{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:01:54Z","timestamp":1782230514612,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T00:00:00Z","timestamp":1694822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Low nasal nitric oxide (nNO) is a typical feature of Primary Ciliary Dyskinesia (PCD). nNO is part of the PCD diagnostic algorithm due to its discriminative power against other lung diseases, such as cystic fibrosis (CF). However, the underlying pathomechanisms are elusive. To better understand NO dysregulation in PCD, the L-arginine\/NO (Arg\/NO) pathway in patients with PCD (pwPCD) and CF (pwCF) and in healthy control (HC) subjects was investigated. In a prospective, controlled study, we measured in 24 pwPCD, 25 age-matched pwCF, and 14 HC the concentrations of the NO precursors Arg and homoarginine (hArg), the arginase metabolite ornithine (Orn), the NO inhibitor asymmetric dimethylarginine (ADMA), and the major NO metabolites (nitrate, nitrite) in sputum, plasma, and urine using validated methods. In comparison to HC, the sputum contents (in \u00b5mol\/mg) of L-Arg (PCD 18.43 vs. CF 329.46 vs. HC 9.86, p &lt; 0.001) and of ADMA (PCD 0.055 vs. CF 0.015 vs. HC 0.010, p &lt; 0.001) were higher. In contrast, the sputum contents (in \u00b5mol\/mg) of nitrate and nitrite were lower in PCD compared to HC (nitrite 4.54 vs. 9.26, p = 0.023; nitrate 12.86 vs. 40.33, p = 0.008), but higher in CF (nitrite 16.28, p &lt; 0.001; nitrate 56.83, p = 0.002). The metabolite concentrations in urine and plasma were similar in all groups. The results of our study indicate that PCD, unlike CF, is associated with impaired NO synthesis in the lung, presumably due to mechano-chemical uncoupling.<\/jats:p>","DOI":"10.3390\/jcm12186010","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T23:32:27Z","timestamp":1694993547000},"page":"6010","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impaired Nitric Oxide Synthetase Activity in Primary Ciliary Dyskinesia\u2014Data-Driven Hypothesis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3931-9492","authenticated-orcid":false,"given":"Lisa","family":"Eggenkemper","sequence":"first","affiliation":[{"name":"University Children\u2019s Hospital, Ruhr-University Bochum, 44791 Bochum, Germany"},{"name":"Department of Internal Medicine and Gastroenterology, Christophorus-Kliniken Coesfeld, Teaching Hospital of University M\u00fcnster, 48653 Coesfeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Schlegtendal","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Maier","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"L\u00fccke","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4307-4232","authenticated-orcid":false,"given":"Folke","family":"Brinkmann","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Ruhr-University Bochum, 44791 Bochum, Germany"},{"name":"Section for Pediatric Pneumology and Allergology, University Medical Center Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibiana","family":"Beckmann","sequence":"additional","affiliation":[{"name":"Core Unit Proteomics, Institute of Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6320-0956","authenticated-orcid":false,"given":"Dimitrios","family":"Tsikas","sequence":"additional","affiliation":[{"name":"Core Unit Proteomics, Institute of Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordula","family":"Koerner-Rettberg","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Ruhr-University Bochum, 44791 Bochum, Germany"},{"name":"Department of Pediatrics, Marien-Hospital Wesel, Teaching Hospital of University of M\u00fcnster, 46483 Wesel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1513\/pats.201103-023SD","article-title":"The Emerging Genetics of Primary Ciliary Dyskinesia","volume":"8","author":"Zariwala","year":"2011","journal-title":"Proc. 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