{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:11:38Z","timestamp":1790629898387,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"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":[[2011,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary ciliary dyskinesia (PCD) is a rare genetic disorder of ciliary structure and function. The diagnosis can be challenging, particularly when using nongenetic assays. The \u201cgold standard\u201d diagnostic test is ultrastructural analysis of respiratory cilia obtained by nasal scrape or brush biopsy. A few specialized centers use high-speed videomicroscopy to examine ciliary beat. Certain beat patterns correlate with ultrastructural defects, and, in some cases, subtle alterations in beat pattern can be seen when ultrastructure is normal. Recent studies have shown that nasal nitric oxide (NO) is very low in patients with PCD compared with healthy control subjects; therefore, this assay may be a useful screening or adjunctive test for PCD. Because acute respiratory illnesses may yield alterations in ciliary ultrastructure, ciliary beat, and nasal NO values, these tests should be performed during a stable baseline period. Identification of an array of PCD genes has provided the opportunity for making a definitive genetic diagnosis for PCD in some cases. All of these approaches have a role in diagnosing PCD. For example, PCD has been confirmed by identifying disease-causing mutations in a heavy dynein chain gene in individuals with normal ciliary ultrastructure but subtle defects in ciliary beat and low nasal NO. Priorities to improve nongenetic diagnostic capability include standardization of nasal NO as a screening test and the development of specialized centers using uniform approaches for the analysis of ciliary ultrastructure and ciliary beat pattern. Another chapter in this issue (see Zariwala and colleagues, pp. 430) addresses the progress toward improved capabilities for definitive genetic testing<\/jats:p>","DOI":"10.1513\/pats.201103-028sd","type":"journal-article","created":{"date-parts":[[2011,9,16]],"date-time":"2011-09-16T20:11:10Z","timestamp":1316203870000},"page":"434-437","source":"Crossref","is-referenced-by-count":74,"title":["The Challenges of Diagnosing Primary Ciliary Dyskinesia"],"prefix":"10.1093","volume":"8","author":[{"given":"Margaret W.","family":"Leigh","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"O'Callaghan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Leicester, Leicester, United Kingdom and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Knowles","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,9,15]]},"reference":[{"key":"2026020502114984700_bib1","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":"2026020502114984700_bib2","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1183\/09031936.00176608","article-title":"Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children","volume":"34","author":"Barbato","year":"2009","journal-title":"Eur Respir J"},{"key":"2026020502114984700_bib3","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"},{"key":"2026020502114984700_bib4","article-title":"Inner dynein arm defects causing primary ciliary dyskinesia: repeat testing required","author":"O'Callaghan","journal-title":"Eur Respir J"},{"key":"2026020502114984700_bib5","first-page":"A1217","article-title":"The diagnostic dilemma of primary ciliary dyskinesia: Findings and experience of the Genetic Disorders of Mucociliary Clearance Consortium [abstract]","volume":"183","author":"Daniels","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"2026020502114984700_bib6","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":"2026020502114984700_bib7","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1183\/09031936.98.12040982","article-title":"Primary ciliary dyskinesia: diagnosis and standards of care","volume":"12","author":"Bush","year":"1998","journal-title":"Eur Respir J"},{"key":"2026020502114984700_bib8","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":"2026020502114984700_bib9","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":"2026020502114984700_bib10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1183\/09031936.00153308","article-title":"Disrupted ciliated epithelium shows slower ciliary beat frequency and increased dyskinesa","volume":"34","author":"Thomas","year":"2009","journal-title":"Eur Respir J"},{"key":"2026020502114984700_bib11","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1378\/chest.10-0175","article-title":"Ciliated air-liquid cultures as an aid to diagnostic testing of primary ciliary dyskinesia (PCD)","volume":"138","author":"Hirst","year":"2010","journal-title":"Chest"},{"key":"2026020502114984700_bib12","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1164\/rccm.200306-782OC","article-title":"Central microtubular agenesis causing primary ciliary dyskinesia","volume":"169","author":"Stannard","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"2026020502114984700_bib13","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1136\/thorax.55.4.314","article-title":"Analysis of ciliary beat pattern and beat frequency using digital high speed imaging: comparison with the photomultiplier and photodiode methods","volume":"55","author":"Chilvers","year":"2000","journal-title":"Thorax"},{"key":"2026020502114984700_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":"2026020502114984700_bib15","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1136\/thorax.58.4.333","article-title":"Functional analysis of cilia and ciliated epithelial ultrastructure in healthy children and young adults","volume":"58","author":"Chilvers","year":"2003","journal-title":"Thorax"},{"key":"2026020502114984700_bib16","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1165\/ajrcmb.23.2.4022","article-title":"Regulation of ciliary beat frequency by the nitric oxide-cyclic guanosine monophosphate signaling pathway in rat airway epithelial cells","volume":"23","author":"Li","year":"2000","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026020502114984700_bib17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1006\/bbrc.1993.1187","article-title":"Modulation of airway epithelial cell ciliary beat frequency by nitric oxide","volume":"191","author":"Jain","year":"1993","journal-title":"Biochem Biophys Res Commun"},{"key":"2026020502114984700_bib18","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/0923-2494(91)90103-P","article-title":"Synthesis of nitric oxide from L-arginine: a recently discovered pathway induced by cytokines with antitumour and antimicrobial activity","volume":"142","author":"Hibbs","year":"1991","journal-title":"Res Immunol"},{"key":"2026020502114984700_bib19","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1097\/00005537-199912000-00023","article-title":"Increased expression of inducible nitric oxide synthase in nasal epithelial cells in patients with allergic rhinitis","volume":"109","author":"Kawamoto","year":"1999","journal-title":"Laryngoscope"},{"key":"2026020502114984700_bib20","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1177\/44.5.8627003","article-title":"Localization of endothelial NOS at the basal microtubule membrane in ciliated epithelium of rat lung","volume":"44","author":"Xue","year":"1996","journal-title":"J Histochem Cytochem"},{"key":"2026020502114984700_bib21","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1183\/09031936.94.07081501","article-title":"Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome","volume":"7","author":"Lundberg","year":"1994","journal-title":"Eur Respir J"},{"key":"2026020502114984700_bib22","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":"2026020502114984700_bib23","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1183\/09031936.03.00305503","article-title":"Nasal nitric oxide measurements for the screening of primary ciliary dyskinesia","volume":"21","author":"Wodehouse","year":"2003","journal-title":"Eur Respir J"},{"key":"2026020502114984700_bib24","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1378\/chest.126.4.1054","article-title":"Nasal nitric oxide measurements to screen children for primary ciliary dyskinesia","volume":"126","author":"Corbelli","year":"2004","journal-title":"Chest"},{"key":"2026020502114984700_bib25","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1136\/adc.75.4.319","article-title":"Reduced upper airway nitric oxide in cystic fibrosis","volume":"75","author":"Balfour-Lynn","year":"1996","journal-title":"Arch Dis Child"},{"key":"2026020502114984700_bib26","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1164\/ajrccm.162.6.2003051","article-title":"Reduced nasal nitric oxide in diffuse panbronchiolitis","volume":"162","author":"Nakano","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"key":"2026020502114984700_bib27","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1046\/j.1365-2222.2002.01379.x","article-title":"Paradoxical low nasal nitric oxide in nasal polyposis","volume":"32","author":"Colantonio","year":"2002","journal-title":"Clin Exp Allergy"},{"key":"2026020502114984700_bib28","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1164\/rccm.200406-710ST","article-title":"Recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide","volume":"171","author":"ATS\/ERS","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"2026020502114984700_bib29","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"}],"container-title":["Proceedings of the American Thoracic Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/8\/5\/434\/66578877\/annalsats_8_5_434.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/8\/5\/434\/66578877\/annalsats_8_5_434.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T07:12:12Z","timestamp":1770275532000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/annalsats\/article\/8\/5\/434\/8441138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2011,9,15]]},"published-print":{"date-parts":[[2011,9,15]]}},"URL":"https:\/\/doi.org\/10.1513\/pats.201103-028sd","relation":{},"ISSN":["1546-3222","1943-5665"],"issn-type":[{"value":"1546-3222","type":"print"},{"value":"1943-5665","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,9]]},"published":{"date-parts":[[2011,9]]}}}