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Nasal nitric oxide (nNO) is extremely low in most people with primary ciliary dyskinesia (PCD) and its measurement is an important contributor to making the diagnosis. Existing guidelines and technical standards focus on nNO measurements in older, cooperative children using chemiluminescence analysers. However, measurements of nNO in pre-school-age children (age 2-5 years) may facilitate early diagnosis and electrochemical rather than chemiluminescence analysers are widely used. Pre-schoolers often need different methods to be employed when measuring nNO. Hence, a European Respiratory Society Task Force has developed this technical standard as the first step towards standardising sampling, analysis and reporting of nNO measured as part of the diagnostic testing for PCD in all age groups, including pre-school-age children. Furthermore, we considered both chemiluminescence and electrochemical analysers that are in use worldwide. There was a paucity of quality evidence for electrochemical analysers and sampling methods used in young children, and the Task Force proposes future research priorities to allow updates of this technical standard., Competing Interests: Conflict of interest: N. Beydon reports educational writing payments as a member of the HERMES examination committee for paediatric respiratory medicine of the European Respiratory Society, and a leadership role as Chair of Group 07.01 of the European Respiratory Society (Paediatric respiratory physiology and sleep), outside the submitted work. P. Latzin reports grants from Vertex and OM Pharma, lecture honoraria from Vertex, Vifor and OM Pharma, and advisory board participation from Polyphor, Santhera (DMC), Vertex, Vifor, OM Pharma and Sanofi Aventis, outside the submitted work. S.D. Davis reports grants from the National Institutes of Health/National Heart, Lung, and Blood Institute, to support the present manuscript, and consulting fees from Parion Sciences and ReCode Therapeutics, and advisory board participation for the PCD Foundation, outside the submitted work. T. Ferkol reports grants from the National Institutes of Health (HL096458) to support the present manuscript, and grants from the National Institutes of Health (HL116211, HL125241, AI146999), National Health and Medical Research Council (NHMRC1043768) and Parion Sciences, advisory board participation for the PCD Foundation, Parion Sciences and Translate Bio, and is past president and executive board member of the American Thoracic Society, outside the submitted work. J.S. Lucas reports grants from AAIR Charity and NIHR Research for patient benefit, and consulting fees from Translate Bio, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Primary ciliary dyskinesia (PCD), a genetically heterogeneous condition enriched in some consanguineous populations, results from recessive mutations affecting cilia biogenesis and motility. Currently, diagnosis requires multiple expert tests., Methods: The diagnostic utility of multigene panel next-generation sequencing (NGS) was evaluated in 161 unrelated families from multiple population ancestries., Results: Most (82%) families had affected individuals with biallelic or hemizygous (75%) or single (7%) pathogenic causal alleles in known PCD genes. Loss-of-function alleles dominate (73% frameshift, stop-gain, splice site), most (58%) being homozygous, even in non-consanguineous families. Although 57% (88) of the total 155 diagnostic disease variants were novel, recurrent mutations and mutated genes were detected. These differed markedly between white European (52% of families carry DNAH5 or DNAH11 mutations), Arab (42% of families carry CCDC39 or CCDC40 mutations) and South Asian (single LRRC6 or CCDC103 mutations carried in 36% of families) patients, revealing a striking genetic stratification according to population of origin in PCD. Genetics facilitated successful diagnosis of 81% of families with normal or inconclusive ultrastructure and 67% missing prior ultrastructure results., Conclusions: This study shows the added value of high-throughput targeted NGS in expediting PCD diagnosis. Therefore, there is potential significant patient benefit in wider and/or earlier implementation of genetic screening., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)