The Berlin-Brandenburg Air Study-A Methodological Study Paper of a Natural Experiment Investigating Health Effects Related to Changes in Airport-Related Exposures.

Objectives: This paper presents the study design of the Berlin-Brandenburg Air study (BEAR-study). We measure air quality in Berlin and Brandenburg before and after the relocation of aircraft (AC) traffic from Tegel (TXL) airport to the new Berlin-Brandenburg airport (BER) and investigate the association of AC-related ultrafine particles (UFP) with health outcomes in schoolchildren. Methods: The BEAR-study is a natural experiment examining schoolchildren attending schools near TXL and BER airports, and in control areas (CA) away from both airports and associated air corridors. Each child undergoes repeated school-based health-examinations. Total particle number concentration (PNC) and meteorological parameters are continuously monitored. Submicrometer particle number size distribution, equivalent black carbon, and gas-phase pollutants are collected from long-term air quality monitoring stations. Daily source-specific UFP concentrations are modeled. We will analyze short-term effects of UFP on respiratory, cardiovascular, and neurocognitive outcomes, as well as medium and long-term effects on lung growth and cognitive development. Results: We examined 1,070 children (as of 30 November 2022) from 16 schools in Berlin and Brandenburg. Conclusion: The BEAR study increases the understanding of how AC-related UFP affect children's health.

Clinical course of new-onset Crohn's disease in children and adolescents in dependency of age, initial location, initial severity level and therapy over the period 2000-2014 based on the Saxon Pediatric IBD-Registry in Germany.

OBJECTIVE: In Saxony, the incidence of Crohn's disease (CD) in children and adolescents increased significantly from 3.3 per 100,000 person-years in 2000 to 5.1 in 2014. The aim of this study was to describe the initial characteristics and the clinical course of CD in children and adolescents and to identify drug treatment options associated with an advantage for a mild course or remission. METHODS: Clinical data were collected from patients who suffered from inflammatory bowel disease (IBD) and were recruited in the Saxon Pediatric IBD-Registry. All children newly diagnosed with CD in this registry in Saxony between 2000 and 2014 were included in this registry study. Characteristics such as age, disease location and extra-intestinal manifestations at diagnosis were accessed. The severity level of the disease at diagnosis as well as at follow-up were analysed by PCDAI index. Patients were divided into 3 groups according to length of follow-up: 1-3 years, 4-6 years and 7-9 years after diagnosis. A logistic regression model was conducted to examine which baseline parameters are associated with disease progression. RESULTS: There were 338 children and adolescents with CD included in this registry study. At diagnosis, the median age of patients was 12.0 (0.7-14.9), 61.5% (n = 208) of the patients were male. The most common disease location observed in pediatric CD patients was the L3 (55%, n = 176). Patients aged 10-14 years were significantly more likely to present an L2 than patients aged 0-4 years (80.3%, n = 53 vs. 19.7%, n = 13, p = 0.01). During the follow-up, data from 71.3% (n = 241) othe patients were available. Disease activity measured by PCDAI decreased in 47.7% (n = 115) of the patients, 40.7% (n = 98) of the patients were stable and increased in 11.6% (n = 28) of the patients. Patients with intermediate/severe disease at onset were more likely to have an active disease at the end of follow up, too (p = 0.00). Logistic regression analysis of the initial characteristics showed that the age at diagnosis, gender, initial location and initial extra-intestinal manifestation are not associated with the progression of the disease (p>0.05). Furthermore, drug treatment options could be identified from our data, which are associated with benefits for a milder course or remission. CONCLUSION: From 2000 to 2014, the health status of most pediatric patients with CD had improved or remained stable. Initial characteristics including age at diagnosis, initial localization and initial extra-intestinal manifestation are not associated with the progression of the disease, only the initial activity by PCDAI.

Current and projected incidence trends of pediatric-onset inflammatory bowel disease in Germany based on the Saxon Pediatric IBD Registry 2000-2014 -a 15-year evaluation of trends.

AIMS: An increasing number of children and adolescents worldwide suffer from inflammatory bowel disease (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). The present work aims to investigate the incidence, prevalence and future trends of IBD in children and adolescents in Saxony, Germany. METHODS: The Saxon Pediatric IBD Registry collected data on patients up to 15 years of age from all 31 pediatric hospitals and pediatric gastroenterologists in Saxony over a 15-year period (2000-2014). In 2019, an independent survey estimated a registry completeness of 95.7%. Age-standardized incidence rates (ASR) per 100,000 person-years (PY) and prevalence per 100,000 children and adolescents were calculated. Evaluation was also been performed in sex and age subgroups. Joinpoint and Poisson regression were used for trend analyses and projections. RESULTS: 532 patients with confirmed IBD during 2000-2014 were included in the epidemiological evaluation. 63.5% (n = 338) patients had CD, 33.1% (n = 176) had UC and 3.4% (n = 18) had unclassified IBD (IBD-U). The 15-year IBD prevalence was 111.8 [95%-CI: 102.3-121.3] per 100,000. The incidence ASR of IBD per 100,000 PY over the whole observation period was 7.5 [6.9-8.1]. ASR for the subtypes were 4.8 [4.3-5.3] for CD, 2.5 [2.1-2.9] for UC and 0.3 [0.1-0.4] for IBD-U. The trend analysis of ASR using the joinpoint regression confirmed a significant increase for incidence of IBD as well as CD. For IBD, the ASR per 100,000 PY increased from 4.6 [2.8-6.3] in 2000 to 8.2 [7.5-13.6] in 2014; projected incidence rates for IBD in Germany are 12.9 [6.5-25.5] in the year 2025 and 14.9 [6.7-32.8] in 2030, respectively. Thus, the number of new IBD diagnoses in Germany would more than triple (325%) in 2030 compared to 2000. The increase is expected to be faster in CD than UC, and be more in males than in females. The expected number of newly diagnosed children with IBD in Germany is projected to rise to about 1,584 [1,512-1,655] in 2025, and to about 1,918 [1,807-2,29] in 2030. CONCLUSION: The incidence of IBD in children and adolescents in Saxony increased at a similar rate as in other developed countries during the observation period. Given this trend, the health care system must provide adequate resources for the care of these young patients in the future.

Incidence trends of pediatric onset inflammatory bowel disease in the years 2000-2009 in Saxony, Germany-first results of the Saxon Pediatric IBD Registry.

AIMS: In developed countries, the incidence of inflammatory bowel disease (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) is increasing. Therefore, we aimed to investigate the incidence rates and trends over time in the population of children and adolescents in one of the federal states of Germany, in Saxony. METHODS: Over the 10-year period 2000-2009 all 31 children's hospitals and pediatric gastroenterologists, respectively in Saxony reported all IBD patients up to 15 years of age to the Saxon Pediatric IBD Registry. The completeness of the registry was estimated as 96.7% by independent surveys in the years 2005-2009. Incidence rates were presented as age-standardized incidence rates (ASR) regarding New European Standard Population 1990 per 100,000 person-years (PY) with 95% confidence intervals [CI]. Joinpoint and linear regression was used for trend analyses. RESULTS: 344 patients with confirmed IBD between 2000-2009 were included in the epidemiological evaluation: 212 (61.6%) patients with CD, 122 (35.6%) with UC and 10 (2.9%) with unclassified IBD (IBD-U). The ASR per 100,000 PY over the whole observation period was 7.2 [6.4-7.9] for IBD, 4.4 [3.8-5.0] for CD, 2.6 [2.1-3.0] for UC and 0.2 [0.1-0.3] for IBD-U. For IBD, the ASR per 100,000 PY increased from 4.6 [2.8-6.3] in 2000 to 10.5 [7.5-13.6] in 2009. The incidence trend analysis of ASRs using the joinpoint regression confirmed a significant increase of IBD as well as UC. The mean age at first diagnosis decreased significantly during the observation period from 11.5 (11.0-13.4) in 2000 to 9.6 (5.1-13.5) years in 2009. The median of the diagnostic latency among IBD patients was 3 months. CONCLUSION: The incidence of IBD in children and adolescents in Saxony was slightly higher than the average of other countries in the same time period and followed the trend towards a general increase of IBD. The age at diagnosis was subject to a very unfavorable downward trend.

Influence of CARD15 mutations on disease activity and response to therapy in 65 pediatric Crohn patients from Saxony, Germany.

OBJECTIVES: Certain genetic variants in the CARD15 gene are accompanied by an enhanced risk to develop Crohn disease with the main activity in the terminal ileum and ensuing stricturing early in life. The objective of this study was to evaluate the relation between CARD15 mutations and overall disease activity and response to therapy in pediatric patients. METHODS: 65 genomic DNA samples from such patients were tested for the presence of three main Crohn associated mutations in CARD15 by direct genomic sequencing. The number of mutations (none, one or two alleles affected) was correlated with body mass index and height, Pediatric Crohn Disease Activity Index, therapy and therapeutical success in terms of body mass index and Pediatric Crohn Disease Activity Index improvement. RESULTS: The authors found a nonsignificant trend of a lower body mass index and higher Pediatric Crohn Disease Activity Index in patients with CARD15 mutations. Physicians uninformed about their CARD15 status prescribed significantly more budesonide and prednisolone intermittently and more alimentary supplementation to these patients. The average improvement in terms of body mass index and Pediatric Crohn Disease Activity Index after 2 years of therapy was roughly similar in all patient groups. CONCLUSIONS: Pediatric Crohn patients with CARD15 mutations have a higher disease activity and need a more intensive therapy. With some exceptions, their medium-term response to therapy is nevertheless satisfying.

CARD15 genotype and phenotype analysis in 55 pediatric patients with Crohn disease from Saxony, Germany.

OBJECTIVES: Crohn disease is a chronic inflammatory bowel disorder that is caused by environmental and genetic factors. Mutations in the CARD15 gene have been recently identified to be associated with the disease. Until now no genetic study has focused directly on a pediatric population. METHODS: The authors sequenced all 12 exons of the CARD15 gene in 55 pediatric patients with Crohn disease from Saxony. Their average age at onset was 11.2 years (1-17.5 years). The authors also evaluated the genotype-phenotype relationship in the patients. RESULTS: Fourteen different polymorphic and/or disease-related nucleotide alterations have been identified in the patients. Sixty-five percent of their genomic DNA samples harbored at least one of six mutations within the CARD15 gene, which previously has been identified as being associated with Crohn disease. The authors found that the cytosine insertion mutation 3020insC was significantly more common in their pediatric population than in patients with Crohn disease (26% versus 11% of the alleles) whose results were reported in the literature. The genotype-phenotype analysis showed that the authors' patients with at least one of the six CARD15 disease-associated mutations had a high risk of inflammation located in the terminal ileum and ascending colon. In 10 of 19 patients with two mutations, intestinal resection surgery was necessary because of stricturing. CONCLUSIONS: In the authors' pediatric patients, the genetic influence on Crohn disease was more pronounced than that reported in any other study, and it strongly affected the clinical phenotype.

Immunodeficiency with recurrent panlymphocytopenia, impaired maturation of B lymphocytes, impaired interaction of T and B lymphocytes, and impaired integrity of epithelial tissue: a variant of idiopathic CD4+ T lymphocytopenia?

Idiopathic CD4+ T lymphocytopenia (ICL) has been defined as a cause of immunodeficiency with a variable clinical course and an unknown etiology. Here we describe a now 18-year-old boy with ICL, chronic mucocutaneous candidiasis (CMC), recurrent abscesses, and relapsing aphthous and ulcerous lesions. In addition to ICL the patient frequently showed a panlymphocytopenia. An increased percentage of gamma+delta+ T lymphocytes and IgD+ IgM+ B lymphocytes, and a decreased percentage of CD21+ B lymphocytes, were observed. In vitro assays showed normal T-cell responses to candidin and T-cell mitogens, but impaired B-cell responses to pokeweed mitogen (PWM). B-cell maturation after stimulation with Staphylococcus aureus Cowan I (SAC) and interleukin 2 (IL-2) was nearly normal. The clinical course of the patient improved substantially on administration of constant low-dose therapy with fluconazole.