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Background: North American standardised testing protocols assume that only nasal Nitric Oxide (nNO) measured during expiration against a mouth resistance (ExRe) in children older than 5 years is a reliable tool for diagnosis of Primary Ciliairy Dyskinesia (PCD). Objectives: To establish the relevance of tidal breathing (TB) nNO measurement as a first line test in young children. Methods: Monocenter retrospective study (2013 - 2019) based on the records of children seen for suspicion of PCD. nNOExRe and nNOTB were measured using CLD 88 sp (EcoPhysics, Suisse). Results: Nasal NO measurement was possible on 460 occasions in 382 children (median [IQR] (range) age of 7.1 [4.8 to 11.1](0.1 to 19.4) years, 167 (43.7%) females). Recorded numbers of nNOExRe and nNOTB were 247 (53%) and 355 (77%); respectively, with 158 (34%) nNOTB on isolation. One hundred and five children 5 years or less performed 24 (19%) nNOExRe and 119 (94%) nNOTB. Among the 81 children with only nNOTB result and based on all available investigations, PCD diagnosis was excluded (n=58, nNOTB 298 [199;391]ppb), confirmed or very probable but pending (n=12 and n=3, nNOTB 42 [28;69]ppb), or unknown (n=8, nNOTB 129 [31;239]ppb). Among children with excluded versus confirmed / pending PCD diagnosis, frequencies of ciliary beat study, electron microscopy, and genetic testing were 15 (26%) versus 9 (60%), 3 (20%) versus 8 (53%), and 0 versus 8 (53%), respectively. Conclusion: In children less than 5 years, the success rate of nNOTB measurements was 94% and allowed stopping PCD workup in 74% of cases in children with medium-low clinical suspicion.

Introduction: Primary ciliary dyskinesia (PCD) is a rare genetic disease characterized by abnormalities in ciliary function, responsible for abnormal mucus clearance and repeated respiratory tract infections. The potential benefit of macrolide antibiotics has been evaluated in variety of chronic respiratory diseases. The efficacy of long-term azithromycine (AZT) has never been studied in PCD patients. Aim: The aim of this retrospective study was to investigate the effect of long-term AZT on the decrease in annual number of pulmonary exacerbations in children with PCD. Materials and Methods: All of our patients followed in our Pediatric center and who received low dose of AZT for more than 6 months were included. The clinical data (rate of pulmonary exacerbations, lung function analyses, ENT symptoms and changes in the airways bacterial colonizations) were collected from 1 year before and up to 5 years after the initiation of the AZT treatment. Results: A total of 31 children were included (11 years +/- 4 years). After 1 year, we observed a significant reduction in the annual number of pulmonary exacerbations (on average 1.7 +/- 2.7 exacerbations per year before treatment versus 0.5 +/- 1 exacerbation per year after 1 year of treatment) and a significant improvement in ENT symptoms. However, the lung function decline was not modified. No difference in the airways colonizations by pathogens, nor emerging antibiotic resistance were observed during the treatment. Conclusion: Our study showed a clinical improvement of PCD children treated by long term AZT. Those results must be confirmed by a larger multicenter study, such as the one currently conducted by the BEAT PCD group.

High speed videomicroscopy (HSV) becomes a key test in primary ciliary dyskinesia (PCD), providing a qualitative evaluation and recently a quantitative analysis of ciliary beating. We aimed to correlate ultrastructural phenotype and ciliary beating Method: 75 PCD patients were prospectively included to reach 15 patients per main ultrastructural phenotypes (combined outer/inner dynein arm defect, outer dynein arm defect, inner dynein arm defect with microtubular disorganization, central complex defect and PCD with normal ultrastructure). Ciliary beating was assessed by the proportion of beating ciliated edges, the ciliary beat frequency (CBF), a qualitative evaluation and a quantitative analysis allowing measuring objective parameters Result: Combined outer/inner dynein arm defect induced a total ciliary immotility, whatever the involved gene; (ii) Outer dynein arm defect induced a minimal residual beating with dramatically low CBF related to increased pause and recovery duration, especially in case of DNAI1 mutations; (iii) Inner dynein arm defect induced a weak proportion of ciliated edges still beating, a decreased beating angle and furthermore a relatively conserved CBF in case of CCDC39 mutations; (iv) Central complex defect induced nearly normal quantitative parameters with a circular gyrating motion in a minority of ciliated edges, whatever the involved gene; (v) PCD with normal ultrastructure induced a wide discrepancy in beating parameters but a frequent increased CBF Conclusion: Quantitative analysis by HSV allows objectively detecting abnormal values of ciliary beating parameters characteristic of each of the main ultrastructural phenotypes reported in PCD.

Introduction: Quality of life is an important parameter in the evaluation of health care and treatments. We have developed the first primary ciliary dyskinesia (PCD) health-related quality of life (HRQoL) measure for children, parents, teenagers and adults (QOL-PCD) in English. Clinical trials on rare diseases like PCD must be conducted in international settings to enrol enough patients, and outcome measures only assess the same thing if translation accounts for the socio-cultural context in which it is understood. This study aims to conduct socio-cultural translations of QOL-PCD into German, Swiss German, Danish, Dutch, French, and Greek. Methodology: We conducted (a) forward translations by 2 independent translators (b) back translation to English of the consensus versions by 1 translator, and (c) cognitive interviews of each age/language version by >5 patients to ensure the “meaning” attributed to each item is similar in different languages and cross-culturally understood. This involved 20 translators, 24 chaired meetings and interviews with 120 patients. Results: Each stage of translation involved comprehensive discussions (>2 hours), resulting in adjustments. 172 items (39-49 items across 4 age groups) were translated averaging 65 working hours per language. Cognitive interviews demonstrated face validity and no missing aspect of HRQoL were identified. International testing additionally provided valuable input on how to proceed for future improvement of QOL-PCD. Conclusion: To meet standards set by international guidelines, this extensive process has produced practical, cross-cultural and equivalent measures for future use as outcome measures in clinical trials.

Introduction: Capillary partial pressure of O 2 (PcapO 2 ) was found to decrease with age in children with primary ciliary dyskinesia (PCD) while PcapCO 2 remained steady. Objectives: To further explore the relationship between PcapO 2 , nasal Nitric Oxide (nNO) output and lung function (LF) in children with PCD. Patients and methods: Retrospective monocentric study in children referred to our national paediatric reference center for rare lung diseases for PCD diagnostic work-up, and in whom ear lobe capillary blood gas was available along with nNO and/or LF measurements. Results: 30 PCD children were included (18 girls, median age 11.5 (0.7 to 18.2) years). Median PcapO 2 was -1.9 (-5.2 to 2.2) z-score, median nNO in 27 children was 61 (20.3 to 697) ppb and median FEV 1 in 24 children was -2 (-4.7 to 2.18) z-score. In univariate analysis, there was a significant relationship between PcapO 2 and nNO, age, and LF indices (see table). In multivariate analysis, there was a significant relationship between PcapO 2 and nNO (p=0.02), and FEF 75% (p Conclusion: In the study children, low PcapO 2 was correlated with decrease nNO output and one LF indice. This could explain the early occurrence of hypoxemia in the course of PCD disease.