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Introduction: Respiratory pathogens are frequently isolated from airway samples in primary ciliary dyskinesia (PCD) patients. Few studies have investigated associations between these pathogens and lung function, with current management based on evidence from cystic fibrosis. We investigated the association between commonly isolated respiratory pathogens and lung function in PCD patients., Methods: Using a cross-sectional design, we prospectively collected clinical and concurrent microbiology data from 408 participants with probable or confirmed PCD, aged ≥5 years, from 12 countries. We used Global Lung Function Initiative 2012 references to calculate forced expiratory volume in 1 s (FEV 1 ) z-scores. For 351 patients (86%) with complete data, we assessed the association of the four most frequently isolated pathogens with lung function by fitting multilevel linear models with country as random intercept, adjusted for age at diagnosis, age at lung function, use of antibiotic prophylaxis and body mass index z-scores., Results: Individuals with Pseudomonas aeruginosa growth in culture had significantly lower FEV 1 z-scores (β= -0.87, 95% CI -1.40- -0.34), adjusted for presence of Haemophilus influenzae , methicillin-sensitive Staphylococcus aureus and Streptococcus pneumoniae , and for covariates. When stratified by age, associations remained strong for adults but not for children. Results were similar when ciliary defects by transmission electron microscopy were included in the models and when restricting analysis to only confirmed PCD cases., Conclusions: We found that P. aeruginosa was associated with worse lung function in individuals with PCD, particularly adults. These findings suggest that it is prudent to aim for P. aeruginosa eradication in the first instance, and to treat exacerbations promptly in colonised patients., Competing Interests: Conflict of interest: M. Boon declares receiving grants or contracts from the Fund Alphonse and Jean Forton, managed by the King Baudouin Foundation, and by the Belgian Cystic Fibrosis Association (number 2020-J1810150-217926); and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Vertex. Conflict of interest: S.B. Carr declares receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Chiesi Pharmaceuticals, and participation on a Data Safety Monitoring Board or Advisory Board for Vertex Pharmaceuticals. Conflict of interest: S. Dillenhöfer declares receiving support for attending meetings and/or travel from Vertex (Advance Program 2022). Conflict of interest: B. Karadag declares receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from VEM Ilac, Abdi Ibrahim and OMRON, and participating on a Data Safety Monitoring Board or Advisory Board for Abdi Ibrahim. Conflict of interest: C. Koerner-Rettberg declares receiving speaker honoraria from Berlin Chemie, and advisory board participation and being a member of the medical board of the German PCD patient organisation. Conflict of interest: V. Martinu declares having received grants or contracts from Ministry of Health of the Czech Republic (grant number NV19-07-00210) and participation on an advisory board for indication of tobramycin in noncystic fibrosis bronchiectasis for Chiesi, and receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Chiesi Pharmaceuticals. Conflict of interest: A. Moreno-Galdó declares receiving personal payment for lectures from AstraZeneca, Sanofi-Pasteur and Janssen, receiving support for attending meetings or travel from Sanofi-Pasteur and Vivisol, participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca and Sanofi-Pasteur, and is President of the Spanish Society of Pediatric Pulmonology. Conflict of interest: U. Ozcelik is Head of the Turkish Respiratory Disease and Cystic Fibrosis Society (unpaid). Conflict of interest: P. Pohunek declares receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GlaxoSmithKline, AstraZeneca and Chiesi, and consulting fees, support for attending meetings and/or travel, and participation on a Data Safety Monitoring Board or Advisory Board from AstraZeneca and GlaxoSmithKline. Conflict of interest: J. Raidt declares receiving the following funds: DFG CRU326 RA3522/1. Conflict of interest: P. Latzin declares receiving grants or contracts from Vertex and OM Pharma, payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Vertex, Vifor and OM Pharma, and participating on a Data Safety Monitoring Board or Advisory Board for the following: Polyphor, Santhera (DMC), Vertex, OM Pharma, Vifor, Allecra and Sanofi Aventis. Conflict of interest: J.S. Lucas declares receiving support for the present manuscript (funds the clinical investigations (spirometry, microbiology)) from NHS England, to the institution; and grants or contracts from COST ACTION to fund the BEATPCD COST Action BM1407, which funded the network that undertook this work, and the institution managed the funding. Conflict of interest: The other authors have nothing to disclose., (Copyright ©The authors 2024.)

In paediatrics, the pulmonary function test (PFT) is most often performed to support the diagnosis or in follow-up of asthma patients. Whatever the pathology responsible for respiratory symptoms and/or functional impairment, repeated PFTs make it possible to establish a prognosis (pulmonary function trajectories…) and to orient preventive interventions. PFT can be performed routinely from the age of three years, provided that the following requirements are met: suitable techniques and equipment, staff trained to apply the techniques and to receive young children, reference values for each technique indicating the limits of normal values and of between-test significant variation. From the age of three, children can be subjected to tidal breathing measurement of: resistance of the respiratory system (oscillometry, Rrs; airflow interruption, Rint) or of airways specific resistance (sRaw) and functional residual capacity (by applying a dilution technique). With maturity, the child will become capable of mobilizing his or her slow vital capacity to measure total lung capacity (TLC), once again by applying a dilution technique, then later by breathing against a closed shutter (plethysmography TLC and Raw). Finally, the child will be able to carry out forced expiration (forced spirometry) along with all of the other PFTs. It is important to take into account the paediatric adaptations specified in the international recommendations regarding the performance, reproducibility and quality of PFTs targeting this population., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: The polysomnography (PSG) is the gold-standard for obstructive sleep apnea (OSA) syndrome diagnosis and assessment under positive airway pressure (PAP) therapies in children. Recently, an innovative digital medicine solution, including a mandibular jaw movement (MJM) sensor coupled with automated analysis, has been validated as an alternative to PSG for pediatric application., Objective: This study aimed to assess the reliability of MJM automated analysis for the assessment of residual apnea/hypopnea events during sleep in children with OSA treated with noninvasive ventilation (NIV) or continuous PAP (CPAP)., Methods: In this open-label prospective non-randomized multicentric trial, we included children aged from 5 to 18 years with a diagnosis of severe OSA. The children underwent in-laboratory PSG with simultaneous MJM monitoring and at-home recording with MJM monitoring 3 months later. Agreement between PSG and MJM analysis in measuring the residual apnea-hypopnea index (AHI) was evaluated by the Bland-Altman method. The treatment effect on residual AHI was estimated for both PSG and MJM analysis., Results: Fifteen (60% males) children were included with a median age of 12 years [interquartile range 8-15]. Two (17%) were ventilated with NIV and 13 (83%) with CPAP. There was a good agreement between MJM-AHI and PSG-AHI with a median bias of -0.25 (95% CI: -3.40 to +2.04) events/h. The reduction in AHI under treatment was consistently significant across the three measurement methods: in-laboratory PSG and MJM recordings in the laboratory and at home., Conclusion: Automated analysis of MJM is a highly reliable alternative method to assess residual events in a small population treated with PAP therapies., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Consistent use of reliable and clinically appropriate outcome measures is a priority for clinical trials, with clear definitions to allow comparability. We aimed to develop a core outcome set (COS) for pulmonary disease interventions in primary ciliary dyskinesia (PCD)., Methods: A multidisciplinary international PCD expert panel was set up. A list of outcomes was created based on published literature. Using a modified three-round e-Delphi technique, the panel was asked to decide on relevant end-points related to pulmonary disease interventions and how they should be reported. First, inclusion of an outcome in the COS was determined. Second, the minimum information that should be reported per outcome. The third round finalised statements. Consensus was defined as ≥80% agreement among experts., Results: During the first round, experts reached consensus on four out of 24 outcomes to be included in the COS. Five additional outcomes were discussed in subsequent rounds for their use in different subsettings. Consensus on standardised methods of reporting for the COS was reached. Spirometry, health-related quality-of-life scores, microbiology and exacerbations were included in the final COS., Conclusion: This expert consensus resulted in a COS for clinical trials on pulmonary health among people with PCD., Competing Interests: Conflict of interest: S. Aliberti has received fees outside of this work from Insmed, Zambon, AstraZeneca, CSL Behring GmbH, Grifols, Fondazione Internazionale MENARINI, MSD Italia S.r.l., Brahms, Physioassist SAS and GlaxoSmithKline. S.D. Dell has received grants outside of this work from Boehringer Ingelheim, Vertex and Sanofi, and she owns the copyright to the PCD-QOL Questionnaires. T.W. Ferkol has received consulting fees from Translate Bio and Arrowhead Pharmaceuticals. R.A. Athanazio has received personal fees outside of this work from Astrazeneca, Chiesi, GSK, Omron, Sanofi, Vertex and Zambon. K.G. Nielsen is part of the European Reference Network on respiratory diseases (ERN-LUNG) and director of PCD CTN. F.C. Ringshauen has received fees outside of this work from AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex and Zambon. M. Shteinberg has received consulting fees from AstraZeneca, Boehringer Ingelheim, Dexcel, Kamada, Synchrony Medical, Trumed and Zambon. J.D. Chalmers has received grants outside of this work from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Gilead Sciences, Grifols, Insmed, Janssen, Novartis, Pfizer and Zambon; and is an associate editor of this journal. The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Objective: We examined relationships between clinical features and pulmonary function before and after inhaled corticosteroid (ICS) treatment in wheezy preschool children, and specifically, whether measuring bronchodilator response (BDR) could predict benefit from ICS., Design: Clinical non-randomised intervention study SETTING: Secondary care., Patients: Preschool children (2 years to <6 years) with recurrent wheeze., Interventions: Inhaled beta-agonist, ICS., Outcome Measures: We measured prebronchodilator and postbronchodilator interrupter resistance (Rint) and symptom scores at 0 (V1), 4 (V2) and 12 (V3) weeks. At V2, those with a predetermined symptom level commenced ICS. Modified Asthma Predictive Index (mAPI) and parental perception of response to bronchodilator were recorded. Response to ICS was defined as a reduction in daily symptom score of >0.26. Positive BDR was defined as fall in Rint of ≥0.26 kPa.s/L, ≥35% predicted or ≥1.25 Z Scores., Results: Out of 138 recruited children, 67 completed the full study. Mean (SD) prebronchodilator Rint at V2 was 1.22 (0.35) kPa.s/L, and fell after starting ICS (V3) to 1.09 (0.33) kPa.s/L (p<0.001), while mean (SD) daily symptom score fell from 0.56 (0.36) to 0.28 (0.36) after ICS (p<0.001). Positive Rint BDR before ICS (at V1 and/or V2), using all three threshold criteria, was significantly associated with response to ICS on symptom scores at V3 (p<0.05). mAPI was not significantly associated with response to ICS, and parents' perception of response to bronchodilator was not related to measured Rint BDR ., Conclusions: Rint BDR may be helpful in selecting which wheezy preschool children are likely to benefit from ICS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A written action plan (WAP) for managing asthma exacerbations is recommended., Objective: We aimed to compare the effect on unscheduled medical contacts (UMCs) of a digital action plan (DAP) accessed via a smartphone web app combined with a WAP on paper versus that of the same WAP alone., Methods: This randomized, unblinded, multicenter (offline recruitment in private offices and public hospitals), and parallel-group trial included children (aged 6-12 years) or adults (aged 18-60 years) with asthma who had experienced at least 1 severe exacerbation in the previous year. They were randomized to a WAP or DAP+WAP group in a 1:1 ratio. The DAP (fully automated) provided treatment advice according to the severity and previous pharmacotherapy of the exacerbation. The DAP was an algorithm that recorded 3 to 9 clinical descriptors. In the app, the participant first assessed the severity of their current symptoms on a 10-point scale and then entered the symptom descriptors. Before the trial, the wordings and ordering of these descriptors were validated by 50 parents of children with asthma and 50 adults with asthma; the app was not modified during the trial. Participants were interviewed at 3, 6, 9, and 12 months to record exacerbations, UMCs, and WAP and DAP use, including the subjective evaluation (availability and usefulness) of the action plans, by a research nurse., Results: Overall, 280 participants were randomized, of whom 33 (11.8%) were excluded because of the absence of follow-up data after randomization, leaving 247 (88.2%) participants (children: n=93, 37.7%; adults: n=154, 62.3%). The WAP group had 49.8% (123/247) of participants (children: n=45, 36.6%; mean age 8.3, SD 2.0 years; adults: n=78, 63.4%; mean age 36.3, SD 12.7 years), and the DAP+WAP group had 50.2% (124/247) of participants (children: n=48, 38.7%; mean age 9.0, SD 1.9 years; adults: n=76, 61.3%; mean age 34.5, SD 11.3 years). Overall, the annual severe exacerbation rate was 0.53 and not different between the 2 groups of participants. The mean number of UMCs per year was 0.31 (SD 0.62) in the WAP group and 0.37 (SD 0.82) in the DAP+WAP group (mean difference 0.06, 95% CI -0.12 to 0.24; P=.82). Use per patient with at least 1 moderate or severe exacerbation was higher for the WAP (33/65, 51% vs 15/63, 24% for the DAP; P=.002). Thus, participants were more likely to use the WAP than the DAP despite the nonsignificant difference between the action plans in the subjective evaluation. Median symptom severity of the self-evaluated exacerbation was 4 out of 10 and not significantly different from the symptom severity assessed by the app., Conclusions: The DAP was used less often than the WAP and did not decrease the number of UMCs compared with the WAP alone., Trial Registration: ClinicalTrials.gov NCT02869958; https://clinicaltrials.gov/ct2/show/NCT02869958., (©Nicole Beydon, Camille Taillé, Harriet Corvol, Judith Valcke, Jean-Jacques Portal, Laurent Plantier, Gilles Mangiapan, Caroline Perisson, Guillaume Aubertin, Alice Hadchouel, Guillaume Briend, Laurent Guilleminault, Catherine Neukirch, Pierrick Cros, Corinne Appere de Vecchi, Bruno Mahut, Eric Vicaut, Christophe Delclaux. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.06.2023.)

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.)

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease in children causing sleep and respiratory disorders that are poorly described in the literature compared to adult forms. This retrospective observational study was performed at the Armand Trousseau University Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France. We retrospectively collected data from lung function tests, nocturnal gas exchange recordings, and polysomnography of 24 children with DM1. 39% of the children with DM1 reported respiratory symptoms indicative of sleep disordered breathing. Three patients (12%) presented with a restrictive respiratory pattern, 10 (42%) with a sleep apnoea syndrome, mainly of obstructive origin (2/10 with severe obstructive sleep apnea syndrome), and 11 (45%) with nocturnal alveolar hypoventilation. Non-invasive ventilation (NIV) was indicated in 9 (37.5%) children, although tolerance was poor. No significant deterioration in respiratory function or nocturnal gas exchange was observed during the NIV-free period. This study provides new and useful insights into DM1 disease evolution in children to better adapt for respiratory follow-up and management. This highlights the need for future research to better understand the origin of respiratory and sleep disorders in patients with DM1., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest related to this article to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The Childhood Asthma Management Program revealed that 25.7% of children with mild to moderate asthma exhibit loss of lung function. The objective was to assess the trajectories of function by means of serial FEV 1 in asthmatic children participating in out-of-hospital follow-up., Methods: A total of 295 children (199 boys) who had undergone at least 10 spirometry tests from the age of 8 were selected from a single-center open cohort. The annualized rate of change (slope) for prebronchodilator FEV 1 (percent predicted) was estimated for each participant and three patterns were defined: significantly positive slope, significantly negative slope, and null slope (non-significant P-value; Pearson test). The standard deviation (SD) of each individual slope was recorded as a variability criterion of FEV 1 ., Results: The median (25 th ; 75 th percentile) age at inclusion and the last visit was 8.5 (8.2; 9.3) and 15.4 (14.8, 16.0) years, respectively. Tracking of function (null slope) was observed in 68.8% of the children, while 27.8% showed a loss of function or reduced growth (negative slope) and 3.4% showed a gain in function (positive slope). The children characterized by loss of function depicted a better initial function and a lower FEV 1 variability during their follow-up than children with tracking or gain of lung function. At the last visit, these children were characterized by a lower lung function than children with tracking or gain of lung function., Conclusion: Better initial FEV 1 value and less FEV 1 variability are associated with loss of lung function or reduced lung growth in asthmatic children.

Rationale: Although children with primary ciliary dyskinesia (PCD) typically have low nasal nitric oxide (nNO), some children with indisputable PCD may have unexplained high nNO concentrations. Objectives: To look for relationships between nNO measures and genetic findings (and cilia motility or ultrastructure when available) in children with PCD with known genotypes. Methods: We retrospectively studied 73 children with PCD (median age, 9.5 [range, 2.1-18.2] yr). nNO was the mean value of a plateau reached while the velum was closed (nNO-VC; threshold, 77 nl ⋅ min -1 ) or was calculated as the average of five peaks obtained during tidal breathing (threshold, 40 nl ⋅ min -1 ). Ciliary beat was classified as either motile (including dyskinetic pattern) or immotile, depending on whether motility was present or absent in all cilia, or as a mixture of motile and immotile cilia. Genotypes were classified as pathogenic mutations in genes known to be associated with high nNO (mild genotype), biallelic truncating mutations in other genes (severe mutations), or putative hypomorphic pathogenic mutations (missense, single amino acid deletion, or moderate splicing mutations) in at least one allele believed to be possibly associated with residual production of a functional protein. Results: nNO was above the discriminant threshold in 16 of 73 (21.9%) children (11 nNO-VC and 5 nNO during tidal breathing). High nNO was less frequent in children with severe mutations (2 of 42) than in those with mild genotypes (7 of 10) or at least one hypomorphic mutation (7 of 21) ( P  < 0.0001). Median (interquartile range) nNO-VC values ( n  = 60) were significantly different in the three genotype groups: severe mutations, 18 (10-26) nl ⋅ min -1 ( n  = 36); possible residual functional protein production (putative hypomorphic mutations), 23 (16-68) nl ⋅ min -1 ( n  = 17); and mild genotypes, 139 (57-216) nl ⋅ min -1 ( n  = 7) ( P  = 0.0002). The higher the cilia motility, the higher the nNO-VC (16 [10-23], 23 [17-56], and 78 [45-93] nl ⋅ min -1 in patients with immotile, dyskinetic motile and immotile, and dyskinetic motile cilia, respectively; P  < 0.0001), while nNO values were scattered across different ultrastructure defects ( P  = 0.07). Conclusions: In children with PCD, high nNO values were linked not only to specific genes but also to potentially hypomorphic mutations in other genes (with possible functional protein production). nNO values increased with the proportion of motile cilia.

Standing height is an essential anthropometric measurement in pediatrics. In children unable to stand upright, measurement of ulna to predict standing height is recommended, but height prediction equations based on the ulna have not been established in children of African ancestry. We hypothesized that such equations would result in lower predicted height compared to using equations derived from non-African children. We measured prospectively standing height and both ulna in 358 African-Caribbean children without bone deformity or muscle disease, referred to two pulmonary function test laboratories. Interobserver variability was low for standing height (n = 54) and ulna measurement (n = 51) (mean biases [95%CI]: -0.02 [-0.99; 0.95] and 0.05 [-0.91; 1.01] cm, respectively), as well as inter-ulna variability (n = 352; mean bias 0.03 95%CI [-0.66; 0.73] cm). We used the mean value of 247 bilateral ulna measurements to calculate prediction equations using a generalized linear model including age, sex, ulna length, and geographic origin group, the latter showing no influence on the model. In the validation population of 107 children, the median difference [inter-quartile range] between standing height and ulna-predicted height was -0.4 [-2.7; 1.0] cm. Of 260 reliable baseline spirometry, there was a strong concordance between bronchial obstruction diagnosis established using standing height or ulna-predicted height (kappa coefficient: 0.85 [0.77; 0.94]) with only 11 (4.3%) children misclassified. The ulna predicted height calculated from African-Caribbean prediction equations resulted in a smaller height than the height calculated using equations derived from non-African children., (© 2022 Wiley Periodicals LLC.)

A repeatability of 10% for NO measurements obtained with the velum closed in the same or both nostrils is relevant, while measurements taken during tidal breathing should aim for a repeatability of 20% and 30%, respectively https://bit.ly/3sMnug6., Competing Interests: Conflict of interest: N. Beydon has nothing to disclose., (Copyright ©The authors 2022.)

Study Objectives: Asthma and obesity are risk factors for obstructive sleep apnea (OSA) in children but their link to OSA severity is uncertain. We aimed at determining whether asthma or obesity was associated with an increased risk of moderate/severe OSA., Methods: Children undergoing a one-night polysomnography for suspicion of OSA were retrospectively included. Univariate and multivariate analyses were conducted to assess the clinical and demographic characteristics linked to moderate/severe OSA (obstructive apnea-hypopnea index ≥ 5 events/h of sleep) with odds ratio and 95% confidence interval reported., Results: Four hundred ninety children (311 [64%] boys) were included with a median [25th; 75th percentile] age of 8.7 [5.4; 12.9] years, 164 (33%) nonasthmatics nonobese, 122 (25%) obese nonasthmatics, 125 (26%) asthmatics nonobese, 79 (16%) asthmatics and obese. Moderate/severe OSA was present in 157 (32%) children (75/157 [48%] obese and 52/157 [33%] asthmatics). Independent factors associated with increased or decreased risk of moderate/severe OSA were obesity and male sex (odds ratio 1.82 [1.16; 2.87], P = .01, and 1.55 [1.02; 2.36], P = .04, respectively), and current asthma, age > 6 years, or behavioral disorders (odds ratio 0.45 [0.29; 0.70], P < .001; 0.44 [0.27; 0.73], P < .001; and 0.55 [0.33; 0.92], P = .02, respectively). Abnormal resistance of the respiratory system (measured in 241 children), but not abnormal spirometry (measured in 213 children), increased the risk of moderate/severe OSA (odds ratio 2.95 [1.46-5.96], P = .003)., Conclusions: In our cohort enriched in obese and asthmatic children, obesity was associated with higher risk of moderate/severe OSA whereas current asthma was not., Citation: Ioan I, Mulier G, Taytard J, Césaire A, Beydon N. Evaluation of obesity and asthma as risk factors for moderate to severe obstructive sleep apnea in children. J Clin Sleep Med . 2022;18(6):1639-1648., (© 2022 American Academy of Sleep Medicine.)

Nasal nitric oxide (nNO) measurements are used in the assessment of patients suspected of having primary ciliary dyskinesia (PCD), but recommendations for performing such measurements have not focused on children and do not include all current practices. To guide the development of a European Respiratory Society-supported technical standard for nNO measurement in children, an international online survey was conducted to better understand current measurement practices among providers involved in PCD diagnostics. 78 professionals responded, representing 65 centres across 18 countries, mainly in Europe and North America. Nearly all centres measured nNO in children and more than half performed measurements before 5 years of age. The test was often postponed in children with signs of acute airway infection. In Europe, the electrochemical technique was more frequently used than chemiluminescence. A similar proportion of centres performed measurements during exhalation against a resistance (49 out of 65) or during tidal breathing (50 out of 65); 15 centres used only exhalation against a resistance and 15 used only tidal breathing. The cut-off values used to discriminate PCD were consistent across centres using chemiluminescence analysers; these centres reported results as an output (nL·min -1 ). Cut-off values were highly variable across centres using electrochemical devices, and nNO concentrations were typically reported as ppb. This survey is the first to determine real-world use of nNO measurements globally and revealed remarkable variability in methodology, equipment and interpretation. These findings will help standardise methods and training., Competing Interests: Conflict of interest: N. Beydon declares no competing interests. Conflict of interest: T. Ferkol declares no competing interests. Conflict of interest: A.L. Harris declares no competing interests. Conflict of interest: M. Colas declares no competing interests. Conflict of interest: S.D. Davis declares grant NIH U54 HL09640958 funded by the Office of Rare Diseases Research (NCATS) in the 36 months prior to manuscript submission, and membership of the PCD Foundation Medical and Scientific Advisory Council. Conflict of interest: E. Haarman declares no competing interests. Conflict of interest: C. Hogg declares no competing interests. Conflict of interest: E. Kilbride declares no competing interests. Conflict of interest: P. Kouis declares no competing interests. Conflict of interest: C.E. Kuehni declares no competing interests. Conflict of interest: P. Latzin declares grants to their institution from Vertex and Vifor; payment to their institution and themself for lectures, presentations, speaker bureaus, manuscript writing or educational events from Vertex, Vifor and OM Pharma; and paid (to their institution and/or themself) participation on data safety monitoring or advisory boards for Polyphor, Santhera (DMC), Vertex, OM Pharma, Vifor and Sanofi Aventis, all in the 36 months prior to manuscript submission. Conflict of interest: D. Marangu declares no competing interests. Conflict of interest: J. Marthin declares no competing interests. Conflict of interest: K.G. Nielsen declares no competing interests. Conflict of interest: P. Robinson declares no competing interests. Conflict of interest: N. Rumman declares no competing interests. Conflict of interest: M. Rutter declares no competing interests. Conflict of interest: W. Walker declares no competing interests. Conflict of interest: J.S. Lucas declares no competing interests., (Copyright ©The authors 2022.)

Coronavirus disease 2019 (COVID-19) has negatively affected the delivery of respiratory diagnostic services across the world due to the potential risk of disease transmission during lung function testing. Community prevalence, reoccurrence of COVID-19 surges and the emergence of different variants of SARS-CoV-2 have impeded attempts to restore services. Finding consensus on how to deliver safe lung function services for both patients attending and for staff performing the tests are of paramount importance. This international statement presents the consensus opinion of 23 experts in the field of lung function and respiratory physiology balanced with evidence from the reviewed literature. It describes a robust roadmap for restoration and continuity of lung function testing services during the COVID-19 pandemic and beyond. Important strategies presented in this consensus statement relate to the patient journey when attending for lung function tests. We discuss appointment preparation, operational and environmental issues, testing room requirements including mitigation strategies for transmission risk, requirement for improved ventilation, maintaining physical distance and use of personal protection equipment. We also provide consensus opinion on precautions relating to specific tests, filters, management of special patient groups and alternative options to testing in hospitals. The pandemic has highlighted how vulnerable lung function services are and forces us to re-think how long-term mitigation strategies can protect our services during this and any possible future pandemic. This statement aspires to address the safety concerns that exist and provide strategies to make lung function tests and the testing environment safer when tests are required., Competing Interests: Conflict of interest: A. McGowan has nothing to disclose. Conflict of interest: P. Laveneziana reports personal fees from Novartis France, Chiesi France and Boehringer France, outside the submitted work. Conflict of interest: S. Bayat has nothing to disclose. Conflict of interest: N. Beydon has nothing to disclose. Conflict of interest: P.W. Boros has nothing to disclose. Conflict of interest: F. Burgos reports participation on a scientific advisory board for Medical Graphics Coorporation Diagnostics. Conflict of interest: M. Fležar has nothing to disclose. Conflict of interest: M. Franczuk reports personal fees from AstraZeneca, Boehringer Ingelheim and Chiesi, outside the submitted work. Conflict of interest: M-A. Galarza has nothing to disclose. Conflict of interest: A.H. Kendrick has nothing to disclose. Conflict of interest: E. Lombardi reports nonfinancial support from AbbVie, personal fees from Angelini and Boehringer, personal fees and nonfinancial support from Chiesi, personal fees from GSK, nonfinancial support from Lusofarmaco, personal fees and nonfinancial support from Novartis, personal fees from Omron, grants and nonfinancial support from Restech, grants and personal fees from Sanofi, personal fees and nonfinancial support from Vertex, and personal fees from Vifor, outside the submitted work. Conflict of interest: J. Makonga-Braaksma has nothing to disclose. Conflict of interest: M.C. McCormack reports royalties from UpToDate, and personal fees from Vera Med, GlaxoSmithKline and Celgene, outside the submitted work. Conflict of interest: L. Plantier has nothing to disclose. Conflict of interest: S. Stanojevic has nothing to disclose. Conflict of interest: I. Steenbruggen has nothing to disclose. Conflict of interest: B. Thompson has nothing to disclose. Conflict of interest: A.L. Coates has nothing to disclose. Conflict of interest: J. Wanger has nothing to disclose. Conflict of interest: D.W. Cockcroft reports participation on a medical advisory board for Pharmaxis. Conflict of interest: B. Culver has nothing to disclose. Conflict of interest: K. Sylvester has nothing to disclose. Conflict of interest: F. de Jongh has nothing to disclose., (Copyright ©The authors 2022.)

Aims: This study addressed two questions: first, does surgical correction of an idiopathic scoliosis increase the volume of the rib cage, and second, is it possible to evaluate the change in lung function after corrective surgery for adolescent idiopathic scoliosis (AIS) using biplanar radiographs of the ribcage with 3D reconstruction?, Methods: A total of 45 patients with a thoracic AIS which needed surgical correction and fusion were included in a prospective study. All patients underwent pulmonary function testing (PFT) and low-dose biplanar radiographs both preoperatively and one year after surgery. The following measurements were recorded: forced vital capacity (FVC), slow vital capacity (SVC), and total lung capacity (TLC). Rib cage volume (RCV), maximum rib hump, main thoracic curve Cobb angle (MCCA), medial-lateral and anteroposterior diameter, and T4-T12 kyphosis were calculated from 3D reconstructions of the biplanar radiographs., Results: All spinal and thoracic measurements improved significantly after surgery (p < 0.001). RCV increased from 4.9 l (SD 1) preoperatively to 5.3 l (SD 0.9) (p < 0.001) while TLC increased from 4.1 l (SD 0.9) preoperatively to 4.3 l (SD 0.8) (p < 0.001). RCV was correlated with all functional indexes before and after correction of the deformity. Improvement in RCV was weakly correlated with correction of the mean thoracic Cobb angle (p = 0.006). The difference in TLC was significantly correlated with changes in RCV (p = 0.041). It was possible to predict postoperative TLC from the postoperative RCV., Conclusion: 3D rib cage assessment from biplanar radiographs could be a minimally invasive method of estimating pulmonary function before and after spinal fusion in patients with an AIS. The 3D RCV reflects virtual chest capacity and hence pulmonary function in this group of patients. Cite this article: Bone Joint J  2022;104-B(1):112-119.

Introduction: Little is known on the effect of SARS-CoV-2 circulation on asthma daily symptoms in children. We compared asthma exacerbations, asthma symptom control and lung function before and after SARS-CoV-2 outbreak in children. Methods: Retrospective study of children with persistent asthma referred for lung function testing. The second quarter of 2020 being a period with nearly no activity, we compared the activity between the first, third and fourth quarters of 2019 and 2020 (Q1-2019 vs. Q1-2020, Q3-2019 vs. Q3-2020 and Q4-2019 vs. Q4-2020). Results: We retrieved 1,871 files in 2019 and 1,548 in 2020. The whole population [2,165 (63.3%) boys] had a median [IQR] age of 9.7 [6.8;13.1] years. There was no difference in age, sex, and ethnicity between 2019 and 2020 populations. Asthma was better controlled during Q4-2020 compared to Q4-2019 ( P = 0.042), and there was a lower proportion of children with at least one exacerbation in the previous 3 months after the reopening, compared to the same period in 2019 ( P < 0.0001). Baseline FEV 1 (Z-score) recorded after the reopening was significantly higher (with less reversibility) compared to the same period before the epidemic ( P < 0.0001). Baseline FEV 1 /FVC (Z-score) was significantly higher during Q3-2020 compared to Q3-2019 ( P = 0.026), with fewer children having a significant reversibility ( P = 0.035). Discussion: We demonstrated a trend toward increased exacerbations just before the recognition of the epidemic, and fewer exacerbations, better asthma symptom control and improvement in the lung function of asthmatic children after the reopening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Taytard, Coquelin and Beydon.)

The obstructive sleep apnoea syndrome (OSAS) affects 1-4% of adolescents. It represents a transitional stage between paediatric and adult OSA and is characterized by specific symptoms. BACKGROUND: The persistence of childhood OSAS during adolescence is not frequent. Risk factors are male sex, obesity and a history of tonsillectomy or adenoidectomy. Symptoms may be misleading such as tiredness and depressive disorders. In adolescence, untreated OSAS may result in neuro-behavioural and cognitive deficits, systemic inflammation, cardiovascular and metabolic disorders. The French Society of Research and Sleep Medicine organized a meeting on OSAS in adolescents. A multidisciplinary group of specialists (pulmonologists, pediatricians, ENT and maxillo-facial surgeons, dentofacial orthopedists/orthodontists, myofunctional therapists and sleep specialists) exchanged their experience, discussed publications and drew up a consensus document on the diagnosis and polysomnographic criteria for OSAS in adolescents. They proposed a practical diagnostic guideline and follow-up for these adolescents. OUTLOOK AND CONCLUSION: A good knowledge of the particularities of this pathology by the physician will lead to an early diagnosis, propose adapted multifactorial treatments and avoid the deleterious consequences of this pathology at adult age., (Copyright © 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: The Mediterranean diet (MD) has known health benefits, but its specific impact on allergy development is unclear. As part of the PARIS birth cohort follow-up, we aimed to investigate the adherence of 8-year-old children to the MD and its association with allergic/respiratory morbidity at school age., Methods: Diet was assessed using a food frequency questionnaire completed by the parents. Adherence to the MD was assessed based on two scores: the KIDMED index and the Mediterranean Diet Score (MDS). Current allergic diseases (asthma, rhinitis, eczema), lung function indices (FEV 1 and FVC), FeNO and specific IgE levels were determined during a health check-up at 8 years. Associations between levels of adherence to the MD and respiratory/allergic morbidity were studied using multivariable logistic and linear regression models adjusted for potential confounders., Results: A total of 975 children were included in the present study, 35.6% with low adherence to the MD, 55.7% with moderate adherence and 8.7% with high adherence according to the KIDMED index. High family socioeconomic status, any breastfeeding at 6 months and consumption of organic food were associated with higher adherence to the MD. Compared with low adherence, high adherence was associated with lower risk of asthma and sensitization at 8 years, as well as higher FEV 1 and FVC., Conclusion: This study suggests a protective effect of high adherence to the MD on allergic and respiratory morbidity at school age. These results need to be confirmed by further longitudinal analyses. A healthy diet may prevent allergic and respiratory morbidity in school-aged children., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Daily levels of ambient air pollution and pollen may affect lung function but have rarely been studied together. We investigated short-term exposure to pollen and air pollution in relation to lung function in school-age children from a French population-based birth cohort., Methods: This study included 1063 children from the PARIS (Pollution and Asthma Risk: an Infant Study) cohort whose lung function and FeNO measurements were performed at age 8 years old. Exposure data were collected up to 4 days before testing. We estimated daily total pollen concentration, daily allergenic risk indices for nine pollen taxa, as well as daily concentrations of three air pollutants (particulate matter less than 10 µm (PM 10 ), nitrogen dioxide (NO 2 ), ozone (O 3 )). Children with similar pollen and air pollution exposure were grouped using multidimensional longitudinal cluster analysis. Associations between clusters of pollen and air pollution exposure and respiratory indices (FEV 1 , FVC, FeNO) were studied using multivariable linear and logistic regression models adjusted for potential confounders., Results: Four clusters of exposure were identified: no pollen and low air pollution (Cluster 1), grass pollen (Cluster 2), PM 10 (Cluster 3) and birch/plane-tree pollen with high total pollen count (Cluster 4). Compared with children in Cluster 1, children in Cluster 2 had significantly lower FEV 1 and FVC levels, and children from Cluster 3 had higher FeNO levels. For FEV 1 and FVC, the associations appeared stronger in children with current asthma. Additional analysis suggested a joint effect of grass pollen and air pollution on lung function., Conclusion: Daily ambient chemical and biological air quality could adversely influence lung function in children., Competing Interests: Competing interests: HA, NB, MT, NBe, IM and FR have nothing to disclose. GL reports personal fees from Novartis Pharma, personal fees from AstraZeneca, personal fees from YSSUP research, during the conduct of the study; personal fees from DBV technologies, personal fees from Aimune therapeutics, outside the submitted work. MB-H reports personal fees from Stallergene, personal fees from ALK, outside the submitted work; personal fees and non-financial support from Stallergene, personal fees and non-financial support from ALK, non-financial support from Astra Zeneca, outside the submitted work. JJ reports grants and personal fees from Novartis, grants and personal fees from AstraZeneca, personal fees from ALK, personal fees from Thermofischer, outside the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Nasal nitric oxide (nNO) measurement is recommended to screen for Primary Ciliary Dyskinesia (PCD) in subjects with suggestive history and symptoms. Clinical use of alternative methods (i.e., breath-hold [BH], tidal breathing [TB]) in children unable to perform the gold standard slow Exhalation against a Resistance (ER) method has not been sufficiently evaluated. We extracted retrospectively (2013-2019) 454 files (374 subjects) containing nNO results. Median [IQR] age at inclusion was 7.0 [4.7-11.0] years, 105 (28.1%) children were younger than 5 years. ER or BH methods were more frequently mastered by children older than 5 years compared to younger children (69.4% and 52.7% vs. 21% and 5.6%, respectively; p < .0001), the latter succeeding only in TB measurement in 77.4% of cases. In 130 files with both ER and BH measurements (nNO-ER and nNO-BH), nNO-BH was 102 [96.2; 108.3]% that of nNO-ER. In 175 files including nNO-ER and nNO-TB measurements, nNO-TB was 64.4 [IQR: 53.7; 80.4]% that of nNO-ER with an excellent correlation between nNO values (r = .94 [95% CI 0.91; 0.95]; p < .0001) and discordance in the interpretation of nNO results in 16 (10.2%) cases. Final PCD diagnosis was similar in patients included before or after 5 years of age (confirmed 16 (15.2%) and 48 (17.8%); excluded 81 (77.1%) and 192 (71.4%), respectively; p = .32). In conclusion, reliable nNO-BH and nNO-ER results are interchangeable. Children tested with ER or with TB method have similar final PCD diagnosis. Alternative methods to measure nNO might be studied further for use in clinical practice., (© 2021 Wiley Periodicals LLC.)

Peripheral (or small) airway obstruction (PAO) is considered a marker of childhood asthma but the techniques able to directly measure it are rarely used in routine. Usual spirometry and plethysmography can detect a certain degree of PAO when reduced forced vital capacity (FVC) is associated to normal forced expiratory volume in 1 s (FEV 1 ) to FVC ratio, and normal total lung capacity (TLC). The frequency of this functional pattern has never been studied in different pediatric respiratory conditions. To assess the prevalence and outcome of PAO in children with different diseases or symptoms, we retrospectively extracted from our database all files of Caucasian subjects encompassing spirometry and plethysmography measurements. Spirometry patterns (normal, airflow limitation [AFL; low FEV 1 /FVC], low FVC [with normal FEV 1 /FVC]) and final functional patterns (normal, AFL, PAO, restrictive [low TLC], or mixed) were described. We included 4394 files recorded in 1794 children (median [IQR] age: 10.7 [9.2-12.9] years). At inclusion, 125 (7%) children had low FVC of which 56 (44.8%, and 3.1% [95% CI 2.3-3.9] of the whole population) had PAO. PAO prevalence increased with age (OR (95% CI) per 2-year-increase: 2.26 (1.59-3.23); p < .001), and was more frequent in chronic bronchial diseases other than asthma (1.6% vs. 8.0%). On repeated tests, PAO frequently normalized (26.1%) or persisted (43.5%), but it less often progressed into AFL (13%) or restrictive (13%) patterns. PAO is an infrequent nonspecific and persistent functional pattern. Its prevalence increases with age and in diagnosis of chronic respiratory diseases other than asthma., (© 2020 Wiley Periodicals LLC.)

Background: As infant feeding may influence allergy development, we aimed to identify groups of infants based on feeding practices and to examine their associations with respiratory health/allergy at 8 years in the PARIS birth cohort., Methods: Data on breastfeeding, consumption of infant formula (regular, pre-/probiotics, partially hydrolysed with hypoallergenic label [pHF-HA], extensively hydrolysed [eHF], soya) and solid food introduction were collected using repeated questionnaires at 1, 3, 6, 9 and 12 months. Infants with similar feeding practices over the first year of life were grouped using multidimensional longitudinal cluster analysis. Respiratory/allergic morbidity was studied at 8 years as symptoms, doctor's diagnoses (asthma, hay fever, eczema, food allergy), and measurement of lung function, FeNO and specific IgE. Associations between feeding-related clusters and respiratory/allergic morbidity were investigated using multivariable logistic and linear regression models adjusted for potential confounders including early respiratory/allergic outcomes and parental history of allergy., Results: Five clusters were identified among 3446 infants: Cluster 1 (45%) mainly fed with regular formula, Cluster 2 (27%) exclusively breastfed during the first 3 months, and three other clusters consuming different types of formula (pre-/probiotics for Cluster 3 [17%], pHF-HA for Cluster 4 [7%], eHF/soya for Cluster 5 [4%]). Compared to Cluster 1, children from Cluster 2 tended to have a lower risk of asthma and children from Cluster 4 had a significant lower lung function (FEV 1 , FVC), higher FeNO and higher risk of sensitization at 8 years., Conclusion: Early pHF-HA use was negatively associated with objective measures of respiratory/allergic morbidity at school age, while children breastfed for at least 3 months seem protected against asthma at 8 years old., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

None: We report the case of a female patient aged 12 years referred to our pediatric sleep unit with a history of central sleep apnea associated with transient episodes of tachypnea on polysomnography recordings. The patient was otherwise healthy, with no personal or family medical history, and had a normal physical and neuropsychological examination. Brain magnetic resonance imaging showed signs of cerebellar vermis dysplasia but without the classical features of the molar tooth sign. The rest of the workup (genetic tests, blood tests, cardiac investigations) was normal except for an increased peripheral chemosensitivity to carbon dioxide and oxygen. The patient was successfully treated with bilevel positive airway pressure. This case report highlights the importance of performing brain magnetic resonance imaging in patients with central sleep apnea to study the cerebellum, beyond the brainstem area. Cerebellar malformations can be found even in the absence of any other neurological condition., (© 2020 American Academy of Sleep Medicine.)

The COVID pandemic has passed its first peak for now in many countries while some are still on the rise, with some facing a second wave of cases. Precautions and infection control measures for both pediatric and adult pulmonary function testing (PFT) have been a topic of debate during the pandemic. Many centers had to close their PFT laboratories during the initial periods of the pandemic and are reopening as the numbers of new cases are decreasing. This review aims to summarize different practices of PFT laboratory management in different countries, including patient appointments, personal protective equipment, testing room requirements and telemedicine during and immediately following the COVID pandemic., (Copyright © 2020. Published by Elsevier Ltd.)

Asthmatic children free of exacerbation with airway obstruction may have low partial pressure of oxygen (PaO 2 ) which can be a marker for future risk, but PaO 2 is scarcely measured during pulmonary function testing. We prospectively included asthmatic children with airway obstruction referred for pulmonary function testing, including blood gas analysis (n = 51). Hypoxaemia, defined as a value lower than - 2 z-score, was present in 15 (29%) children, and 37 (72%) children had a significant reversibility after bronchodilator administration. The multivariable model showed a positive influence of baseline forced expiratory volume in 1 s (FEV 1 ) on PaO 2 (β coefficient 0.69, [95% CI: 0.07; 1.30]; P = 0.03), whereas uncontrolled asthma and FEV 1 reversibility negatively influenced it (β coefficient - 1.59 [95% CI: - 2.74; - 0.44]; P = 0.01; and - 0.07 [95% CI: - 0.13; - 0.02]; P = 0.01, respectively). As a consequence, children with uncontrolled symptoms of asthma and FEV 1 reversibility ≥ 12% were significantly more at risk of having hypoxaemia compared to children with well/partly controlled asthma or no significant reversibility of FEV 1 .Conclusion: Among obstructive asthmatic children without current exacerbation, hypoxaemia is more likely to be seen in children with uncontrolled asthma and a significant post-bronchodilator FEV 1 reversibility, in favour of different pathophysiology and treatment requirements of their airway obstruction.What is Known:• Recommendations are to treat asthmatic children in order to control respiratory symptom and maintain normal pulmonary function.• Asthmatic children free of exacerbation may have different pathophysiology for airway obstruction (central, peripheral, inflammatory, spasticity, remodelling) and should be treated according the pathophysiology of their airway disease.What is New:• In obstructive asthmatic children free of current exacerbation, the presence of hypoxaemia (ventilation-perfusion mismatch) is influenced by asthma control and post-bronchodilator reversibility, independently of the level of baseline airway obstruction.• The presence of hypoxaemia in obstructive asthmatic children free of current exacerbation can be highly suspected by the composite index "uncontrolled asthma + FEV 1 reversibility ≥ 12%" which may guide treatment.

Background: There is a high prevalence of obstructive sleep apnea (OSA) in children with Down syndrome (DS), sometimes associated with alveolar hypoventilation., Objective: To compare transcutaneous partial pressure of carbon dioxide (PtcCO 2 ) and pulse oximetry (SpO 2 ) in children with DS and in control children with OSA., Patients and Methods: This retrospective case-control study involved children followed in Trousseau Hospital (Paris) Sleep Center. Polysomnography (PSG) recordings and clinical files of children with DS were reviewed to identify clinical signs of OSA and comorbidities associated with DS. Controls were children who presented with OSA of ENT origin without other comorbidities (exceptions: two overweight, one obese, and three with well-controlled asthma). DS subjects and controls were matched for age and apnea hypopnea index., Results: There were 28 children in each group. Mean PtcCO 2 during sleep was significantly higher in patients with DS compared to controls (44 mm Hg vs 42 mm Hg, P = .001). Five (21%) patients with DS met the American Academy of Sleep medicine criteria for hypoventilation, compared to one (4%) in the control group. The mean PtcO 2 during sleep was significantly lower in patients with DS (77 mm Hg vs 82 mm Hg, P = .003)., Conclusions: This is the first study to compare nocturnal gas exchange in children with DS to a control group of children with similar OSA. Our data demonstrate that children with DS have increased PtcCO 2 regardless of the presence of OSA and its severity. This may be due to respiratory muscle hypotonia and/or ventilatory control alteration in patients with DS., (© 2020 Wiley Periodicals, Inc.)

Cilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs and IDAs). Defects in ODAs and IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. PCD mutations in assembly factors have been shown to cause a combined ODA-IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the absence of only IDAs in respiratory cilia. Analyses of both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach revealed an IDA defect restricted to a subset of single-headed IDAs that are different in flagella and cilia, whereas TTC12 depletion in the ciliate Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella., (Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Few studies have investigated the 24-hour respiratory health effects of personal black carbon (BC) and ultrafine particles (UFP) exposure in schoolchildren. The objective of this study was to investigate these associations with the lung function in children 10-years old with and without persistent respiratory symptoms., Methods: We conducted a cross-sectional study in 305 children (147 and 158 with and without persistent respiratory symptoms, respectively) from three European birth-cohorts: PARIS (France) and INMA Sabadell and Valencia (Spain). Personal 24-hour measurements of exposure concentrations to BC and UFP were performed by portable devices, before lung function testing. Forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and the fraction of exhaled nitric oxide (FeNO) were determined., Results: There was no association of UFP with lung function parameters or FeNO whereas the increase in 24-hour BC exposure concentrations was related to a statistically significant decrease in lung function parameters only among children with persistent respiratory symptoms [-96.8 mL (95% Confidence Interval CI: -184.4 to -9.1 mL) in FVC, and -107.2 mL (95% CI: -177.5 to -36.9 mL) in FEV 1 for an inter-quartile range of 1160 ng/m 3 exposure increase]. A significant positive association between BC and FeNO was observed only in children with persistent respiratory symptoms with current wheezing and/or medication to improve breathing [FeNO increases with +6.9 ppb (95% CI: 0.7 to 13.1 ppb) with an inter-quartile range BC exposure increase]., Conclusion: Children suffering from persistent respiratory symptoms appear to be more vulnerable to BC exposure., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: The reference technique to measure the diffusing capacity of the lung for carbon monoxide (DLco) is the single-breath method (sb). For patients unable to perform this method, the rebreathing method (rb) can be used. However, the clinical relevance of DLCOrb has not been evaluated. The aim of this study was to assess the feasibility of the rb method in children seen in a clinical setting and its relationships with sb method., Subjects and Method: We prospectively included children referred for 1) a suspected or confirmed interstitial lung disease (ILD group) (DLCOsb and DLCOrb measurements) ; 2) controlled asthma with normal lung function (DLCOrb measurements to derive DLCOrb/KCOrb expected values). DLCOrb was computed from the decrease in CO and Helium concentrations during tidal breathing in a rebreathing bag., Results: Data on DLCOrb measurements were available for 53 (91%) children in the ILD group and 48 (91%) control children (mean (range) 11.5 (4.3-18.2) and 9.5 (4-17) years ; respectively). In the ILD group, high or moderate correlations were found between raw DLCOrb and DLCOsb values (rhô=0.82 ; P<0.0001) and between KCOrb and KCOsb (rhô=0.62 ; P<0.0001), respectively. Results expressed as percentage predicted were moderately correlated (rhô=0.55 ; P=0.0003 for DLCO ; rhô=0.51 ; P=0.001 for KCO)., Conclusion: DLCOrb is easy to perform in children and gives values that are highly correlated to DCLOsb. Our preliminary results are in favour of a possible clinical use after further validation., (Copyright © 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

The 10-year-old European syllabus for paediatric respiratory medicine (PRM; also known as paediatric pulmonology) was updated by a consensus-based method using an expert task force for redrafting, and a subsequent Delphi process to achieve consensus. There was a high degree of consensus for the final syllabus, which has been streamlined and made more relevant to current practice. All modules are now mandatory apart from the undertaking of research projects, which is optional. Although there are still a number of countries in Europe which do not recognise PRM as a separate subspecialty, there are paediatric respiratory physicians practising in every country in Europe, and a current and harmonised European syllabus in the subspecialty remains important for defining the training and areas of practice of PRM practitioners., Competing Interests: Conflict of interest: R. Primhak has nothing to disclose. Conflict of interest: N. Tabin is an employee of the European Respiratory Society. Conflict of interest: N. Beydon has nothing to disclose. Conflict of interest: J. Bhatt has nothing to disclose. Conflict of interest: E. Eber has nothing to disclose. Conflict of interest: J. Hammer has nothing to disclose. Conflict of interest: A. Martinez-Gimeno has nothing to disclose. Conflict of interest: F. Midulla has nothing to disclose. Conflict of interest: R. Nenna has nothing to disclose. Conflict of interest: J. Paton has nothing to disclose. Conflict of interest: R. Ross Russell has nothing to disclose.

Background: Sleep-disordered breathing (SDB), including obstructive sleep apnea syndrome, is often underestimated because it requires a burdensome test (ie, polysomnography) to ensure diagnosis. To improve polysomnography referral, it is of utmost importance to validate efficient alternative screening tools. This study aimed to provide a translation and a cross-cultural validation of the Pediatric Sleep Questionnaire (PSQ) into French to obtain an easy-to-use and reliable screening tool. The psychometric properties of the French version were also determined., Methods: The process of cross-cultural adaptation was carried out following these steps: forward-backward translation, evaluation by an expert committee, and pretesting of the pre-final version. Reliability of the French-PSQ version was assessed by Cronbach's alpha coefficients and Spearman's correlation on a convenient sample of 201 children (aged between 2 and 17 years). Construct validity was determined by factor analysis of principal components., Results: Internal consistency was within an adequate range for all subscales: 0.711 for snoring, 0.559 for sleepiness, 0.682 for behavioral problems, and 0.776 for the whole questionnaire. Spearman's correlation analysis comparing questionnaires administered two weeks apart showed good correlation coefficients for all subscales (snoring: 0.642, sleepiness: 0.846, behavioral problems: 0.780, and entire SRBD scale: 0.835). Factor analysis performed to assess the structure of the French-SRBD scale confirmed the same four factors described in the original questionnaire ("breathing," "behavior," "sleepiness," and "other")., Conclusion: The French version of the PSQ has been successfully cross-culturally adapted and showed good psychometric properties, suggesting that it is useful as a tool to screen sleep-disordered breathing in French-speaking children., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Natural course and co-occurrence of asthma, eczema, and allergic rhinitis through childhood are still not fully documented. We aim to identify and characterize profiles based on the time course, severity, and apparent triggers of respiratory/allergy symptoms in school-aged children., Methods: Data on occurrence, severity, and triggers of asthma, rhinitis, and dermatitis symptoms were collected annually during the follow-up of the PARIS birth cohort. Children with similar symptom trajectories until 8-9 years were grouped into profiles using multidimensional (all symptoms considered simultaneously) cluster analysis. Associations between profiles and different health outcomes were analyzed using logistic or linear regression models., Results: Six distinct symptomatic profiles were identified. A profile was defined by persistent dermatitis symptoms, associated with sensitization to food and aeroallergens. Two profiles were characterized by wheezing: one with early transient wheezing and the other with persistent wheezing related to doctor-diagnosed asthma, airway obstruction, and perennial aeroallergen sensitization. Three profiles were characterized by rhinitis symptoms: one non-allergic and two allergic, either with persistent rhinitis symptoms related to allergic multimorbidity and sensitization to perennial aeroallergens, or with late-onset symptoms, related to both pollen and perennial aeroallergens sensitization as well as low lung function., Conclusion: This study brings further insights into the developmental profiles of respiratory/allergic outcomes from birth to school age. The identified profiles clearly differed regarding objective features such as diagnosed morbidity, sensitization, or lung function measurements, thus highlighting their biologic and clinical relevance. Allergic rhinitis profiles deserve particular attention, since they were likely to be involved in multimorbidity patterns., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Aim: Using a non-invasive lung function technique (interrupter resistance, Rint), we aimed to determine whether a dose-response to salbutamol could be detected in wheezy preschool children and if so, which dose of salbutamol should be administered to routinely evaluate bronchial reversibility., Method: Wheezy children (3 to <7 years) were enrolled in a prospective multicenter study. Rint was measured at baseline, and after random assignment to a first dose (100 or 200 μg) and a second dose (cumulative dose: 400, 600, or 800 μg) of salbutamol. Data were analyzed using mixed modeling approach with an inhibitory maximal effect (I max ) model, to account for a sparse sampling design. Simulations were performed to predict the percentage of children with significant Rint reversibility at several doses., Results: Final results were available in 99 children out of 106 children included. The model adequately fitted the data, showing satisfactory goodness-of-fit plots and a low residual error of 8%. Children with uncontrolled symptoms had lower I max (ie, showed less reversibility) compared to children with totally/partly controlled symptoms (0.23 vs. 0.31, P < 0.001). Dose to reach 50% of I max (D 50 ) was 51 μg. According to simulations, 88.1% of children with significant reversibility at dose 800 μg would already show significant reversibility at 400 μg., Conclusion: Interrupter resistance was able to measure a dose-response curve to salbutamol in wheezy preschool children, which was similar to that of older patients. Young children require a high dose of salbutamol to correctly assess airway bronchodilator response, especially these with poor symptom control., (© 2018 Wiley Periodicals, Inc.)

Bronchial challenge with the direct bronchoconstrictor agent methacholine is commonly used for the diagnosis of asthma. The "Lung Function" thematic group of the French Pulmonology Society (SPLF) elaborated a series of guidelines for the performance and the interpretation of methacholine challenge testing, based on French clinical guideline methodology. Specifically, guidelines are provided with regard to the choice of judgment criteria, the management of deep inspirations, and the role of methacholine bronchial challenge in the care of asthma, exercise-induced asthma, and professional asthma., (Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Rationale: Although the effects of traffic-related air pollution on respiratory exacerbations have been well documented, its impact on lung function in childhood remains unclear., Objectives: Our aim was to investigate the associations of prenatal, early, and lifetime traffic-related air pollution exposure with lung function at 8-9 years studying possible effect modification by sex, sensitization at 8-9 years, and early lower respiratory tract infections., Methods: We conducted this study among 788 children from the PARIS (Pollution and Asthma Risk: an Infant Study) birth cohort. Lung function tests were performed during the medical examination at 8-9 years. Traffic-related air pollution exposure during each trimester of pregnancy was estimated using nitrogen oxides background measurements. Postnatal traffic-related air pollution exposure was assessed by a nitrogen oxides air dispersion model at both residential and daycare/school addresses. Associations between lung function and traffic-related air pollution exposure were analyzed by multiple linear regression models., Results: Higher prenatal nitrogen oxides levels, especially during the second trimester of pregnancy, were associated with a lower forced expiratory flow at 25-75% of the forced vital capacity, but there were no significant associations between prenatal nitrogen oxide levels and forced vital capacity, forced expiratory volume during 1 second, or the forced expiratory volume during 1 second/forced vital capacity ratio overall. Postnatal traffic-related air pollution exposure was associated with lower lung function among children with early lower respiratory tract infections or sensitization at 8-9 years, but not in the full cohort. In children with early repeated lower respiratory tract infections, an interquartile increase in lifetime nitrogen oxides exposure was associated with both a lower forced expiratory volume during 1 second (-62.6 ml; 95% confidence interval = -107.0 to -18.1) and forced vital capacity (-55.7 ml; 95% confidence interval = -109.5 to -1.8), but was not associated with the forced expiratory volume during 1 second/forced vital capacity ratio. There was an association between greater early postnatal nitrogen oxide exposure and a lower forced expiratory volume during 1 second/forced vital capacity ratio among sensitized children (-0.65%; 95% confidence interval = -1.25 to -0.05)., Conclusions: This study sheds new light, suggesting associations between postnatal traffic-related air pollution exposure and reduced lung function may be enhanced by early, repeated lower respiratory tract infections or allergic sensitization.

Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) both entail bronchiectasis and pulmonary impairment as measured using spirometry, during childhood. We aimed at looking whether blood gas exchanges progressed differently between CF and PCD children in a retrospective study of repeated measurements. Comparisons between groups (Wilcoxon-Mann-Whitney and Chi-squared tests) and a mixed linear model, adjusted for age, evaluated associations between diseases and PaO 2 , PaCO 2, or PaO 2- PaCO 2 ratio. Among 42 PCD and 73 CF children, 62% and 59% had respectively bronchiectasis (P = 0.75). Spirometry and blood gases were similar at inclusion (PaO 2 median [IQR] PCD -1.80 [-3.40; -0.40]; CF -1.80 [-4.20; 0.60] z-scores; P = 0.72). PaO 2 and PaO 2 -PaCO 2 ratio similarly and significantly decreased with age in both groups (P < 0.01) whereas PaCO 2 increased more in CF (P = 0.02) remaining within the range of normal (except for one child). To conclude, gas exchange characteristics, similarly initially impaired in PCD and CF children, tended to less deteriorate with time in PCD children who could benefit from an early diagnosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: A written action plan (WAP) reduces emergency visits for asthma exacerbations. However, a WAP is underused and often focused on asthma control. The innovation is an AppWeb that includes an expert software aimed at diagnosing the level of severity of asthma exacerbations and delivering a personalized digital action plan (DAP) when patients are in urgent need of medical advice. Symptoms describing the level of severity of asthma exacerbations and the consequent treatments have been established by working groups of the French Respiratory Societies (SPLF and SP2A for adults and children, respectively). The main objective of the study is to evaluate the effect of the DAP on the frequency of urgent medical attendance. Secondary objectives are to evaluate adherence to the DAP compared to a WAP and the qualitative satisfaction of patients using the DAP., Methodology: A randomized, prospective, comparative, multicenter study on two parallel groups, conducted in private practice and in hospitals. In both arms, asthmatic patients (240 children aged 6 to 12 years and 270 adults aged 18 to 50 years) with severe asthma exacerbation(s) during the previous year and an Internet connection via a smartphone or a tablet computer, will have at their disposal a WAP and one arm will have, in addition, the DAP. Included patients will be followed up every three months for one year., Expected Results: A decrease in the number of urgent medical attendances and better adherence in the WAP+DAP group compared to the WAP group., (Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Paediatric obstructive sleep apnoea syndrome (OSAS) is a highly prevalent condition carrying increased risk for impaired cognitive and cardiovascular function. The standard diagnosis consists of full-night polysomnography (PSG), but limited access to PSG leads to substantial under-diagnosis. The use of a validated and simple diagnostic screening tool to predict OSAS could prioritise night sleep recordings in children at risk of OSAS, and help in clinical decision-making., Objective: This study aimed to prospectively assess the performance of the French version of the severity hierarchy score (SHS) in paediatric OSAS. This score consists of a discriminative subset of six respiratory items, and has already been validated in English for screening OSAS in the general paediatric population., Methods: A total of 96 children (mean age 7.1 ± 2.4 years; BMI z-score: -0.03 ± 1.50) were recruited; they had been were referred to two academic sleep centres in France for the putative diagnosis of sleep-disordered breathing. The parents completed the SHS questionnaire prior to PSG. Sensitivity and specificity of the SHS for detecting moderate OSAS, defined by an apnoea-hypopnoea index (AHI) of ≥5/hours of total sleep time (TST), were assessed, and ROC analysis was performed., Results: An SHS score of >2.75 exhibited an 82% sensitivity, 81% specificity, and 92% negative predictive value for detecting an AHI of ≥5/hour TST in the cohort., Conclusion: The French version of the SHS emerged as favourably suited for the screening for OSAS in children., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Asthma is a common problem in children and, if inadequately controlled, may seriously diminish their quality of life. Inhaled short-acting beta2 agonists such as salbutamol are usually prescribed as 'reliever' medication to help control day-to-day symptoms such as wheeze. As with many medications currently prescribed for younger children (defined as those aged 2 years 6 months to 6 years 11 months), there has been no pre-licensing age-specific pharmacological testing; consequently, the doses currently prescribed (200-1000 μg) may be ineffective or likely to induce unnecessary side effects. We plan to use the interrupter technique to measure airway resistance in this age group, allowing us for the first time to correlate inhaled salbutamol dose with changes in clinical response. We will measure urinary salbutamol levels 30 min after dosing as an estimate of salbutamol doses in the lungs, and also look for genetic polymorphisms linked to poor responses to inhaled salbutamol., Methods: This is a phase IV, randomised, controlled, observer-blinded, single-centre trial with four parallel groups (based on a sparse sampling approach) and a primary endpoint of the immediate bronchodilator response to salbutamol so that we can determine the most appropriate dose for an individual younger child. Simple randomisation will be used with a 1:1:1:1 allocation., Discussion: The proposed research will exploit simple, non-invasive and inexpensive tests that can mostly be performed in an outpatient setting in order to help develop the evidence for the correct dose of salbutamol in younger children with recurrent wheeze who have been prescribed salbutamol by their doctor., Trial Registration: EudraCT2014-001978-33, ISRCTN15513131. Registered on 8 April 2015.