{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:42:40Z","timestamp":1792669360761,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"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":[[2014,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Patients with congenital heart disease with heterotaxy exhibit a high prevalence of abnormal airway ciliary motion and low nasal nitric oxide, characteristics associated with primary ciliary dyskinesia, a reflection of the role of motile cilia in airway clearance and left\u2013right patterning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the potential broader clinical significance of airway ciliary dysfunction in congenital heart disease, we assessed the prevalence of ciliary dysfunction versus respiratory symptoms in patients with congenital heart disease with or without heterotaxy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with a broad spectrum of congenital heart disease were recruited (n\u2009=\u2009218), 39 with heterotaxy. Nasal nitric oxide measurements and nasal biopsies for ciliary motion video microscopy were conducted. Sinopulmonary symptoms were reviewed by questionnaire.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A high prevalence of ciliary motion defects (51.8%) and low or borderline low nasal nitric oxide levels (35.5%) were observed in patients with congenital heart disease with or without heterotaxy. Patients with ciliary motion defects or low nasal nitric oxide showed increased sinopulmonary symptoms, with most respiratory symptoms seen in those with both abnormal ciliary motion and low nitric oxide. Multivariate analysis showed that abnormal ciliary motion and low nasal nitric oxide were more important in determining risk of sinopulmonary symptoms than heterotaxy status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with congenital heart disease without heterotaxy exhibit a high prevalence of abnormal ciliary motion and low nasal nitric oxide. This was associated with more sinopulmonary symptoms. These findings suggest that patients with a broad spectrum of congenital heart disease and respiratory symptoms may benefit from screening for ciliary dysfunction and implementation of medical interventions to reduce sinopulmonary morbidities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.201405-222oc","type":"journal-article","created":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T16:29:26Z","timestamp":1412958566000},"page":"1426-1432","source":"Crossref","is-referenced-by-count":43,"title":["Airway Ciliary Dysfunction and Sinopulmonary Symptoms in Patients with Congenital Heart Disease"],"prefix":"10.1093","volume":"11","author":[{"given":"Andrea S.","family":"Garrod","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of the University of Pittsburgh Medical Center (UPMC), and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maliha","family":"Zahid","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tian","sequence":"additional","affiliation":[{"name":"Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Francis","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Khalifa","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Devine","sequence":"additional","affiliation":[{"name":"Department of Pathology, Children\u2019s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George C.","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Leatherbury","sequence":"additional","affiliation":[{"name":"Children\u2019s National Medical Center, Washington, D.C"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia W.","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,11,1]]},"reference":[{"key":"2026012303492330400_bib1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1164\/rccm.201301-0059CI","article-title":"Primary ciliary dyskinesia: recent advances in diagnostics, genetics, and characterization of clinical disease","volume":"188","author":"Knowles","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303492330400_bib2","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1513\/pats.201103-024SD","article-title":"Update of respiratory tract disease in children with primary ciliary dyskinesia","volume":"8","author":"Sagel","year":"2011","journal-title":"Proc Am Thorac Soc"},{"key":"2026012303492330400_bib3","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/ajmg.1219","article-title":"Clinical aspects of defects in the determination of laterality","volume":"101","author":"Aylsworth","year":"2001","journal-title":"Am J Med Genet"},{"key":"2026012303492330400_bib4","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1378\/chest.13-1704","article-title":"Genetic Disorders of Mucociliary Clearance Consortium. Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: insights into situs ambiguus and heterotaxy","volume":"146","author":"Shapiro","year":"2014","journal-title":"Chest"},{"key":"2026012303492330400_bib5","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1161\/CIRCULATIONAHA.106.649038","article-title":"Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia","volume":"115","author":"Kennedy","year":"2007","journal-title":"Circulation"},{"key":"2026012303492330400_bib6","first-page":"3742","article-title":"Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia","volume":"117","author":"Tan","year":"2007","journal-title":"J Clin Invest"},{"key":"2026012303492330400_bib7","doi-asserted-by":"crossref","first-page":"H2102","DOI":"10.1152\/ajpheart.01118.2011","article-title":"Congenital heart disease and the specification of left\u2013right asymmetry","volume":"302","author":"Francis","year":"2012","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026012303492330400_bib8","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1016\/j.jacc.2006.07.053","article-title":"Early and late results of the modified Fontan operation for heterotaxy syndrome: 30 years of experience in 142 patients","volume":"48","author":"Bartz","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"2026012303492330400_bib9","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.jtcvs.2010.07.082","article-title":"Increased postoperative and respiratory complications in patients with congenital heart disease associated with heterotaxy","volume":"141","author":"Swisher","year":"2011","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2026012303492330400_bib10","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1164\/rccm.200406-710ST","article-title":"ATS\/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005","volume":"171","author":"American Thoracic Society","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303492330400_bib11","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1513\/AnnalsATS.201305-110OC","article-title":"Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia","volume":"10","author":"Leigh","year":"2013","journal-title":"Ann Am Thorac Soc"},{"key":"2026012303492330400_bib12","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jpeds.2011.03.007","article-title":"Diagnostic value of nasal nitric oxide measured with non-velum closure techniques for children with primary ciliary dyskinesia","volume":"159","author":"Mateos-Corral","year":"2011","journal-title":"J Pediatr"},{"key":"2026012303492330400_bib13","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/ppul.21402","article-title":"Genetic Disorders of Mucociliary Clearance Consortium. Diagnostic yield of nasal scrape biopsies in primary ciliary dyskinesia: a multicenter experience","volume":"46","author":"Olin","year":"2011","journal-title":"Pediatr Pulmonol"},{"key":"2026012303492330400_bib14","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S0091-6749(03)01799-8","article-title":"Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia","volume":"112","author":"Chilvers","year":"2003","journal-title":"J Allergy Clin Immunol"},{"key":"2026012303492330400_bib15","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1513\/pats.201103-028SD","article-title":"The challenges of diagnosing primary ciliary dyskinesia","volume":"8","author":"Leigh","year":"2011","journal-title":"Proc Am Thorac Soc"},{"key":"2026012303492330400_bib16","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1164\/rccm.200903-0459OC","article-title":"Diagnostic testing of patients suspected of primary ciliary dyskinesia","volume":"181","author":"Stannard","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303492330400_bib17","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1161\/CIRCULATIONAHA.111.079780","article-title":"High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy","volume":"125","author":"Nakhleh","year":"2012","journal-title":"Circulation"},{"key":"2026012303492330400_bib18","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.jtcvs.2013.06.018","article-title":"Increased postoperative respiratory complications in heterotaxy congenital heart disease patients with respiratory ciliary dysfunction","volume":"147","author":"Harden","year":"2014","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2026012303492330400_bib19","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/GIM.0b013e3181a53562","article-title":"Clinical and genetic aspects of primary ciliary dyskinesia\/Kartagener syndrome","volume":"11","author":"Leigh","year":"2009","journal-title":"Genet Med"},{"key":"2026012303492330400_bib20","first-page":"A2087","article-title":"Airway ciliary dysfunction and increased sinopulmonary symptoms in congenital heart disease patients with and without heterotaxy [abstract]","volume":"187","author":"Garrod","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303492330400_bib21","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1097\/MOP.0b013e328329cddb","article-title":"Primary ciliary dyskinesia: improving the diagnostic approach","volume":"21","author":"Leigh","year":"2009","journal-title":"Curr Opin Pediatr"},{"key":"2026012303492330400_bib22","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1164\/rccm.200303-365OC","article-title":"Primary ciliary dyskinesia: diagnostic and phenotypic features","volume":"169","author":"Noone","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303492330400_bib23","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/1750-1172-7-78","article-title":"Quantitative analysis of ciliary beating in primary ciliary dyskinesia: a pilot study","volume":"7","author":"Papon","year":"2012","journal-title":"Orphanet J Rare Dis"},{"key":"2026012303492330400_bib24","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1183\/09031936.00153308","article-title":"Disrupted ciliated epithelium shows slower ciliary beat frequency and increased dyskinesia","volume":"34","author":"Thomas","year":"2009","journal-title":"Eur Respir J"},{"key":"2026012303492330400_bib25","first-page":"58","article-title":"Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and may be modulated by nasal glucocorticoids","volume":"99","author":"Kharitonov","year":"1997","journal-title":"J Allergy Clin Immunol"},{"key":"2026012303492330400_bib26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/humu.20656","article-title":"Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations","volume":"29","author":"Schwabe","year":"2008","journal-title":"Hum Mutat"},{"key":"2026012303492330400_bib27","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1378\/chest.124.2.633","article-title":"Nitric oxide metabolites are not reduced in exhaled breath condensate of patients with primary ciliary dyskinesia","volume":"124","author":"Csoma","year":"2003","journal-title":"Chest"},{"key":"2026012303492330400_bib28","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.rmed.2012.11.021","article-title":"Upper and lower airway nitric oxide levels in primary ciliary dyskinesia, cystic fibrosis and asthma","volume":"107","author":"Walker","year":"2013","journal-title":"Respir Med"},{"key":"2026012303492330400_bib29","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1183\/09031936.99.13614069","article-title":"Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia","volume":"13","author":"Karadag","year":"1999","journal-title":"Eur Respir J"},{"key":"2026012303492330400_bib30","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1183\/09031936.00032610","article-title":"Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia","volume":"37","author":"Marthin","year":"2011","journal-title":"Eur Respir J"},{"key":"2026012303492330400_bib31","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1136\/thorax.57.7.586","article-title":"Nitric oxide in chronic airway inflammation in children: diagnostic use and pathophysiological significance","volume":"57","author":"Narang","year":"2002","journal-title":"Thorax"},{"key":"2026012303492330400_bib32","doi-asserted-by":"crossref","first-page":"e89675","DOI":"10.1371\/journal.pone.0089675","article-title":"Culture of primary ciliary dyskinesia epithelial cells at air\u2013liquid interface can alter ciliary phenotype but remains a robust and informative diagnostic aid","volume":"9","author":"Hirst","year":"2014","journal-title":"PLoS One"},{"key":"2026012303492330400_bib33","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1378\/chest.10-0175","article-title":"Ciliated air\u2013liquid cultures as an aid to diagnostic testing of primary ciliary dyskinesia","volume":"138","author":"Hirst","year":"2010","journal-title":"Chest"},{"key":"2026012303492330400_bib34","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/000164800750001116","article-title":"Ciliary function analysis for the diagnosis of primary ciliary dyskinesia: advantages of ciliogenesis in culture","volume":"120","author":"Jorissen","year":"2000","journal-title":"Acta Otolaryngol"},{"key":"2026012303492330400_bib35","first-page":"333","article-title":"Secondary ciliary dyskinesia is absent after ciliogenesis in culture","volume":"54","author":"Jorissen","year":"2000","journal-title":"Acta Otorhinolaryngol Belg"},{"key":"2026012303492330400_bib36","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1750-1172-9-11","article-title":"Primary ciliary dyskinesia: critical evaluation of clinical symptoms and diagnosis in patients with normal and abnormal ultrastructure","volume":"9","author":"Boon","year":"2014","journal-title":"Orphanet J Rare Dis"},{"key":"2026012303492330400_bib37","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1183\/09031936.00046209","article-title":"A 20-year experience of electron microscopy in the diagnosis of primary ciliary dyskinesia","volume":"35","author":"Papon","year":"2010","journal-title":"Eur Respir J"}],"container-title":["Annals of the American Thoracic Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/11\/9\/1426\/66551673\/annalsats_11_9_1426.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/11\/9\/1426\/66551673\/annalsats_11_9_1426.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:49:33Z","timestamp":1769158173000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/annalsats\/article\/11\/9\/1426\/8431811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,1]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2014,11,1]]},"published-print":{"date-parts":[[2014,11,1]]}},"URL":"https:\/\/doi.org\/10.1513\/annalsats.201405-222oc","relation":{},"ISSN":["2329-6933","2325-6621"],"issn-type":[{"value":"2329-6933","type":"print"},{"value":"2325-6621","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,11]]},"published":{"date-parts":[[2014,11,1]]}}}