{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:51:08Z","timestamp":1790481068330,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"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":[[2013,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Several extrapulmonary disorders have been linked to cigarette smoking. Smoking is reported to cause cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the airway, and is also associated with pancreatitis, male infertility, and cachexia, features characteristic of cystic fibrosis and suggestive of an etiological role for CFTR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To study the effect of cigarette smoke on extrapulmonary CFTR function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Demographics, spirometry, exercise tolerance, symptom questionnaires, CFTR genetics, and sweat chloride analysis were obtained in smokers with and without chronic obstructive pulmonary disease (COPD). CFTR activity was measured by nasal potential difference in mice and by Ussing chamber electrophysiology in vitro. Serum acrolein levels were estimated with mass spectroscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Healthy smokers (29.45 \u00b1 13.90 mEq), smokers with COPD (31.89 \u00b1 13.9 mEq), and former smokers with COPD (25.07 \u00b1 10.92 mEq) had elevated sweat chloride levels compared with normal control subjects (14.5 \u00b1 7.77 mEq), indicating reduced CFTR activity in a nonrespiratory organ. Intestinal current measurements also demonstrated a 65% decrease in CFTR function in smokers compared with never smokers. CFTR activity was decreased by 68% in normal human bronchial epithelial cells exposed to plasma from smokers, suggesting that one or more circulating agents could confer CFTR dysfunction. Cigarette smoke\u2013exposed mice had decreased CFTR activity in intestinal epithelium (84.3 and 45%, after 5 and 17 wk, respectively). Acrolein, a component of cigarette smoke, was higher in smokers, blocked CFTR by inhibiting channel gating, and was attenuated by antioxidant N-acetylcysteine, a known scavenger of acrolein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Smoking causes systemic CFTR dysfunction. Acrolein present in cigarette smoke mediates CFTR defects in extrapulmonary tissues in smokers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201304-0733oc","type":"journal-article","created":{"date-parts":[[2013,9,16]],"date-time":"2013-09-16T17:46:29Z","timestamp":1379353589000},"page":"1321-1330","source":"Crossref","is-referenced-by-count":183,"title":["Cigarette Smoke Induces Systemic Defects in Cystic Fibrosis Transmembrane Conductance Regulator Function"],"prefix":"10.1093","volume":"188","author":[{"given":"S. Vamsee","family":"Raju","sequence":"first","affiliation":[{"name":"Department of Medicine"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia L.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center"},{"name":"UAB Lung Health Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford A.","family":"Courville","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmel M.","family":"McNicholas","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental, and Integrative Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Sloane","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Sabbatini","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry","family":"Tidwell","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Ping","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center"},{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Fortenberry","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb W.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A.","family":"Boydston","sequence":"additional","affiliation":[{"name":"Southern Research Institute, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Clancy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry E.","family":"Bowen","sequence":"additional","affiliation":[{"name":"Southern Research Institute, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.","family":"Accurso","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Edwin","family":"Blalock","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center"},{"name":"UAB Lung Health Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Dransfield","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center"},{"name":"UAB Lung Health Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center"},{"name":"UAB Lung Health Center"},{"name":"Department of Cell, Developmental, and Integrative Biology"},{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,1]]},"reference":[{"key":"2026032100412904800_bib1","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1056\/NEJMra043184","article-title":"Cystic fibrosis","volume":"352","author":"Rowe","year":"2005","journal-title":"N Engl J Med"},{"key":"2026032100412904800_bib2","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1164\/rccm.200909-1434OC","article-title":"Cystic fibrosis transmembrane conductance regulator channel dysfunction in non-cystic fibrosis bronchiectasis","volume":"181","author":"Bienvenu","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100412904800_bib3","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1056\/NEJM199809033391001","article-title":"Mutations of the cystic fibrosis gene in patients with chronic pancreatitis","volume":"339","author":"Sharer","year":"1998","journal-title":"N Engl J Med"},{"key":"2026032100412904800_bib4","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1056\/NEJM199506013322204","article-title":"Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens","volume":"332","author":"Chillon","year":"1995","journal-title":"N Engl J Med"},{"key":"2026032100412904800_bib5","article-title":"Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis","author":"Cote","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2026032100412904800_bib6","first-page":"119","article-title":"Effect of cigarette smoking on semen quality of infertile men","volume":"48","author":"Gaur","year":"2007","journal-title":"Singapore Med J"},{"key":"2026032100412904800_bib7","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/01.mcp.0000208449.73101.ac","article-title":"Chronic obstructive pulmonary disease: effects beyond the lungs","volume":"12","author":"Balasubramanian","year":"2006","journal-title":"Curr Opin Pulm Med"},{"key":"2026032100412904800_bib8","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1093\/ije\/30.3.540","article-title":"Cigarette smoking and diabetes mellitus: evidence of a positive association from a large prospective cohort study","volume":"30","author":"Will","year":"2001","journal-title":"Int J Epidemiol"},{"key":"2026032100412904800_bib9","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1164\/rccm.200508-1330OC","article-title":"Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers","volume":"173","author":"Cantin","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100412904800_bib10","doi-asserted-by":"crossref","first-page":"L894","DOI":"10.1152\/ajplung.00376.2004","article-title":"Inhibition of chloride secretion in human bronchial epithelial cells by cigarette smoke extract","volume":"288","author":"Kreindler","year":"2005","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026032100412904800_bib11","doi-asserted-by":"crossref","first-page":"e39809","DOI":"10.1371\/journal.pone.0039809","article-title":"A pharmacologic approach to acquired cystic fibrosis transmembrane conductance regulator dysfunction in smoking related lung disease","volume":"7","author":"Sloane","year":"2012","journal-title":"PLoS ONE"},{"key":"2026032100412904800_bib12","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1056\/NEJMoa0909825","article-title":"Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation","volume":"363","author":"Accurso","year":"2010","journal-title":"N Engl J Med"},{"key":"2026032100412904800_bib13","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s00109-011-0787-6","article-title":"Suppression of CFTR premature termination codons and rescue of CFTR protein and function by the synthetic aminoglycoside NB54","volume":"89","author":"Rowe","year":"2011","journal-title":"J Mol Med (Berl)"},{"key":"2026032100412904800_bib14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/978-1-61779-117-8_7","article-title":"Measurement of ion transport function in rectal biopsies","volume":"741","author":"Hug","year":"2011","journal-title":"Methods Mol Biol"},{"key":"2026032100412904800_bib15","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00109-006-0045-5","article-title":"Clinical doses of amikacin provide more effective suppression of the human CFTR-G542X stop mutation than gentamicin in a transgenic CF mouse model","volume":"84","author":"Du","year":"2006","journal-title":"J Mol Med (Berl)"},{"key":"2026032100412904800_bib16","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1164\/rccm.200501-155OC","article-title":"Reactive species mediate inhibition of alveolar type II sodium transport during mycoplasma infection","volume":"173","author":"Hickman-Davis","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100412904800_bib17","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/rcm.960","article-title":"Determination of patterns of biologically relevant aldehydes in exhaled breath condensate of healthy subjects by liquid chromatography\/atmospheric chemical ionization tandem mass spectrometry","volume":"17","author":"Andreoli","year":"2003","journal-title":"Rapid Commun Mass Spectrom"},{"key":"2026032100412904800_bib18","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1056\/NEJMoa1105185","article-title":"A CFTR potentiator in patients with cystic fibrosis and the G551D mutation","volume":"365","author":"Ramsey","year":"2011","journal-title":"N Engl J Med"},{"key":"2026032100412904800_bib19","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1399-0004.2011.01804.x","article-title":"Cystic fibrosis mutations for p.F508del compound heterozygotes predict sweat chloride levels and pancreatic sufficiency","volume":"82","author":"Sebro","year":"2011","journal-title":"Clin Genet"},{"key":"2026032100412904800_bib20","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1542\/peds.97.4.524","article-title":"Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis","volume":"97","author":"Farrell","year":"1996","journal-title":"Pediatrics"},{"key":"2026032100412904800_bib21","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/nm.2409","article-title":"Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography","volume":"17","author":"Liu","year":"2011","journal-title":"Nat Med"},{"key":"2026032100412904800_bib22","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1164\/rccm.200509-1377OC","article-title":"Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials","volume":"174","author":"Wilschanski","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100412904800_bib23","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/15287398509530647","article-title":"Comparative deposition of inhaled aerosols in experimental animals and humans: a review","volume":"15","author":"Schlesinger","year":"1985","journal-title":"J Toxicol Environ Health"},{"key":"2026032100412904800_bib24","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1165\/rcmb.2009-0453OC","article-title":"Do airway epithelium air-liquid cultures represent the in vivo airway epithelium transcriptome?","volume":"44","author":"Dvorak","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026032100412904800_bib25","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1167\/iovs.06-0248","article-title":"Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid","volume":"48","author":"Jia","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2026032100412904800_bib26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/mnfr.200700412","article-title":"Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease","volume":"52","author":"Stevens","year":"2008","journal-title":"Mol Nutr Food Res"},{"key":"2026032100412904800_bib27","doi-asserted-by":"crossref","first-page":"401","DOI":"10.2165\/00044011-200525060-00005","article-title":"High-dose N-acetylcysteine in patients with exacerbations of chronic obstructive pulmonary disease","volume":"25","author":"Zuin","year":"2005","journal-title":"Clin Drug Investig"},{"key":"2026032100412904800_bib28","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/S0140-6736(05)66456-2","article-title":"Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial","volume":"365","author":"Decramer","year":"2005","journal-title":"Lancet"},{"key":"2026032100412904800_bib29","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1378\/chest.12-2357","article-title":"High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study","volume":"144","author":"Tse","year":"2013","journal-title":"Chest"},{"key":"2026032100412904800_bib30","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1513\/pats.201001-014AW","article-title":"Cellular response to cigarette smoke and oxidants: adapting to survive","volume":"7","author":"Cantin","year":"2010","journal-title":"Proc Am Thorac Soc"},{"key":"2026032100412904800_bib31","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1096\/fj.11-192377","article-title":"Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration","volume":"26","author":"Clunes","year":"2012","journal-title":"FASEB J"},{"key":"2026032100412904800_bib32","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1378\/chest.13-0274","article-title":"Acquired CFTR dysfunction in the lower airways in COPD","volume":"144","author":"Dransfield","year":"2013","journal-title":"Chest"},{"key":"2026032100412904800_bib33","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1056\/NEJMoa021322","article-title":"The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease","volume":"350","author":"Celli","year":"2004","journal-title":"N Engl J Med"},{"key":"2026032100412904800_bib34","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1053\/j.gastro.2010.09.046","article-title":"Type of CFTR mutation determines risk of pancreatitis in patients with cystic fibrosis","volume":"140","author":"Ooi","year":"2011","journal-title":"Gastroenterology"},{"key":"2026032100412904800_bib35","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1056\/NEJM199809033391002","article-title":"Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis","volume":"339","author":"Cohn","year":"1998","journal-title":"N Engl J Med"},{"key":"2026032100412904800_bib36","doi-asserted-by":"crossref","first-page":"e32112","DOI":"10.1371\/journal.pone.0032112","article-title":"Suppression of adenosine-activated chloride transport by ethanol in airway epithelia","volume":"7","author":"Raju","year":"2012","journal-title":"PLoS ONE"},{"key":"2026032100412904800_bib37","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/lary.23278","article-title":"Cystic fibrosis transmembrane conductance regulator modulation by the tobacco smoke toxin acrolein","volume":"122","author":"Alexander","year":"2012","journal-title":"Laryngoscope"},{"key":"2026032100412904800_bib38","doi-asserted-by":"crossref","first-page":"e38038","DOI":"10.1371\/journal.pone.0038038","article-title":"Acrolein induces endoplasmic reticulum stress and causes airspace enlargement","volume":"7","author":"Kitaguchi","year":"2012","journal-title":"PLoS ONE"},{"key":"2026032100412904800_bib39","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1126\/science.1704151","article-title":"Generation of cAMP-activated chloride currents by expression of CFTR","volume":"251","author":"Anderson","year":"1991","journal-title":"Science"},{"key":"2026032100412904800_bib40","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1124\/jpet.106.114678","article-title":"Inhibition of acrolein-induced apoptosis by the antioxidant N-acetylcysteine","volume":"321","author":"Tanel","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"2026032100412904800_bib41","doi-asserted-by":"crossref","first-page":"C262","DOI":"10.1152\/ajpcell.00070.2005","article-title":"Oxidant stress suppresses CFTR expression","volume":"290","author":"Cantin","year":"2006","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026032100412904800_bib42","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/toxsci\/kfq101","article-title":"Cadmium regulates the expression of the CFTR chloride channel in human airway epithelial cells","volume":"116","author":"Rennolds","year":"2010","journal-title":"Toxicol Sci"},{"key":"2026032100412904800_bib43","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1165\/rcmb.2007-0452OC","article-title":"Role of oxygen availability in CFTR expression and function","volume":"39","author":"Guimbellot","year":"2008","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026032100412904800_bib44","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/B978-0-12-385928-0.00001-8","article-title":"CFTR expression regulation by the unfolded protein response","volume":"491","author":"Bartoszewski","year":"2011","journal-title":"Methods Enzymol"},{"key":"2026032100412904800_bib45","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1513\/pats.200709-148ET","article-title":"Comorbidities in chronic obstructive pulmonary disease","volume":"5","author":"Chatila","year":"2008","journal-title":"Proc Am Thorac Soc"},{"key":"2026032100412904800_bib46","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1054\/clnu.1999.0079","article-title":"Pathogenesis of malnutrition in cystic fibrosis, and its treatment","volume":"19","author":"Pencharz","year":"2000","journal-title":"Clin Nutr"},{"key":"2026032100412904800_bib47","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0140-6736(95)91431-5","article-title":"Male fertility in cystic fibrosis","volume":"346","author":"Dodge","year":"1995","journal-title":"Lancet"},{"key":"2026032100412904800_bib48","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1378\/chest.10-1252","article-title":"Systemic manifestations of COPD","volume":"139","author":"Nussbaumer-Ochsner","year":"2011","journal-title":"Chest"},{"key":"2026032100412904800_bib49","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1161\/01.CIR.0000056767.69054.B3","article-title":"Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease","volume":"107","author":"Sin","year":"2003","journal-title":"Circulation"},{"key":"2026032100412904800_bib50","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1183\/09031936.00152005","article-title":"Upregulation of pro-inflammatory cytokines in the intercostal muscles of COPD patients","volume":"30","author":"Casadevall","year":"2007","journal-title":"Eur Respir J"},{"key":"2026032100412904800_bib51","doi-asserted-by":"crossref","first-page":"429","DOI":"10.2147\/COPD.S2066","article-title":"Modeling the impact of COPD on the brain","volume":"3","author":"Borson","year":"2008","journal-title":"Int J Chron Obstruct Pulmon Dis"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/188\/11\/1321\/67235609\/ajrccm_188_11_1321.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/188\/11\/1321\/67235609\/ajrccm_188_11_1321.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:43:24Z","timestamp":1774068204000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/188\/11\/1321\/8506289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,1]]},"references-count":51,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2013,12,1]]},"published-print":{"date-parts":[[2013,12,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201304-0733oc","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718113095.793506138","asserted-by":"object"}]},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,12]]},"published":{"date-parts":[[2013,12,1]]}}}