{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:24:34Z","timestamp":1792805074522,"version":"4.5.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Although airway abnormalities are common in patients with cystic fibrosis (CF), it is unknown whether they are all secondary to postnatal infection and inflammation, which characterize the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To learn whether loss of the cystic fibrosis transmembrane conductance regulator (CFTR) might affect major airways early in life, before the onset of inflammation and infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied newborn CFTR\u2212\/\u2212 pig trachea, using computed tomography (CT) scans, pathology, and morphometry. We retrospectively analyzed trachea CT scans in young children with CF and also previously published data of infants with CF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>We discovered three abnormalities in the porcine CF trachea. First, the trachea and mainstem bronchi had a uniformly small caliber and cross-sections of trachea were less circular than in controls. Second, trachealis smooth muscle had an altered bundle orientation and increased transcripts in a smooth muscle gene set. Third, submucosal gland units occurred with similar frequency in the mucosa of CF and control airways, but CF submucosal glands were hypoplastic and had global reductions in tissue-specific transcripts. To learn whether any of these changes occurred in young patients with CF, we examined CT scans from children 2 years of age and younger, and found that CF tracheas were less circular in cross-section, but lacked differences in lumen area. However, analysis of previously published morphometric data showed reduced tracheal lumen area in neonates with CF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings in newborn CF pigs and young patients with CF suggest that airway changes begin during fetal life and may contribute to CF pathogenesis and clinical disease during postnatal life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201004-0643oc","type":"journal-article","created":{"date-parts":[[2010,7,11]],"date-time":"2010-07-11T16:54:02Z","timestamp":1278867242000},"page":"1251-1261","source":"Crossref","is-referenced-by-count":183,"title":["Loss of Cystic Fibrosis Transmembrane Conductance Regulator Function Produces Abnormalities in Tracheal Development in Neonatal Pigs and Young Children"],"prefix":"10.1093","volume":"182","author":[{"given":"David K.","family":"Meyerholz","sequence":"first","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Stoltz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Namati","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa"},{"name":"Wellman Center for Photomedicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro A.","family":"Pezzulo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V.","family":"Rector","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Suter","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Radiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"McLennan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa"},{"name":"Department of Radiology"},{"name":"Department of Biomedical Engineering"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo J.","family":"Tearney","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Zabner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Paul B.","family":"McCray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Welsh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa"},{"name":"Department of Molecular Physiology and Biophysics, and"},{"name":"Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,11,15]]},"reference":[{"key":"2026032504261918700_BIB1","first-page":"1066","volume-title":"Science","year":"1989"},{"key":"2026032504261918700_BIB2","year":"2001"},{"key":"2026032504261918700_BIB3","first-page":"1992","volume-title":"N Engl J Med","year":"2005"},{"key":"2026032504261918700_BIB4","first-page":"1891","volume-title":"Lancet","year":"2009"},{"key":"2026032504261918700_BIB5","first-page":"1133","volume-title":"Am J Respir Crit Care Med","year":"2005"},{"key":"2026032504261918700_BIB6","first-page":"1350","volume-title":"Am J Respir Crit Care Med","year":"2002"},{"key":"2026032504261918700_BIB7","first-page":"107","volume-title":"Pediatr Pulmonol","year":"2010"},{"key":"2026032504261918700_BIB8","first-page":"1078","volume-title":"Chest","year":"2000"},{"key":"2026032504261918700_BIB9","first-page":"271","volume-title":"Respir Physiol Neurobiol","year":"2007"},{"key":"2026032504261918700_BIB10","first-page":"1018","volume-title":"Am J Respir Crit Care Med","year":"2006"},{"key":"2026032504261918700_BIB11","first-page":"7392","volume-title":"J Biol Chem","year":"2006"},{"key":"2026032504261918700_BIB12","first-page":"240","volume-title":"Eur J Pediatr","year":"1982"},{"key":"2026032504261918700_BIB13","first-page":"36","volume-title":"Hum Pathol","year":"1981"},{"key":"2026032504261918700_BIB14","first-page":"195","volume-title":"Hum Pathol","year":"1976"},{"key":"2026032504261918700_BIB15","first-page":"303","volume-title":"Am J Pathol","year":"1982"},{"key":"2026032504261918700_BIB16","first-page":"53","volume-title":"Pediatrics","year":"1949"},{"key":"2026032504261918700_BIB17","first-page":"1837","volume-title":"Science","year":"2008"},{"key":"2026032504261918700_BIB18","first-page":"1377","volume-title":"Am J Pathol","year":"2010"},{"key":"2026032504261918700_BIB19","first-page":"29ra31","volume-title":"Sci Transl Med","year":"2010"},{"key":"2026032504261918700_BIB20","first-page":"141","volume-title":"Dev Biol","year":"2008"},{"key":"2026032504261918700_BIB21","first-page":"361","volume-title":"J Anat","year":"2000"},{"key":"2026032504261918700_BIB22","first-page":"1429","volume-title":"Nat Med","year":"2006"},{"key":"2026032504261918700_BIB23","first-page":"745","volume-title":"Gastrointest Endosc","year":"2008"},{"key":"2026032504261918700_BIB24","first-page":"2953","volume-title":"Opt Express","year":"2003"},{"key":"2026032504261918700_BIB25","first-page":"267","volume-title":"Nat Genet","year":"2003"},{"key":"2026032504261918700_BIB26","first-page":"15545","volume-title":"Proc Natl Acad Sci USA","year":"2005"},{"key":"2026032504261918700_BIB27","first-page":"189","volume-title":"Am J Respir Cell Mol Biol","year":"2009"},{"key":"2026032504261918700_BIB28","year":"2010"},{"key":"2026032504261918700_BIB29","first-page":"154","volume-title":"J Pediatr","year":"2004"},{"key":"2026032504261918700_BIB30","first-page":"153","volume-title":"Thorax","year":"2007"},{"key":"2026032504261918700_BIB31","first-page":"81","volume-title":"Respir Med","year":"2002"},{"key":"2026032504261918700_BIB32","first-page":"1134","volume-title":"Respir Care","year":"2007"},{"key":"2026032504261918700_BIB33","first-page":"325","volume-title":"Vet Pathol","year":"2009"},{"key":"2026032504261918700_BIB34","year":"1985"},{"key":"2026032504261918700_BIB35","first-page":"865","volume-title":"Histol Histopathol","year":"2005"},{"key":"2026032504261918700_BIB36","first-page":"3231","volume-title":"J Physiol","year":"2008"},{"key":"2026032504261918700_BIB37","first-page":"577","volume-title":"Radiology","year":"2009"},{"key":"2026032504261918700_BIB38","first-page":"86","volume-title":"J Anat","year":"2008"},{"key":"2026032504261918700_BIB39","first-page":"50710","volume-title":"J Biol Chem","year":"2002"},{"key":"2026032504261918700_BIB40","first-page":"431","volume-title":"FASEB J","year":"2005"},{"key":"2026032504261918700_BIB41","first-page":"113","volume-title":"Respir Res","year":"2006"},{"key":"2026032504261918700_BIB42","first-page":"573","volume-title":"Am J Respir Cell Mol Biol","year":"1993"},{"key":"2026032504261918700_BIB43","first-page":"e4283","volume-title":"PLoS ONE","year":"2009"},{"key":"2026032504261918700_BIB44","first-page":"217","volume-title":"Am J Respir Cell Mol Biol","year":"2009"},{"key":"2026032504261918700_BIB45","first-page":"226","volume-title":"Thorax","year":"2005"},{"key":"2026032504261918700_BIB46","first-page":"837","volume-title":"Am J Respir Crit Care Med","year":"2008"},{"key":"2026032504261918700_BIB47","first-page":"320","volume-title":"Am J Respir Cell Mol Biol","year":"2006"},{"key":"2026032504261918700_BIB48","first-page":"590","volume-title":"Science","year":"2008"},{"key":"2026032504261918700_BIB49","first-page":"1019","volume-title":"Cell","year":"2008"},{"key":"2026032504261918700_BIB50","first-page":"1210","volume-title":"Nature","year":"2008"},{"key":"2026032504261918700_BIB51","first-page":"161","volume-title":"Exp Lung Res","year":"1997"},{"key":"2026032504261918700_BIB52","first-page":"167","volume-title":"Anat Embryol (Berl)","year":"1986"},{"key":"2026032504261918700_BIB53","year":"1953"},{"key":"2026032504261918700_BIB54","first-page":"218","volume-title":"Acta Anat (Basel)","year":"1976"},{"key":"2026032504261918700_BIB55","first-page":"388","volume-title":"Br J Exp Pathol","year":"1973"},{"key":"2026032504261918700_BIB56","first-page":"L15","volume-title":"Am J Physiol","year":"1991"},{"key":"2026032504261918700_BIB57","first-page":"1710","volume-title":"Chest","year":"2007"},{"key":"2026032504261918700_BIB58","first-page":"209","volume-title":"Respir Med","year":"1995"},{"key":"2026032504261918700_BIB59","first-page":"77","volume-title":"Clin Rev Allergy Immunol","year":"2002"},{"key":"2026032504261918700_BIB60","first-page":"509","volume-title":"Annu Rev Physiol","year":"2009"},{"key":"2026032504261918700_BIB61","first-page":"132","volume-title":"Thorax","year":"1960"},{"key":"2026032504261918700_BIB62","first-page":"L694","volume-title":"Am J Physiol","year":"1999"},{"key":"2026032504261918700_BIB63","first-page":"47","volume-title":"Proc Am Thorac Soc","year":"2004"},{"key":"2026032504261918700_BIB64","first-page":"293","volume-title":"Pediatr Pulmonol","year":"2002"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/182\/10\/1251\/67505325\/ajrccm_182_10_1251.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/182\/10\/1251\/67505325\/ajrccm_182_10_1251.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T08:27:28Z","timestamp":1774427248000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/182\/10\/1251\/8515253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11]]},"references-count":64,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2010,11,15]]},"published-print":{"date-parts":[[2010,11,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201004-0643oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,11]]},"published":{"date-parts":[[2010,11]]}}}