEJMoa043891"},{"doi-asserted-by":"publisher","key":"e_1_2_10_20_1","DOI":"10.1016\/S0140-6736(16)00576-6"},{"doi-asserted-by":"publisher","key":"e_1_2_10_21_1","DOI":"10.1097\/01.mcp.0000245714.89632.b2"},{"doi-asserted-by":"publisher","key":"e_1_2_10_22_1","DOI":"10.1056\/NEJMoa043900"},{"doi-asserted-by":"publisher","key":"e_1_2_10_23_1","DOI":"10.1172\/jci.insight.124863"},{"doi-asserted-by":"publisher","key":"e_1_2_10_24_1","DOI":"10.1056\/NEJM199409083311003"},{"doi-asserted-by":"publisher","key":"e_1_2_10_25_1","DOI":"10.1164\/rccm.201311-1932OC"},{"doi-asserted-by":"publisher","key":"e_1_2_10_26_1","DOI":"10.1007\/s40261-019-00861-x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_27_1","DOI":"10.1183\/13993003.02652-2017"},{"doi-asserted-by":"publisher","key":"e_1_2_10_28_1","DOI":"10.1084\/jem.20120562"},{"doi-asserted-by":"publisher","key":"e_1_2_10_29_1","DOI":"10.1002\/ar.22783"},{"doi-asserted-by":"publisher","key":"e_1_2_10_30_1","DOI":"10.1513\/pats.200409-046TA"},{"doi-asserted-by":"publisher","key":"e_1_2_10_31_1","DOI":"10.1073\/pnas.1323633111"},{"doi-asserted-by":"publisher","key":"e_1_2_10_32_1","DOI":"10.1126\/science.1255825"},{"doi-asserted-by":"publisher","key":"e_1_2_10_33_1","DOI":"10.1126\/science.1255825"},{"doi-asserted-by":"crossref","unstructured":"Holliday Z. M. Launspach J. L. Durairaj L. Singh P. K. Zabner J. &Stoltz D. A.2021.Effects of Tham Nasal Alkalinization on Airway Microbial Communities: a Pilot Study in Non\u2010CF and CF Adults. Annals of Otology Rhinology Laryngology.","key":"e_1_2_10_34_1","DOI":"10.1101\/2021.02.14.21251657"},{"doi-asserted-by":"publisher","key":"e_1_2_10_35_1","DOI":"10.1034\/j.1399-3003.1999.13e39.x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_36_1","DOI":"10.1042\/bj3180319"},{"doi-asserted-by":"publisher","key":"e_1_2_10_37_1","DOI":"10.1002\/cphy.c150028"},{"doi-asserted-by":"publisher","key":"e_1_2_10_38_1","DOI":"10.1172\/JCI43466"},{"doi-asserted-by":"publisher","key":"e_1_2_10_39_1","DOI":"10.1001\/archpedi.1962.02080020005001"},{"doi-asserted-by":"publisher","key":"e_1_2_10_40_1","DOI":"10.1186\/s40635\u2010021\u201000374\u2010y"},{"doi-asserted-by":"publisher","key":"e_1_2_10_41_1","DOI":"10.1164\/ajrccm.156.1.9512074"},{"doi-asserted-by":"publisher","key":"e_1_2_10_42_1","DOI":"10.1016\/S0022-5223(19)36458-X"},{"doi-asserted-by":"publisher","key":"e_1_2_10_43_1","DOI":"10.1186\/1471-2466-11-45"},{"doi-asserted-by":"publisher","key":"e_1_2_10_44_1","DOI":"10.1016\/j.ceca.2014.02.001"},{"doi-asserted-by":"publisher","key":"e_1_2_10_45_1","DOI":"10.1371\/journal.pone.0054473"},{"doi-asserted-by":"publisher","key":"e_1_2_10_46_1","DOI":"10.3389\/fphar.2019.01662"},{"doi-asserted-by":"publisher","key":"e_1_2_10_47_1","DOI":"10.1038\/s41598-018-36695-4"},{"doi-asserted-by":"publisher","key":"e_1_2_10_48_1","DOI":"10.1038\/nm1028"},{"doi-asserted-by":"publisher","key":"e_1_2_10_49_1","DOI":"10.1067\/mhn.2001.113145"},{"doi-asserted-by":"publisher","key":"e_1_2_10_50_1","DOI":"10.2165\/00003495-199855020-00003"},{"doi-asserted-by":"publisher","key":"e_1_2_10_51_1","DOI":"10.1002\/14651858.CD007168.pub2"},{"doi-asserted-by":"publisher","key":"e_1_2_10_52_1","DOI":"10.1164\/rccm.201804-0734OC"},{"doi-asserted-by":"publisher","key":"e_1_2_10_53_1","DOI":"10.1073\/pnas.1703228114"},{"doi-asserted-by":"publisher","key":"e_1_2_10_54_1","DOI":"10.1038\/nature11130"},{"doi-asserted-by":"publisher","key":"e_1_2_10_55_1","DOI":"10.1073\/pnas.2121731119"},{"doi-asserted-by":"publisher","key":"e_1_2_10_56_1","DOI":"10.1073\/pnas.91.12.5340"},{"doi-asserted-by":"publisher","key":"e_1_2_10_57_1","DOI":"10.1080\/107175400455155"},{"doi-asserted-by":"publisher","key":"e_1_2_10_58_1","DOI":"10.1038\/nrdp.2015.10"},{"doi-asserted-by":"publisher","key":"e_1_2_10_59_1","DOI":"10.1034\/j.1399-3003.1999.14c30.x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_60_1","DOI":"10.1164\/ajrccm.153.5.8630593"},{"doi-asserted-by":"publisher","key":"e_1_2_10_61_1","DOI":"10.1164\/rccm.201708-1616OC"},{"doi-asserted-by":"publisher","key":"e_1_2_10_62_1","DOI":"10.1001\/jama.2012.5214"},{"doi-asserted-by":"publisher","key":"e_1_2_10_63_1","DOI":"10.1073\/pnas.87.23.9188"},{"doi-asserted-by":"publisher","key":"e_1_2_10_64_1","DOI":"10.1016\/j.jcf.2015.05.009"},{"doi-asserted-by":"publisher","key":"e_1_2_10_65_1","DOI":"10.1056\/NEJMra1300109"},{"key":"e_1_2_10_66_1","first-page":"390","article-title":"Effect of chest physiotherapy on the removal of mucus in patients with cystic fibrosis","volume":"127","author":"Sutton P. P.","year":"1983","journal-title":"American Review of Respiratory Disease"},{"key":"e_1_2_10_67_1","first-page":"CD007168","article-title":"Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis","volume":"7","author":"Tam J.","year":"2013","journal-title":"Cochrane Database Systematic Review"},{"doi-asserted-by":"publisher","key":"e_1_2_10_68_1","DOI":"10.1172\/JCI83922"},{"doi-asserted-by":"publisher","key":"e_1_2_10_69_1","DOI":"10.1146\/annurev.physiol.70.113006.100702"},{"doi-asserted-by":"publisher","key":"e_1_2_10_70_1","DOI":"10.1164\/ajrccm.154.6.8970383"},{"doi-asserted-by":"publisher","key":"e_1_2_10_71_1","DOI":"10.1152\/ajplung.1991.261.6.L361"},{"volume-title":"The Online Metabolic and Molecular Bases of Inherited Disease","year":"2019","author":"Welsh M. J.","key":"e_1_2_10_72_1"},{"doi-asserted-by":"publisher","key":"e_1_2_10_73_1","DOI":"10.1042\/bj3340685"},{"doi-asserted-by":"publisher","key":"e_1_2_10_74_1","DOI":"10.1046\/j.1469-7580.2002.00098.x"},{"issue":"488","key":"e_1_2_10_75_1","first-page":"e5","article-title":"Acidic submucosal gland pH and elevated protein concentration produce abnormal cystic fibrosis mucus","volume":"54","author":"Xie Y.","year":"2020","journal-title":"Developmental Cell"},{"doi-asserted-by":"publisher","key":"e_1_2_10_76_1","DOI":"10.1016\/S1569-1993(11)60021-0"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15340","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.14814\/phy2.15340","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15340","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T09:45:51Z","timestamp":1703583951000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.15340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":75,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.14814\/phy2.15340"],"URL":"https:\/\/doi.org\/10.14814\/phy2.15340","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"type":"print","value":"2051-817X"},{"type":"electronic","value":"2051-817X"}],"subject":[],"published":{"date-parts":[[2022,9]]},"assertion":[{"value":"2022-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15340"}}