BACKGROUND: In primary ciliary dyskinesia (PCD) there is no single diagnostic test. Different predictive tools have been proposed to guide referral of high-risk patients for further diagnostic workup. We aimed to test clinical index (CI) on a large unselected cohort and compare its characteristics with other widely used tools-PICADAR and NA-CDCF. METHODS: CI, PICADAR, and NA-CDCF scores were calculated in 1401 patients with suspected PCD referred to our center. Their predictive characteristics were analyzed using receiver operating characteristics (ROC) curves and compared to each other. Nasal nitric oxide (nNO) was measured in 569 patients older than 3 years. RESULTS: PCD was diagnosed in 67 (4.8%) patients. CI, PICADAR, and NA-CDCF scores were higher in PCD than in nonPCD group (all p < 0.001). The area under the ROC curve (AUC) for CI was larger than for NA-CDCF (p = 0.005); AUCPICADAR and AUCNA-CDCF did not differ (p = 0.093). An overlap in signs and symptoms among tools was identified. PICADAR could not be assessed in 86 (6.1%) patients without chronic wet cough. For CI laterality or congenital heart defects assessment was not necessary. nNO further improved predictive power of all three tools. CONCLUSION: CI is a feasible predictive tool for PCD that may outperform PICADAR and NA-CFCD.

Department of Histology and Embryology 2nd Faculty of Medicine Charles University 150 00 Prague Czech Republic

Department of Paediatrics 2nd Faculty of Medicine Charles University and Motol University Hospital 150 06 Prague Czech Republic

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Wallmeier J., Nielsen K.G., Kuehni C.E., Lucas J.S., Leigh M.W., Zariwala M.A., Omran H. Motile ciliopathies. Nat. Rev. Dis. Primers. 2020;6:77–106. doi: 10.1038/s41572-020-0209-6. PubMed DOI

Armengot-Carceller M., Reula A., Mata-Roig M., Pérez-Panadés J., Milian-Medina L., Carda-Batalla C. Understanding Primary Ciliary Dyskinesia: Experience From a Mediterranean Diagnostic Reference Centre. J. Clin. Med. 2020;9:810. doi: 10.3390/jcm9030810. PubMed DOI PMC

Shoemark A., Rubbo B., Legendre M., Fassad M.R., Haarman E.G., Best S., Bon I.C.M., Brandsma J., Burgel P.R., Carlsson G., et al. Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia. Eur. Respir. J. 2021;57:2002359. doi: 10.1183/13993003.02359-2020. PubMed DOI

Kuehni C.E., Frischer T., Strippoli M.P., Maurer E., Bush A., Nielsen K.G., Escribano A., Lucas J.S., Yiallouros P., Omran H., et al. ERS Task Force on Primary Ciliary Dyskinesia in Children. Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Eur. Respir. J. 2010;36:1248–1258. doi: 10.1183/09031936.00001010. PubMed DOI

Shoemark A., Dell S., Shapiro A., Lucas J.S. ERS and ATS diagnostic guidelines for primary ciliary dyskinesia: Similarities and differences in approach to diagnosis. Eur. Respir. J. 2019;54:1901066. doi: 10.1183/13993003.01066-2019. PubMed DOI

Shoemark A., Rubbo B., Haarman E., Hirst R.A., Hogg C., Jackson C.L., Nielsen K.G., Papon J.F., Robinson P., Walker W.T., et al. The Controversies and Difficulties of Diagnosing Primary Ciliary Dyskinesia. Am. J. Respir. Crit. Care. Med. 2020;201:120–122. doi: 10.1164/rccm.201907-1334LE. PubMed DOI PMC

Halbeisen F.S., Shoemark A., Barbato A., Boon M., Carr S., Crowley S., Hirst R., Karadag B., Koerner-Rettberg C., Loebinger M.R., et al. Time trends in diagnostic testing for primary ciliary dyskinesia in Europe. Eur. Respir. J. 2019;54:1900528. doi: 10.1183/13993003.00528-2019. PubMed DOI

Lucas J.S., Barbato A., Collins S.A., Goutaki M., Behan L., Caudri D., Dell S., Eber E., Escudier E., Hirst R.A., et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur. Respir. J. 2017;49:1601090. doi: 10.1183/13993003.01090-2016. PubMed DOI PMC

Djakow J., Rozehnalova E., Havlisova M., Svobodova T., Pohunek P. Clinical index to evaluate the risk of primary ciliary diskinesia in children. Eur. Respir. J. 2012;40(Suppl. 56):2844.

Djakow J. Ph.D. Thesis. Charles University in Prague; Prague, Czech Republic: 2015. Aspects of Identification of Patients with Primary Ciliary Dyskinesia’.

Behan L., Dimitrov B.D., Kuehni C.E., Hogg C., Carroll M., Evans H.J., Goutaki M., Harris A., Packham S., Walker W.T., et al. PICADAR: A diagnostic predictive tool for primary ciliary dyskinesia. Eur. Respir. J. 2016;47:1103–1112. doi: 10.1183/13993003.01551-2015. PubMed DOI PMC

Leigh M.W., Ferkol T.W., Davis S.D., Lee H.S., Rosenfeld M., Dell S.D., Sagel S.D., Milla C., Olivier K.N., Sullivan K.M., et al. Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents. Ann. Am. Thorac. Soc. 2016;13:1305–1313. doi: 10.1513/AnnalsATS.201511-748OC. PubMed DOI PMC

Palmas K., Shanthikumar S., Robinson P. Assessment of primary ciliary dyskinesia predictive tools. Eur. Respir. J. 2020;56:2001169. doi: 10.1183/13993003.01169-2020. PubMed DOI

American Thoracic Society. European Respiratory Society ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am. J. Respir Crit Care Med. 2005;171:912–930. doi: 10.1164/rccm.200406-710ST. PubMed DOI

Chilvers M.A., O’Callaghan C. Analysis of ciliary beat pattern and beat frequency using digital high speed imaging: Comparison with the photomultiplier and photodiode methods. Thorax. 2000;55:314–317. doi: 10.1136/thorax.55.4.314. PubMed DOI PMC

Rubbo B., Shoemark A., Jackson C.L., Hirst R., Thompson J., Hayes J., Frost E., Copeland F., Hogg C., O’Callaghan C., et al. National PCD Service, UK. Accuracy of High-Speed Video Analysis to Diagnose Primary Ciliary Dyskinesia. Chest. 2019;155:1008–1017. doi: 10.1016/j.chest.2019.01.036. PubMed DOI

Rutland J., Dewar A., Cox T., Cole P. Nasal brushing for the study of ciliary ultrastructure. J. Clin. Pathol. 1982;35:357–359. doi: 10.1136/jcp.35.3.357. PubMed DOI PMC

Gil H.I., Lee T., Jeong B.H., Lee H., Choe J., Ahn K., Hong S.D., Jeon K., Koh W.J., Kim J.S., et al. Additional role of bronchial mucosal biopsy for ciliary structural abnormality in diagnosis of primary ciliary dyskinesia. J. Thorac. Dis. 2019;11:839–847. doi: 10.21037/jtd.2019.02.24. PubMed DOI PMC

Shoemark A., Boon M., Brochhausen C., Bukowy-Bieryllo Z., De Santi M.M., Goggin P., Griffin P., Hegele R.G., Hirst R.A., Leigh M.W., et al. International consensus guideline for reporting transmission electron microscopy results in the diagnosis of primary ciliary dyskinesia (BEAT PCD TEM Criteria) Eur. Respir. J. 2020;55:1900725. doi: 10.1183/13993003.00725-2019. PubMed DOI

Martinů V., Dvorakova P., Uhlik J., Varenyiova Z., Borek-Dohalska L., Pohunek P. Kdy pomýšlet na řasinkové dysfunkce? Čes-Slov. Pediat. 2020;75:401–409.

Lucas J.S., Davis S.D., Omran H., Shoemark A. Primary ciliary dyskinesia in the genomics age. Lancet Respir. Med. 2020;8:202–216. doi: 10.1016/S2213-2600(19)30374-1. PubMed DOI

Goutaki M., Halbeisen F.S., Barbato A., Crowley S., Harris A., Hirst R.A., Karadag B., Martinu V., Morgan L., O’Callaghan C., et al. Late Diagnosis of Infants with PCD and Neonatal Respiratory Distress. J. Clin. Med. 2020;9:2871. doi: 10.3390/jcm9092871. PubMed DOI PMC

Shapiro A.J., Dell S.D., Gaston B., O’Connor M., Marozkina N., Manion M., Hazucha M.J., Leigh M.W. Nasal Nitric Oxide Measurement in Primary Ciliary Dyskinesia. A Technical Paper on Standardized Testing Protocols. Ann. Am. Thorac. Soc. 2020;17:e1–e12. doi: 10.1513/AnnalsATS.201904-347OT. PubMed DOI PMC

Rademacher J., Buck A., Schwerk N., Price M., Fuge J., Welte T., Ringshausen F.C. Nasal Nitric Oxide Measurement and a Modified PICADAR Score for the Screening of Primary Ciliary Dyskinesia in Adults with Bronchiectasis. Pneumologie. 2017;71:543–548. doi: 10.1055/s-0043-111909. PubMed DOI