Search

Freerk Prenzel1,2 *, Regina Treudler1,3 *, Tobias Lipek,1,2 Maike vom Hove,1,2 Paula Kage,1,3 Simone Kuhs,1,4 Thorsten Kaiser,1,4 Maximilian Bastl,5 Jan Bumberger,6– 8 Jon Genuneit,9,10 Thomas Hornick,8,11 Stefan Klotz,8,12 Julia Zarnowski,1,3 Maren Boege,1,13 Veit Zebralla,1,13 Jan-Christoph Simon,1,3 Susanne Dunker8,11 1Leipziger Interdisciplinary Center for Allergy (LICA), Comprehensive Allergy Center, Leipzig, Germany; 2University of Leipzig, Medical Center, Department of Pediatrics, Leipzig, Germany; 3University of Leipzig, Medical Center, Department of Dermatology, Venerology and Allergy, Leipzig, Germany; 4University of Leipzig, Medical Center, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig, Germany; 5Medical University of Vienna, Department of Otorhinolaryngology, Vienna, Austria; 6Helmholtz-Centre for Environmental Research (UFZ), Department Monitoring and Exploration Technologies, Leipzig, Germany; 7Helmholtz-Centre for Environmental Research (UFZ), Research Data Management, Leipzig, Germany; 8German Centre for Integrative Biodiversity Research (iDiv) Halle, Jena, Leipzig, Germany; 9Pediatric Epidemiology, Department of Pediatrics, Medical Faculty, Leipzig University, Leipzig, Germany; 10German Center for Child and Youth Health, Leipzig/ Dresden, Dresden, Germany; 11Helmholtz-Centre for Environmental Research (UFZ), Department Physiological Diversity, Leipzig, Germany; 12Helmholtz-Centre for Environmental Research (UFZ), Department Community Ecology, Halle, Germany; 13University of Leipzig, Medical Center, Department of Otorhinolaryngology, Head and Neck Surgery, Leipzig, Germany*These authors contributed equally to this workCorrespondence: Susanne Dunker, Helmholtz Centre for Environmental Research – UFZ, Leipzig, Germany, Tel +49 341 9733170, Email susanne.dunker@ufz.dePurpose: Ailanthus altissima is one of the world’s most invasive species with a globally problematic spread. Pollen is dispersed locally and partially airborne. We aimed at investigating if (i) A. altissima pollen can be detected in relevant quantity in the air and if (ii) sensitization to A. altissima can be detected in patients with seasonal exacerbation of atopic diseases.Patients and Methods: We recorded distribution of A. altissima in Leipzig, Germany. In 2019 and 2020, pollen was collected with a Hirst-type pollen trap placed on the roof of the University Hospital. Specific IgE investigations were performed in children and adults with history of atopic diseases with deterioration between May and July. We analysed specific IgE for A. altissima, Alternaria sp., birch, grasses, profilins, polcalcins and crossreacting carbohydrates.Results: We found abundant growth of A. altissima and pollen was detected from early June to mid-July with a maximum pollen concentration of 31 pollen/m3. Out of 138 patients (63 female, 69 children/adolescents), 95 (69%) had seasonal allergic rhinitis, 84 (61%) asthma, and 43 (31%) atopic dermatitis. Sensitization to A. altissima was shown in 59 (42%). There were no significant differences between age groups. In 59% of patients sensitized (35/59), there was no sensitization to possibly cross-reacting structures.Conclusion: Sensitization to A. altissima pollen could be detected in 42% of our patients with atopic diseases, suggesting allergenic potential of this neophyte. In the context of further spread with climate change, eradication strategies and population-based sensitization studies are needed.Keywords: allergy, invasive species, neophyte, pollinosis, pollen count

OBJECTIVES Magnetic resonance imaging (MRI) of the lungs is challenging for several reasons, mainly due to the respiratory motion, low proton density, and rapid T2* decay. Recent MR sequences with ultrashort TE (UTE) coupled with respiratory compensation promise to overcome these obstacles. So far, there are very few studies on the relevance of these sequences in children. The aim of the study was to compare the diagnostic value of a respiratory-self-gated three-dimensional UTE sequence versus a conventional respiratory-triggered T2-weighted turbo spin echo (T2-TSE) sequence in a pediatric collective. STUDY DESIGN Seventy-one patients between 0 and 18 years of age, who were scheduled for a thoracic MRI based on diverse clinical indications, were examined on a 3T MRI system. The UTE and T2-TSE sequences were evaluated by two readers regarding quality features and visualization of eight common pathology patterns. RESULTS The image quality of both sequences was equally high, with UTE depicting pleural and central bronchi more clearly. In pathologies, UTE was superior to T2-TSE for so-called "MR-negative pathologies", significant for air trapping, and in tendency for bullae and cysts. In all remaining pathologies, T2-TSE proved to be at least equivalent to UTE. CONCLUSIONS At present, UTE cannot serve as a universal replacement for conventional T2-TSE for all pathologies. It yields, however, a substantial benefit in the context of hyperinflation, emphysema, cysts, or pathologies of the bronchial system.

We recorded distribution ofWe found abundant growth ofSensitization to

Cystic fibrosis (CF) is one of the most common inherited and life-shortening pulmonary diseases in the Caucasian population. With the widespread introduction of newborn screening and the development of modulator therapy, tremendous advances have been made in recent years both in diagnosis and therapy. Since paediatric CF patients tend to be younger and have lower morbidity, the type of imaging modality that should be used to monitor the disease is often debated. Computed tomography (CT) is sensitive to many pulmonary pathologies, but radiation exposure limits its use, especially in children and adolescents. Conventional pulmonary magnetic resonance imaging (MRI) is a valid alternative to CT and, in most cases, provides sufficient information to guide treatment. Given the expected widespread availability of sequences with ultra-short echo times, there will be even fewer reasons to perform CT for follow-up of patients with CF. This review aims to provide an overview of the process and results of monitoring CF with MRI, particularly for centres not specialising in the disease.

Obesity and bronchial asthma are very common diseases in children and adolescents, associated with a considerable burden of disease, reduced quality of life and comorbidities. Obesity is a significant risk factor for bronchial asthma. On the one hand, obesity leads to changes in the mechanics and function of the lungs and chest. On the other hand, obesity-associated inflammatory processes with increased production of leptin and cytokines may trigger bronchial inflammation with the appearance of asthmatic symptoms. The diseases are also linked by genetic factors. Physical activity and weight reduction have a significant benefit. Pharmacotherapy must be based on the pattern of inflammation. This article summarizes the current state of the literature on the association of asthma and obesity and presents current and possible future treatment options.

BACKGROUND Children suffering from bronchial diseases need assistance from nurses in the use of inhalation devices. PURPOSE We aimed to assess nurses' skills and knowledge concerning drug administration with inhalation devices in hospitalized pediatric patients. METHODS An expert panel defined medication errors in drug administration with inhalation devices in children. We monitored 241 inhalation procedures to investigate nurses' inhalation technique skills. Twenty-nine nurses completed a questionnaire to assess nurses' knowledge. RESULTS Skills: In 93 of 241 (39%) inhalation procedures, the mask/mouthpiece did not fit airtight. In none of the 11 inhalations administering a glucocorticoid, the patient's mouth was thoroughly cleaned afterward. Knowledge: Ten of 29 nurses (34%) thought a distance between mask and the patient's face was acceptable. Only 16 of 29 (55%) knew that it is necessary to thoroughly clean the patient's mouth after the inhalation of budesonide. CONCLUSIONS We found that education on inhalation procedures including practical training is required to increase patient safety.

ZUSAMMENFASSUNGOmalizumab ist das bisher am meisten untersuchte Biologikum bei Nahrungsmittelallergie. Bisherige Studien und Fallberichte sprechen für eine protektive Wirkung von Omalizumab bei schwerer Nahrungsmittelallergie mit rezidivierenden Anaphylaxien nach akzidenteller Ingestion der Allergene. Eine Hinzunahme von Omalizumab zur oralen Toleranzinduktion kann die Nebenwirkungen vermindern, die vertragene Allergenmenge erhöhen und die Zeit bis zum Erreichen der Erhaltungsdosis reduzieren. Ob dieser Effekt auch ohne eine kontinuierliche Gabe von langfristiger Dauer ist, müssen weitere Untersuchungen zeigen.

Background Atopic diseases and behavioural difficulties in children have both been on the rise in recent decades. This study seeks to assess associations between atopic diseases and behavioural difficulties, examining the differences considering child age and how behavioural difficulties were reported (via self-report or parent-report). Methods Data on behavioural difficulties, assessed through the Strengths and Difficulties Questionnaire (SDQ), and on atopic diseases, assessed through the participant’s medical history, were available for 2701 study participants aged 3 to 18 years. Associations between atopic diseases and behavioural difficulties were evaluated using linear regression analyses. We split the study sample into two groups. I: 3-to 10-year-olds/parent-reported SDQ (n = 1764), II: 11- to 18-year-olds/parent-reported SDQ (n = 937) and self-reported SDQ (n = 915). All analyses were adjusted for age, gender, and socioeconomic status. Results In younger children, atopic dermatitis was strongly associated with higher total difficulties scores, more emotional problems and conduct problems, and more symptoms of hyperactivity/inattention. Parents reported higher total difficulties scores, more emotional problems, and more peer-relationship problems for adolescents with bronchial asthma and other allergies, whereas the adolescents themselves reported more peer relationship problems. Conclusion In younger children, atopic dermatitis is associated with internalizing and externalizing problems. In adolescents, bronchial asthma and other allergies are associated with a greater level of internalizing problems only. The findings further suggest that parents of adolescents are more likely to perceive associations between atopic diseases and behavioural difficulties than the adolescents themselves.

Objectives Sweat chloride testing (SCT) is the mainstay for the diagnosis of cystic fibrosis (CF) and biomarker in the evaluation of CFTR-modifying drugs. To be a reliable and valid tool, analytical variance (CVA) must be minimized. However, external quality assessments have revealed significant deviations in routine clinical practice. Our goal was to identify and quantify technical errors through proficiency testing and simulations. Methods Chloride concentrations of three blinded samples (each as triplicates) were measured in 9 CF centers using a chloridometer in a routine setting. Technical errors were simulated and quantified in a series of measurements. We compared imprecision and bias before and after a counseling session by evaluating coefficients of variation (CV), adherence to tolerance limits, and inter-rater variability coefficients. Results Pipetting errors resulting in changes in sample volume were identified as the main source of error with deviations up to 41%. After the counseling session, the overall CVA decreased from 7.6 to 5.2%, the pass rate increased from 67 to 92%, and the inter-rater variability diminished. Significant deviations continued to be observed in individual centers. Conclusions Prevention of technical errors in SCT decreases imprecision and bias. Quality assurance programs must be established in all CF centers, including staff training, standard operating procedures, and proficiency testing.

Objective To assess the exercise capacity, exercise habits, and lung function of preterm born children with bronchopulmonary dysplasia (BPD) compared to term born controls at school age. Methods Cardiopulmonary exercise test (CPET) by cycle ergometer and pulmonary function test were performed in children with BPD (n = 42) and compared with a term born control group (n = 42). Daily activity, participation in sports and respiratory symptoms were assessed by questionnaire. Results Children with BPD versus controls had significantly lower values for oxygen consumption (VO2 [mL/min] 1442 ± 417 vs. 1766 ± 541), minute ventilation (VE [L/min] 48 ± 14.92 vs. 60 ± 18.33), and workload (W [watt] 96.1 ± 16.7 vs. 110.6 ± 17.2) at peak exercise and a lower anaerobic threshold (VO2 AT [mL/min] 1183 ± 345 vs. 1382 ± 398). When corrected for weight, only for the workload (2.7 ± 0.5 vs. 3.1 ± 0.5, p = 0.0013) did significant differences persist. The forced expiratory volume in 1 s and forced expiratory flow between 25 and 75% of expired forced vital capacity were significantly reduced in the BPD group (p Conclusion Compared to term born controls, children with BPD at school age show airflow obstruction, a lower workload in CPET, and more respiratory symptoms related to physical activity. The comparable oxygen consumption based on weight suggests a functionally normal alveolar compartment.

Objectives: Pediatric lymphocytic interstitial pneumonia (LIP) and follicular bronchiolitis (FB) are poorly characterized lymphoproliferative disorders. We present and quantify demographics, radiological and histopathologic patterns, treatments and their responses, and outcomes in non-HIV-infected children with LIP and FB. Methods: This structured registry-based study included a retrospective chart review, blinded analysis of imaging studies and lung biopsies, genetic testing, and evaluation of treatments and outcomes. Results: Of the 13 patients (eight females) studied, eight had FB, four had combined LIP/FB, and one had isolated LIP; diagnoses were highly concordant between the pathologists. Most patients became symptomatic during the first 2 years of life, with a mean lag time to diagnosis of 4 years. The most common symptoms were coughing and respiratory infections (11 out of 13 each), dyspnea (10 out of 13), and wheezing (eight out of 13). Autoantibodies were found in eight out of 13 patients. In three patients, disease-causing mutations in the COPA gene were identified. CT revealed hilar lymphadenopathy (five out of 12), ground-glass opacity (eight out of 12), consolidation (five out of 12), and cysts (four out of 13). Systemic steroids as intravenous pulses (11 out of 13) or oral intake (10 out of 13) were the main treatments and showed high response rates of 100% and 90%, respectively. Within the mean observation period of 68 months, all children had chronic courses, eight out of 13 had severe diseases, two died, and one worsened. Conclusions: Children with LIP/FB have chronic diseases that occurred in early childhood and were commonly associated with immune dysregulation as well as high morbidity and mortality. Early diagnosis and treatment may be crucial to improve the outcome.

The management of atopic diseases such as severe asthma, severe atopic dermatitis, and severe food allergy in childhood is challenging. In particular, there are safety concerns regarding the use of high-dose corticosteroids. The recent development of biologicals and their approval for the treatment of children offer a new, very promising, and more personalized therapy option. Omalizumab, mepolizumab, and dupilumab are currently approved as add-on treatments of severe asthma in children and have been shown to be effective in improvement of asthma control and reduction of exacerbations. Dupilumab is the only biological approved for the treatment of atopic dermatitis in adolescents so far. It has been demonstrated to significantly improve symptoms of atopic dermatitis.However, safety data for biologicals used in atopic diseases in children and adolescents are still very limited. Biologicals are generally considered to be safe in adults. These data are often extrapolated to children. Additionally, data for long-term use are lacking. Thus, the safety profiles of those biologicals cannot yet be conclusively assessed.

The management of atopic diseases such as severe asthma, severe atopic dermatitis, and severe food allergy in childhood is challenging. In particular, there are safety concerns regarding the use of high-dose corticosteroids. The recent development of biologicals and their approval for the treatment of children offer a new, very promising, and more personalized therapy option. Omalizumab, mepolizumab, and dupilumab are currently approved as add-on treatments of severe asthma in children and have been shown to be effective in improvement of asthma control and reduction of exacerbations. Dupilumab is the only biological approved for the treatment of atopic dermatitis in adolescents so far. It has been demonstrated to significantly improve symptoms of atopic dermatitis.However, safety data for biologicals used in atopic diseases in children and adolescents are still very limited. Biologicals are generally considered to be safe in adults. These data are often extrapolated to children. Additionally, data for long-term use are lacking. Thus, the safety profiles of those biologicals cannot yet be conclusively assessed.

Zusammenfassung Die Mukoviszidose oder Cystische Fibrose (CF) ist eine autosomal rezessiv vererbte Stoffwechselerkrankung und mit einer regional schwankenden Inzidenz von ca. 1:3.300–1:5.800 eine der häufigsten angeborenen Stoffwechselerkrankungen in Deutschland. Durch eine mutationsbedingte verminderte oder fehlende Funktion von Chloridkanälen kommt es hier zu einer Veränderung der Sekretzusammensetzung aller exokrinen Drüsen. Die mittlere Lebenserwartung von Mukoviszidose-Patienten konnte durch verbesserte Behandlungsstrategien auf mittlerweile über 40 Jahre erheblich gesteigert werden. Es hat sich dabei gezeigt, dass eine frühzeitige Diagnosestellung einen positiven Einfluss auf Krankheitsverlauf, Lebensqualität und Lebenserwartung der betroffenen Patienten hat. Diese Erkenntnis führte in den letzten 10 Jahren europaweit zur Aufnahme der Mukoviszidose in regionale und nationale Neugeborenenscreening-Programme. Mit dem Beschluss des Gemeinsamen Bundesausschusses zur Einführung des Mukoviszidosescreenings im August 2015 wurde Mukoviszidose nun auch in Deutschland als weitere Zielkrankheit in die Kinderrichtlinien aufgenommen und ist nach Veröffentlichung im Bundesanzeiger somit bundeseinheitlich als Bestandteil des deutschen Neugeborenenscreening-Programms vorgeschrieben. Das Procedere beinhaltet ein Stufenscreening mit der Kombination von Immunreaktivem Trypsin (IRT) und Pankreatitis-assoziiertem Protein (PAP) mit zusätzlicher Mutationsanalytik. Dank einer deutschlandweit früheren Diagnosestellung wird ein verbessertes Langzeitoutcome von Mukoviszidose-Patienten erwartet.

Epilepsy and bronchial asthma are frequent in adolescents. Data on adolescents' experiences with their disease and on their expectations for the future, however, is scarce. Patients of a university hospital aged 12 to 17 with epilepsy or bronchial asthma were interviewed based on a questionnaire. Forty-five patients with epilepsy and 47 with bronchial asthma were interviewed. Adolescents with epilepsy felt more impaired by their disease (median 2.5; Q25/Q75 0.75/3.0; 6-level Likert scales: 0 = not at all, 5 = very strong) than those with asthma (1.0; 0/3.0; p = 0.017). Seventy-nine patients (85.9%) had never used the Internet to gain information about their disease. Adolescents with epilepsy felt more limited in their career possibilities by their disease (2.0; 0/4.0) than those with asthma (0; 0/2.0; p = 0.001) and had a higher level of concern about passing their disease on to their children (3.0; 0/4.0) than their peers with asthma (1.5; 1.5/3.0; p = 0.016). Girls with epilepsy were more anxious (4.0; 0.5/5.0) than girls with asthma (0; 0/4.0) about complications of the disease regarding pregnancy (p = 0.019).As well adolescents with epilepsy as with asthma described limitations of their daily life and concerns about the future. What is Known: • Epilepsy and bronchial asthma are frequent chronic diseases in adolescents. • Those diseases can affect psychosocial development. What is New: • Adolescents with epilepsy and bronchial asthma described a high burden of their disease, and most adolescents had not used the Internet to inform themselves on their disease. • Especially adolescents with epilepsy fear limitations in their job possibilities, inheritance of their disease and complications in their prospective pregnancy.

Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, male infertility, and randomization of the left/right body axis as a result of defects of motile cilia and sperm flagella. We identified loss-of-function mutations in the open-reading frame C11orf70 in PCD individuals from five distinct families. Transmission electron microscopy analyses and high-resolution immunofluorescence microscopy demonstrate that loss-of-function mutations in C11orf70 cause immotility of respiratory cilia and sperm flagella, respectively, as a result of the loss of axonemal outer (ODAs) and inner dynein arms (IDAs), indicating that C11orf70 is involved in cytoplasmic assembly of dynein arms. Expression analyses of C11orf70 showed that C11orf70 is expressed in ciliated respiratory cells and that the expression of C11orf70 is upregulated during ciliogenesis, similar to other previously described cytoplasmic dynein-arm assembly factors. Furthermore, C11orf70 shows an interaction with cytoplasmic ODA/IDA assembly factor DNAAF2, supporting our hypothesis that C11orf70 is a preassembly factor involved in the pathogenesis of PCD. The identification of additional genetic defects that cause PCD and male infertility is of great importance for the clinic as well as for genetic counselling.

Background Type 1 diabetes mellitus (T1DM) is characterized by an immunological reaction that is dominated by type-1 T helper (Th1) cells, whereas immunoglobulin E (IgE)-mediated allergies are associated with Th2 cell. According to the Th1/Th2-hypothesis, the immune system is said to either develop into the direction of Th1 or Th2 cells. This would mean that a child developing T1DM is unlikely to develop an IgE-mediated allergy and vice versa. Objective The aim of the study was to investigate the association between the prevalence of T1DM and IgE-mediated allergies. Methods We designed a prospective case control study with 94 children and adolescents with T1DM and 188 age- and sex-matched control children. The basis of our investigations was a questionnaire concerning the family and children's history as to the presence of IgE-mediated allergies. Moreover, the following blood investigations were done: total serum IgE, specific IgE antibodies to major inhalant allergens, and a multiplex cytokine analysis measuring levels of specific cytokines representing either Th1- or Th2- cytokines. Results Children with T1DM reported the presence of IgE-mediated allergies significantly more often than children of the control group. Children with T1DM had significantly higher tumor necrosis factor alpha (TNFα) levels than healthy controls. Levels of interleukin-2 (IL-2) and IL-6 were higher in the groups of children with the presence of a personal history of allergies, regardless of the presence of T1DM. Conclusions Our results suggest that T1DM is associated with a higher risk of a self-reported presence of IgE-mediated allergies and that the Th1/Th2-hypothesis may be an oversimplification.

Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, male infertility and randomization of the left/right body axis caused by defects of motile cilia and sperm flagella. We identified loss-of-function mutations in the open reading frame C11ORF70 in PCD individuals from five distinct families. Transmission electron microscopy analyses and high resolution immunofluorescence microscopy demonstrate that loss-of-function mutations in C11ORF70 cause immotility of respiratory cilia and sperm flagella, respectively, due to loss of axonemal outer (ODAs) and inner dynein arms (IDAs), indicating that C11ORF70 is involved in cytoplasmic assembly of dynein arms. Expression analyses of C11ORF70 showed that C11ORF70 is expressed in ciliated respiratory cells and that the expression of C11ORF70 is upregulated during ciliogenesis, similar to other previously described cytoplasmic dynein arm assembly factors. Furthermore, C11ORF70 shows an interaction with cytoplasmic ODA/IDA assembly factor DNAAF2, supporting our hypothesis that C11ORF70 is a novel preassembly factor involved in the pathogenesis of PCD. The identification of a novel genetic defect that causes PCD and male infertility is of great clinical importance as well as for genetic counselling.

Epinephrine auto-injectors are used for first aid in anaphylactic emergencies by non-healthcare professionals, e.g., (pre-)school teachers. We developed an education session for preschool teachers addressing allergies, anaphylactic emergencies, and administering auto-injectors. We assessed their attitudes and knowledge in allergies and anaphylactic emergency by a questionnaire and monitored their practical performance in administering auto-injectors before the education session, directly after, and 4-12 weeks after the session. From 75 teachers giving their consent to participate, 81% had children with allergies under their supervision and 3% had already administered medication from an available rescue kit. The knowledge of triggers of allergies increased from 9 to 55% directly and to 33% 4-12 weeks after the session (both p 0.001, compared to baseline). Directly after the session, the number of teachers who felt well-prepared for an anaphylactic emergency rose from 11 to 88%, which decreased to 79% 4-12 weeks thereafter (each p 0.001). The number of auto-injector administrations without any drug-related problems increased from 3 to 35% directly after the session and shrunk to 16% 4-12 weeks afterwards (both p 0.025).A single education session substantially improved preschool teachers' attitudes and knowledge in allergies and anaphylactic emergencies. Additionally, their practical performance in auto-injector administration increased. What is Known: • Food allergies are increasing among children. • The knowledge about allergies and anaphylactic emergencies is poor. What is New: • The proportion of teachers who felt well-prepared for an anaphylactic emergency increased after a single education session. • The proportion of auto-injector administrations without any drug-related problems additionally increased due to an education session.

Background:Impaired glucose metabolism and cystic fibrosis (CF)-related diabetes (CFRD) are associated with insufficient weight gain and impaired lung function in children and adolescents with CF. We have asked whether imminent CFRD may be a cause of poor growth in children and adolescents.Methods:A retrospective case control study including 32 patients with CF with or without diabetes was conducted. Sixteen pairs, matched according to age, gender and exocrine pancreatic insufficiency, were analysed. Standard deviation scores (SDS) of height, growth, weight, body mass index (BMI), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and forced expiratory flow at 75% of expired FVC (FEF75) were recorded during a mean observation period of 13 years per patient.Results:SDS of height and weight were reduced in CF patients with diabetes compared to those without, not only at the point of diagnosis (both pConclusions:Deteriorating growth, reduced weight and impaired lung function are related to the development of CFRD and are obvious several years before the actual diagnosis of diabetes.

Cystic fibrosis (CF) is an inherited disease with a defect in epithelial chloride transport that results in a multisystem disease. Although pulmonary disease remains the primary cause of morbidity and mortality, focal biliary cirrhosis and portal hypertension may develop in up to 8% of these patients. Liver transplantation (TX) is an accepted therapy and shows good results. We report on a patient with cystic fibrosis homozygous for the most common CFTR mutation delta F 508 who received a combined heterotopic liver and pancreas transplantation at the age of 18 yr. He suffered from CFRD, which untypically required high doses of insulin. In addition, the patient had pulmonary complications, was chronically colonized with multiresistant Pseudomonas aeruginosa (MBL) and had an allergic bronchopulmonary aspergillosis (ABPA). The patient remained in stable health for 54 months post-TX and was able to live a nearly normal life. With a follow-up of five yr, the function of the liver and pancreas allografts was excellent. However, and sadly, his pulmonary function continued to deteriorate from progression of his CF, and he died of respiratory failure due to a severe pneumonia and septicemia at the age of 23 yr and five months.

Background: Data on the long-term outcome of children after specific venom immunotherapy (VIT) are limited. Therefore, we assessed sting recurrence and anaphylaxis relapse rates as well as adherence to anaphylaxis guidelines with regard to the availability of emergency equipment and education status. Methods: For this long-term survey, data of 311 children with a history of anaphylactic reactions to hymenoptera stings were collected by chart review. We included patients who were treated with a 3-year VIT between 1993 and 2009 and had completed a questionnaire. Results: Forty of the 311 patients were included. Mean VIT duration was 3.1 years. Of the 40 patients included, 29 children (72.5%) received VIT with vespid venom, 9 with bee venom, and 2 patients with both venoms. During a mean follow-up period of 13 years, 20/40 patients (50%) suffered re-stings. Six of the 20 (30%) patients developed again anaphylactic symptoms (grade 1 n = 5, grade 3 n = 1); 2 were allergic to vespid and 4 to bee venom. Of the entire cohort, only 5/40 (12.5%) had appropriate emergency kits according to the guidelines of the European Academy of Allergy and Clinical Immunology. Among the patients who had emergency kits available, one third (5/15) felt uncertain about the correct application of the medication. Less than two thirds of our population (25/40) affirmed that they have been educated in emergency management. The vast majority (95%; 38/40) of our patients did not have allergy follow-ups after VIT completion. Conclusions: Anaphylactic relapses are not uncommon, and there are considerable deficits in the emergency management of patients. Hence, comprehensive standardized anaphylaxis education programs as well as regular follow-ups of the allergy status are crucial.

Background Chronic rhinosinusitis is a hallmark of Cystic fibrosis (CF) impairing the patients' quality of life and overall health. However, therapeutic options have not been sufficiently evaluated. Bronchial inhalation of mucolytic substances is a gold standard in CF therapy. Previously, we found that sinonasal inhalation of dornase alfa as vibrating aerosol reduces symptoms of chronic rhinosinusitis more effectively than NaCl 0.9% (net treatment benefit: −5.87±2.3 points, p=0.017; SNOT-20 total score). This multicenter study compares the effect of NaCl 6.0% vs. NaCl 0.9% following the protocol from our preceding study with dornase alfa. Methods Sixty nine CF patients with chronic rhinosinusitis in eleven German CF centers were randomized to receive sinonasal vibrating inhalation of either NaCl 6.0% or NaCl 0.9% for 28days. After 28days of wash-out, patients crossed over to the alternative treatment. The primary outcome parameter was symptom score in the disease-specific quality of life Sino-Nasal Outcome Test-20 (SNOT-20). Additionally, pulmonary function was assessed, as well as rhinomanometry and inflammatory markers in nasal lavage (neutrophil elastase, interleukin (IL)-1β, IL-6, and IL-8) in a subgroup. Results Both therapeutic arms were well tolerated and showed slight improvements in SNOT-20 total scores (NaCl 6.0%: −3.1±6.5 points, NaCl 0.9%: −5.1±8.3 points, ns). In both treatment groups, changes of inflammatory parameters in nasal lavage from day 1 to day 29 were not significant. We suppose that the irritating properties of NaCl 6.0% reduced the suitability of the SNOT-20 scores as an outcome parameter. Alternative primary outcome parameters such as MR-imaging or the quantity of sinonasal secretions mobilized with both saline concentrations were, however, not feasible. Conclusion Sinonasal inhalation with NaCl 6.0% did not lead to superior results vs. NaCl 0.9%, whereas dornase alfa had been significantly more effective than NaCl 0.9%.

ZusammenfassungDie bronchopulmonale Dysplasie (BPD) stellt eine der bedeutendsten Komplikationen der Frühgeburtlichkeit dar. Sie ist nach wie vor die häufigste chronische Lungenerkrankung im Kleinkindesalter. Frühgeborene mit BPD können bis ins Erwachsenenalter hinein unter pulmonalen Einschränkungen wie Atemwegsobstruktion und Überblähung sowie persistierenden respiratorischen Beschwerden leiden. Frühgeborene aus der Surfactant-Ära scheinen gleichermaßen von den Langzeitfolgen der BPD betroffen zu sein. Unklar ist, ob ein mögliches besseres Langzeitoutcome durch das Überleben von immer unreiferen Frühgeborenen verdeckt wird. Beim Management von Patienten mit chronischer Lungenerkrankung nach BPD sollte auf eine Abgrenzung zum Asthma bronchiale geachtet werden. Bisher konnte kein positiver Effekt einer Therapie mit inhalativen Steroiden beobachtet werden. Die Anwendung von inhalativen Bronchodilatatoren wird bisher nur bei Anzeichen einer reversiblen Atemwegsobstruktion oder Exazerbationen empfohlen.

Type 1 diabetes mellitus (T1DM) is characterized by an immunological reaction that is dominated by type-1 T helper (Th1) cells, whereas immunoglobulin E (IgE)-mediated allergies are associated with Th2 cell. According to the Th1/Th2-hypothesis, the immune system is said to either develop into the direction of Th1 or Th2 cells. This would mean that a child developing T1DM is unlikely to develop an IgE-mediated allergy and vice versa.The aim of the study was to investigate the association between the prevalence of T1DM and IgE-mediated allergies.We designed a prospective case control study with 94 children and adolescents with T1DM and 188 age- and sex-matched control children. The basis of our investigations was a questionnaire concerning the family and children's history as to the presence of IgE-mediated allergies. Moreover, the following blood investigations were done: total serum IgE, specific IgE antibodies to major inhalant allergens, and a multiplex cytokine analysis measuring levels of specific cytokines representing either Th1- or Th2- cytokines.Children with T1DM reported the presence of IgE-mediated allergies significantly more often than children of the control group. Children with T1DM had significantly higher tumor necrosis factor alpha (TNFα) levels than healthy controls. Levels of interleukin-2 (IL-2) and IL-6 were higher in the groups of children with the presence of a personal history of allergies, regardless of the presence of T1DM.Our results suggest that T1DM is associated with a higher risk of a self-reported presence of IgE-mediated allergies and that the Th1/Th2-hypothesis may be an oversimplification.

Abnormal Ca 2+ inward current through cardiac Ca 2+ channels during ischemia has been shown to be an initial signal for activation of myocardial Ca 2+ -dependent enzymes. This study investigated the contribution of cardiac L- and T-type Ca 2+ channels in the calpain-mediated myocardial damage following myocardial infarction. Myocardial infarction was induced by permanent ligation of the left coronary artery. Infarcted rats were orally treated with placebo, amlodipine (L-channel blockade; 4 mg/kg/day) or mibefradil (L-/T-channel blockade; 10 mg/kg/day) beginning 7 days before induction of myocardial infarction. Gene expression, protein levels and enzyme activity of calpains I and II were measured 1, 3, 7 and 14 days postcoronary occlusion in the noninfarcted and infarcted myocardium. Infarct size, left ventricular dilation and interstitial collagen volume fraction were determined in picrosirius red-stained hearts. Myocardial infarction induced an up-regulation of calpain I mRNA, protein and activity in the noninfarcted myocardium (maximum 14 days postinfarction), whereas mRNA, protein and activity of calpain II were maximally increased in the infarcted myocardium 3 days postinfarction. Fourteen days postinfarction, infarct size was 49%, the left ventricle was dilated and interstitial collagen volume fraction was increased. Amlodipine-inhibited mRNA, protein and activity up-regulation of calpain I decreased interstitial collagen volume fraction and infarct size. Mibefradil-attenuated mRNA, protein and activity up-regulation of calpain II at all four time points measured and of calpain I at 7 and 14 days postinfarction reduced infarct size and prevented left ventricular dilation. Infarction-induced cardiac hypertrophy was accompanied by an up-regulation of calpain I, whereas calpain II was up-regulated in the infarcted myocardium. Cardiac L- and T-type Ca 2+ channel blockade differentially reduced postinfarction remodeling associated with selective inhibition of cardiac calpains I and II, respectively.

The calpains have been proposed to be activated following cardiac ischaemia and to contribute to myocyte damage after myocardial infarction (MI). In this study, the activity of calpains I and II in the infarcted and non-infarcted rat myocardium and the action of the selective calpain inhibitor, CAL 9961, has been investigated. MI was induced by permanent ligation of the left coronary artery. One, 3, 7 and 14 days post MI, the enzymes calpain I and II were separated from homogenates of the interventricular septum (IS) and left ventricular free wall (LVFW) by chromatography on DEAE-Sepharose. The activity of the calpains was measured in sham-operated and MI animals chronically treated with placebo or CAL 9961 (15 mg kg−1 d−1 s.c.) in a synthetic substrate assay. Treatment was started 3 days before MI induction. Calpain I activity reached highest values in IS 14 days post MI, whereas maximum activity of calpain II was measured in LVFW 3 days post MI. In experiments in vitro, CAL 9961 completely inhibited both calpains. In vivo, chronic treatment of MI animals with CAL 9961 partially prevented the increase in calpain I activity in IS and reduced calpain II activity in LVFW to sham levels. Our findings demonstrate that calpains I and II are activated after MI, however, both enzymes differ in their regional and temporal activation within the infarcted myocardium. Chronic inhibition of these enzymes with CAL 9961 might limit the calpain-induced myocardial damage and preserve cardiac structural integrity post MI. British Journal of Pharmacology (2002) 135, 1951–1958; doi:10.1038/sj.bjp.0704661

We report the case of a 9-year-old boy with extensive pleural fibrosis and contraction of the affected hemithorax secondary to pleural tuberculosis (TB), who was successfully treated with a 6 months course of the standard WHO regimen. Although well described for the adult population, this complication is rare among children and to our knowledge, no such case has been described since the widespread introduction of antitubercular therapy in the 1950s. This case underscores the importance of appropriate follow-up and administration of chemoprophylaxis after TB exposure.

Background: Indeterminate colitis (IC) remains an enigmatic inflammatory bowel disease (IBD) phenotype. It is currently not clear whether it constitutes merely a problem of terminology, classification, or possibly an early stage of IBD distinct from Crohn's disease (CD) and ulcerative colitis (UC). Methods: We analysed epidemiological data of studies comparing IC, UC and CD. We selected 14 studies investigating paediatric patients (10 prospective and 4 retrospective) and 18 studies investigating adult IBD patients (11 prospective and 7 retrospective) for this analysis. Results: Compared to adults ( n = 15,776) the frequency of IC is higher in children ( n = 6262) (children 12.7% versus adults 6.0%, p < 0.0001). This difference between children and adults has been detected irrespective whether prospective or retrospective studies were selected. In both, children and adults IC was more frequent in prospective studies compared to retrospective studies (children p = 0.0004; adults p = 0.0024). Conclusions: IC has been detected in a substantial proportion of paediatric patients with IBD. IC is more frequently found in children compared to adults. Further studies are required to clarify whether IC represents an IBD phenotype associated with childhood disease onset or whether the high IC frequency is due to difficulties in establishing a UC or CD diagnosis. * Abbreviations : IBD : inflammatory bowel disease IC : indeterminate colitis UC : ulcerative colitis CD : Crohn's disease

Objectives Chronic rhinosinusitis significantly impairs CF patients' quality of life. The PariSinus™ device effectively delivers vibrating aerosols to paranasal sinuses. Previously, we demonstrated a significant reduction of sinonasal symptoms by inhalation of dornase alfa with the device (JCF 2014). Bronchially inhaled hypertonic saline (3–7%) was shown to reduce pulmonary symptoms and exacerbations in CF. Aims of this multicentre, double-blind, controlled, crossover trial were to assess effects of hypertonic (6%) and isotonic saline on sinonasal outcome measures. Methods 69 CF patients were randomised to inhale either hypertonic or isotonic saline for 28 days with the PariSinus™. After 28 days of wash-out patients crossed over to the alternative treatment. The primary outcome parameter was upper airway symptoms / disease-specific QoL (Sino-Nasal Outcome Test-20 – SNOT-20). Results Sinonasal inhalation of isotonic and hypertonic saline was well tolerated. Both arms showed slight but not significant reductions of SNOT-20 scores (6% –3.1±6.5pts/0.9% –5.1±8.3pts). Interestingly, a post-hoc analysis of the single therapeutic periods revealed a significant improvement, especially for isotonic saline. We additionally present changes in rhinoscopy, rhinomanometry, and cytokines in nasal lavage. Conclusion Compared to sinonasal inhalation with dornase alfa, effects of isotonic and hypertonic saline on sinonasal symptoms did not reach significance. Possibly, SNOT-20 is not the best outcome parameter for therapy with hypertonic saline due to irritating properties, even if patients reported effective mobilization of mucus, which is difficult to quantify in both airway levels.

1. The calpains have been proposed to be activated following cardiac ischaemia and to contribute to myocyte damage after myocardial infarction (MI). In this study, the activity of calpains I and II in the infarcted and non-infarcted rat myocardium and the action of the selective calpain inhibitor, CAL 9961, has been investigated. 2. MI was induced by permanent ligation of the left coronary artery. One, 3, 7 and 14 days post MI, the enzymes calpain I and II were separated from homogenates of the interventricular septum (IS) and left ventricular free wall (LVFW) by chromatography on DEAE-Sepharose. The activity of the calpains was measured in sham-operated and MI animals chronically treated with placebo or CAL 9961 (15 mg kg(-1) d(-1) s.c.) in a synthetic substrate assay. Treatment was started 3 days before MI induction. 3. Calpain I activity reached highest values in IS 14 days post MI, whereas maximum activity of calpain II was measured in LVFW 3 days post MI. In experiments in vitro, CAL 9961 completely inhibited both calpains. In vivo, chronic treatment of MI animals with CAL 9961 partially prevented the increase in calpain I activity in IS and reduced calpain II activity in LVFW to sham levels. 4. Our findings demonstrate that calpains I and II are activated after MI, however, both enzymes differ in their regional and temporal activation within the infarcted myocardium. Chronic inhibition of these enzymes with CAL 9961 might limit the calpain-induced myocardial damage and preserve cardiac structural integrity post MI.

Objective To assess and compare long-term pulmonary outcomes in former preterm-born, very low birth weight (VLBW) children with and without bronchopulmonary dysplasia (BPD) born in the surfactant era. Study design Pulmonary function tests (ie, spirometry, body plethysmography, and gas transfer testing) were performed in children with a history of VLBW and BPD (n = 28) and compared with a matched preterm-born VLBW control group (n = 28). Medical history was evaluated by questionnaire. Results At time of follow-up (mean age, 9.5 years), respiratory symptoms (36% vs 8%) and receipt of asthma medication (21% vs 0%) were significantly more frequent in the preterm-born children with previous BPD than in those with no history of BPD. The children with a history of BPD had significantly lower values for forced expiratory volume in 1 second (z-score -1.27 vs -0.4; P =.008), forced vital capacity (z-score -1.39 vs -0.71 z-score; P =.022), and forced expiratory flow rate at 50% of forced vital capacity (z-score -2.21 vs -1.04; P =.048) compared with the preterm control group. Conclusion Preterm-born children with a history of BPD are significantly more likely to have lung function abnormalities, such as airway obstruction and respiratory symptoms, at school age compared with preterm-born children without BPD. © Copyright 2014 Mosby Inc. All rights reserved.