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Introduction: Childhood interstitial lung disease (chILD) is a heterogeneous group of mostly chronic respiratory disorders. Assessment of health-related quality of life (HrQoL) in chILD has become increasingly important in clinical care and research. The aim of this study was to assess differences between patient-reported (self) and caregiver-reported (proxy) HrQoL scores., Methods: This study used data obtained from the chILD-EU Register. After inclusion (baseline), the patient's health status was followed up at predefined study visits. At each study visit, caregivers and patients were handed validated, age-specific HrQoL questionnaires. HrQoL data entered at baseline were used to compare self- and proxy-reported HrQoL scores. For the longitudinal analysis, we compared HrQoL scores between the baseline and the next follow-up visit., Results: No differences between patient- and caregiver-reported HrQoL scores were found for school functioning, chILD-specific questionnaire score, and physical health summary score. Self-reported HrQoL scores were higher for the subscales emotional functioning (77.4 vs. 70.7; p < .001), social functioning (81.9 vs. 76.2; p < .001), as well as psycho-social summary score (76.5 vs. 71.8; p < .001) and total score (74.7 vs. 70.8; <.001). The longitudinal analysis showed that a significant change in a patient-reported HrQoL score resulted in a significant change in a caregiver-reported HrQoL score after a mean time of 11.0 months (SD 9.4)., Conclusions: We found a good agreement between children- and caregiver-related HrQoL scores. In chILD, caregivers are able to sense changes in children's HrQoL scores over time and may be used as a proxy for children unable to complete HrQoL questionnaires., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: We recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in lung morphology detected by magnetic resonance imaging (MRI) in adolescent and adult patients with cystic fibrosis (CF). However, real-world data on the effect of ETI on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported. The aim of this study was therefore to examine the effect of ETI on the LCI and the lung MRI score in children aged 6-11 years with CF and one or two F508del alleles., Methods: This prospective, observational, multicentre, post-approval study assessed the longitudinal LCI up to 12 months and the lung MRI score before and 3 months after initiation of ETI., Results: A total of 107 children with CF including 40 heterozygous for F508del and a minimal function mutation (F/MF) and 67 homozygous for F508del (F/F) were enrolled in this study. Treatment with ETI improved the median (interquartile range (IQR)) LCI in F/MF (-1.0 (-2.0- -0.1); p<0.01) and F/F children (-0.8 (-1.9- -0.2); p<0.001) from 3 months onwards. Further, ETI improved the median (IQR) MRI global score in F/MF (-4.0 (-9.0-0.0); p<0.01) and F/F children (-3.5 (-7.3- -0.8); p<0.001)., Conclusions: ETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least one F508del allele in a real-world setting. Our results support early initiation of ETI to reduce or even prevent lung disease progression in school-age children with CF., Competing Interests: Conflicts of interest: M. Stahl, S.Y. Graeber and S. Thee are participants of the Berlin Institute of Health (BIH)-Charité Clinician Scientist Program, and J. Röhmel is participant of the Case Analysis and Decision Support (CADS) program funded by Charité – Universitätsmedizin Berlin and the BIH. M. Stahl reports an Independent Research Innovation Award and honoraria for lectures and participation in advisory boards, all by Vertex Pharmaceuticals Incorporated, outside of the submitted work; she is Chairman of the German CF Research Council (FGM), Treasurer of the German Society of Paediatric Pulmonology (GPP) and was Secretary of the Group CF of the Paediatric Assembly of the ERS. M. Dohna is a participant of the Ellen-Schmidt Habilitationsförderung funded by the Hannover Medical School. S.Y. Graeber reports grants from the German CF Foundation and Vertex Pharmaceuticals Incorporated, and honoraria from Chiesi GmbH and Vertex Pharmaceuticals Incorporated for lectures and participation in advisory boards, outside of the submitted work. O. Sommerburg reports grants and honoraria from Vertex Pharmaceuticals Incorporated for lectures, outside of the submitted work. S.T. Pallenberg is a member of the Else-Kröner Forschungskolleg TITUS. A. Voskrebenzev reports a grant and honoraria for lectures from Siemens Healthineers, outside of the submitted work, holds a patent for a method of quantitative magnetic resonance lung imaging (Voskrebenzev, Gutberlet, Vogel-Claussen; number EP3107066, US-2016-0367200-Al 22.12.2016), and is a stockholder and CEO of BioVisioneers GmbH. K. Schütz reports payments for attending meetings and/or travel from Vertex Pharmaceuticals Incorporated, outside of the submitted work. G. Hansen reports receipt of consultation fees from Sanofi GmbH, outside of the submitted work. F. Doellinger reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Bayer Vital, Berlin-Chemie Menarini, Boehringer Ingelheim and Chiesi GmbH, payment for expert testimony from Calyx, and support for attending meetings from Bayer. E. Steinke reports grants from Berlin Institute of Health at Charité Berlin, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Vertex Pharmaceuticals Incorporated. S. Thee reports honoraria for lectures and payment for attending meetings and/or travel from Vertex Pharmaceuticals Incorporated and Viatris, outside of the submitted work. J. Röhmel reports honoraria for lectures from Vertex Pharmaceuticals Incorporated, outside the submitted work; additionally, he is work package leader in BEAT-PCD (ERS-CRC). M.O. Wielpütz reports a grant from Vertex Pharmaceuticals Incorporated, and receipt of consulting fees and honoraria for lectures from Vertex Pharmaceuticals Incorporated and Boehringer Ingelheim, outside of the submitted work. L. Naehrlich reports receipt of fees for a data quality project of the German CF Registry. He is the medical lead of the German CF Registry, the pharmacovigilance study manager of the European Cystic Fibrosis Society Patient Registry and part of the Trial Steering Committee for CF STORM. He also reports grants from the German Center for Lung Research, Vertex Pharmaceuticals and Mukoviszidose Institute, and receipt of medical writing services from Articulate Science. J. Vogel-Claussen reports grants from BMBF, Siemens Healthineers, AstraZeneca, Boehringer Ingelheim and GSK, royalties or licenses from Siemens Healthineers, receipt of consulting fees from AstraZeneca, honoraria for lectures from Siemens Healthineers, AstraZeneca, Boehringer Ingelheim, GSK, Roche, Coreline Soft and Bayer, payments for attending meetings and/or travel from Vertex Pharmaceuticals Incorporated, Bayer, GSK and AstraZeneca, and holds a patent for a method of quantitative magnetic resonance lung imaging (Voskrebenzev, Gutberlet, Vogel-Claussen; number EP3107066, US-2016-0367200-Al 22.12.2016). B. Tümmler reports support for the present study from Bundesministerium für Forschung und Technologie, grants from the German Research Foundation (DFG; CRC 900; Excellence cluster “RESIST”), consultancy fees from Helmholtz Institut für Infektionsforschung, payment or honoraria for lectures, presentations, manuscript writing or educational events from Vertex Pharmaceutical (Germany) Incorporated, participation on a data and safety monitoring board or advisory board with Vertex Pharmaceuticals Incorporated, and leadership roles with Christiane Herzog Stiftung and the Microbiome/Metagenome Group of the German Center for Lung Research (DZL). M.A. Mall reports grants from the German Research Foundation (DFG; SFB-TR 84, and project 450557679) and the German Innovation Fund (01NVF19008), outside of the submitted work. Additionally, he reports receipt of consulting fees from AbbVie, Antabio, Arrowhead, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Prieris, Recode, Santhera, Splisense and Vertex Pharmaceuticals Incorporated, of honoraria for lectures from Vertex Pharmaceuticals Incorporated and participation in advisory boards from AbbVie, Antabio, Arrowhead, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Pari and Vertex Pharmaceuticals Incorporated, and of payment for travel from Vertex Pharmaceuticals Incorporated and Boehringer Ingelheim, all outside of the submitted work. He is a Fellow of ERS (FERS). A-M. Dittrich reports support for the present study from the German Center for Lung Research (DZL), Vertex Pharmaceuticals Incorporated and European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN), grants from Vertex Pharmaceuticals Incorporated, ECFS-CTN, DFG and Christiane Herzog Stiftung, consultancy fees from the c4c consortium, GSK and European Cystic Fibrosis Society. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Background: Hymenoptera venom is one of the most frequent causes of anaphylaxis. Studies from adults indicate the clinical profiles and risk factors of Hymenoptera venom-induced anaphylaxis (VIA). Much less is known about pediatric VIA., Objective: To understand elicitor- and age-related factors determining pediatric VIA by analyzing data from the anaphylaxis registry., Methods: We selected pediatric VIA, pediatric food-induced anaphylaxis (FIA), and adult VIA cohorts from the anaphylaxis registry and performed a comparative data analysis regarding elicitors, symptoms, and management., Results: We identified 725 pediatric patients with VIA, 3,149 with pediatric FIA, and 5,534 with adult VIA. In pediatric VIA, boys were more frequently affected, atopy was not increased, and the onset of the reaction after exposure was fast (≤30 min; 91%) compared with pediatric FIA. Symptoms in pediatric VIA were age dependent, and although respiratory symptoms occurred most frequently besides skin symptoms in both pediatric patients with VIA and FIA, cardiovascular symptoms were more frequently reported in pediatric patients with VIA than pediatric patients with FIA. The analysis of pediatric versus adult VIA revealed clear differences in the frequency of involved organ systems (skin: 93% vs 78%; respiratory: 77% vs 64%; and cardiovascular: 61% vs 85%). For both pediatric and adult VIA, the rates of adrenaline application by a professional were low (29% vs 31%) but hospitalization rates were higher in children than in adults (61% vs 42%). Venom immunotherapy was frequently initiated regardless of age (78% each)., Conclusions: Pediatric VIA is more frequent in boys, symptoms are age dependent, and hospitalization is often required. Adrenaline should be applied according to current guidelines. Venom immunotherapy is an important treatment option in pediatric VIA and should be considered in severely affected children., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are characterized by inherited impaired mucociliary clearance leading to chronic progressive lung disease as well as chronic rhinosinusitis (CRS). The diseases share morphological and functional commonalities on magnetic resonance imaging (MRI) of the lungs and paranasal sinuses, but comparative MRI studies are lacking. Objectives: To determine whether PCD shows different associations of pulmonary and paranasal sinus abnormalities on MRI and lung function test results in children (infants to adolescents) compared with children with CF. Methods: Eighteen children with PCD (median age, 9.5 [IQR, 3.4-12.7] yr; range, 0-18 yr) and 36 age-matched CF transmembrane conductance regulator modulator-naive children with CF (median age, 9.4 [3.4-13.2] yr; range, 0-18 yr) underwent same-session chest and paranasal sinus MRI as well as spirometry (to determine forced expiratory volume in 1 s percent predicted) and multiple-breath washout (to determine lung clearance index z -score). Pulmonary and paranasal sinus abnormalities were assessed using previously validated chest MRI and CRS-MRI scoring systems. Results: Mean chest MRI global score was similar in children with PCD and CF (15.0 [13.5-20.8] vs. 15.0 [9.0-15.0]; P  = 0.601). Consolidations were more prevalent and severe in children with PCD (56% vs. 25% and 1.0 [0.0-2.8] vs. 0.0 [0.0-0.3], respectively; P  < 0.05). The chest MRI global score correlated moderately with forced expiratory volume in 1 second percent predicted in children with PCD and children with CF ( r  = -0.523 and -0.687; P  < 0.01) and with lung clearance index in children with CF ( r  = 0.650; P  < 0.001) but not in PCD ( r  = 0.353; P  = 0.196). CRS-MRI sum score and mucopyocele subscore were lower in children with PCD than in children with CF (27.5 [26.3-32.0] vs. 37.0 [37.8-40.0] and 2.0 [0.0-2.0] vs. 7.5 [4.8-9.0], respectively; P  < 0.01). CRS-MRI sum score did not correlate with chest MRI score in PCD ( r  = 0.075-0.157; P  = 0.557-0.788) but correlated moderately with MRI morphology score in CF ( r  = 0.437; P  < 0.01). Conclusions: MRI detects differences in lung and paranasal sinus abnormalities between children with PCD and those with CF. Lung disease does not correlate with CRS in PCD but correlates in CF.

Newborn screening (NBS) for cystic fibrosis (CF) based on pancreatitis-associated protein (PAP) has been performed for several years. While some influencing factors are known, there is currently a lack of information on the influence of seasonal temperature on PAP determination or on the course of PAP blood concentration in infants during the first year of life. Using data from two PAP studies at the Heidelberg NBS centre and storage experiments, we compared PAP determinations in summer and winter and determined the direct influence of temperature. In addition, PAP concentrations measured in CF-NBS, between days 21-35 and 36-365, were compared. Over a 7-year period, we found no significant differences between PAP concentrations determined in summer or winter. We also found no differences in PAP determination after 8 days of storage at 4 °C, room temperature or 37 °C. When stored for up to 3 months, PAP samples remained stable at 4 °C, but not at room temperature ( p = 0.007). After birth, PAP in neonatal blood showed a significant increasing trend up to the 96th hour of life ( p < 0.0001). During the first year of life, blood PAP concentrations continued to increase in both CF- (36-72 h vs. 36-365 d p < 0.0001) and non-CF infants (36-72 h vs. 36-365 d p < 0.0001). Seasonal effects in central Europe appear to have a limited impact on PAP determination. The impact of the increase in blood PAP during the critical period for CF-NBS and beyond on the applicability and performance of PAP-based CF-NBS algorithms needs to be re-discussed.

Rationale: Lumacaftor/ivacaftor was approved for the treatment of patients with cystic fibrosis who are homozygous for F508del aged 2 years and older following positive results from phase three trials. However, the improvement in CFTR function associated with lumacaftor/ivacaftor has only been studied in patients over 12 years of age, while the rescue potential in younger children is unknown. Methods: In a prospective study, we aimed to evaluate the effect of lumacaftor/ivacaftor on the CFTR biomarkers sweat chloride concentration and intestinal current measurement as well as clinical outcome parameters in F508del homozygous CF patients 2-11 years before and 8-16 weeks after treatment initiation. Results: A total of 13 children with CF homozygous for F508del aged 2-11 years were enrolled and 12 patients were analyzed. Lumacaftor/ivacaftor treatment reduced sweat chloride concentration by 26.8 mmol/L ( p = 0.0006) and showed a mean improvement in CFTR activity, as assessed by intestinal current measurement in the rectal epithelium, of 30.5% compared to normal ( p = 0.0015), exceeding previous findings of 17.7% of normal in CF patients homozygous for F508del aged 12 years and older. Conclusion: Lumacaftor/ivacaftor partially restores F508del CFTR function in children with CF who are homozygous for F508del, aged 2-11 years, to a level of CFTR activity seen in patients with CFTR variants with residual function. These results are consistent with the partial short-term improvement in clinical parameters., Competing Interests: MS declares concerning grants or contracts from any entity: MBW overreader Service and RIA grant from Vertex Pharmaceuticals; concerning participation on a Data Safety Monitoring Board or Advisory Board: payment to institution from Vertex Pharmaceuticals; concerning leadership or fiduciary role in other board, society, committee or advocacy group: Chairman FGM (unpaid), Secretary Group CF ERS (unpaid), Treasurer GPP (unpaid). MM received grants from Vertex Pharmaceuticals and personal fees for participation in advisory boards or consulting from Abbvie, Antabio, Arrowhead Pharmaceuticals, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotech, Pieris Pharmaceuticals, Santhera, Sterna Biologicals, Vertex Pharmaceuticals, outside the submitted work. OS received payments from Vertex Pharmaceuticals for lectures. OS, SH, AK, and JB participated in official clinical intervention trials (Vertex Pharmaceuticals) with regular payment to the institution within the last 36 months. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Berges, Graeber, Hämmerling, Yu, Krümpelmann, Stahl, Hirtz, Scheuermann, Mall and Sommerburg.)

Rationale: We recently demonstrated that triple-combination CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in airway and intestinal epithelia to 40-50% of normal in patients with cystic fibrosis (CF) with one or two F508del alleles. In previous studies, this improvement of CFTR function was shown to improve clinical outcomes; however, effects on the lung clearance index (LCI) determined by multiple-breath washout and abnormalities in lung morphology and perfusion detected by magnetic resonance imaging (MRI) have not been studied. Objectives: To examine the effect of ELX/TEZ/IVA on LCI and lung MRI scores in patients with CF and one or two F508del alleles aged ⩾12 years. Methods: This prospective, observational, multicenter, postapproval study assessed LCI and lung MRI scores before and 8-16 weeks after initiation of ELX/TEZ/IVA. Measurements and Main Results: A total of 91 patients with CF, including 45 heterozygous for F508del and a minimal function mutation (MF) and 46 homozygous for F508del , were enrolled in this study. Treatment with ELX/TEZ/IVA improved LCI in F508del /MF (-2.4; interquartile range [IQR], -3.7 to -1.1; P  < 0.001) and F508del homozygous (-1.4; IQR, -2.4 to -0.4; P  < 0.001) patients. Furthermore, ELX/TEZ/IVA improved the MRI global score in F508del /MF (-6.0; IQR, -11.0 to -1.3; P  < 0.001) and F508del homozygous (-6.5; IQR, -11.0 to -1.3; P  < 0.001) patients. Conclusions: Our data demonstrate that improvement of CFTR function by ELX/TEZ/IVA improves lung ventilation and abnormalities in lung morphology, including airway mucus plugging and wall thickening, in adolescent and adult patients with CF and one or two F508del alleles in a real-world, postapproval setting. Clinical trial registered with www.clinicaltrials.gov (NCT04732910).

Introduction: Acute exacerbations (AEs) increase morbidity and mortality of patients with chronic pulmonary diseases. Little is known about the characteristics and impact of AEs on children's interstitial lung disease (chILD)., Methods: The Kids Lung Register collected data on AEs, the clinical course and quality of life (patient-reported outcomes - PRO) of rare paediatric lung diseases. Characteristics of AEs were obtained., Results: Data of 2822 AEs and 2887 register visits of 719 patients with chILD were recorded. AEs were characterised by increased levels of dyspnoea (74.1%), increased respiratory rate (58.6%) and increased oxygen demand (57.4%). Mostly, infections (94.4%) were suspected causing an AE. AEs between two register visits revealed a decline in predicted FEV1 (median -1.6%, IQR -8.0 to 3.9; p=0.001), predicted FVC (median -1.8%, IQR -7.5 to 3.9; p=0.004), chILD-specific questionnaire (median -1.3%, IQR -3.6 to 4.5; p=0.034) and the physical health summary score (median -3.1%, IQR -15.6 to 4.3; p=0.005) compared with no AEs in between visits. During the median observational period of 2.5 years (IQR 1.2-4.6), 81 patients died. For 49 of these patients (60.5%), mortality was associated with an AE., Conclusion: This is the first comprehensive study analysing the characteristics and impact on the clinical course of AEs in chILD. AEs have a significant and deleterious effect on the clinical course and health-related quality of life in chILD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Previous studies suggest that PAP-based CF protocols are suitable for newborn screening (NBS) for cystic fibrosis (CF) when newborns designated as CFSPID should not be detected. However, there are still discussions about the performance of IRT/PAP algorithms. We present the final results of a pilot study evaluating a IRT/PAP protocol with an IRT-dependent safety net (SN) conducted from 2008 to 2016 in southwestern Germany on nearly 500,000 newborns., Methods: To achieve reliable data, all newborns were screened using both the PAP-based and a DNA-based CFNBS algorithm. PAP quantification and genetic analysis of the four most common CFTR mutations in Germany were performed in all newborns with IRT≥99.0 percentile. NBS was rated positive if either PAP was ≥1.6 µg/l and/or at least one CFTR mutation was detected. In addition, an IRT-dependent SN resulted in positive rating for both protocols if IRT was ≥99.9 percentile. To evaluate the IRT/PAP protocol, its performance was compared to that of the IRT/DNA protocol., Results: The IRT/PAP protocol with IRT-based SN used in the study achieved a sensitivity of 94%, if false-negative detected neonates with meconium ileus and those designated as CFSPID were excluded from analysis. CF/CFSPID ratio was 92. However, PPV of the IRT/PAP+SN protocol was with 10.3% very low., Conclusions: PAP-based CFNBS protocols can be used, if less detection of CFSPID is desired. The IRT/PAP protocol with IRT-dependent SN evaluated here achieved adequate sensitivity but should probably be used in combination with a third-tier test to also achieve an acceptable PPV., Competing Interests: Declarations of Competing Interest During the conduct of the study Dr. Sommerburg reports grants from German Federal Ministry of Education and Research and personal fees from Vertex Pharmaceuticals, both outside of the submitted work. Dr. Mall reports grants from German Federal Ministry of Education and Research, personal fees and other from Boehringer Ingelheim, personal fees from Arrowhead Pharmaceuticals, personal fees and other from Vertex Pharmaceuticals, personal fees from Santhera, personal fees from Galapagos, personal fees from Sterna Biologicals, personal fees from Enterprise Therapeutics, and personal fees from Antabio, all outside the submitted work. All other authors have nothing to disclose., (Copyright © 2021. Published by Elsevier B.V.)

Rationale: Previous cross-sectional studies have demonstrated that chest magnetic resonance imaging (MRI) is sensitive to detect early lung disease in infants and preschool children with cystic fibrosis (CF) without radiation exposure. However, the ability of MRI to detect the progression of lung disease and the impact of early diagnosis in preschool children with CF remains unknown. Objectives: To investigate the potential of MRI to detect progression of early lung disease and impact of early diagnosis by CF newborn screening (NBS) in preschool children with CF. Methods: An annual MRI was performed from diagnosis over 4 years in a cohort of 96 preschool children with CF (age, 0-4 yr) who received concurrent diagnoses on the basis of NBS ( n  = 28) or clinical symptoms ( n  = 68). MRI scans were evaluated using a dedicated morphofunctional score, and the relationship between longitudinal MRI score and respiratory symptoms, pulmonary exacerbations, upper airway microbiology, and mode of diagnosis was determined. Measurements and Main Results: The MRI global score increased in the total cohort of children with CF during preschool years ( P  < 0.001) and was associated with cough, pulmonary exacerbations ( P  < 0.0001), and the detection of Staphylococcus aureus and Haemophilus influenzae ( P  < 0.05). MRI-defined abnormalities in lung morphology-especially airway wall thickening/bronchiectasis-were lower in children with CF diagnosed by NBS than in children with clinically diagnosed CF throughout the observation period ( P  < 0.01). Conclusions: MRI detected progression of early lung disease and benefits of early diagnosis by NBS in preschool children with CF. These findings support MRI as a sensitive outcome measure for diagnostic monitoring and early intervention trials in preschool children with CF. Clinical trial registered with www.clinicaltrials.gov (NCT02270476).

Background: Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents., Methods: Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre., Results: 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004)., Conclusions: The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown., Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM/IVA therapy., Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM/IVA therapy., Results: Patients with CF receiving LUM/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g/L after two years ( p < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L ( p < 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 µmol/L ( p < 0.01)., Conclusions: CFTR modulator therapy with LUM/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF.

The dimethylchloronium salt [Me 2 Cl][Al(OTeF 5 ) 4 ] is used to methylate electron-deficient aromatic systems in Friedel-Crafts type reactions as shown by the synthesis of N-methylated cations, such as [MeNC 5 F 5 ] + , [MeNC 5 F 4 I] + , and [MeN 3 C 3 F 3 ] + . To gain a better understanding of such fundamental Friedel-Crafts reactions, the role of the dimethylchloronium cation has been evaluated by quantum-chemical calculations., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

A new chloronium-containing salt, [Me 2 Cl][Al(OTeF 5 ) 4 ], was synthesized on multigram scale by means of a simple one-pot procedure. The isolated product can be handled at room temperature and used as a strong electrophilic methylation agent. This is demonstrated by the methylation of the very weak bases P(CF 3 ) 3 , PF 3 , MeI, and MeBr., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hemoptysis is rare in children and adolescents. We describe an 11-year-old girl who presented with hemoptysis, cough, and exertional dyspnea. Radiologic and bronchoscopic assessment revealed a pedunculated mass in the right main stem bronchus with a ball valve effect. Carcinoid or hemangioma was suspected as cause of the mass. The tumor could be excised bronchoscopically, and histologic examination showed a capillary hemangioma. In the literature, bronchial hemangiomas are described in infants and adults. This case demonstrates that bronchial hemangioma should also be taken into consideration as a cause of hemoptysis in adolescents., (© 2017 Wiley Periodicals, Inc.)

Background: Cystic fibrosis (CF) lung disease starts in the first months of life often before the onset of clinical symptoms. Multiple breath washout (MBW) detects abnormal lung function in infants and young children in the laboratory setting., Objective: The aim of this study was to determine the feasibility of MBW in 0- to 4-year-old children with CF and non-CF controls in the clinical setting., Methods: Fourteen children with CF (mean age 1.3 ± 1.0 years) and 26 age-matched non-CF controls were sedated with chloral hydrate and MBW was performed with sulfur hexafluoride., Results: MBW measurements were successful in 27 of 40 children (67.5%). The mean lung clearance index (LCI) was significantly higher in CF patients compared to non-CF controls (p = 0.006). Further, the frequency of elevated LCI (z-score >1.96) was significantly increased in CF patients compared to controls (p = 0.0003)., Conclusions: We conclude that MBW is feasible and sensitive to detect abnormal lung function in infants and young children with CF in the clinical setting.

A 9-month-old girl presented with massive bilateral diffuse nephroblastomatosis. After response to actinomycin D and vincristine over a period of 1 year, the nephroblastomatosis continuously progressed under this treatment. As retinoic acid signaling is critical for normal renal development and nephroblastomatosis seems histologically as undifferentiated embryonal tissue, we added 13-cis retinoic acid to the chemotherapy regimen. Three months thereafter, kidney volumes declined significantly over a period of 1 year. Interestingly, nephroblastomatosis-associated acquired von Willebrand disease also resolved. Retinoic acid maybe a novel nontoxic treatment option for nephroblastomatosis requiring further systematic evaluation.