Stressful life events in childhood and allergic sensitization.

Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children as well as the association between early stressful life events and atopic eczema (AE). Within the LISA plus (Life style - Immune system - Allergy) study, blood samples from children of 6 years of age were analyzed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines IFN-γ and IL-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. Furthermore, lifetime prevalence of AE and incidence after the assessment period of life events were compared. Our data suggest that separation/ divorce of parents increase childrens risk of developing AE later in life. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-γ concentrations in childrens blood but not with neuropeptide levels. Thus, the neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2-shifted immune response in children with separated/divorced parents.

[Preventive advice-giving: self-assessment of general practitioners in Brandenburg]. / Präventive Beratung: Selbsteinschätzungen Brandenburger Hausärzte.

INTRODUCTION: Improving individual health behaviour is a promising approach especially in cardiovascular prevention. In general practice, preventive advice-giving is hitherto put into practice insufficiently. The study explores which role general practitioners are willing and able to play in behaviour-oriented prevention. METHODS: 50% of general practitioners in Brandenburg (n=748) were randomly selected for the study. A standardised questionnaire was mailed to them in which their attitudes towards preventive advice-giving were measured using Likert scaling. Participation was anonymous. RESULTS: 37% of the physicians answered the questionnaire. Almost all of them see it as their responsibility to inform patients about possible reduction of lifestyle-dependent health risks and to motivate them accordingly. Self-assessment concerning advisory skills is predominantly positive (best for physical activity, worst for smoking cessation and sexual risk behaviour advice). Time resources for behaviour-oriented prevention are sparse. For this reason, the delegation of many advisory tasks to physician assistants is regarded positively. CONCLUSION: Most physicians see themselves as willing and able to perform behaviour-oriented prevention. Nevertheless, realising this task seems to be difficult, e. g., concerning the frame conditions of general practice. The role of general practitioners in prevention and health promotion should be defined more accurately.

Chronic rhinosinusitis in Europe--an underestimated disease. A GA²LEN study.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common health problem, with significant medical costs and impact on general health. Even so, prevalence figures for Europe are unavailable. In this study, conducted by the GA²LEN network of excellence, the European Position Paper on Rhinosinusitis and nasal Polyps (EP³OS) diagnostic criteria are applied to estimate variation in the prevalence of Chronic rhinosinusitis (CRS) for Europe. METHOD: A postal questionnaire was sent to a random sample of adults aged 15-75 years in 19 centres in Europe. Participants reported symptoms of CRS, and doctor diagnosed CRS, allergic rhinitis, age, gender and smoking history. Definition of CRS was based on the EP³OS diagnostic criteria: the presence of more than two of the symptoms: (i) nasal blockage, (ii) nasal discharge, (iii) facial pain/pressure or (iv) reduction in sense of smell, for >12 weeks in the past year--with at least one symptom being nasal blockage or discharge. RESULTS: Information was obtained from 57,128 responders living in 19 centres in 12 countries. The overall prevalence of CRS by EP³OS criteria was 10.9% (range 6.9-27.1). CRS was more common in smokers than in nonsmokers (OR 1.7: 95% CI 1.6-1.9). The prevalence of self-reported physician-diagnosed CRS within centres was highly correlated with the prevalence of EP³OS-diagnosed CRS. CONCLUSION: This is the first European international multicentre prevalence study of CRS. In this multicentre survey of adults in Europe, about one in ten participants had CRS with marked geographical variation. Smoking was associated with having CRS in all parts of Europe.

Use of a common food frequency questionnaire (FFQ) to assess dietary patterns and their relation to allergy and asthma in Europe: pilot study of the GA2LEN FFQ.

BACKGROUND/OBJECTIVES: Comparable international data on food and nutrient intake is often hindered by the lack of a common instrument to assess food intake. The objective of this study was within the Global Allergy and Asthma European Network of Excellence (GA(2)LEN), we developed and piloted a food frequency questionnaire (FFQ) to assess its validity in Europe. SUBJECTS/METHODS: Five countries participating in GA(2)LEN took part in the pilot study. A total of 200 adults aged 31-75 years were invited to complete a FFQ in two occasions and to give a blood sample. The intra-class correlation coefficient (ICC) was used to assess repeatability of the FFQ. Plasma phospholipid fatty acids (FAs) were analysed by gas chromatography. Pearson correlation was used to analyse the correlation between estimated dietary FA intake and plasma phospholipid FA levels. RESULTS: A total of 177 participants (89%) had complete data on FFQ(1) and plasma phospholipid FAs. In all, 152 participants (76%) completed both FFQs. ICCs between macronutrients ranged from 0.70 (saturated FAs) to 0.78 (proteins) and between 0.70 (retinol) and 0.81 (vitamin D) for micronutrients. Dietary n-3 FAs showed a good correlation with total plasma phospholipid n-3 FAs and with docosahexaenoic acid in the whole sample (0.40) and in individual countries. Poor correlations were observed for other FAs. CONCLUSIONS: The GA(2)LEN FFQ is an appropriate tool to estimate dietary intake for a range of nutrients across Europe regardless of cultural and linguistic differences. The FFQ seems to be useful to estimate the intake of n-3 FAs but not other FAs.

Counseling overweight patients: analysis of preventive encounters in primary care.

OBJECTIVE: The increasing prevalence of obesity requires particularly primary care providers to take action. The aim of this study was to analyze general practitioners (GPs) encounters with overweight and obese patients in primary care to test the hypothesis that patients with a BMI ≥ 30 kg/m² would have longer consultations focusing on lifestyle-related issues like nutrition and physical activity than those with a BMI < 30 kg/m². DESIGN: Cross sectional comparison of audiotaped encounters of patients with a BMI ≥ 30 kg/m² and those with a BMI < 30 kg/m². SETTING: Twelve GP surgeries in Berlin, Germany. PARTICIPANTS: Fifty patients who agreed to have preventive check-up encounters audiotaped. MAIN OUTCOME MEASURES: Based on the Roter Interaction ANALYSIS: System (RIAS) we assessed duration of encounter and the prevalence of GP statements regarding cardiovascular risks, nutrition and physical activity. RESULTS: An increased BMI was found to be a predictor for the length of encounters (P = 0.01), whereas the content of talks was mainly determined by the individual of GP and sex of the GP. Statements regarding cardiovascular risks were most frequent, followed by those regarding nutrition and physical activity. In this study the assessed physiological parameters were not associated with the specific contents of preventive encounters like nutrition or physical activity (P > 0.05). CONCLUSIONS: Our results indicate that GPs rarely use the check-up program to conduct lifestyle consultations with obese patients. Barriers to lifestyle counseling and possible solutions are discussed with a view to promoting individualized and target management of overweight patients.

The natural history of allergic rhinitis in childhood.

The distinction between 'seasonal' and 'perennial' allergic rhinitis (AR) is not always adequate. The 'Allergic Rhinitis and its Impact on Asthma' (ARIA) work group suggested a new classification for AR based on severity and duration of symptoms. Our primary aim was to describe the natural history and burden of AR according to the new ARIA criteria in a population-based birth cohort study of children up to 13 yr. We defined symptoms as 'severe' (impairment of daily activities) or 'mild' (no impairment) and 'persistent' (duration > 1 month) or 'intermittent' (

Patent foramen ovale is not associated with an increased risk of stroke recurrence.

BACKGROUND AND PURPOSE: Despite numerous studies suggesting a relationship between paradoxical embolism from a patent foramen ovale (PFO) and stroke, the role of PFO as a risk factor for cerebral ischaemia remains controversial. We therefore sought to determine the association between a RLS detected by contrast-enhanced transcranial Doppler ultrasonography (c-TCD) and recurrent stroke in an unselected population sample. METHODS: We analyzed the records of 763 patients with diagnosis of cerebral ischaemia at our institution. All patients had undergone TCD-based detection of RLS. Embolic signals have been measured both under resting conditions and after performing a Valsalva maneuver. For follow-up, all patients were contacted by mail, which included a standardized questionnaire. Endpoints of follow-up were defined as recurrence of cerebral ischaemia, occurrence of myocardial infarction or death from any cause. RESULTS: Follow-up data were available in 639 patients (83.7%). At baseline, a RLS was detected in 140 (28%) men and in 114 (42%) women. Ten shunt-carriers (1.6%) and 32 patients (5.0%) without RLS had suffered a recurrent stroke. After adjustment for age, sex, and atrial fibrillation, the hazard ratio of RLS for stroke recurrence was 0.86 (95% CI 0.41-1.79). The condition of RLS at rest adjusted for age, sex, stroke subtype, and cardiovascular risk factors was not found to increase the risk of stroke substantially (HR 1.16 [95% CI 0.41-3.29]) CONCLUSION: Our data suggest that the risk of recurrent stroke in subjects with PFO is not significantly increased in comparison with subject without it.

Dynamic evolution of serum immunoglobulin E to airborne allergens throughout childhood: results from the Multi-Centre Allergy Study birth cohort.

BACKGROUND: Allergic rhinoconjunctivitis and asthma evolve dynamically throughout childhood. Yet, data on the evolution of serum levels of IgE antibodies against airborne allergens throughout the first decade of life are scarce. OBJECTIVE: To describe the patterns of new and persistent sensitization against airborne allergens including remission from birth to 10 years of age and the long-term clinical outcomes up to the age of 13 years. METHODS: In 273 children from the Multi-Centre Allergy Study, a German birth cohort, IgE levels were determined against airborne allergens (Dermatophagoides pteronyssinus, cat and dog dander, birch and grass species pollens) at 2, 5, 7, and 10 years of age (ImmunoCAP, Phadia); allergic rhino-conjunctivitis and asthma were ascertained at the 13 years of age through a standardized questionnaire (International Study of Asthma and Allergies in Childhood). RESULTS: The prevalence of sensitization to each allergen increased steadily throughout childhood, and a hierarchy of sensitization prevalence (grass>birch>mites>cat>dog) was maintained from 5 years of age onwards. A mono-sensitization state was relatively short (measurable half-life=3 years) as additional sensitizations were acquired frequently, and relatively soon after the first one. Remission of weak sensitization (UNICAP classes 1-2) was also quite frequent, especially before 5 years of age. By contrast, stronger IgE responses (>3.5 kU/L) were invariably persistent. Early sensitization was associated with a higher tendency for poly-sensitization at 10 years of age and allergic rhino-conjunctivitis and/or asthma at 13 years of age. CONCLUSIONS: IgE responses against airborne allergens undergo dynamic changes throughout childhood, with a high frequency of new sensitization or remission. The long-term persistence and the clinical impact of IgE responses are affected by the intensity of IgE sensitization and the age of its onset.

Longitudinal trends of total and allergen-specific IgE throughout childhood.

BACKGROUND: The development and the quantitative relationship between allergen-specific IgE (S-IgE) responses and total IgE (T-IgE), during childhood and adolescence have not been described and understood in detail. The objective of this study was to describe and compare the longitudinal trends of serum levels of S-IgE and T-IgE during childhood. METHODS: We analysed data from participants in the MAS birth cohort study at 2, 5, 7 and 10 years of age (n = 273) and at 1, 3, 5, 6, 7, 10 and 13 years (n = 84). Total-IgE and the overall level of specific-IgE against nine locally relevant airborne and food allergens were determined by FEIA (ImmunoCAP). Allergic rhino-conjunctivitis and asthma were ascertained by questionnaires. RESULTS: Longitudinal patterns of T-IgE levels from age 1 to 13 years were highly heterogeneous (declining, flat or increasing with different profiles). From 5 years of age, logarithmic (log(10)) transformed values of T-IgE and of S-IgE levels tend to follow a parallel trend, so that their relation remained constant throughout school age. A flat trend of T-IgE vs a constantly increasing trend of T-IgE was associated with a low or, respectively, high rate of wheezing at 13 years of age. CONCLUSIONS: Beginning at the age of 5 years, total serum IgE levels in children from an industrialized country evolved in parallel with overall S-IgE levels. Therefore, variations in T-IgE levels at school age closely reflect variations in overall S-IgE levels. Further studies are required to strengthen the biological and clinical implication of this novel finding.

Lesion patterns in patients with cryptogenic stroke with and without right-to-left-shunt.

BACKGROUND AND PURPOSE: Despite numerous studies, the role of patent foramen ovale (PFO) as a risk factor for stroke due to paradoxical embolism is still controversial. On the assumption that specific lesion patterns, in particular multiple acute ischaemic lesions on diffusion-weighted magnetic resonance imaging, indicate a cardioembolic origin, we compared the MRI findings in stroke patients with right-to-left shunt (RLS) and those without. METHODS: The records of 486 patients with diagnosis of cerebral ischaemia were reviewed. For detection of RLS, contrast-enhanced transcranial Doppler (c-TCD) was carried out in all patients. An MRI scan of the brain was performed in all patients. Affected vascular territories were divided into anterior cerebral artery, middle cerebral artery, vertebrobasilar artery system including posterior cerebral artery, brain stem and cerebellar stroke, and strokes occurring in more than one territory. RESULTS: We did not find a specific difference in neuroradiological lesion patterns in patients with RLS compared with patients without RLS. In particular, 23 of 165 patients (13.9%) with RLS showed multiple ischaemic lesions on MRI in comparison with 45 of 321 patients (14.0%) without RLS (P = 0.98). These findings also applied for the subgroup of cryptogenic strokes with and without RLS. CONCLUSION: We found no association between an ischaemic lesion pattern that is considered as being typical for stroke due to cardiac embolism and the existence of PFO. Therefore, our findings do not provide any support for the common theory of paradoxical embolism as a major cause of stroke in PFO carriers.

Stress-related maternal factors during pregnancy in relation to childhood eczema: results from the LISA Study.

BACKGROUND: Stress has been suggested to impact the onset and exacerbation of eczema and other atopic disorders. Whether early exposure to stress-related factors might exert long-term effects remains to be clarified. OBJECTIVE: The objective of this study was to investigate whether stress-related maternal factors during pregnancy are associated with childhood eczema during the first 6 years of life. METHODS: Data from 3004 children from a prospective German birth cohort study (LISA) were analyzed. Information from maternity certificates and questionnaire information on unwanted pregnancy were used to evaluate stress-related maternal factors during pregnancy. Prevalence data for physician-diagnosed eczema were available up to the age of 6 years. RESULTS: Maternal factors during pregnancy were positively associated with childhood eczema in terms of cumulative prevalence up to the age of 2 years (adjusted odds ratio, 1.48; 95% confidence interval, 0.95-2.30) after adjusting for potential confounders. Beyond the second year no increased risk was observed. CONCLUSIONS: The results of this study suggest that stress-related maternal factors during pregnancy are associated with an increased risk of childhood eczema during the first 2 years of life. The impact of postnatal stress such as parental divorce or separation on this association could not be clarified. Future studies should therefore further elucidate how prenatal and postnatal stress interact and whether prenatal stress might have a programming effect. If future studies confirm the findings of this study, reducing maternal stress during pregnancy might be a possible target in the primary prevention of eczema during childhood.

Long-term effectiveness of behavioural interventions to prevent smoking among children and youth.

OBJECTIVES: To evaluate the long-term effectiveness of recent behavioural interventions in the prevention of cigarette use among children and youth and to compare the effectiveness of different school-based, community-based and multisectorial intervention strategies. METHODS: A structured search of databases and a manual search of reference lists was conducted. Randomised controlled trials published in English or German between August 2001 and August 2006 targeting youths up to 18 years of age were assessed independently by two researchers according to predefined inclusion criteria and with regard to methodological quality. Data abstraction was performed and crosschecked by two researchers. Where appropriate, pooled effect estimates were calculated and tested in sensitivity analyses. RESULTS: Of 3555 articles, 35 studies met the inclusion criteria. The follow-up duration ranged from 12 months to 120 months. Although the overall effectiveness of prevention programs showed considerable heterogeneity, the majority of studies reported some positive long-term effects for behavioural smoking prevention programs. There was evidence that community-based and multisectorial interventions were effective in reducing smoking rates; in contrast, the evidence for school-based programs alone was inconclusive. Regardless of the type of intervention, the reductions observed in smoking rates were only modest. CONCLUSIONS: The present work identified moderate evidence for the effectiveness of behavioural interventions to prevent smoking. Although evidence for the effectiveness of school-based interventions was inconclusive, evidence for the effectiveness of community-based and multisectorial interventions was somewhat stronger. Future research should investigate the effectiveness of specific intervention components and the cost-effectiveness of interventions analysed in methodologically high-quality studies.

Having children after surviving cancer in childhood or adolescence - results of a Berlin survey.

OBJECTIVE: To assess the desire to have children, the actual number of children, and children's health in a survey of 752 adult survivors of paediatric or adolescent cancer in Berlin, Germany. PATIENTS: The German Childhood Cancer Registry ( Deutsches Kinderkrebsregister, DKKR) listed 752 paediatric cancer patients who had been treated in 1 of the 2 paediatric oncology centres in Berlin since 1980 and were 18 years of age or older at the time of the survey. METHODS: A 4-page questionnaire assessing pubertal development, fertility, the desire to have children, the actual number of children, and children's health was sent to 574 former patients located using data from the DKKR and German Residents' Registration Office. RESULTS: In total, 45% (n=260) of patients (140 women, 120 men) returned the questionnaire. The mean age was 10.9 years at the time of diagnosis and 24.3 years at the time of the present survey. Various aspects of puberty were assessed to evaluate pubertal development. Of all study participants, 77% indicated a general desire to have children. Reasons given for not having children included 'Still too early to have children' (67%), 'Fear that my child will develop cancer' (9%), and 'Fear that cancer will recur' (6%). Transient amenorrhoea, lasting from 1 to 30 months, occurred in 25 of 74 patients after chemo- and radiotherapy. Five of 136 participants indicated that they had already reached menopause. Seventeen per cent of all participants or their partners had already been pregnant. The miscarriage rate was 13%. Thirty participants gave birth to or fathered a total of 41 children, of whom 40 were healthy and 1 was born with a foot deformity (Pes equinovarus). Among participants' children, mean weight at birth was 3 458 g, and mean head circumference was 35 cm. DISCUSSION: The desire to have children was lower among our survey participants than in the general population of the same age (77% vs. 90%). Participants' fears that their children might develop cancer or that their own cancer might recur are often unfounded. Paediatric cancer survivors, relatives, and attending physicians should be well informed about this issue by paediatric oncologists. The proportion of miscarriages, mean weight at birth, and mean head circumference at birth in our study were comparable to the German general population. OUTLOOK: We intend to conduct a nationwide survey entitled 'Fertility after Chemo- and Radiotherapy in Paediatric and Adolescent Patients' (FeCt). The aim is to gain valuable data with a larger number of participants and more statistical power to determine whether specific cytotoxic drugs or radiation increase the risk of infertility, and if so, at what doses. For the study, the DKKR has the addresses of more than 5 000 former patients in Germany who are now adults. The results will be used to plan future treatment optimisation studies, and to assess the need for prophylactic measures in cases where fertility-compromising therapies are unavoidable. This nationwide survey 'FeCt' will be supported by the Deutsche Kinderkrebsstiftung.

Primary versus secondary immunoglobulin E sensitization to soy and wheat in the Multi-Centre Allergy Study cohort.

BACKGROUND: IgE sensitization to soy and wheat is classified as 'primary' when generated by food ingestion and 'secondary' when it as a consequence of primary sensitization to cross-reacting pollen antigens via inhalation. The age-specific relevance of these categories of sensitization throughout childhood is unknown. OBJECTIVE: To monitor the natural course of IgE sensitization against common food allergens in childhood in relation to sensitization against cross-reactive airborne allergens. METHODS: The German Multi-Centre Allergy Study with follow-up from birth to age 13 recruited initially 1314 children. IgE antibody levels against cow's milk, hen's egg, soy, wheat, mites, cat and dog dander, birch and grass pollens were tested. Longitudinal data were analysed from the 273 children with sera obtained at age 2, 5, 7 and 10 years of age. RESULTS: The point prevalence of sensitization (>1.0 kU/L) to milk and egg allergens progressively decreased from about 4% at 2 years to <1% at 10 years. By contrast, the prevalence of IgE to wheat and soy progressively increased with age, from 2% to 7% (soy) and from 2% to 9% (wheat). At 10 years of age, IgE to grass pollen was detected in 97% and 98% of the children reacting against soy and wheat, respectively; IgE to birch pollen was observed in 86% and 82% of the children reacting against soy and wheat, respectively. Early IgE sensitization to soy or wheat preceded that to grass or birch pollen in only 4% and 8% of participants sensitized to soy and wheat, respectively. CONCLUSION: IgE sensitization to soy and wheat is relatively uncommon and mostly primary in early infancy, more frequent and mostly secondary to pollen sensitization at school age. Clinical Implications Awareness should be raised to avoid unnecessary diet restrictions due to the high frequency of clinically irrelevant, secondary sensitization to soy and wheat in schoolchildren with pollinosis.

Atopic eczema in children: another harmful sequel of divorce.

BACKGROUND: Different lifestyle factors seem to be associated with the risk for atopic diseases and some studies suggest that stress increases the risk of allergic sensitization, asthma and atopic eczema. Only few studies have investigated the association of early stressful life events and atopic eczema (AE) in children. SUBJECTS AND METHODS: Parents of participants of the ongoing LISA birth cohort study were asked to give information on life events, such as severe disease or death of a family member, unemployment, or divorce of the parents. Lifetime prevalence of AE and incidence after the assessment period for life events were compared. RESULTS: Prevalence of AE until the age of 4 years was 21.4%. Reported life events within the first 2 years were: severe disease (17.5%) or death (8.4%) of a family member, divorce/separation (3.4%), and unemployment (2.7%). Divorce/separation was associated with a significantly [odds ratio (OR) 3.59, 95% confidence interval (CI) 1.69-7.66] increased and disease with a significantly (OR 0.29, 95% CI 0.13-0.68) decreased incidence of AE for the subsequent 2 years of life. No effect was seen for unemployment. CONCLUSIONS: Divorce/separation of the parents and severe disease of a family member influence the risk of developing AE.

[Recommendations of Bavarian Muscle Centers of the German Neuromuscular Disease Society for home ventilation of neuromuscular diseases of adult patients]. / Empfehlungen der bayerischen Muskelzentren in der DGM zur Heimbeatmung bei neuromuskulären Erkrankungen Erwachsener.

During recent years home ventilation has been shown to be useful for a growing number of patients with neuromuscular diseases and respiratory insufficiency caused by weakness of the respiratory muscles. Despite its technical simplicity, home ventilation leads to a number of social, ethical, medical and infrastructural problems. This consensus paper discusses the special situation of patients with neuromuscular diseases in home ventilation and describes the current thinking in the following topics: (1) definition of home ventilation; (2) aims of home ventilation; (3) indications and preconditions of home ventilation; (4) techniques and forms of home ventilatory support; (5) preparation for and practical questions of home ventilation; (6) stopping home ventilation.

Low- and high-risk malignant melanoma--I. Evaluation of clinical and histological prognosticators in 585 cases.

In 585 cases with primary cutaneous stage I malignant melanoma (294 disease-free for at least 5 yr, 291 with later metastases) prognostic parameters were examined. The most effective proved to be tumor thickness and mitotic activity, particularly when combined as a prognostic index. Furthermore, vascular invasion, ulceration in thick tumors (thickness greater than or equal to 3.0 mm), severe cellular atypia, the small, lymphocytic-like cell type and the absence of an inflammatory reaction were closely associated with a high rate of metastatic cases. Less relevant prognostic factors were the level of invasion, sex, site, tumor breadth, clinical diameters and infiltrative growth. Tumor type, age, duration and an adjacent nevocellular nevus were not significantly associated with the occurrence of later metastases. Furthermore, the growth-type (exo- or endophytic) did not have a bearing on the prognosis.