Search

Little is known about motor competence and the longitudinal development of motor performance among youth with cystic fibrosis (CF). In this study, we assessed aspects of motor performance in different age groups of young patients with CF and compared them with a healthy reference group of same aged children. We also examined the development of motor performance among different age groups of these children with CF, using The Deutscher Motorik Test (DMT) to assess attributes of health-related and motor performance-related fitness. We used an incremental ergometer cycle test to determine maximal exercise capacity (expressed as peak workload). We evaluated and recorded habitual physical activity (PA) as measured by the number of steps per day and the time spent in different PA intensities (expressed in metabolic equivalents). In total, 31 children and adolescents with CF agreed to participate (13 girls,18 boys) aged 6–17 years ( M = 11.3, SD =3.3 years); they had a mean one second forced expiratory volume (expressed as a percentage of predicted value [% pred]) of 87.2% ( SD = 22.3%). We found their values of health-related and motor performance-related fitness to be significantly lower ( p

Das zystische Nephrom ist ein seltener Nierentumor des Kindesalters. 70 % der Falle sind mit einer DICER1-Mutation assoziiert und stellen somit den zweithaufigsten Tumor des DICER1-Syndroms dar. Wir stellen den Fall eines 15 Monate alten Jungen mit DICER1-Syndrom mit einem zystischen Nephrom vor. Der Organerhalt war nicht moglich. Aufgrund der hohen Pradisposition fur Keimzelltumoren sind auch nach Nephrektomie weitere Kontrollen bis in das Erwachsenenalter notwendig.

Der Ubergang von einer kindorientierten zu einer erwachsenenorientierten Gesundheitsfursorge bei Patienten mit Mukoviszidose (zystischer Fibrose [CF]) hat in den letzten Jahrzehnten an Bedeutung gewonnen, da die Lebenserwartung von Menschen mit Mukoviszidose kontinuierlich gestiegen ist. Der Ubergangsprozess (Transition) beginnt gewohnlich in der Adoleszenz und wird mit dem physischen Transfer des jungen Erwachsenen in die Erwachsenenmedizin abgeschlossen. Die historisch als „Kinderkrankheit“ geltende Mukoviszidose ruckt durch das steigende Alter der Patienten zunehmend in den Fokus der Erwachsenenmedizin. Hier gilt es, entsprechende medizinische Versorgungsstrukturen fur diese komplexe Erkrankung vorzuhalten und Kapazitaten zu schaffen, um die Kinderkliniken zu entlasten, die haufig die Versorgung bereits erwachsener Patienten aufrechterhalten haben. Die altersbedingt erhohte Komplikationsrate stellt spezielle Anforderungen an die Versorgung von erwachsenen Mukoviszidosepatienten. Hierzu zahlen nicht nur das Erkennen und Behandeln von Komplikationen, sondern auch eine medizinische Versorgungsstruktur, die darauf ausgerichtet ist, die mit der Mukoviszidose assoziierten Komorbiditaten wie den Diabetes mellitus oder die CF-Hepatopathie adaquat zu versorgen. Ein Behandlerteam aus Arzten, erfahrener CF-Pflege, Physiotherapie, Ernahrungstherapie, Psychologie und sozialem Dienst muss in der weiterfuhrenden Versorgung zu Verfugung gestellt werden, um dem Anspruch an eine allumfassende Behandlung der komplexen Erkrankung Mukoviszidose gerecht zu werden.

Purpose Sleep disturbances and poor sleep quality are known to be present in patients with CF. Regular physical activity plays an important role in the treatment of CF patients due to its positive influence on progression of disease and quality of life. The aim of this work is to create a home-based sleep and activity profile and to investigate the influence of habitual physical activity (HPA) on sleep quality in children, adolescents, and adults with CF. Methods A total of 109 CF patients (64 male, mean age 22.7 ± 12.0 years; mean ppFEV1 63.0 ± 26.7) were equipped with an actigraph for a home-based collection of data on sleep and activity over 4 weeks. Results Age, FEV1, and BMI affect sleep and activity in CF patients. Especially younger age and higher FEV1 show a great influence on certain aspects of sleep (SE, TST, TIB, WASO, # of awakenings) and activity and its different intensities. General HPA does not affect sleep, but there is a strong correlation between times spent in vigorous to very vigorous intensities and better sleep quality. Conclusion Besides younger age and higher FEV1, daily activity in higher intensities influences sleeping behavior of CF patients in a positive way. Patients with poor sleep quality and sleep disturbances possibly benefit from an intensification of physical activity in the home environment. Trail registration number: 14–6117-BO (University Duisburg-Essen) and NCT 03518697 (clinical trials).

Summary Background Tezacaftor–ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8–24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor–ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor–ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation. Methods Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor–ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor–ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov ( NCT02565914 ). Findings Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor–ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor–ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor–ivacaftor-treated F/F participants versus untreated matched historical controls. Interpretation Tezacaftor–ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor–ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor–ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes. Funding Vertex Pharmaceuticals Incorporated.

Background:Transition from child-oriented to adult-oriented health care in Cystic Fibrosis (CF) has become more important over recent decades as the survival of people with this disease has increased. The transition process usually begins in adolescence, with full transfer completed in early adulthood.Objective:This study investigated the impact of a short-term transfer program on clinical markers in an adult CF cohort still being managed by pediatricians.Methods:Clinically relevant data from the year before (T-1), the time of Transfer (T) and the year after the transfer (T+1) were analysed retrospectively.Results:39 patients (median age 29.0 years; 64% male) were transferred between February and December 2016. Lung function had declined significantly in the year before transfer (in % predicted: Forced Expiratory Volume in 1 second (FEV), 62.8vs.57.7,pvs.71.1,pP. aeruginosa, Methicillin-Resistant Staphylococcus aureus (MRSA) andBurkholderiasp. during the observation period. The number of patient contacts increased significantly in the year after versus the year before transfer (inpatient: 1.51vs.2.51,pvs.3.41,pConclusions:Our data show that, within the framework of a structured transfer process, it is possible to transfer a large number of adult CF patients, outside a classic transition program, from a pediatric to an adult CF center in a short period of time, without any relevant changes in clinical markers and, stability.

IntroductionMassive haemoptysis is a life-threatening event in advanced cystic fibrosis (CF) lung disease with bronchial artery embolisation (BAE) as standard of care treatment. The aim of our study was to scrutinise short-term and long-term outcomes of patients with CF and haemoptysis after BAE using coils.MethodsWe carried out a retrospective cohort study of 34 adult patients treated for massive haemoptysis with super selective bronchial artery coil embolisation (ssBACE) between January 2008 and February 2015. Embolisation protocol was restricted to the culprit vessel(s) and three lobes maximum. Demographic data, functional end-expiratory volume in 1 s in % predicted (FEV1% pred.) and body mass index before and after ssBACE, sputum colonisation, procedural data, time to transplant and time to death were documented.ResultsPatients treated with ssBACE showed significant improvement of FEV1% pred. after embolisation (p=0.004) with 72.8% alive 5 years post-ssBACE. Mean age of the patients was 29.9 years (±7.7). Mean FEV1% pred. was 45.7% (±20.1). Median survival to follow-up was 75 months (0–125). Severe complication rate was 0%, recanalisation rate 8.8% and 5-year-reintervention rate 58.8%. Chronic infection with Pseudomonas aeruginosa was found in 79.4%, Staphylococcus areus in 50% and Aspergillus fumigatus in 47.1%.DiscussionssBACE is a safe and effective treatment for massive haemoptysis in patients with CF with good results for controlling haemostasis and excellent short-term and long-term survival, especially in severely affected patients with FEV

BACKGROUND: Home noninvasive ventilation (NIV) improves disease courses of patients with respiratory insufficiency due to neuromuscular diseases. Data about appropriate ventilator settings for pediatric patients are missing. METHODS: In this retrospective study, ventilator settings of 128 subjects with neuromuscular disease aged 0–17 y with NIV were compared between 4 age groups (< 1 y, 0–5 y, 6–11 y, and 12–17 y). Additionally, correlations of ventilator settings with age and vital capacity were investigated in an ungrouped approach. RESULTS: Ventilator backup rate decreased significantly with age, leading to significant backup rate differences between all groups except the oldest two. Median (interquartile range) backup rates were 36 (11.5), 24 (4), 20 (4), and 20 (3) breaths/min in groups 1–4, respectively. Median [IQR] expiratory positive airway pressures (4 [0.5], 4 [0], 4 [0], 4 [1] cm H(2)O, respectively) and median [IQR] inspiratory positive airway pressures (12 [1.5], 12 [5], 12 [2.3], and 14 [4] cm H(2)O, respectively) showed no significant differences. However, correlation analyses indicated an increase of inspiratory positive airway pressure with age and decreasing FVC, as well as an increase of backup rates with decreasing FVC. CONCLUSIONS: Similar NIV settings fit all age groups of pediatric subjects with neuromuscular disease. Thus, we propose an expiratory positive airway pressure of 4–5 cm H(2)O, an inspiratory pressure delta of 8–10 cm H(2)O, and an age-oriented backup rate as a starting point for NIV titration. Patients with advanced disease stages might require slightly higher inspiratory positive airway pressures and backup rates.

Introduction Hypersensitivity pneumonitis (HP) in children is a severe interstitial lung disease and potentially, a chronic condition, if not treated appropriately. No evidence-based guidelines are available; in particular, the role of systemic glucocorticoid therapy is unclear. Methods The aim of this randomized, double-blind, placebo-controlled, parallel-group, multi-center, phase II trial in pediatric HP was to assess the outcome of HP in children after 6 months of treatment and to compare 3 months of treatment with oral prednisolone or placebo. Results After 1.5 years and the inclusion of only four children, we terminated the study prematurely. Two of the children randomized to prednisolone did not achieve the predefined response of FVC to normal. One child treated with placebo recovered to normal, similar to another child treated with prednisolone. All children treated with steroids developed drug-related side effects. Discussion This uncompleted study illustrates the urgent medical need for evidence-based treatment protocols for this condition. We discuss the hurdles which were specific for completion of this trial in a rare condition. Among other options, we suggest the inclusion of children into an all-age study of HP, as in adults the same questions are unanswered.

Extramural langzeitbeatmete Kinder und Jugendliche sind trotz fortlaufender Steigerung der Pravalenz noch immer selten, und die Grunderkrankungen sind sehr vielseitig. Die groste Gruppe bilden neuromuskulare Erkrankungen. Fur diese Patienten ist die nichtinvasive oder invasive Beatmung in sich rehabilitativ, insbesondere wenn ein kompetentes Uberleitmanagement auf die optimale Teilhabe und Kommunikation abzielt sowie durch Schulung Sicherheit im Alltag und in Notfallen generiert. Durch fortlaufende Betreuung am Kompetenzzentrum sollte eine etwaige Moglichkeit fur ein Weaning bzw. eine Dekanulierung evaluiert und leitliniengerecht genutzt werden. Neben einer ambulanten rehabilitativen Betreuung besteht gerade bei komplexeren Krankheitsbildern und auch bei Palliativpatienten Bedarf an stationarer medizinischer Rehabilitation. Die Patienten sollten in einem stabilen Zustand sein, und die respiratorische Sicherheit sollte gegeben sein, oft unterstutzt durch eine gut geschulte, vertraute Begleitperson. Die Rehabilitationsziele sollten definiert und realistisch sein. Bei schwer erkrankten Patienten setzt die Erreichung nicht nur ein breit gefachertes biopsychosoziales Therapieangebot voraus, sondern ist auch eine Frage der personellen Ressourcen und Kompetenzen der Klinik und damit von Tagessatzen, die die hoheren Kosten decken.

Background. Regular physical activity plays an important role in the treatment of patients with cystic fibrosis (CF). This study is aimed at investigating the effects of a 12-month partially supervised exercise program on attributes of health-related and motor performance fitness, lung function (ppFEV1), BMI, and habitual physical activity (HPA, steps/day) in adults with CF. Methods. Attributes of health-related and motor performance fitness were examined at the beginning (T0), after 6 (T1), and 12 months (T2) on the basis of five test items: forward bend (FB), bent knee hip extension (HE), plank leg raise (PLR), standing long jump (SLJ), and standing on one leg (OLS). Additionally, we recorded HPA by accelerometry, peak exercise performance ( W peak ) by an incremental cycle test, ppFEV1, and BMI. During the first six months, there was close supervision by an experienced sport therapist. Results. 26 CF patients (8 female, mean age 26.5 ± 7.9 years; ppFEV1 53.7 ± 21.0 ) completed the exercise program. Significant improvements were recorded from T0 to T1 (FB: p ≤ 0.05 ; PLR, OLS: p ≤ 0.01 ) and from T0 to T2 (FB, PLR: p ≤ 0.01 and HE, OLS: p ≤ 0.05 ). W peak , ppFEV1, BMI, and HPA showed no significant improvement between the single test points and over the entire study period (all p > 0.05 ). Conclusion. Our results show trainability of adults with CF in aspects of health-related and motor performance fitness during a partially supervised exercise program. Close supervision positively influences the results. Using a simple test setup seems to be a promising tool for evaluating the effects of exercise programs in CF and could serve as an additional outcome parameter in future clinical trials. Trial registration: ClinicalTrials.gov (retrospectively registered May 8, 2018).

Introduction In pediatric patients, flexible bronchoscopy requires deep sedation. Different sedation regimes are common, but only some of them include opioids. Due to their antitussive effect, the use of short-acting opioids may be beneficial for this particular indication, but additional respiratory depression may lead to an increase in adverse events. Here, we systematically compared sedation regimes in children undergoing flexible bronchoscopy with either propofol alone, or a combination of propofol and remifentanil. The primary outcome parameter was the frequency of coughing episodes during the intervention. Secondary outcome parameters were frequency and types of complications, patient satisfaction, examiner satisfaction, and recovery time after finishing the sedation. Methods Fifty children aged 1-17 years undergoing flexible bronchoscopy under deep sedation with propofol were randomly assigned to two groups: PR receiving propofol and remifentanil and PP receiving propofol only. Sedation depth was predefined as Comfort Score 10-13. Results We found significantly less coughing episodes ([med (IQR)] PR: 0.73 (0.28-2.45)/min; PP: 1.98 (1.26-3.12)/min; p = .010) and shorter recovery time in Group PR (PR: 13.5 (8-17.5) min; PP: 21.0 (14-27) min; p = .011). Examiner's satisfaction was higher in Group PR (PR: 10 (8-10); PP: 9 (7-9); p = .012). The number of adverse events, patient satisfaction, and required propofol dose during the intervention did not differ between groups. Conclusion We suggest the combination of propofol with remifentanil instead of using propofol alone in pediatric procedural sedation for flexible bronchoscopy.

Objective To examine the effect of intrathecal application of nusinersen on the respiratory function in terms of vital capacity in pediatric patients with spinal muscular atrophy (SMA). SMA is characterized by on-going muscular atrophy and weakness that lead to respiratory insufficiency. In recent years therapy with nusinersen has been shown to improve motor function in patients with SMA. Methods We retrospectively analyzed data from 12 pediatric patients (aged 4–12 years) with SMA II or III (7 walkers, 5 sitters) treated with nusinersen. We examined forced vital capacity (FVC) at baseline (i.e., before treatment) and 180 and 300 days after initiation of treatment. Results No significant difference in the ranks of FVC of patients with SMA at baseline and day 300 was found and, thus, stable FVCs are implied (n = 6; Z = - 0.105, pexact = 1.000; Medianbaseline = 96.0%, 95%-CI [86.5, 110.5]; Medianday300 = 96.0%, 95%-CI [92.0, 109.5]; s. Table 1). This also applied to the comparison between baseline and day 180 (n = 7; Z = 0.00, pexact = 1.00; Medianbaseline = 93.0%, 95%-CI [85.0, 110.0]; Medianday180 = 91.0%, 95%-CI [72.0, 118.0]) and day 180 and 300 (n = 9; Z = - 0.533, pexact = .652; Medianday180 = 95.0%, 95%-CI [72.0, 118.0]; Medianday300 = 90.0%, 95%-CI [74.0, 105.0]). Conclusion Nusinersen therapy alone may not improve lung function of pediatric patients with SMA type II or III.

Background: Diagnosis and treatment of paediatric tuberculosis resistant to both isoniazid and rifampicin (MDR-pTB) remain challenging due to paucibacillary disease, low sensitivity and specificity of diagnostic tools and frequently changing guidelines Aims and objective: This study aimed to describe epidemiology, clinical characteristics and outcome of MDR-TB among children and adolescents in Germany. Methods: We collected all cases of MDR-pTB registered in Germany from 2010 to 2020 and compared their data to an adequate control sample with drug-sensitive TB. Results: 52 subjects with MDR-pTB (24 active MDR-TB, 28 MDR-LTBI) and 56 controls were included. The annual incidence of MDR-TB rose from two in 2010 to nine in 2020. Time to diagnosis was longer in MDR-pTB compared to drug-sensitive TB (43 vs. 8 days, p Conclusions: Early diagnosis, identification of potential MDR index, appropriate treatment and follow-up are essential in MDR-pTB. Therefore, better cooperation between clinics and public health care is required in Germany. In children with an MDR-TB index case or in those born in a MDR high-incidence country, bacteriological confirmation including PCR-based susceptibility testing should always be initiated. The individual drug regimen has to be adapted to the patients’ or index’ susceptibility testing results.

BACKGROUND: Sleep disturbances and poor sleep quality are a known phenomenon in patients with Cystic Fibrosis (CF). Habitual physical activity (HPA) plays an important role in the treatment of CF patients due to its positive influence on progression of disease and quality of life. The aim of this work is to create a home-based sleep and activity profile and to investigate the influence of habitual physical activity (HPA) on sleep quality of children, adolescents and adults with CF. METHODS: One hundred and nine CF patients (64 male, mean age 22.7±12.0 years; mean ppFEV1 63.0±26.7) were equipped with an actigraph (Actigraph Corp., Pensacola, FL, United States) for home-based collection of activity and sleep data for a total of 4 weeks. Evaluation of recorded raw data was performed by ActiLife software, Version 6.11.9 (Actigraph Corp., Pensacola, FL, United States). RESULTS: CF patients under the age of 18 show the best sleep efficiency (92%±3%), the longest time in bed (TIB) (545±71 min) and Total Sleep Time (504±72 min) and the lowest Wake after sleep Onset (WASO) (39±15 min). With increasing age there is a decrease in Sleep efficiency (SE) (P0.05). In terms of lung function, CF patients with FEV1 values > 70%pred. have the best SE (92%±3%), the highest TST (490±72 min) and TIB (531±71 min) and the lowest WASO (39±13 min). As FEV1 deteriorates, a change in sleeping behavior can be detected. SE (P0.05) decrease, whereas WASO (P>0.05) increases. Interestingly, there is no difference in the number of awakenings between the different age and FEV1 groups (all P>0.05). Statistical analysis was performed using version 25 of the SPSS statistics package (SPSS Inc., Chicago, USA). CONCLUSIONS: Besides younger age and higher FEV1, daily activity in higher intensities influences sleep of CF patients in a positive way. Patients with poor quality and disturbances of sleep possibly benefit from an intensification of physical activity in the home environment.

Introduction: chILD comprises various rare respiratory conditions and partially overlaps with adult ILD. Lung fibrosis is the most common disease entity in adults; however, there are no data on the prevalence, clinical, radiological and histopathological presentation of pulmonary fibrosis in chILD. Aim: To assess the prevalence of fibrosis in lung biopsies from the international management platform, the European chILD registry (NCT02852928), and to correlate paediatric lung fibrosis with radiological findings. Methods: Features of fibrosis in biopsies were defined by the presence of any of the following: description of interstitial fibrosis, fibroblastic foci or honeycombing. A histological diagnosis of chronic pneumonitis of infancy (CPI) was also included. Fibrosis by chest computed tomography (CT) scans was defined by the presence of linear or reticular opacities, honeycombing, traction bronchiectasis or architectural distortion. Results: Lung biopsies were available for 149/825 chILD cases (18%); 46 biopsies (31%) had features of fibrosis and 11 were identified by CPI pattern alone. Mean age at biopsy was 6.4 years (range 0–26). Thirty cases were related to alveolar surfactant region (ABCA3: n=11; SFTPC: n=3), five to systemic disease processes (e.g. connective tissue disease: n=2) and three to immunodeficiency. Individual cases accounted for the other categories. Only 21/46 cases (46%) with biopsy-proven features of fibrosis had fibrosis features by CT. Conclusions: Features of fibrosis were already present in 31% of cases with a diagnostic lung biopsy. Concordance between biopsy- and CT-diagnosed fibrosis was lower than expected and requires further evaluation.

Pompe disease is a rare metabolic myopathy caused by deficiency of lysosomal α-glucosidase. Reduced enzyme activity results in abnormal intra- and extralysosomal glycogen deposition as well as impaired cellular function and autophagy. Age at manifestation and severity of disease depend on residual enzyme activity. Enzyme replacement therapy (ERT) is available since 2006. In infantile onset Pompe disease, the most severe form, markedly prolonged survival has resulted in a new phenotype with symptoms and problems not encountered previously. In addition, it became apparent that antibody formation against the recombinant human enzyme may adversely affect the response to ERT. This review summarizes new knowledge gained in the last years concerning care of pediatric patients with Pompe disease and gives recommendations for diagnostics, treatment, and follow-up.Morbus Pompe ist eine seltene metabolische Myopathie, bei der ein Mangel an lysosomaler Alpha-Glukosidase zur pathologischen intra- und extralysosomalen Speicherung von Glykogen sowie zu gestörter Autophagie führt. Je nach Alter bei Beginn können klassisch infantile sowie kindliche, juvenile und adulte Formen unterschieden werden. Alter bei Manifestation und Schweregrad hängen von der Enzym-Restaktivität ab. Seit 2006 ist eine Enzymersatztherapie (EET) verfügbar. Das verlängerte Überleben von Patienten mit infantiler Verlaufsform führt zum Auftreten neuer Symptome, die bisher bei diesen Kindern nicht beschrieben wurden. Zudem hat sich gezeigt, dass eine Antikörperbildung gegen das rekombinante humane Enzym den Erfolg der EET negativ beeinflussen kann. Dieser Artikel fasst neue Erkenntnisse zusammen, die in den letzten Jahren hinsichtlich neuer klinischer Symptome und therapeutischer Probleme gewonnen wurden, und gibt Empfehlungen für Initialdiagnostik, Behandlung und Verlaufserfassung des Morbus Pompe im Kindesalter.

BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization. (PROSPERO: CRD42020178187).

The aim of this study was to examine motor performance and trainability in youths with cystic fibrosis (CF).Twenty-two children and adolescents (11 f/11 m), age range 6-17 years (11.3 ± 3.3 years), mean FEV1 91.0 ± 21.7% pred.finished the partially monitored 12-months exercise program. Patients performed the Deutsche Motorik Test (DMT) to assess flexibility, balance, strength, power and totalmotor performance. An incremental ergometer cycle test was used to assess maximal exercise capacity (Wpeak). All tests were performed before (T1), after 6 months of monitored exercise training (T3) and another 6 months without monitoring (T4).Motor Competence in total and test-items of the DMT (except foreward bend) improved to T3 (p .05). No further improvement could be observed after the end of the monitoring (T3). However, the values remained stable at the improved level (T4). Girls scored lower in test items depending on strength/power but scored higher in balancing compared to boys (p .05). Wpeak and FEV1 were not influenced by the training program. From T3 to T4 a slight decrease was observed (p ≤ .05).The findings demonstrate benefits of an individualizedmonitored long-term exercise intervention on motor performance in CF with improvements of test-tasks to predicted normal. Monitoringseems to be a facilitator in maintaining motivation toward physical activity as no further increase in motor performance was observed after stopping supervision. The results suggest that an individually tailored monitoredregular exercise program should include all aspects of physical fitness with a variety of movement experiences.

Objective While out-of-center testing was introduced as an alternative for the diagnosis of obstructive sleep apnea in adults, polysomnography (PSG) is still considered mandatory in the diagnosis of sleep-disordered breathing (SDB) in children. The purpose of this study was to validate the outpatient screening device ApneaLink ® in comparison to PSG in children and adolescents for the diagnosis of SDB. Methods Sixty consecutive children and adolescents (10.4 ± 6.2, 0–22 years) with suspected SDB admitted to the sleep laboratory underwent simultaneous recording with full PSG and the screening device ApneaLink ® based on flow measurement and oxygen saturation. Results The mean apnea–hypopnea index (AHI) was 11.8 ± 19.7 in PSG and 10.3 ± 12.0 in ApneaLink ® . When the AHI threshold was set to 5/h to diagnose SDB, the overall sensitivity for ApneaLink ® was 79% and the specificity was 63%. After reducing the AHI threshold to 1/h, the sensitivity and specificity were 94% and 29%. In children older than 10 years, the performance of ApneaLink ® improved (AHI 5/h: sensitivity 80%, specificity 64%; AHI 1/h: sensitivity 100%, specificity 50%). Conclusion These results show that the outpatient screening device ApneaLink ® reliably identifies SDB in preselected children older than 10 years. In contrast, it may not be used for the exclusion of SDB.

OBJECTIVES The lung clearance index (LCI) is determined by multiple-breath washout lung function (MBW). It is increasingly used as an endpoint in clinical trials. Chest physiotherapy (CP) is part of routine cystic fibrosis (CF) care. Whether the LCI is useful in detecting short-term treatment effects of CP has not been sufficiently investigated. We assessed the short-term influence of CP with highly standardized high-frequency chest wall oscillation (HFCWO) on the LCI in CF patients. METHODS In this randomized controlled study, the LCI was obtained in 20 CF patients (7-34 years) hospitalized for infective pulmonary exacerbation prior to and immediately after a single treatment of HFCWO. Twenty-one control group CF patients (7-51 years) received no treatment. We calculated the coefficient of repeatability (CR) to estimate the clinical relevance of possible treatment effects. RESULTS HFCWO improved (ie, decreased) the LCI by a median of 0.9 (range −0.45; 3.47; P = 0.002); the LCI decreased in 15 of 20 intervention group patients. In five patients the decrease in LCI exceeded the CR (2.15), indicating a clinically relevant treatment effect; in five patients the LCI increased but did not exceed the CR. The LCI did not change significantly in the control group patients. CONCLUSIONS HFCWO can have a short-term decreasing effect on the LCI, but the treatment response is heterogeneous. In future trials using LCI as an endpoint, the timing of CP in relation to MBW should be considered a possible bias.

Background: Life expectancy in Cystic Fibrosis (CF) patients is low which may rise personal questions regarding spiritual issues to cope. Aims and Objectives: Aims of our study were to explore which spiritual needs are of relevance and their association with indicators of quality of life or disease progression in adolescents and adults with CF. Methods: Cross-sectional multi-center survey using standardized questionnaires (i.e., SpNQ, BMLSS, GrAw-7). Descriptive statistics, analyses of variance, first order correlations and regression analyses were applied. Results: 115 patients (20 adolescents, 95 adults) with a mean age of 30.4±13.1 years participated in the survey. Needs for Attention/Affirmation (AA) (1.59±.86) and for inner peace (IP) (1,39±.97) scored highest, while religious needs (RN) (.51±.78) and existential needs (EN) (.69±.75) scored low. Usage of a respirator was associated with higher AA (F=10.1; p=.002) and IP (F=6.2; p=.015), and being on the waiting list for lung transplantation (LTX) was associated with higher AA (F=4.8, p=.030), higher EN (F=5.3; p=.023) and higher RN (F=15.5 (p Conclusions: Needs for AA and IP are important for patients with CF; RN become more relevant for patients on a waiting list for LTX. Evaluation of patient´s needs can provide clinicians with useful information to further support them in difficult life situations.

Home non-invasive ventilation improves morbidity and mortality patients with respiratory insufficiency due to neuromuscular disease. Evidence-based information on adequate ventilator settings for paediatric patients is missing. In a single-centre retrospective study, we analysed ventilator settings for 128 patients aged 0-17 years with home non-invasive ventilation on account of respiratory insufficiency due to neuromuscular disease. In four defined age groups (

BACKGROUND: Culturing of bronchoalveolar lavage (BAL) fluid is a commonly used method for pathogen detection in pneumonia. However, the sensitivity is low, especially in patients pre-treated with anti-infective agents. The early detection of a pathogen is crucial for the outcome of respiratory tract infections. For bloodstream infections, a multiplex polymerase chain reaction (PCR) assay (SeptiFast®, SF) is available for improved pathogen detection from blood. OBJECTIVE: The aim of the present study was to determine whether the SF assay is applicable to the BAL of children with pulmonary infections and whether the frequency of pathogen detection is enhanced by the use of this multiplex PCR method. METHODS: We investigated 70 BAL samples of 70 children simultaneously by culture and multiplex PCR. The frequency of pathogen detection was compared. RESULTS: Pathogens were detected more frequently by SF than by culture (83% vs. 31%; p

Background In patients with severe neurological impairment, recurrent respiratory tract infections frequently occur as a result of impaired clearance of airway secretions and microbial airway colonisation. We hypothesised that inhaled antibiotic therapy may improve the morbidity of these patients. Methods A retrospective data analysis of 20 patients (11 nontracheotomised and nine tracheotomised) with neurological impairment and microbial airway colonisation was carried out at a children's university hospital. Two questionnaires that asked about the number of respiratory tract infections, antibiotic therapies and hospitalisations were distributed to the patients/caregivers: a first questionnaire representing the 12 months prior to the initiation of inhaled antibiotics and a second questionnaire describing the first 12 months under therapy. Results During the first 12 months of therapy, the frequency of respiratory tract infections among all participants was reduced from a mean of 6.8 episodes (median (interquartile range (IQR)) 6.0 (4.0–10.0) episodes) to a mean of 2.5 episodes (median (IQR) 2.0 (1.0–3.0) episodes; p, Inhaled antibiotic therapy offers a novel approach to the prevention of respiratory tract infections in patients with severe neurological impairment who have chronic microbial airway colonisation and recurrent respiratory tract infections http://bit.ly/2HQRyz0

Background and objective Inherited neuromuscular disorders (NMD) inevitably result in severe lung volume restriction and cough insufficiency associated with high morbidity and mortality. The aim of this retrospective study was to evaluate whether the airways of patients with NMD are colonized with potential pathogenic microorganisms that might contribute to the pulmonary morbidity in NMD. Methods In this cross-sectional study, cough swabs were obtained and cultured for microbiological analyses from 77 patients with NMD and different degrees of lung volume restriction and cough insufficiency. Upper airway microbial colonization was compared to lung function parameters and cough peak flow values. Results Upper airway microbial colonization with potential pathogenic pathogens was identified in 39/77 (51%) of the subjects. Upper airway microbial colonization was associated with lower forced vital capacity (% pred.) 26.6 ± 19.7 versus 41.8 ± 20.4, P

Objectives: Aspergillus fumigatus is the most prevalent filamentous fungus in the respiratory tract of patients with cystic fibrosis (CF). The aim of this prospective multicentre study was to investigate the prevalence of azole-resistant A. fumigatus (ARAF) in respiratory secretions from CF patients across Germany and to characterize ARAF isolates by phenotypic and molecular methods. Methods: Twelve tertiary care centres from Germany participated in the study. In total, 2888 A. fumigatus isolates from 961 CF patients were screened for ARAF by using azole-containing agar plates. Antifungal susceptibility testing of isolates was performed by broth microdilution according to EUCAST guidelines. Analysis of mutations mediating resistance was performed using PCR and sequencing of the cyp51A gene. Furthermore, genotyping by microsatellite PCR was performed. Results: Of a total of 2888 A. fumigatus isolates, 101 isolates from 51 CF patients were found to be azole resistant (prevalence per patient 5.3%). The Essen centre had the highest prevalence (9.1%) followed by Munich (7.8%), Munster (6.0%) and Hannover (5.2%). Most ARAF isolates (n = 89) carried the TR34/L98H mutation followed by eight G54E/R, one TR46/Y121F/T289A and one F219S mutation. In two isolates no mutation was found. Genotyping results showed no major clustering. Forty-five percent of CF patients with ARAF had previously received azole therapy. Conclusions: This is the first multicentre study analysing the prevalence of ARAF isolates in German CF patients. Because of a resistance rate of up to 9%, susceptibility testing of A. fumigatus isolates from CF patients receiving antifungal treatment should be part of standard diagnostic work-up.

We report the case of a 19-years-old patient who presented with a perplexing variety of symptoms which included remarkable facial features, intellectual disability, granulomatous upper lip swelling (previously diagnosed as Melkersson–Rosenthal syndrome), Crohn’s-like disease, non-productive cough, and a granulomatous mass localized in the left lung. Chronic granulomatous disease (CGD) was diagnosed using dihydrorhodamine 123 assay that showed low levels of phagocytic NADPH-oxidase. DNA sequencing revealed a heterozygous mutation in the NCF-1 gene on chromosome 7. As remarkable facial features and psychomotor retardation are not associated with CGD, a more detailed genetic work-up using fluorescence in situ hybridization was performed. A microdeletion in 7q11.23 on one allele indicated Williams–Beuren syndrome (WBS). The NCF-1 gene and its two pseudogenes are part of a highly repetitive region within 7q11.23 and are prone to recombination events and deletions. Such deletions can involve both the WBS critical region and the NCF-1 wildtype gene, as was the case for our patient. The second allele of the NCF-1 gene was affected by the frequent c.75.76delGT mutation that stems from a recombination of the NCF-1 wildtype gene with one of its pseudogenes. In conclusion, patients with NCF-1-deficient CGD may also harbor microdeletions that result in WBS or other hereditary disorders; therefore, it is important to perform a thorough genetic analysis in order to initiate appropriate therapy for these patients. CA Soukup

Inherited neuromuscular disorders inevitably result in severe lung volume restriction associated with high morbidity and mortality. The aim of this retrospective study was to evaluate the long-term effects of the regular use of mechanical insufflation/exsufflation on the course of the vital capacity. This retrospective data analysis included 21 patients (16.1 ± 6.5 years) with neuromuscular disorders and severe lung volume restriction using nocturnal noninvasive ventilation. The patients were advised to regularly use the mechanical insufflation/exsufflation twice a day for 10 minutes applying sets of three insufflation/exsufflation breath via face mask irrespective of respiratory tract infection. Data on the course of vital capacity were collected 2 years prior and 2 years after the introduction of regular use of mechanical insufflation/exsufflation. Before the introduction of mechanical insufflation/exsufflation vital capacity decreased from 0.71 ± 0.38 L to 0.50 ± 0.24 L in the last year and from 0.88 ± 0.45 L to 0.71 ± 0.38 L in the next to last year. In the first year, after regular use of mechanical insufflation/exsufflation vital capacity significantly increased by 28% (from 0.50 L to 0.64 L)—after the second year the vital capacity increase remained stable (0.64 vs. 0.65 L). These data suggest that the regular use of mechanical insufflation/exsufflation improves vital capacity in patients with neuromuscular disorders and severe lung volume restriction.

Background: Bloodstream pathogens can be identified by multiplex PCR (SeptiFast (SF)) or blood culture (BC); whether these pathogens are present in cystic fibrosis (CF) patients during febrile pulmonary exacerbations (FPE) has not been sufficiently studied. Methods: In this prospective observational study, blood from CF patients experiencing FPE was tested with SF and BC before the initiation of antibiotic treatment. Results: After contaminants had been excluded, 9 of 72 blood samples tested positive by BC or SF. SF exclusively detected four pathogens; BC, one. Pulmonary pathogen transmission was likely in all cases except for 2 cases of candidaemia, which were believed to be caused by catheter-related infections. For three cases, test results caused us to change the antibiotic regimen. Sensitivity (85.7% vs. 42.9%) and negative predictive value (98.4% vs. 87.0%) tended to be higher for SF than for BC. Conclusions: The results of SF and BC show that bacteraemia and fungaemia are present in CF patients during FPE and may affect antibiotic therapy. SF can help rule out catheter-related bloodstream infections. OA gold

Introduction. Antibiotic treatment regimens againstPseudomonas aeruginosalung infection in cystic fibrosis (CF) patients often include aminoglycoside antibiotics that may cause chronic renal failure after repeated courses. Aminoaciduria is an early marker of acute aminoglycoside-induced renal tubular dysfunction. We hypothesized that urinary amino acid reabsorption is decreased after repeated once-daily tobramycin therapies.Methods. In this prospective cross-sectional study creatinine clearance was estimated by the Schwartz and the Cockcroft-Gault formula. Tubular amino acid reabsorption was determined by ion exchange chromatography in 46 patients with CF who received multiple tobramycin courses (6.3±10.1(1–57)) in a once-daily dosing regimen and 10 who did not.Results. Estimated creatinine clearance employing the Cockcroft-Gault was mildly reduced in 17/46 (37%) of the patients who received tobramycin and 5/10 (50%) of the patients who did not but in none using the Schwartz formula. No association with lifetime tobramycin courses was found. Tubular amino acid reabsorption was not influenced by the amount of once-daily tobramycin courses.Conclusion. Clinically not significant reduction of eCCL occurred in a minority of CF patients. However, chronic tubular dysfunction was not present in patients with CF repeatedly treated with tobramycin in the once-daily dosing scheme.

Background In pediatric neuromuscular disorders (NMD), respiratory muscle weakness parallels respiratory failure. The objectives of this study are (1) to evaluate respiratory muscle capacity in neuromuscular children and (2) to assess the relationship between vital capacity, respiratory muscle performance, and alveolar ventilation during sleep and wakefulness. Methods Inspiratory vital capacity (IVC), peak inspiratory pressure (PIP), mouth occlusion pressure (P 0.1 ), and noninvasive tension-time index of the respiratory muscles (TTImus) were studied in 80 NMD subjects (12.1 ± 3.3 years) and 80 healthy children (11.1 ± 2.2 years). Subjects' results were compared with arterial blood gases and polysomnography. Results In 15 NMD subjects with normal ventilation IVC and PIP were reduced to 70% predicted but TTImus was normal. In 50 NMD subjects with nocturnal hypoventilation IVC and PIP were lower than 50% predicted, TTImus was doubled compared with the control group. In 15 NMD subjects with diurnal and nocturnal hypoventilation IVC and PIP were below 30% predicted, TTImus was increased fourfold, and thus the main determinant of respiratory failure. Conclusions In NMD children, reduced IVC and PIP result in increased respiratory muscle load and disturbed ventilation. TTImus is an important noninvasive determinant of disturbed ventilation in children with NMD.

Background There is only sparse data on the use of non-invasive ventilation (NIV) in acute respiratory failure (ARF) in infants and children. For this setting we investigated feasibility and efficacy of NIV and aimed to identify early predictors for treatment failure. Patients and Methods Retrospective chart review was performed for all patients treated with NIV for ARF from 2003 to 2010 on an 8-bed pediatric intensive care unit of a tertiary university hospital. Results Seventy-four patients were treated with NIV. One patient did not tolerate mask ventilation and needed immediate invasive ventilation. Intubation rate of the remaining patients was 23% and mortality 15%. Institution of NIV led to significant improvement of both respiratory and heart rate in all patients within the first hour and to further stabilization within the next 8–10 hr. In patients with NIV success blood gases improved significantly 1–2 hr after starting NIV. Multivariate analysis identified low pH after 1–2 hr to be an individual risk factor for NIV failure. Other factors tested were age, underlying disease, acute respiratory insufficiency versus post-extubation failure (PEF), and 1–2 hr after starting NIV oxygen saturation, respiratory rate, PCO2, and FiO2. Patients with PEF tended to show better outcomes compared to those with acute respiratory insufficiency. Conclusion NIV can be effective in infants and children with ARF. Low pH 1–2 hr after start of NIV is associated with NIV failure. It may therefore be useful in the decision to continue or stop mask ventilation. Pediatr. Pulmonol. 2011; 46:1114–1120. © 2011 Wiley Periodicals, Inc.

Thrombolysis is the only effective pharmaceutical therapy in acute ischemic stroke in humans but has a high risk of intracerebral hemorrhage. We aimed to establish an animal model to study changes of coagulation and fibrinolytic parameters during thromboembolic ischemic stroke and thrombolysis with recombinant tissue plasminogen activator (rt-PA). We used a thromboembolic stroke model in the rat. Animals were treated with rt-PA thrombolysis (n=10) and compared with untreated (n=10), sham operated (n=10) and control animals (n=20). Coagulation parameters (APTT, PT, TT, fibrinogen, AT III, TAT) and fibrinolytic parameters (t-PA antigen concentration, t-PA activity, PAI-1 concentration, PAI activity, plasminogen, antiplasmin) were measured at two time points (2.5 and 5h after stroke induction) with a battery of commercially available test kits. We observed an (1) initiation of coagulation and inhibition of fibrinolysis by the operation procedure itself, (2) simultaneous activation of fibrinolysis and its inhibitors after stroke induction and (3) potent initiation of fibrinolysis and consumption of fibrinolysis inhibitors after rt-PA therapy of stroke. We established a model system to monitor coagulation and fibrinolysis during thrombolytic therapy of stroke in the rat. This model may be used to study the influence of these parameters on hemorrhagic stroke transformation and outcome in experimental stroke in future.

Advanced stages of Duchenne muscular dystrophy (DMD) result in severe lung volume decline and are associated with high respiratory morbidity and mortality. The aim of this study was to investigate whether lung volume decline in subjects with DMD is associated with ventilation inhomogeneity measured with the multiple-breath washout technique.This cross-sectional study of lung function included 45 subjects with DMD and 16 healthy controls using multiple-breath washout, spirometry, and cough peak flow.Subjects with DMD exhibited an elevated lung clearance index (> 7.0) defined as the cumulative exhaled volume divided by the functional residual capacity to lower the sulfur hexafluoride concentration below 2.5% compared with controls (8.16 ± 2.55 vs 6.23 ± 0.46, P < .001). Lung clearance index elevation was negatively correlated with vital capacity (% predicted: r = -0.79, P < .001) and cough peak flow (L/min: r = -0.41, P = .005). Furthermore, dead-space ventilation (dead-space-to-tidal-volume ratio) and functional residual capacity showed a positive correlation with lung clearance index elevation (r = 0.81 and 0.48, P < .001). An FVC of < 24% predicted lung clearance index elevation with a sensitivity of 96% and a specificity of 80%.Moderate-to-severe lung volume decline in subjects with DMD is associated with ventilation inhomogeneity. Lung clearance index elevation may be the result of altered ventilation geometry or retention of airway secretions in the infection-free DMD subject. OA embargo

Sleep disordered breathing is a common but under-diagnosed complication causing sleep disturbance and daytime symptoms in children with spinal muscular atrophy. Non-invasive (positive pressure) ventilation is an established treatment of respiratory failure; its role in treatment of sleep disordered breathing though remains controversial. Aim of this study was to verify the hypothesis that nocturnal non-invasive ventilation has beneficial impact on breathing during sleep, sleep quality and daytime complaints in children with spinal muscular atrophy. Twelve children with spinal muscular atrophy type I or II (7.8+/-1.9 years) underwent polysomnography and were asked to fill out a symptom questionnaire. Seven patients (six with spinal muscular atrophy I and one with spinal muscular atrophy II) had sleep disordered breathing and received non-invasive ventilation during sleep. Five less severely affected patients (one with spinal muscular atrophy I and four with spinal muscular atrophy II) had no sleep disordered breathing and served as reference group. Patients were restudied after 6-12 months. In patients with sleep disordered breathing both sleep architecture and disease related symptoms were significantly worse than in the reference-group. Non-invasive ventilation during sleep completely eliminated disordered breathing, normalized sleep architecture and improved symptoms (P