[Management of Adult Community-Acquired Pneumonia and Prevention - Update 2021 - Guideline of the German Respiratory Society (DGP), the Paul-Ehrlich-Society for Chemotherapy (PEG), the German Society for Infectious Diseases (DGI), the German Society of Medical Intensive Care and Emergency Medicine (DGIIN), the German Viological Society (DGV), the Competence Network CAPNETZ, the German College of General Practitioneers and Family Physicians (DEGAM), the German Society for Geriatric Medicine (DGG), the German Palliative Society (DGP), the Austrian Society of Pneumology Society (ÖGP), the Austrian Society for Infectious and Tropical Diseases (ÖGIT), the Swiss Respiratory Society (SGP) and the Swiss Society for Infectious Diseases Society (SSI)]. / Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie ­ Update 2021.

The present guideline provides a new and updated concept of the management of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2016.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment.The recommendations aim at the same time at a structured assessment of risk for adverse outcome as well as an early determination of treatment goals in order to reduce mortality in patients with curative treatment goal and to provide palliation for patients with treatment restrictions.

Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer.

Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4-5.6) versus 10.3 months (95% CI: 8.6-12.0), P < 0.001; OS 15.0 months (95% CI: 5.0-24.9) versus 50.0 months (95% CI: 22.9-77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3-4.1) versus 6.2 months (95% CI: 1.8-10.5), P = 0.021; OS 2.0 months (95% CI: 0.0-4.6) versus 9.0 months (95% CI: 6.1-11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9-7.2) versus 14.0 months (95% CI: 8.0-20.1), P < 0.001; OS 17.0 months (95% CI: 6.7-27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1-10.7) versus 9.9 months (95% CI: 6.4-13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.

[Biomarkers in Diagnosis, Treatment and Prognosis of Infectious Lung Diseases]. / Biomarker in der Diagnostik, Therapie und Prognose infektiöser Lungenerkrankungen.

Biomarkers play an important role in the management of infectious pulmonary diseases, even though there is only limited evidence that biomarker-guided therapies are superior to clinical strategies.Well-established indications for the use of biomarkers are the guidance of the duration of antibiotic therapy in community-acquired pneumonia (CAP) by PCT, the decision against the use of antibiotics by CRP or PCT in ambulatory settings, and the evaluation of CAP treatment by CRP or PCT kinetics.In the prognostic assessment of CAP, the standard biomarkers of acute organ dysfunction should be given priority, e. g. leukocyte and platelet counts, creatinine/urea and lactate, in combination with clinical signs and symptoms.MR-pro-ADM could enrich diagnostics in the future. Genetic transcriptome analysis is a completely new and promising concept.

[Epidemiology, Diagnosis and Treatment of Adult Patients with Nosocomial Pneumonia - Update 2017 - S3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy, the German Radiological Society and the Society for Virology]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie ­ Update 2017.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However, infections on general wards are increasing. A central issue are infections with multidrug resistant (MDR) pathogens which are difficult to treat in the empirical setting potentially leading to inappropriate use of antimicrobial therapy.This guideline update was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and treatment of HAP on the basis of quality of evidence and benefit/risk ratio.This guideline has two parts. First an update on epidemiology, spectrum of pathogens and antimicrobials is provided. In the second part recommendations for the management of diagnosis and treatment are given. New recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia and prolonged infusion of antibacterial drugs have been added. The statements to risk factors for infections with MDR pathogens and recommendations for monotherapy vs combination therapy have been actualised. The importance of structured deescalation concepts and limitation of treatment duration is emphasized.

[Criteria for treating MRSA in sputum]. / Kriterien zur Behandlung von MRSA im Sputum?

Methicillin-resistant strains of Staphylococcus aureus (MRSA) are of particular significance for the management of patients with airway infections, since the disease course is often complicated and treatment rendered difficult by multiple resistance. Their prevalence is now slowly declining, but still alarmingly high. Hospital-acquired infections are predominant, but hospital-associated and community-acquired infections do occur, as do rare infections with livestock-acquired strains. Non-nosocomial strains are characterized by different pathogenic factors and a different spectrum of antibacterial resistance; they often have a threatening disease course. Anti-infectives with activity against MRSA are unusual and have particular toxicity profiles. On the other hand, MRSA colonization is eliminated spontaneously in healthy people and acute bronchitis is treatable by common oral antibiotics. However, chronic airway infection in bronchiectasis and other forms of structural airway damage requires a complex systemic and local treatment approach for pathogen elimination.

[Management of Adult Community-acquired Pneumonia and Prevention - Update 2016]. / Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie und Prävention - Update 2016.

The present guideline provides a new and updated concept of treatment and prevention of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2009.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment as well as primary and secondary prevention.

[A practically orientated clinical HIV update for ENT physicians]. / Praktisch orientiertes klinisches HIV-Update für HNO-Ärzte.

Basic knowledge concerning the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) is useful for ENT physicians. Although HIV patients are usually stably asymptomatic nowadays due to modern therapy, HIV often manifests in ENT symptoms, such as neck lumps, sore throat, difficulty swallowing and dysgeusia. After infection, an initial increase in viral load can cause, among other symptoms, oral ulcers and pharyngitis. Once the immune system is compromised by the attack on CD4 lymphocyte cells, HIV-related diseases can occur: oral mycoses (particularly candidosis) and viral infections (including warts), aphthous ulcers, gingivitis, salivary gland diseases and malignancies (e. g. intraoral Kaposi's sarcoma). Neck lymphadenopathy is frequent. Markers of disease severity are the clinical symptoms, viral load and CD4 helper cell count. HIV treatment (antiretroviral therapy, ART) is a combination of at least three antiviral drugs.

Peer problems are associated with elevated serum leptin levels in children.

BACKGROUND: Leptin is thought to act as an important mediator in stress reactions. To date, no study has examined the association between psychological stress and leptin levels in children. This study aimed to assess the association between emotional symptoms and peer problems and serum leptin levels in children aged 10 years of the two population-based GINI-plus and LISA-plus birth cohorts. METHOD: Cross-sectional data from 2827 children aged 10 years were assessed with regard to leptin concentrations in serum and behavioral problems using the parent-reported Strengths and Difficulties Questionnaire (SDQ). Linear regression modeling was applied to determine the likelihood of elevated leptin levels in children with emotional symptoms and peer problems, controlling for socio-economic status (SES), body mass index (BMI), fasting serum leptin levels, pubertal development and sex hormones. RESULTS: We found that increases in emotional symptoms (exp ß adj = 1.03, s.e. = 0.02, p < 0.04) and peer problems (exp ß adj = 1.05, s.e. = 0.01, p = 0.0001) were significantly associated with higher serum leptin levels controlled for BMI and sociodemographic factors. Similar results were found when the fasting serum leptin sample was examined (exp ß adj = 1.08, s.e. = 0.04, p = 0.0294). Gender-stratified analyses showed a significant relationship between serum leptin and peer problems in girls (exp ß adj = 1.05, s.e. = 0.02, p = 0.03), and a borderline significant association in boys (exp ß adj = 1.04, s.e. = 0.02, p = 0.05). CONCLUSIONS: Children with peer problems have higher stress and eat more, acquire a higher body fat mass and thus, through increased leptin resistance, exhibit higher leptin levels.

Epidemiology of urticaria in infants and young children in Germany--results from the German LISAplus and GINIplus Birth Cohort Studies.

BACKGROUND: Although urticaria is considered one of the most frequent skin diseases, reliable epidemiologic data are scarce. OBJECTIVE: To evaluate the incidence and cumulative prevalence of urticaria in infants and children up to age of 10, to characterize the relationship of specific IgE levels (food and inhalative allergens) with urticaria, and to monitor the joint occurrence of urticaria with other diseases, such as eczema, asthma, and hay fever. METHODS: The study population consisted of two prospective birth cohort studies: the LISAplus and GINIplus studies. Information on physician-diagnosed urticaria, asthma, eczema, or hay fever was collected using self-administered questionnaires completed by the parents. Blood samples were drawn, and specific immunoglobulin E measured at 2 (only LISAplus), 6 and 10 yr of age. RESULTS: The incidence of urticaria was approximately 1% per year of age. The cumulative prevalence of urticaria in children up to the age of 10 yr was 14.5% for boys and 16.2% for girls. Cumulative prevalence of urticaria at the age of ten was significantly (p < 0.05) associated with allergic sensitization to peanut, soy, and wheat flour, but not with inhalant allergens. Both a parental history of atopy/urticaria and the children's diagnosis of asthma, eczema, and hay fever were strongly related (p < 0.0001) to the occurrence of urticaria. CONCLUSIONS: Urticaria is a frequent event during childhood, with highest incidence in infants and preschool children. Comorbidity with atopic disease is high.

Therapy and prophylaxis of opportunistic infections in HIV-infected patients: a guideline by the German and Austrian AIDS societies (DAIG/ÖAG) (AWMF 055/066).

INTRODUCTION: There was a growing need for practical guidelines for the most common OIs in Germany and Austria under consideration of the local epidemiological conditions. MATERIALS AND METHODS: The German and Austrian AIDS societies developed these guidelines between March 2010 and November 2011. A structured Medline research was performed for 12 diseases, namely Immune reconstitution inflammatory syndrome, Pneumocystis jiroveci pneumonia, cerebral toxoplasmosis, cytomegalovirus manifestations, candidiasis, herpes simplex virus infections, varizella zoster virus infections, progressive multifocal leucencephalopathy, cryptosporidiosis, cryptococcosis, nontuberculosis mycobacteria infections and tuberculosis. Due to the lack of evidence by randomized controlled trials, part of the guidelines reflects expert opinions. The German version was accepted by the German and Austrian AIDS Societies and was previously published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF; German Association of the Scientific Medical Societies). CONCLUSION: The review presented here is a translation of a short version of the German-Austrian Guidelines of opportunistic infections in HIV patients. These guidelines are well-accepted in a clinical setting in both Germany and Austria. They lead to a similar treatment of a heterogeneous group of patients in these countries.

FADS gene cluster modulates the effect of breastfeeding on asthma. Results from the GINIplus and LISAplus studies.

BACKGROUND: The protective effect of breastfeeding (BF) on the development of asthma has been widely recognized, even if not all results have been consistent. Gene variants of the FADS gene cluster have a major impact on fatty acid composition in blood and in breast milk. Therefore, we evaluated the influence of the FADS1 FADS2 gene cluster polymorphisms on the association between BF and asthma. METHODS: The analysis was based on data (N=2245) from two German prospective birth cohort studies. Information on asthma and BF during the first 6 months was collected using questionnaires completed by the parents. Logistic regression modelling was used to analyse the association between exclusive BF and ever having asthma stratified by genotype. RESULTS: In the stratified analyses, BF for 3 or 4 months after birth had a protective effect for heterozygous and homozygous carriers of the minor allele (adjusted odds ratio between 0.37 (95% CI: 0.18-0.80) and 0.42 (95% CI: 0.20-0.88). Interaction terms of BF with genotype were significant and ranged from -1.17 (P-value: 0.015) to -1.33 (0.0066). Moreover, heterozygous and homozygous carriers of the minor allele who were exclusively breastfed for 5 or 6 months after birth had a reduced risk of asthma [0.32 (0.18-0.57) to 0.47 (0.27-0.81)] in the stratified analyses. For individuals carrying the homozygous major allele, BF showed no significant effect on the development of asthma. CONCLUSIONS: The association between exclusive BF and asthma is modified by the genetic variants of FADS genotypes in children.

Growth velocity during infancy and onset of asthma in school-aged children.

BACKGROUND: Growth velocities during infancy might affect the risk of asthma in childhood. This study examines the association between peak height and weight velocities during the first 2 years of life and onset of asthma and wheeze up to 10 years of age. METHODS: Data from 9086 children who participated in the GINIplus and LISAplus birth cohorts were analyzed. Information on asthma was requested annually from 1 to 10 years and information on wheeze at 1, 2, 4, 6, and 10 years. Peak height and weight velocities were calculated using height and weight measurements obtained between birth and 2 years of age. Cox proportional hazards models and generalized linear mixed models were calculated after adjustment for potential confounding factors including birth weight and body mass index at 10 years of age. RESULTS: Per interquartile range increase in peak weight velocity (PWV), the risk of asthma increased significantly (adjHR: 1.22; CI: 1.02-1.47). The relationship between peak height velocity (PHV) and onset of asthma was nonsignificant (adjHR: 1.08; CI: 0.88-1.31). Wheeze was not significantly associated with PHV or with PWV (adjOR: 1.07; CI: 0.64-1.77 and adjOR: 1.11; CI: 0.68-1.79, respectively). CONCLUSIONS: Weight gain during infancy is positively associated with physician-diagnosed asthma in school-aged children.

Association of gas cooking with children's respiratory health: results from GINIplus and LISAplus birth cohort studies.

UNLABELLED: Previous studies have found inconsistent results on the association between asthma in children and gas cooking emissions. We aimed to assess the effects of the long-term exposure to gas cooking on the onset of asthma and respiratory symptoms, focusing on wheezing, in children from two German birth cohorts: LISAplus and GINIplus. A total of 5078 children were followed until the age of 10 years. Asthma, wheezing, gas cooking, and exposure to other indoor factors were assessed through parental reported questionnaires administered periodically. Logistic and multinomial regressions adjusting for potential confounders were performed. The prevalence of asthma and persistent wheezing was higher among children exposed to gas cooking but the results were not statistically significant. Exposure to gas cooking was positively associated (P-value < 0.05) with exposure to other indoor factors (dampness, environmental tobacco smoke, and pets). Our results did not show a statistically significant association between the exposure to gas cooking and children's respiratory health. PRACTICAL IMPLICATIONS: These analyses are consistent with the assumption of no effect of the exposure to low doses of nitrogen dioxide. The strong positive associations found between gas cooking and other indoor factors highlight the importance of considering other indoor factors when assessing health effects of gas cooking. Low-dose exposure to indoor nitrogen dioxide through gas cooking might not contribute to increase the risk of asthma and respiratory symptoms in children.

[Two German Birth Cohorts: GINIplus and LISAplus]. / Die zwei deutschen Geburtskohorten GINIplus und LISAplus.

Numerous chronic diseases in childhood and adulthood have their origins in perinatal life and are potentially influenced by trans-generational epigenetic processes. Therefore, prospective birth cohorts can substantially contribute to our knowledge about the etiology of diseases including modifiable risk factors. The two population-based German birth cohorts GINIplus and LISAplus aim to describe the natural course of chronic diseases and intermediate phenotypes in childhood and its determinants, and to identify potential genetic effect modifications. In the mid-1990s, 5,991 (GINIplus) and 3,097 (LISAplus) healthy, term newborns were recruited for long-term follow-up in four regions of Germany. The follow-up rate for the first 10 years was about 55%. We analyzed the growth and development of overweight, infections and allergic diseases, mental and oral health, metabolic and inflammatory parameters and the role of potential risk factors including genetics. The results of these two birth cohorts substantially contribute to the current knowledge about the natural course of these health parameters. These data were included in many international projects and consortia for purposes of international comparisons of prevalence and consistency of findings, and to increase the power of the analyses.

[Epidemiology, diagnosis and treatment of adult patients with nosocomial pneumonia. S-3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie. S-3 Leitlinie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V., der Deutschen Gesellschaft für Infektiologie e.V., der Deutschen Gesellschaft für Hygiene und Mikrobiologie e.V., der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. und der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However infections on general wards are also increasing. A central issue are infections with multi drug resistant (MDR) pathogens which are difficult to treat particularly in the empirical setting potentially leading to inappropriate use of antimicrobial therapy. This guideline was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and therapy of HAP on the basis of quality of evidence and benefit/risk ratio. The guideline has two parts. First an update on epidemiology, spectrum of pathogens and antiinfectives is provided. In the second part recommendations for the management of diagnosis and treatment are given. Proper microbiologic work up is emphasized for knowledge of the local patterns of microbiology and drug susceptibility. Moreover this is the optimal basis for deescalation in the individual patient. The intensity of antimicrobial therapy is guided by the risk of infections with MDR. Structured deescalation concepts and strict limitation of treatment duration should lead to reduced selection pressure.

Respiratory health in children, and indoor exposure to (1,3)-ß-D-glucan, EPS mould components and endotoxin.

For a long time, exposure to mould and dampness-derived microbial components was considered a risk factor for the development of respiratory diseases and symptoms. Some recent studies suggested that early childhood exposure to mould components, such as (1,3)-ß-D-glucan and extracellular polysaccharides (EPSs), may protect children from developing allergy. We investigated the association of exposure to (1,3)-ß-D-glucan, EPS and endotoxin with asthma and allergies in 6-yr-old children. This investigation was the follow-up to a nested case-control study among three European birth cohorts. Children from two ongoing birth cohort studies performed in Germany (n = 358) and one in the Netherlands (n = 338) were selected. Levels of (1,3)-ß-D-glucan, EPS and endotoxin were measured in settled house dust sampled from children's mattresses and living-room floors when the children were, on average, 5 yrs of age. At the age of 6 yrs, health outcome information was available for 678 children. In the two German subsets, domestic EPS and endotoxin exposure from children's mattresses were significantly negatively associated with physician-diagnosed asthma (OR per interquartile range increase 0.60 (95% CI 0.39-0.92) and 0.55 (95% CI 0.31-0.97), respectively). In addition, EPS exposure was inversely related to physician-diagnosed allergic rhinitis (OR 0.50, 95% CI 0.31-0.81). For the Dutch population, no associations were observed between exposure to microbial agents and respiratory health outcomes. We found inverse associations between domestic exposure to EPS and endotoxin from children's mattresses, and doctor-diagnosed asthma and rhinitis in German, but not in Dutch, school children. The reasons for the differences between countries are not clear.

FADS gene variants modulate the effect of dietary fatty acid intake on allergic diseases in children.

BACKGROUND: The association between dietary fatty acid intake and the development of atopic diseases has been inconsistent. This could be due to inter-individual genetic differences in fatty acid metabolism. OBJECTIVE: The aim of the current study was to assess the influence of FADS1 FADS2 gene cluster polymorphisms on the association between dietary fatty acid intake and atopic diseases and allergic sensitization in 10-year-old children. METHODS: The analysis was based on data from two German prospective birth cohort studies. Data on margarine and fatty acid intake were collected using a food frequency questionnaire. Information on atopic diseases was collected using a questionnaire completed by the parents. Specific IgE against common food and inhalant allergens were measured. Six variants of the FADS1 FADS2 gene cluster (rs174545, rs174546, rs174556, rs174561, rs174575 and rs3834458) were tested. Logistic regression modelling, adjusted for gender, age, maternal education level and study centre, was used to analyse the association between fatty acid intake and atopic diseases stratified by genotype. RESULTS: No significant association was found between the six FADS single nucleotide polymorphisms (SNPs) and allergic diseases or atopic sensitization. The total n-3/total n-6 ratio was positive associated with an increased risk of hayfever in homozygous major allele carriers ranging from an adjusted odds ratios of 1.25 (95%-CI: 1.00-1.57) to 1.31 (95%-CI: 1.01-1.69) across the six tested SNPs although this association was not significant anymore after correcting for multiple testing. Daily margarine intake was significantly associated with asthma [1.17 (1.03-1.34) to 1.22 (1.06-1.40)] in individuals carrying the homozygous major allele. This association was also significant after correcting for multiple testing. CONCLUSIONS & CLINICAL RELEVANCE: The association between dietary intake of fatty acids and allergic diseases might be modulated by FADS gene variants in children.

Association between attendance of day care centres and increased prevalence of eczema in the German birth cohort study LISAplus.

BACKGROUND: Day care centre attendance is much more common in East than in West Germany. Although there is evidence that early day care might be protective against atopic diseases, several studies have shown a higher prevalence of childhood eczema in East Germany compared to West Germany. OBJECTIVES: To compare prevalence and cumulative incidence of eczema in a birth cohort study in East and West Germany and to identify risk factors that are associated with eczema, which might explain regional differences. METHODS: We used data from the ongoing population-based birth cohort study Influence of Life-style factors on the development of the Immune System and Allergies in East and West Germany Plus the influence of traffic emissions and genetics. In 1997, 3097 children from study areas in East and West Germany were recruited. Cumulative incidence and 1-year prevalences of eczema up to the age of 6 years were determined from yearly questionnaires. Cox regression and generalized estimating equations/logistic regression were used to quantify regional differences and to identify risk factors that might explain them. RESULTS: Prevalence and incidence of eczema were higher in children living in East Germany than those living in West Germany. We identified 11 risk factors that showed significant regional differences. From these factors, only 'day care attendance during the first 2 years of life' was significantly associated with eczema (odds ratio 1.56, 95% confidence interval CI 1.31-1.86). The regional differences in eczema could be explained by differences in early day care utilization. CONCLUSION: Day care centre attendance is associated with an increased prevalence and incidence of eczema. Regional differences in eczema prevalence could be explained by regional differences in utilization of early day care.

Infant eczema, infant sleeping problems, and mental health at 10 years of age: the prospective birth cohort study LISAplus.

BACKGROUND: Cross-sectional studies suggest an association between eczema and mental health problems, possibly modified by sleeping problems, but prospective evidence is missing. We aimed to prospectively investigate the relationship between infant eczema (within first 2 years of age), infant sleeping problems (within first 2 years of age), and the risk of mental health problems at 10 years of age. METHODS: Between 1997 and 1999, a population-based birth cohort was recruited in Munich, Leipzig, Wesel, and Bad Honnef, Germany, and followed until 10 years of age. Physician-diagnosed eczema, parent-reported sleeping problems, and known environmental risk factors for atopy were regularly assessed until 10 years of age. Mental health was measured using the Strengths and Difficulties Questionnaire (parent version) at 10 years of age. We applied logistic regression modeling adjusting for environmental and lifestyle factors, allergic comorbidity, and family history of eczema. RESULTS: From the original cohort of 3097 neonates, 1658 (54%) were followed until age 10, while 1578 (51%) were eligible for analysis. In the fully adjusted model, children with infant eczema were at increased risk of hyperactivity/inattention at 10 years of age [odds ratio (OR) 1.78; 95% confidence interval (95% CI) 1.02-3.09]. Infant eczema with concurrent sleeping problems predicted emotional problems [OR 2.63; 95% confidence interval (95% CI) 1.20-5.76] and conduct problems (OR 3.03; 95% CI 1.01-9.12) at 10 years of age. CONCLUSIONS: Infant eczema with concurrent sleeping problems appears to be a risk factor for the development of mental health problems.

Metabolic alterations in adipose tissue during the early phase of experimental endotoxemia in humans.

Adipose tissue plays an important role in energy homeostasis; however, there is only little knowledge about its metabolic activity during critical illness or sepsis. We assessed adipose tissue metabolic activity and local blood flow during experimental endotoxemia in otherwise healthy humans. In a prospective, placebo controlled and randomized experiment we measured changes in lactate, glycerol, and pyruvate concentrations in microdialysate samples of femoral adipose tissue after an intravenous bolus of lipopolysaccharide (LPS, 4 ng/kg). Intravenous endotoxin caused an early and constant increase in interstitial pyruvate, while formation of lactate in adipose tissue was not affected. In contrast, lactate levels in serum were elevated significantly after 90 min (p<0.05) and likewise, serum glycerol concentrations rose 90 min after LPS treatment (p<0.05) and 60 min earlier than in adipose tissue. Subcutaneous adipose tissue blood perfusion increased 2-fold while there was a strong decline in skin blood flow. Pyruvate accumulation in subcutaneous adipose tissue is an early marker of endotoxemia. While adipose tissue is a major source of serum glycerol and lactate in humans during physiological conditions, it contributes only little to increased serum lactate and glycerol levels during endotoxemia.