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Abstract Background Primary ciliary dyskinesia (PCD) is a rare genetical disease with malfunction of the motile cilia leading to impaired muco-ciliary clearance in the respiratory tract. There is no cure for PCD, only supportive therapy aimed at minimizing the progression of the disease and improving the patient’s quality of life (QoL). Physical activity (PA) is one of these recommended supportive therapies for people with PCD (pwPCD). However, there is no scientific evidence to support this recommendation. In addition, regular medical advice to increase PA remains largely ineffective in pwPCD. Methods To test the main hypothesis, that an individualized and supported PA program leads to a better QoL 6 months after randomization (QoL-PCD questionnaire) compared to usual recommendation in pwPCD, 158 pwPCD aged 7 to 55 years are to be included in this multi-center randomized controlled trial (RCT). After the screening visit, a 1:1 randomization stratified by age group and FEV1 will be performed. A QoL-PCD questionnaire, motor test, and lung function will be carried out at regular intervals in both groups. PA is recorded in both groups using activity trackers during the study period. The main aim of the trial is to estimate the difference in the change of QoL between the groups after 6 months. Therefore, our full analysis set consists of all randomized patients and analysis is performed using the intention-to-treat principle. Statistical software R ( http://www.r-project.org ) is used. Ethical approvement without any reservations: RUB Bochum Ethics Committee (No. 23–7938; December 4, 2023). Recruitment start: March 2024. Discussion Limitations result from the rarity of PCD with its broad disease spectrum and the large age range. These are reduced by stratified randomization and the measurement of the individual change in QoL as primary endpoint. In our view, only a PA program tailored to individual needs with close contact to trainers offers the chance to meet personal needs of pwPCD and to establish PA as a pillar of therapy in the long term. The study protocol explains all procedures and methods of recruitment, implementation of the study visits and intervention, measures for patient and data safety, and for minimizing risks and bias. Trial registration German Clinical Trials Register (DRKS) 00033030. Registered on December 7, 2023. Update 10 July 2024. Study protocol version 10 Version 1.2; 12 June 2024

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 (FEV1) 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 FEV1 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.

SARS-CoV-2 infection rates in children and adolescents are often underestimated due to asymptomatic or oligosymptomatic infections. Seroprevalence studies can reveal the magnitude of “silent” infections in this age group and help to assess the risk of infection for children but also their role in spreading the disease. In total, 2045 children and their parents from the Ruhr region were finally included after the exclusion of drop-outs. Seroconversion rates among children of all age groups increased from 0.5% to 8% during the study period and were about three to fourfold higher than the officially registered PCR-based infection rates. Only 41% recalled symptoms of infection; 59% were asymptomatic. In 51% of the infected children, at least one parent also developed SARS-CoV-2 antibodies. Depending on local incidences, the rates of seroconversion rose to different levels during the study period. Although the dynamics of infection within the study cohort mirrors local incidence, the figure of SARS-CoV-2 infections in children and adolescents appears to be high. Reported contact with SARS-CoV-2-infected individuals in the same household carries a high risk of infection.

BackgroundLong-term neurological complaints after SARS-CoV-2 infection occur in 4–66% of children and adolescents. Controlled studies on the integrity of the peripheral nerve system are scarce. Therefore, we examined the somatosensory function in children and adolescents after SARS-CoV-2 infection in a case-control study compared with age-matched individuals.Materials and MethodsEighty-one subjects after SARS-CoV-2 infection (n = 44 female, 11.4 ± 3.5 years, n = 75 SARS-CoV-2 seropositive, n = 6 PCR positive during infection and SARS-CoV-2 seronegative at the time point of study inclusion, n = 47 asymptomatic infection) were compared to 38 controls without SARS-CoV-2 infection (26 female, 10.3 ± 3.4 years, n = 15 with other infection within last 6 months). After standardised interviews and neurological examinations, large fibre (tactile and vibration detection thresholds) and small fibre (cold and warm detection thresholds, paradoxical heat sensation) functions were assessed on both feet following a validated protocol. After z-transformation of all values, all participants were compared to published reference values regarding the number of abnormal results. Additionally, the mean for all sensory parameters values of both study groups were compared to an ideal healthy population (with z-value 0 ± 1), as well as with each other, as previously described. Statistical analyses: t-test, Chi-squared test, and binominal test.FindingsNone of the controls, but 27 of the 81 patients (33%, p < 0.001) reported persistent complaints 2.7 ± 1.9 (0.8–8.5) months after SARS-CoV-2 infection, most often reduced exercise capacity (16%), fatigue (13%), pain (9%), or paraesthesia (6%). Reflex deficits or paresis were missing, but somatosensory profiles showed significantly increased detection thresholds for thermal (especially warm) and vibration stimuli compared to controls. Approximately 36% of the patients after SARS-CoV-2, but none of the controls revealed an abnormal sensory loss in at least one parameter (p < 0.01). Sensory loss was characterised in 26% by large and 12% by small fibre dysfunction, the latter appearing more frequently in children with prior symptomatic SARS-CoV-2 infection. Myalgia/paraesthesia was indicative of somatosensory dysfunction. In all eight re-examined children, the nerve function recovered after 2–4 months.InterpretationThis study provides evidence that in a subgroup of children and adolescents previously infected with SARS-CoV-2, regardless of their complaints, the function of large or small nerve fibres is presumably reversibly impaired.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients.

BackgroundPersistent respiratory symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adults are frequent, and there can be long-term impairment of pulmonary function. To date, only preliminary evidence is available on persistent respiratory sequelae of SARS-CoV-2 in children and adolescents. Our objective was to examine the long-term effects of symptomatic and asymptomatic SARS-CoV-2 infections on pulmonary function in this age group in a single-center, controlled, prospective study.MethodsParticipants with serological or polymerase chain reaction-based evidence of SARS-CoV-2 infection were recruited from a population-based study of seroconversion rates. Multiple-breath washout (MBW), body plethysmography, and diffusion capacity testing were performed for children and adolescents. Participants were interviewed about their symptoms during the acute phase of infection and long-lasting symptoms. Cases were compared with SARS-CoV-2 seronegative controls from the same population-based study with and without history of respiratory infection within 6 months prior to assessment. Primary endpoints were differences in pulmonary function, including diffusion capacity and MBW, between participants with and without evidence of SARS-CoV-2 infection. Secondary endpoints included correlation between lung function and long-lasting symptoms as well as disease severity.FindingsIn total, 73 seropositive children and adolescents (5–18 years) were recruited after an average of 2.6 months (range 0.4–6.0) following SARS-CoV-2 infection. Among 19 patients (27.1%) who complained of persistent or newly emerged symptoms since SARS-CoV-2, 8 (11.4%) reported respiratory symptoms. No significant differences were detected in frequency of abnormal pulmonary function when comparing cases with 45 controls, including 14 (31.1%) with a history of previous infection (SARS-CoV-2: 12, 16.4%; controls: 12, 27.7%; odds ratio 0.54, 95% confidence interval 0.22–1.34). Only two patients with persistent respiratory symptoms showed abnormal pulmonary function. Multivariate analysis revealed reduced forced vital capacity (p = 0.012) in patients with severe SARS-CoV-2 infection.InterpretationPulmonary function is rarely impaired in children and adolescents after SARS-CoV-2 infection, except from those with severe infection, and did not differ between SARS-CoV-2 and other previous infections, suggesting that SARS-CoV-2 is not more likely to cause pulmonary sequelae than other infections. The discrepancy between persisting respiratory symptoms and normal pulmonary function suggests a different underlying pathology such as dysfunctional breathing.

In the current SARS-CoV-2 pandemic, wearing a face mask is mandatory again during school lessons. There are no controlled studies in children to date indicating an effect on cognitive performance from wearing face masks. In a randomized controlled trial, we analysed the influence of face masks on cognitive performance of pupils during regular school lessons. Pupils (n = 133, fifth to seventh grade) were randomized by alternating allocation into control (with masks, n = 65) and intervention groups (without mask, n = 68). After two school lessons with (control) and without (intervention) face masks in class, all pupils performed digital tests for cognitive performance regarding attention and executive functions (switch, Corsi block-tapping, 2-back and flanker task). Overall, there were no significant differences in cognitive performance between both groups, masks vs. no masks. Wearing face masks has no significant influence on attention and executive functions of pupils and can still be recommended during school lessons.