Background Home ventilation represents the cornerstone of treatment for ventilatory insufficiency in children. Objective Overview of the most important aspects of home ventilation in children and adolescents Material and method Narrative review incorporating the literature and practical experience. Results Despite the sometimes low level of evidence, home ventilation is becoming increasingly more important in pediatrics. The evaluation of the indications for home ventilation is sometimes complex, while the establishment is technically relatively simple. The long-term care of pediatric patients with home ventilation requires not only proven expertise but also adequate personnel and equipment. Limitations to the use of home ventilation must be recognized. Conclusion Home ventilation has a high and still increasing relevance in pediatric medicine. The growing patient population must be met with increasing expertise and improved care structures.

ZusammenfassungDie Muskeldystrophie Typ Duchenne ist die häufigste erbliche Muskelerkrankung im Kindesalter. Neben der progredienten Einschränkung der Motorik und der kardialen Beteiligung stehen die aus der Muskelschwäche resultierende restriktive Lungenerkrankung und die Hustenschwäche im Vordergrund. Die spezifische kinderpneumologische Therapie hat das Überleben und die Lebensqualität der betroffenen Jungen maßgeblich verbessert. Zu den Aufgaben des Kinder-Pneumologen gehören das Monitoring der Lungenfunktion, die Polysomnographie, der Beginn und die Anpassung der nichtinvasiven oder invasiven nächtlichen Beatmung und die Optimierung des Sekretmanagements. Aber auch die Komplettierung der Impfungen, die Ernährungstherapie, die Behandlung interkurrierender Atemwegsinfektionen sowie die Beratung und Schulung sind wichtige Aufgaben des Kinder-Pneumologen. In diesem Beitrag werden die Aspekte der pneumologischen Behandlung von Kindern mit neuromuskulären Erkrankungen am Beispiel der Muskeldystrophie Typ Duchenne im Zusammenspiel mit den anderen Fachdisziplinen aufgezeigt.

Die Heimbeatmungstherapie stellt die zentrale Therapiesäule der ventilatorischen Insuffizienz im Kindesalter dar. Überblick über die wichtigsten Aspekte der Heimbeatmung im Kindes- und Jugendalter Narratives Review unter Einbeziehung von Literatur und Praxiserfahrung Die Heimbeatmungstherapie hat trotz z. T. niedrigem Evidenzniveau einen zunehmenden Stellenwert in der Pädiatrie. Die Indikationsstellung ist teilweise komplex, während die Etablierung technisch eher simpel ist. Die Langzeitbetreuung von pädiatrischen Patienten mit Heimbeatmung erfordert neben ausgewiesener Expertise eine adäquate personelle und apparative Ausstattung. Grenzen der Möglichkeiten der Heimbeatmung sind anzuerkennen. Pädiatrische Beatmungsmedizin hat eine hohe und weiter zunehmende Relevanz. Dem wachsenden Patientenkollektiv ist mit zunehmender Expertise und verbesserter Versorgungsstruktur zu begegnen.

Duchenne muscular dystrophy is the most common inherited neuromuscular disease in children. In addition to the progressive loss of motor skills and cardiac involvement, respiratory muscle weakness leads to a restrictive lung disease and cough insufficiency. Specific respiratory interventions have significantly improved survival and quality of life of the affected boys. The pediatric pulmonologist's tasks include monitoring of the lung function, polysomnography, starting and adjusting of non-invasive or invasive nocturnal ventilation and optimizing of secretion management. Providing of vaccinations, enhancing of nutrition, treatment of intercurrent infections, and provision of advice and training are important tasks for the pediatric pulmonologist. This article emphasizes on the tasks for the pediatric pulmonologist in the treatment of children with neuromuscular diseases i. e. Duchenne muscular dystrophy in interaction with the other specialist disciplines.

Background: Long COVID (LC) is a diagnosis that requires exclusion of alternative somatic and mental diseases. The aim of this study was to examine the prevalence of differential diagnoses in suspected pediatric LC patients and assess whether adult LC symptom clusters are applicable to pediatric patients. Materials and Methods: Pediatric presentations at the Pediatric Infectious Diseases Department of the University Hospital Essen (Germany) were assessed retrospectively. The correlation of initial symptoms and final diagnoses (LC versus other diseases or unclarified) was assessed. The sensitivity, specificity, negative and positive predictive values of adult LC symptom clusters were calculated. Results: Of 110 patients, 32 (29%) suffered from LC, 52 (47%) were diagnosed with alternative somatic/mental diseases, and 26 (23%) remained unclarified. Combined neurological and respiratory clusters displayed a sensitivity of 0.97 (95% CI 0.91–1.00) and a negative predictive value of 0.97 (0.92–1.00) for LC. Discussion/Conclusions: The prevalence of alternative somatic and mental diseases in pediatric patients with suspected LC is high. The range of underlying diseases is wide, including chronic and potentially life-threatening conditions. Neurological and respiratory symptom clusters may help to identify patients that are unlikely to be suffering from LC.

The number of children with tracheostomies with and without home mechanical ventilation has grown continuously in recent years. For some of these children, the need for tracheostomy resolves and the child can be weaned from the tracheal cannula. Choosing the optimal time point for decannulation after elaborated prior diagnostic work-up needs careful consideration. The decannulation process requires an interdisciplinary team; however, these specialized structures for the experienced care of these children with tracheostomy are not available in all areas. The Working Group on Chronic Respiratory Insufficiency in the German Speaking Pediatric Pneumology Society (GPP) developed these recommendations to guide through a decannulation process. Initial evaluation of decannulation feasibility starts in the outpatient clinic with a detailed history, examination, and a speaking valve trial and is followed by an inpatient workup including sleep study, airway endoscopy and possibly modifications of the tracheal cannula. Downsizing the tracheal cannula allows a stepwise controlled weaning prior to removal of the tracheal cannula. After shrinking of the tracheostomy, the final surgical closure is performed.Conclusion: An algorithm with diagnostic and therapeutic procedures for a safe and successful decannulation process is proposed.

Introduction: Recently, cystic fibrosis transmembrane regulator modulator therapy with elexacaftor/tezacaftor/ivacaftor has become available for children with cystic fibrosis (CF) carrying at least one F508del mutation. Objective: To assess the intermediate term effects of elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis in a real-world setting. Methods: We performed a retrospective analysis of records of children with cystic fibrosis, who started elexacaftor/tezacaftor/ivacaftor between 8/2020 and 10/2022. Pulmonary function tests, nutritional status, sweat chloride and laboratory data were assessed before, 3 and 6 months after the start of elexacaftor/tezacaftor/ivacaftor respectively. Results: Elexacaftor/tezacaftor/ivacaftor was started in 22 children 6–11 years and in 24 children 12–17 years. Twenty-seven (59%) patients were homozygous for F508del (F/F) and 23 (50%) patients were transitioned from ivacaftor/lumacaftor (IVA/LUM) or tezacaftor/ivacaftor (TEZ/IVA) to elexacaftor/tezacaftor/ivacaftor. Overall, mean sweat chloride concentration decreased by 59.3 mmol/L (95% confidence interval: −65.0 to −53.7 mmol/L, p < 0.0001) under elexacaftor/tezacaftor/ivacaftor. Sweat chloride concentration also decreased significantly after transition from IVA/LUM or TEZ/IVA to elexacaftor/tezacaftor/ivacaftor (−47.8 mmol/l; 95% confidence interval: −57.6 to −37.8 mmol/l, n = 14, p < 0.0001). Sweat chloride reduction was more marked in children with the F/F than in those with the F/MF genotype (69.4 vs 45.9 mmol/L, p < 0.0001). At 3 months follow-up, body-mass-index-z-score increased by 0.31 (95% CI, 0.2–0.42, p < 0.0001) with no further increase at 6 months. BMI-for-age-z-score was more markedly improved in the older group. Overall pulmonary function (percent predicted FEV 1 ) at 3 months follow-up increased by 11.4% (95% CI: 8.0–14.9, p < 0.0001) with no further significant change after 6 months. No significant differences were noted between the age groups. Children with the F/MF genotype had a greater benefit regarding nutritional status and pulmonary function tests than those with the F/F genotype. Adverse events led to elexacaftor/tezacaftor/ivacaftor dose reduction in three cases and a temporary interruption of therapy in four cases. Conclusion: In a real-world setting, elexacaftor/tezacaftor/ivacaftor therapy had beneficial clinical effects and a good safety profile in eligible children with cystic fibrosis comparable to previously published data from controlled clinical trials. The positive impact on pulmonary function tests and nutritional status seen after 3 months of elexacaftor/tezacaftor/ivacaftor therapy was sustained at 6 months follow-up.

Mucorales are a large order of ubiquitous saprophytic zygomycete fungi and act as opportunistic pathogens in humans. In pediatric patients, little is known about the role of Mucorales in airway colonization and infection or their role as contaminants of respiratory samples. Currently, polymerase chain reaction (PCR) is the most sensitive mode of detection Mucorales in clinical specimen. In this study, we aimed to determine the prevalence of Mucorales in bronchoalveolar lavage samples (BAL) from a large, diverse group of pediatric patients. We performed commercial Mucorales PCR (MucorGenius®, Pathonostics, Maastricht, NL, USA) on 102 thawed BAL samples of 100 patients. Mucorales PCR was negative in all samples. Our data suggest that Mucorales spp. have a low prevalence in paediatric airways and do not frequently contaminate pediatric BAL samples.

Objectives: People with cystic fibrosis (pwCF) are at risk for infection with nontuberculous mycobacteria (NTM). The epidemiology and screening practice of NTM among pwCF in Germany are largely unknown and require investigation. Methods: We analyzed the data of the German Cystic Fibrosis Registry from 2016 to 2020 for NTM. The annual prevalence and incidence of any NTM, Mycobacterium abscessus complex (MABC), Mycobacterium avium complex (MAC), Mycobacterium gordonae, and other mycobacteria were determined and correlated to patient characteristics. Patients with incident MABC and MAC infection were compared. Results: The annual NTM prevalence and incidence remained stable between 7.53% and 8.76%, as well as 3.31% and 4.95%, respectively, among the approximately 6000 registry participants. MABC was the most common NTM, whereas only the prevalence of MAC increased slightly. In each year, only about one-third of all patients were screened for NTM. An association between NTM infections and Aspergillus fumigatus infection and/or allergic bronchopulmonary aspergillosis was observed. On average, patients with incident MAC infection were older than patients with MABC infection. Conclusion: The NTM burden in pwCF in Germany remained unchanged between 2016 and 2020. MABC was the dominant species detected, whereas only MAC infections increased with time and patient age. The previously observed association of Aspergillus fumigatus and NTM was reaffirmed. Awareness of NTM needs to be improved.

Background: Mycobacterium (M.) chimaera is a non-tuberculous mycobacterium (NTM) that belongs to M. avium complex (MAC). In patients with cystic fibrosis (CF), MAC can cause bronchopulmonary infections that can be prolonged and difficult to treat. MAC infections of sites other than the lungs or central catheters are rare and almost exclusively associated with immunodeficiency. Case presentation: We present a case of an 8-year-old CF patient (delF508 homozygous) with recurrent pulmonary exacerbations, gradual clinical deterioration, B-symptoms (fever, fatigue, weight loss, night sweat), elevated transaminases and intermittent detection of M. chimaera in the sputum without radiological signs of NTM-associated lung disease with a central venous port-catheter. Next-generation sequencing (NGS) revealed M. chimaera port infection that was also confirmed by mycobacterial culture. The patient recovered within 4 weeks after removal of the catheter and initiation of MAC targeted antimicrobial therapy. Electron microscopy of the catheter illustrated the presence of mycobacteria in a biofilm. Conclusions: MAC central venous catheter infection needs to be considered in immunocompetent people. NGS is a valuable tool for rapid identification of rare infections. MAC capability of biofilm formation renders catheter removal the central therapeutic intervention for the clearance of the infection.

Background Cough suppression assessed by embarrassment about coughing has been shown in adolescents with cystic fibrosis (CF) and negatively affects health-related quality of life (HRQoL) and clinical indicators of disease severity in adolescent females. However, whether cough suppression exists in adults has been studied as little as its effects on clinical and psychological outcomes beyond adolescence. Methods Seventy-one subjects completed the self-reported 'Cystic Fibrosis Questionnaire-Revised (CFQ-R + 14)' and a self-report questionnaire about cough suppression, health-related perspectives, and therapy adherence. The status of CF disease was quantified in terms of the percentage of predicted forced expiratory volume in one second (ppFEV 1 ), body mass index (BMI), Pseudomonas aeruginosa, pancreatic status, and CF-related diabetes (CFRD). Additional demographic data for sex, age, graduation, employment, and marital status were assessed. Results CS exists in adult CF and is associated with impaired HRQoL but not the overall CF disease status regarding BMI, ppFEV 1 , or health-related perspectives. Despite a higher prevalence of cough suppression in women, no effect of sex regarding either outcome measure was observed. Conclusion The results of this study suggest that mental health indicators have an impact on cough suppression.

Gain-of-function variants in the stimulator of interferon response cGAMP interactor 1 ( STING1 ) gene cause STING-Associated Vasculopathy with onset in Infancy (SAVI). Previously, only heterozygous and mostly de novo STING1 variants have been reported to cause SAVI. Interestingly, one variant that only leads to SAVI when homozygous, namely c.841C>T p.(Arg281Trp), has recently been described. However, there are no entries in public databases regarding an autosomal recessive pattern of inheritance. Here, we report four additional unrelated SAVI patients carrying c.841C>T in homozygous state. All patients had interstitial lung disease and displayed typical interferon activation patterns. Only one child displayed cutaneous vasculitis, while three other patients presented with a relatively mild SAVI phenotype. Steroid and baricitinib treatment had a mitigating effect on the disease phenotype in two cases, but failed to halt disease progression. Heterozygous c.841C>T carriers in our analysis were healthy and showed normal interferon activation. Literature review identified eight additional cases with autosomal recessive SAVI caused by c.841C>T homozygosity. In summary, we present four novel and eight historic cases of autosomal recessive SAVI. We provide comprehensive clinical data and show treatment regimens and clinical responses. To date, SAVI has been listed as an exclusively autosomal dominant inherited trait in relevant databases. With this report, we aim to raise awareness for autosomal recessive inheritance in this rare, severe disease which may aid in early diagnosis and development of optimized treatment strategies.

Background:Absent or abnormal senses of smell and taste have been frequently reported during both acute and long COVID in adult patients. In contrast, pediatric patients who test positive for SARS-CoV-2 are often asymptomatic and the loss of smell and/or taste has been infrequently reported. After observing several young patients with COVID-associated anosmia and ageusia at our clinic, we decided to investigate the incidence of subsequent eating disorders in these patients and in SARS-CoV-2 positive patients who did not experience anosmia and ageusia during the same period. Material and methods:A single-site retrospective cohort study of 84 pediatric patients with suspected long COVID who were treated in the Pediatric Infectious Diseases Outpatient Clinic at the University Hospital Essen were evaluated for persistent symptoms of COVID-19. Smell and taste dysfunction as well as eating behaviors were among the signs and symptoms analyzed in this study. Results:24 out of 84 children and adolescents described smell and taste dysfunction after confirmed or suspected SARS-CoV-2 infections. A large number of these patients (6 out of 24) demonstrated increased fixation on their eating behavior post-COVID and over time these patients developed anorexia nervosa. Discussion/Conclusion:In this study we saw a possible association of long-lasting post-COVID smell and taste dysfunction with subsequent development of eating disorders. This observation is worrisome and merits further investigation by healthcare providers at multiple clinical sites.

High-flow nasal therapy (HFNT) is a safe and simple way to deliver humidified air and oxygen for respiratory support in infants and children. HFNT is well established in an inpatient setting, but home HFNT lacks evidence. In the current study, we studied characteristics and outcomes of pediatric patients with home HFNT. In a monocentric retrospective analysis of data for 10 years (April 2010-April 2020), patient characteristics from the time point of the first discharge from hospital with home HFNT-treatment and the subsequent course were analyzed. Patients were divided into three HFNT indication groups: (1) bronchopulmonary dysplasia (BPD), (2) upper airway obstruction (UAO), and (3) other indications. Forty patients received home HFNT in the study period. Seventeen patients were treated for BPD, 15 for UAO, and 8 had other indications. Twenty-two patients (55%) were successfully weaned from HFNT (12 [70.6%] BPD, 7 [46.7%] UAO, 3 [37.5%] other), while seven patients (17.5%) died during follow-up (4 BPD, 2 UAO, 1 other). Twenty-three patients (57.5%) required (intermittent) additional oxygen application (14 [82.4%] BPD, 6 [40%] UAO, 4 [50%] other). Weaning success and need for additional oxygen were significantly more probable in BPD patients compared to the UOA group. In conclusion, HFNT plays an increasing role in home treatment of respiratory insufficiency of various etiologies in childhood. It often represents a temporary intervention, especially for children with BPD but might also serve as long-term treatment for children in whom other forms of ventilatory support are not feasible or desired.

Background Respiratory involvement defines the clinical outcome of neuromuscular diseases (NMD). The lung clearance index (LCI) is a marker of lung ventilation inhomogeneity and indicates small airway disease. It is determined by mulitple breath washout lung function (MBW). The merit of LCI is undisputed for primary lung diseases like cystic fibrosis, but its role in NMD is unclear. Methods We investigated the role of MBW in patients with NMD and the effect of two different tracer gases and cough assist devices on the LCI. Patients and controls performed MBW with nitrogen (N 2 ) and sulfur hexafluoride (SF 6 ), whereas the latter analysis was repeated after the use of a cough assist device in the NMD group. LCI was compared to forced vital capacity (FVC) and peak cough flow (PCF). Results 24 NMD patients (12 Duchenne Muscular Dystrophy, 8 Spinal Muscular Atrophy, 4 other NMDs) and 15 healthy controls were enrolled. In the NMD group, overall LCI N 2 was higher than LCI SF 6 (9.67 ± 1.56 vs. 8.71 ± 1.47; mean ± SD; p < 0.033). In controls, LCI N 2 did not differ significantly from LCI SF 6 (7.03 ± 0.37 vs. 7.05 ± 0.67; p = 0.882). Both LCI N 2 and LCI SF 6 were significantly higher in NMD patients as in controls (9.67 ± 1.56 vs. 7.03 ± 0.37, p < 0.001, and 8.71 ± 1.478.65 vs. 7.05 ± 0.67, p < 0.001). In the NMD group, both LCI N 2 and LCI SF 6 showed a negative correlation to FVC (r = − 0.525; p = 0.008 and r = − 0.526; p = 0.008, respectively) and PCF (r = − 0.590; p = 0.002 and r = − 0.641; p = 0.001, respectively). LCI N 2 and LCI SF 6 correlated well in the NMD group. LCI SF 6 did not change significantly after the use of the cough assist in NMD patients (n = 22; 8.65 ± 1.52 pre vs. 8.79 ± 2.03 post, p = 0.667). Conclusion Lung involvement of patients with neuromuscular diseases goes beyond weakness of respiratory muscles. MBW with both N 2 and SF 6 is suitable to detect ventilation inhomogeneity in NMD patients with respiratory impairment. Cough assist devices with low to moderate pressure levels do not immediately improve the LCI.

M. tuberculosis is the single infectious agent responsible for most deaths worldwide outside of pandemics. Diseases due to non-tuberculous mycobacteria (NTM) are increasing in many regions of the world. The two molecular assays GenoType CM direct® (GTCMd) (Bruker, Billerica, MA, USA) and VisionArray Myco® (VAM) (ZytoVision, Bremerhaven, Germany) are based on the DNA/DNA hybridization technique, and allow for the identification of tuberculous and the most clinically relevant non-tuberculous mycobacterial species from clinical specimens. We evaluated the performance of both assays for the identification of mycobacteria from 65 clinical specimens of 65 patients and compared it with the results of conventional culture. Based on conventional culture that recovered 37 mycobacterial isolates including 11 tuberculous and 26 NTM isolates, sensitivity, specificity, positive predictive value and negative predictive value were 89.2%, 81.5%, 86.8% and 84.6% for GTCMd and 73.0%, 96.3%, 96.4% and 72.2% for VAM. Additionally, GTCMd identified mycobacteria from five and VAM from one culture-negative sample. Both assays identified a mycobacterium in one sample overgrown by other microorganisms. Two M. abscessus subsp. abscessus isolates grown from culture were identified as M. chelonae by GTCMd assay. In conclusion, both assays improve the rapid identification of mycobacteria directly from clinical specimens.

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. (c)? 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Der Übergang von einer kindorientierten zu einer erwachsenenorientierten Gesundheitsfürsorge 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 Übergangsprozess (Transition) beginnt gewöhnlich in der Adoleszenz und wird mit dem physischen Transfer des jungen Erwachsenen in die Erwachsenenmedizin abgeschlossen. Die historisch als „Kinderkrankheit“ geltende Mukoviszidose rückt durch das steigende Alter der Patienten zunehmend in den Fokus der Erwachsenenmedizin. Hier gilt es, entsprechende medizinische Versorgungsstrukturen für diese komplexe Erkrankung vorzuhalten und Kapazitäten zu schaffen, um die Kinderkliniken zu entlasten, die häufig die Versorgung bereits erwachsener Patienten aufrechterhalten haben. Die altersbedingt erhöhte Komplikationsrate stellt spezielle Anforderungen an die Versorgung von erwachsenen Mukoviszidosepatienten. Hierzu zählen nicht nur das Erkennen und Behandeln von Komplikationen, sondern auch eine medizinische Versorgungsstruktur, die darauf ausgerichtet ist, die mit der Mukoviszidose assoziierten Komorbiditäten wie den Diabetes mellitus oder die CF-Hepatopathie adäquat zu versorgen. Ein Behandlerteam aus Ärzten, erfahrener CF-Pflege, Physiotherapie, Ernährungstherapie, Psychologie und sozialem Dienst muss in der weiterführenden Versorgung zu Verfügung gestellt werden, um dem Anspruch an eine allumfassende Behandlung der komplexen Erkrankung Mukoviszidose gerecht zu werden.