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Background EAACI guidelines emphasize the importance of patient history in diagnosing food allergy (FA) and the need for studies investigating its value using standardized allergy‐focused questionnaires. Objective To determine the contribution of reaction characteristics, allergic comorbidities and demographics to prediction of FA in individuals experiencing food‐related adverse reactions. Methods Adult and school‐age participants in the standardized EuroPrevall population surveys, with self‐reported FA, were included. Penalized multivariable regression was used to assess the association of patient history determinants with “probable” FA, defined as a food‐specific case history supported by relevant IgE sensitization. Results In adults (N = 844), reproducibility of reaction (OR 1.35 [95% CI 1.29‐1.41]), oral allergy symptoms (OAS) (4.46 [4.19‐4.75]), allergic rhinitis (AR) comorbidity (2.82 [2.68‐2.95]), asthma comorbidity (1.38 [1.30‐1.46]) and male sex (1.50 [1.41‐1.59]) were positively associated with probable FA. Gastrointestinal symptoms (0.88 [0.85‐0.91]) made probable FA less likely. The AUC of a model combining all selected predictors was 0.85 after cross‐validation. In children (N = 670), OAS (2.26 [2.09‐2.44]) and AR comorbidity (1.47 [CI 1.39‐1.55]) contributed most to prediction of probable FA, with a combined cross‐validation‐based AUC of 0.73. When focusing on plant foods, the dominant source of FA in adults, the pediatric model also included gastrointestinal symptoms (inverse association), and the AUC increased to 0.81. Conclusions In both adults and school‐age children from the general population, reporting of OAS and of AR comorbidity appear to be the strongest predictors of probable FA. Patient history particularly allows for good discrimination between presence and absence of probable plant FA., In support of expert opinion, data collected in a standardized manner all across Europe reveal that information available from patient history can accurately predict IgE sensitization corresponding to a food‐specific case history (probable FA). OAS and AR comorbidity are strongly associated with presence of FA and GI symptoms with absence of FA (particularly plant FA) in adults and children. Abbreviations: AA, allergic asthma; AR, allergic rhinitis; FA, food allergy; GI, gastrointestinal; OAS, oral allergy symptoms

Background There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012. Methods A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC Results Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication. Conclusions False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.

Robust biological markers of dietary exposure are essential in improving the understanding of the link between diet and health outcomes. Polyphenolic compounds, including flavonoids, have been proposed to mitigate the risk of chronic diseases where oxidative stress and inflammation play a central role. Biomarkers can provide objective measurement of the levels of polyphenolic compounds. In this study, we provide methodology to identify potential candidate markers of polyphenol intake in human serum. Seventeen participants from the UK arm of the Global Allergy and Asthma Network of Excellence (GA2LEN) had their dietary intake estimated using a validated food frequency questionnaire, and serum samples were assessed using mass spectrometry to identify potential candidate markers. 144 features were assigned identities, of these we identified four biologically relevant compounds (rhamnazin 3-rutinoside, 2-galloyl-1,4-galactarolactone methyl ester, 2″,32″-di-O-p-coumaroylafzelin and cyclocommunin), which were significantly increased in the serum of participants with high predicted level of fruit and vegetable intake. 2-galloyl-1,4-galactarolactone methyl ester was strongly correlated with total flavonoids (r = 0.62; P = 0.005), flavan-3-ols (r = 0.67; P = 0.002) as well as with other four subclasses. Rhamnazin 3-rutinoside showed strong correlation with pro-anthocyanidins (r = 0.68; P = 0.001), flavones (r = 0.62; P = 0.005). Our results suggest that serum profiling for these compounds might be an effective way of establishing the relative intake of flavonoids and could contribute to improve the accuracy of epidemiological methods to ascertain flavonoid intake.

Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD). Objective: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV1-to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks. Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

Purpose To report the front corneal versus central and paracentral corneal changes after Bowman layer transplantation for keratoconus in a tertiary hospital in the United Kingdom. Methods Five eyes of 5 patients receiving Bowman layer transplant for advanced keratoconus in Royal Gwent Hospital (Newport, United Kingdom) were included. Preoperative and postoperative visual acuity; Kmax; Kmean, and corneal cylinder in the front cornea, 4.5 mm central, and 6 mm central; and corneal thickness were analyzed. Results Corneal flattening and reduction in corneal astigmatism was observed, more marked in the central and paracentral zone, allowing for improvement in best-corrected visual acuity with the aid of visual correction in 4 eyes. Conclusions These results support previous data reporting Bowman layer transplantation as a useful strategy in the treatment of advanced keratoconus and suggest greater attention may be focused on central or paracentral corneal changes.

Background The geographical variation and temporal increase in the prevalence of food sensitization (FS) suggest environmental influences. Objective To investigate how environment, infant diet, and demographic characteristics, are associated with FS in children and adults, focusing on early-life exposures. Methods Data on childhood and adult environmental exposures (including, among others, sibship size, day care, pets, farm environment, and smoking), infant diet (including breast-feeding and timing of introduction to infant formula and solids), and demographic characteristics were collected from 2196 school-age children and 2185 adults completing an extensive questionnaire and blood sampling in the cross-sectional pan-European EuroPrevall project. Multivariable logistic regression was applied to determine associations between the predictor variables and sensitization to foods commonly implicated in food allergy (specific IgE ≥0.35 kUA/L). Secondary outcomes were inhalant sensitization and primary (non–cross-reactive) FS. Results Dog ownership in early childhood was inversely associated with childhood FS (odds ratio, 0.65; 95% CI, 0.48-0.90), as was higher gestational age at delivery (odds ratio, 0.93 [95% CI, 0.87-0.99] per week increase in age). Lower age and male sex were associated with a higher prevalence of adult FS (odds ratio, 0.97 [95% CI, 0.96-0.98] per year increase in age, and 1.39 [95% CI, 1.12-1.71] for male sex). No statistically significant associations were found between other evaluated environmental determinants and childhood or adult FS, nor between infant diet and childhood FS, although early introduction of solids did show a trend toward prevention of FS. Conclusions Dog ownership seems to protect against childhood FS, but independent effects of other currently conceived environmental and infant dietary determinants on FS in childhood or adulthood could not be confirmed.

BACKGROUND: A clear understanding of the differences in the epidemiology of food allergy between rural and urban populations may provide insights into the causes of increasing prevalence of food allergy in the developed world.OBJECTIVE: We used a standardized methodology to determine the prevalence and types of food-specific allergic sensitization and food allergies in schoolchildren from urban and rural regions of China, Russia, and India.METHODS: The current study is a multicenter epidemiological survey of children recruited from 5 cities in China (Hong Kong and Guangzhou), Russia (Tomsk), and India (Bengaluru and Mysore) and 1 rural county in Southern China (Shaoguan). A total of 35,549 children aged 6 to 11 years from 3 countries participated in this survey. Random samples of children from 3 countries were first screened by the EuroPrevall screening questionnaire. Children with and without a history of adverse reactions to foods were then recruited for the subsequent case-control comparative studies. We determined the prevalence rates of food-specific IgE sensitization and food allergies using the predefined criteria.RESULTS: The prevalence rates of food-specific IgE sensitization (>= 0.7 kU/L) to at least 1 food were 16.6% in Hong Kong, 7.0% in Guangzhou, 16.8% in rural Shaoguan, 8.0% in Tomsk, and 19.1% in India. Using a definition of probable food allergy as reporting allergic symptoms within 2 hours of ingestion of a specific food plus the presence of allergic sensitization to the specific food (positive IgE and/or positive skin prick test result), the prevalence of food allergy was highest in Hong Kong (1.50%), intermediate in Russia (0.87%), and lowest in Guangzhou (0.21%), Shaoguan (0.69%), and India (0.14%). For children recruited from Hong Kong, both sensitization and food allergy were significantly higher in children who were born and raised in Hong Kong when compared with those who were born in mainland China and migrated to Hong Kong, highlighting the importance of early-life exposures in affecting the subsequent development of food sensitization and food allergy.CONCLUSIONS: There are wide variations in the prevalence of food-specific IgE sensitization and food allergy in the 3 participating countries. Food allergy appears to be less common when compared with developed countries. The variations in the prevalence of food allergen sensitization cannot be explained by the differences in the degree of urbanization. Despite the high prevalence of food-specific IgE sensitization in India and rural China, food allergy is still extremely uncommon. In addition to IgE sensitization, other factors must play important roles resulting in the clinical manifestations of food allergies. (C) 2019 American Academy of Allergy, Asthma & Immunology

Background and aim: Colorectal cancer [CRC] is highly prevalent worldwide, with dietary habits being a major risk factor. We systematically reviewed and meta-analysed the observational evidence on the association between CRC and dietary patterns [DP] derived from Principal Component Analysis. Design: PRISMA guidelines were followed. Web of Science, Medline/PubMed, EMBASE, and The Cochrane Library were searched to identify all eligible papers published up to July 2017. Any pre-defined cancer in the colon was included, namely colon-rectal cancer (CRC), colon cancer (CC), rectal cancer (RC), or proximal and distal CC, if available. Western (WDP) and prudent (PDP) dietary patterns were compared as a proxy to estimate ‘unhealthy’ (Rich in meat and processed foods) and ‘healthy’ diets (containing fruits or vegetables), respectively. Meta-analyses were carried out using random effects model to calculate overall risk estimates. Relative risks (RR) and 95% confidence intervals were estimated comparing the highest versus the lowest categories of dietary patterns for any of the forms of colon cancer studied. Results: 28 studies were meta-analysed. A WDP was associated with increased risk of CRC (RR 1.25; 95% CI 1.11, 1.40), and of CC (RR 1.30; 95% CI 1.11, 1.52). A PDP was negatively associated with CRC (RR 0.81; 95% CI 0.73, 0.91). Sensitivity analyses showed that individuals from North- and South- American countries had a significantly higher risk of CRC than those from other continents. Conclusion: A PDP might reduce the risk of CRC. Conversely, a WDP is associated with a higher risk of disease.

Rationale: Evidence supporting the association of chronic obstructive pulmonary disease or airflow obstruction with use of solid fuels is conflicting and inconsistent. Objectives: To assess the association of airflow obstruction with self-reported use of solid fuels for cooking or heating. Methods: We analyzed 18,554 adults from the BOLD (Burden of Obstructive Lung Disease) study, who had provided acceptable post-bronchodilator spirometry measurements, and information on use of solid fuels. The association of airflow obstruction with use of solid fuels for cooking or heating was assessed by sex, within each site, using regression analysis. Estimates were stratified by national income and meta-analyzed. We performed similar analyses for spirometric restriction, chronic cough, and chronic phlegm. Measurements and Main Results: We found no association between airflow obstruction and use of solid fuels for cooking or heating (odds ratio [OR] for men, 1.20 [95% confidence interval (CI), 0.94–1.53]; OR for women, 0.88 [95% CI, 0.67–1.15]). This was true for low-/middle- and high-income sites. Among never-smokers, there was also no evidence of an association of airflow obstruction with use of solid fuels (OR for men, 1.00 [95% CI, 0.57–1.76]; OR for women, 1.00 [95% CI, 0.76–1.32]). Overall, we found no association of spirometric restriction, chronic cough, or chronic phlegm with the use of solid fuels. However, we found that chronic phlegm was more likely to be reported among female never-smokers and those who had been exposed for 20 years or longer. Conclusions: Airflow obstruction assessed from post-bronchodilator spirometry was not associated with use of solid fuels for cooking or heating.

Residential greenness and lung function in a prospective cohort of European adults : The ECRHS study

ObjectivesTo characterise peak cardiac troponin levels, in patients presenting with acute myocardial infarction (AMI), according to their comorbid condition and determine the influence of peak cardiac troponin (cTn) levels on mortality.MethodsWe included patients with the first admission for AMI in the UK. We used linear regression to estimate the association between eight common comorbidities (diabetes mellitus, previous angina, peripheral arterial disease, previous myocardial infarction (MI), chronic kidney disease (CKD), cerebrovascular disease, chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD)) and peak cTn. Peak cTn levels were adjusted for age, sex, smoking status and comorbidities. Logistic regression and restricted cubic spline models were employed to investigate the association between peak cTn and 180-day mortality for each comorbidity.Results330 367 patients with ST elevation myocardial infarction and non-ST elevation myocardial infarction were identified. Adjusted peak cTn levels were significantly higher in patients with CKD (adjusted % difference in peak cTnT for CKD=42%, 95% CI 13.1 to 78.4) and significantly lower for patients with COPD, previous angina, previous MI and CHF when compared with patients without the respective comorbidities (reference group) (cTnI; COPD=−21.7%, 95% CI −29.1 to −13.4; previous angina=−24.2%, 95% CI −29.6 to −8.3; previous MI=−13.5%, 95% CI −20.6 to −5.9; CHF=−28%, 95% CI −37.2 to −17.6). Risk of 180-day mortality in most of the comorbidities did not change substantially after adjusting for peak cTn. In general, cTnI had a stronger association with mortality than cTnT.ConclusionsIn this nationwide analysis of patients presenting with AMI, comorbidities substantially influenced systemic concentrations of peak cTn. Comorbid illness is a significant predictor of mortality regardless of peak cTn levels and should be taken into consideration while interpreting cTn both as a diagnostic and prognostic biomarker.

BackgroundHistorical data suggest 15% of laboratory animal workers develop IgE sensitisation and 10% symptoms of laboratory animal allergy (LAA), including occupational asthma. Individually ventilated cages (IVCs) are replacing conventional open cages; we sought to evaluate their impact on the development of LAA.MethodsWe surveyed 750 laboratory animal workers and measured airborne Mus m 1 (mouse allergen) levels in seven UK institutions. We compared the prevalence of sensitisation to mouse proteins (by specific IgE assay or skin prick test) and of work-related allergic symptoms in IVC-only and open cage units.ResultsFull-shift Mus m 1 levels were lower in IVC than open cage units (geometric mean 1.00 (95% CI 0.73–1.36) versus 8.35 (95% CI 6.97–9.95) ng·m−3; p−3). Primary analyses on data from 216 participants with ≤3 years exposure to mice revealed a lower prevalence of sensitisation in those working in IVC units compared with conventional cage units (2.4% (n=2) versus 9.8% (n=13); p=0.052). Sensitisation in IVC units varied from 0% to 12.5%; the use of fitted respiratory protection was less common in IVC units where prevalence of sensitisation was higher. Work-related allergy symptoms were more frequently reported by mouse-sensitised individuals (46.7% versus 10.9%; pConclusionIn contemporary practice, LAA is now largely preventable with the use of IVC systems and the judicious use of appropriate respiratory protection.

OBJECTIVES: The standard approach to the assessment of occupational exposures is through the manual collection and coding of job histories. This method is time-consuming and costly and makes it potentially unfeasible to perform high quality analyses on occupational exposures in large population-based studies. Our aim was to develop a novel, efficient web-based tool to collect and code lifetime job histories in the UK Biobank, a population-based cohort of over 500 000 participants. METHODS: We developed OSCAR (occupations self-coding automatic recording) based on the hierarchical structure of the UK Standard Occupational Classification (SOC) 2000, which allows individuals to collect and automatically code their lifetime job histories via a simple decision-tree model. Participants were asked to find each of their jobs by selecting appropriate job categories until they identified their job title, which was linked to a hidden 4-digit SOC code. For each occupation a job title in free text was also collected to estimate Cohen’s kappa (κ) inter-rater agreement between SOC codes assigned by OSCAR and an expert manual coder. RESULTS: OSCAR was administered to 324 653 UK Biobank participants with an existing email address between June and September 2015. Complete 4-digit SOC-coded lifetime job histories were collected for 108 784 participants (response rate: 34%). Agreement between the 4-digit SOC codes assigned by OSCAR and the manual coder for a random sample of 400 job titles was moderately good [κ=0.45, 95% confidence interval (95% CI) 0.42–0.49], and improved when broader job categories were considered (κ=0.64, 95% CI 0.61–0.69 at a 1-digit SOC-code level). CONCLUSIONS: OSCAR is a novel, efficient, and reasonably reliable web-based tool for collecting and automatically coding lifetime job histories in large population-based studies. Further application in other research projects for external validation purposes is warranted.

Background: Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit–risk profile for patients with relapsing–remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM. Objective: We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minimum 3 years ENDORSE). Methods: In ENDORSE, patients randomized to DMF 240 mg twice (BID) or thrice daily (TID) in DEFINE/CONFIRM continued this dosage, and those initially randomized to placebo (PBO) or glatiramer acetate (GA) were re-randomized to DMF 240 mg BID or TID. Results: For patients continuing DMF BID (BID/BID), annualized relapse rates were 0.202, 0.163, 0.139, 0.143, and 0.138 (years 1–5, respectively) and 63%, 73%, and 88% were free of new or enlarging T2 hyperintense lesions, new T1 hypointense lesions, and gadolinium-enhanced lesions, respectively, at year 5. Adverse events (AEs; serious adverse events (SAEs)) were reported in 91% (22%; BID/BID), 95% (24%; PBO/BID), and 88% (16%; GA/BID) of the patients. One case of progressive multifocal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia. Conclusion: Treatment with DMF was associated with continuously low clinical and magnetic resonance imaging (MRI) disease activity in patients with RRMS. These interim data demonstrate a sustained treatment benefit and an acceptable safety profile with DMF.

ObjectivesTo integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses.MethodsSystematic searches MEDLINE and Embase based on predetermined criteria. Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ≥20 weeks of treatment; short-term: Results212 RCTs and 19 observational studies were included. Compared with combined long-acting beta-adrenoceptor agonists and long-acting muscarinic antagonists (LABA+LAMA), triple therapy (LABA+LAMA+inhaled corticosteroid) was significantly more effective at reducing exacerbations (long-term 0.85 (95% CI: 0.78 to 0.94; short-term 0.67 (95% CI: 0.49 to 0.92)) and mortality (0.72 (95% CI: 0.59 to 0.89)) but was also associated with increased pneumonia (1.35 (95% CI: 1.10 to 1.67)). No differences in lung function (0.02 (95% CI: −0.10 to 0.14)), health-related quality of life (−1.12 (95% CI: −3.83 to 1.59)) or other adverse events (1.02 (95% CI: 0.96 to 1.08)) were found. Most of the observational evidence trended in the same direction as pooled RCT data.ConclusionFurther evidence, especially pragmatic trials, are needed to fully understand the characteristics of patient subgroups who may benefit from triple therapy and for those whom the extra risk of adverse events, such as pneumonia, may outweigh any benefits.PROSPERO registration numberCRD42018088013.

Background Around 16 000 people in the UK work with laboratory animals with 75% of procedures being carried out on mice. Historical data, based largely on work with rats, suggest 15% develop IgE sensitisation to laboratory animal proteins and 10% clinical symptoms of laboratory animal allergy (LAA). The main risk factor for LAA is exposure to respirable aeroallergens. In recent years, conventional open cages have been replaced by individually ventilated cages (IVC) and while lower ambient aeroallergen levels are reported, the impact on LAA incidence is unknown. Methods We surveyed laboratory animal workers at seven UK research institutions. Participants completed a questionnaire about work practices, underwent skin prick testing (to common aeroallergens and mouse epithelium) and had bloods taken for measurement of specific IgE to mouse epithelium and urine. We compared airborne Mus m 1 (the major mouse allergen) levels and the prevalence of sensitisation to mouse proteins in IVC-only and open cage units. Results 750 individuals were recruited (response rate 85%); primary analyses were performed on data from 216 participants with Conclusions In contemporary practice, the prevalence of sensitisation to mouse proteins is generally low and significantly so in those who have worked only in IVC units. The variation in sensitisation in IVC units was not fully explained by lower aeroallergen levels but also appears related to use of respiratory protective equipment, perhaps a proxy for a proactive approach to occupational health and safety. Our results suggest that LAA is now largely preventable using a combined approach of allergen control measures with IVCs and adherence to ‘good practice’.

Epidemiological studies suggest menopause, especially at an early age, is associated with lower lung function. This association may be causal or could be explained by residual confounding (e.g. smoking). We used a Mendelian randomization (MR) approach, which is not affected by classical confounding, to assess the causal effect of age at menopause on lung function. Using UK Biobank data of 94 742 naturally post-menopausal women (age 41–71), we performed MR analyses on the effect of age at menopause on lung function (FVC, FEV1, FEV1/FVC), restriction (FVC In contrast to the observational findings of higher FEV1 and FVC, and slightly higher FEV1/FVC ratio, associated with increased age at menopause, the MR analysis showed statistically lower FEV1 and FEV1/FVC and a higher risk of obstruction, with no effect on FVC or restriction (figure 1). Women with early menopause ( Our MR analyses suggest that early menopause has a protective effect on airway obstruction, contradicting observational findings. This might be explained by shorter exposure to female sex hormones, specifically estrogens, which seems to support previous research in mice showing that estrogens may contribute to airway remodeling. (ALEC, EU Grant #633212).

Background: Laboratory a, nimal workers are at risk of developing laboratory animal allergy caused by sensitisation to animal proteins. Previous studies have suggested that workers may 9take-out9 allergen from the workplace putting non-exposed individuals with whom they have contact at risk of sensitisation. Aim: To determine if 9take-out9 allergen is detectable in laboratory animal workers Methods: Dermal wipes were taken from the forehead, palm and back of hands of laboratory animal workers on arrival and on leaving work. Wipes were also taken from a sample of non-exposed workers. Mus m 1 was extracted from the wipes and levels quantified using an ELISA (Indoor Biotechnologies). Values under the limit of assay detection (LOD; 0.2ng/ml) were assigned the value 0.1ng/ml. Results: 61 exposed workers were sampled. Mus m 1 was not detectable in samples from 5 (100%) non-exposed individuals. Allergen levels were significantly higher on leaving the animal units than on arrival (table). There was no significant difference in 9take-out9 allergen between workers in individually ventilated cage units and open cage units. Table: Mus m1 (ng/ml) from wipes Conclusions: ‘Take-out’ allergen is low, but detectable, in workers regardless of the cage type used; the clinical implications of this are not yet known.

Background: Pubertal exposures in boys may affect their child9s health, even if conception occurs years later. Method: From the Health Survey for England, an annual household survey, we collated data on children living with biological (BIOL) & non-biological (N-BIOL) parent/s. We assessed the association of a child’s asthma with parental smoking adjusting for other parent’s smoking, parental factors (asthma, age at birth, educational level), household income, child’s age & sex, & year of survey using logistic regression with clustering by family. Results: Among 27,490 children (14,481 families,17 surveys) there was an association of child’s asthma with pre-conception BIOL paternal smoking, but not preconception BIOL maternal smoking (Table). Compared to BIOL children of lifetime non-smoking fathers, children of fathers who smoked under 15 years of age and stopped before conception had an increased risk of asthma (1.71 95%CI 1.23 – 2.37), an association not seen with N-BIOL fathers (0.29 95%CI 0.03 -2.44) (interaction p=0.04). Adjusted OR (95% CI) of childs asthma by parental smoking Conclusion: Fathers preconception and pubertal smoking is associated with offspring asthma but only if the child is biologically related, and even with extensive adjustment for social factors and the other parents smoking

Background: In the UK c.12,000 people have occupational exposure to laboratory animals and are at risk of developing laboratory animal allergy (LAA) with potentially serious consequences. Recent changes in animal research have rendered much of the LAA literature outdated, with mice replacing rats as the main animal model and individually ventilated cages (IVC) used to reduce cross-infection and produce a controlled microenvironment in place of conventional cages (CC). Aim: To design an evidence based code of practice to reduce occurrence of LAA in contemporary animal research facilities. Methods: The SPIRAL study comprised a cross-sectional survey of 750 laboratory animal workers exposed to mice at UK research institutions and over 500 exposure measurements of Mus m 1 (mouse urinary protein), the major risk factor for LAA. Results: Prevalence of sensitisation to mice was lower in IVC units compared with CC units (2.6% vs 9.6%); some units had no recently sensitised workers. Mus m 1 levels were lower in IVC compared with CC units with both personal sampling and background monitoring but varied 8 fold between different IVC units. Certain tasks e.g. handling soiled bedding were associated with highest Mus m 1 levels. Regression analysis found around half of an individual’s Mus m 1 exposure was explained by a combination of unit, job title and tasks performed. Conclusion: LAA now appears to be preventable. Whilst IVCs are important, units should not become complacent and other factors such as strict adherence to local guidelines e.g. for use of respiratory protection for high exposure tasks, and access to a high quality occupational health service unit, are likely to be key.

Evidence on whether early puberty increases the risk of adult asthma is suggestive but inconclusive in women, and very scarce in men. To overcome the issue of residual confounding in observational studies and provide evidence on casual effects, we used Mendelian randomization (MR) with 332 SNPs as instrumental variables for age at menarche in women, and 18 SNPs for age at voice breaking in men. Age at menarche was categorised as early ( 14), while age at voice breaking was recorded and analysed as at a younger, average or older age. Based on 243,316 women and 192,067 men from UK Biobank (9.2% and 6.3% with post-pubertal asthma, respectively), we find detrimental effects of early puberty on asthma. In women, an 8% increase in asthma risk for early and an 8% decrease for late menarche suggest a linear effect of pubertal timing. Similar effects are observed in males, even though the power is lower and the confidence intervals much wider (Figure). There is evidence of modest pleiotropy, but our findings are consistent across different methods robust to pleiotropy (Figure). We show detrimental effects of early puberty on asthma. As similar patterns are seen in both sexes, the effect in women is unlikely to be mediated by female sex hormones as hypothesised, suggesting instead a role of common (biological or psychological) factors related to early physical development. [ALEC, EU Grant #633212]

Observational studies suggest menopause, especially at an early age, is associated with lower lung function. This association may be causal or could be explained by residual confounding (e.g. smoking). We used Mendelian randomization (MR) to assess the causal effect of age at menopause on lung function. Using UK Biobank data of 94,742 naturally post-menopausal women (age 41-71), we performed MR analyses of the effect of age at menopause on FVC, FEV1 and FEV1/FVC, using 55 uncorrelated SNPs as instrumental variables (IVs) for age at menopause. We examined heterogeneity across IVs to assess pleiotropy. The corresponding observational associations were evaluated using linear regression adjusted for confounders. The observational analysis showed a statistically significant increase in FEV1, FVC and FEV1/FVC per year increase in age at menopause, while the MR analysis showed a statistically significant reduction in FEV1 and FEV1/FVC, with no effect on FVC. Although there was heterogeneity suggesting pleiotropy (I2>41, p

Background Observational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males. Methods and findings MR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 × 10−5) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 × 10−4), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking. Conclusions This large MR study provides evidence for a causal detrimental effect of early puberty on asthma, and does not support previous observational findings of a U-shaped relationship between pubertal timing and asthma. Common biological or psychological mechanisms associated with early puberty might explain the similarity of our results in females and males, but further research is needed to investigate this. Taken together with evidence for other detrimental effects of early puberty on health, our study emphasises the need to further investigate and address the causes of the secular shift towards earlier puberty observed worldwide., Using genetic instruments, Cosetta Minelli and colleagues probe the causal nature of associations between early puberty, late puberty, and late-onset asthma., Author summary Why was this study done? Worldwide there has been a shift towards earlier puberty over time, possibly due to changes in childhood lifestyle and levels of adiposity. Early puberty has been linked to an increased risk of asthma in women, but findings are inconsistent across studies, and little research has been done in men. There is some suggestion that late puberty might also increase the risk of asthma. Studies performed so far have some methodological limitations that make it difficult to distinguish true effects from spurious findings. What did the researchers do and find? We studied the effect of age at puberty on asthma in women and men using Mendelian randomisation, an approach that exploits genetic data to overcome some limitations of classical observational studies. From the UK Biobank study, we analysed data on approximately 240,000 women and approximately 190,000 men with available genetic data and self-reported information on asthma and age at puberty (menarche for women and voice breaking for men). We found that women and men with early puberty had an increased risk of asthma of 8% and 7%, respectively. We found no evidence of a detrimental effect of late puberty on asthma. What do these findings mean? These findings, together with suggestions of other detrimental effects of early puberty on health, emphasise the importance of evaluating the overall evidence on health effects of early puberty. The similarity of findings in females and males might be explained by common biological or psychological factors related to early puberty, but further research is needed to investigate this.

Background: Flavonoids exert anti-inflammatory properties and modulate oxidative stress in vitro, suggesting a protective effect on lung function, but epidemiological studies examining this association are scarce. Methods: A stratified random sample was drawn from the GA2LEN screening survey, in which 55,000 adults aged 15 to 75 answered a questionnaire on respiratory symptoms. Post-bronchodilator spirometry was obtained from 2850 subjects. Forced vital capacity (FVC), the ratio between the forced exhaled volume in 1 second (FEV1) and FVC (FEV1/FVC), FVC below lower limit of normal (FVC < LLN), and FEV1/FVC < LLN were calculated. Intake of the six main subclasses of flavonoids was estimated using the GA2LEN Food Frequency Questionnaire. Adjusted associations between outcomes and each subclass of flavonoids were examined with multivariate regressions. Simes’ procedure was used to test for multiple comparisons. Results: A total of 2599 subjects had valid lung function and dietary data. A lower prevalence of FVC < LLN (airway restriction) was observed in those with higher total flavonoid (adjusted odds ratio (aOR), higher vs. lowest quintile intake 0.58; 95% Confidence Interval (CI) 0.36, 0.94), and pro-anthocyanidin intakes (aOR 0.47; 95% CI 0.27, 0.81). A higher FEV1/FVC was associated with higher intakes of total flavonoids and pro- anthocyanidins (adjusted correlation coefficient (a β-coeff 0.33; 0.10, 0.57 and a β-coeff 0.44; 95% CI 0.19, 0.69, respectively). After Simes’ procedure, the statistical significance of each of these associations was attenuated but remained below 0.05, with the exception of total flavonoids and airway restriction. Conclusions: This population-based study in European adults provides cross-sectional evidence of a positive association of total flavonoid intake and pro-anthocyanidins and ventilatory function, and a negative association with spirometric restriction in European adults. View Full-Text

Background Most studies on the relationship between helminth infections and atopic disorders have been conducted in (sub)tropical developing countries where exposure to multiple parasites and lifestyle can confound the relationship. We aimed to study the relationship between infection with the fish-borne helminth Opishorchis felineus and specific IgE, skin prick testing, and atopic symptoms in Western Siberia, with lifestyle and hygiene standards of a developed country. Methods Schoolchildren aged 7–11 years were sampled from one urban and two rural regions. Skin prick tests (SPT) and specific IgE (sIgE) against food and aeroallergens were measured, and data on allergic symptoms and on demographic and socioeconomic factors were collected by questionnaire. Diagnosis of opisthorchiasis was based on PCR performed on stool samples. Results Of the 732 children included, 34.9% had opisthorchiasis. The sensitization to any allergen when estimated by positive SPT was 12.8%, while much higher, 24.0%, when measured by sIgE. Atopic symptoms in the past year (flexural eczema and/or rhinoconjunctivitis) were reported in 12.4% of the children. SPT was positively related to flexural eczema and rhinoconjunctivitis, but not to wheezing. Opisthorchiasis showed association with lower SPT response, as well as borderline association with low IgE reactivity to any allergen. However, the effect of opisthorchiasis on SPT response was not mediated by IgE, suggesting that opisthorchiasis influences SPT response through another mechanism. Opisthorchiasis also showed borderline association with lower atopic symptoms. Conclusions There is a negative association between a chronic helminth infection and skin prick test reactivity even in a developed country.

Purpose In Phase III studies (DEFINE [Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting MS]/CONFIRM [Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis]), delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). Post hoc analyses of integrated data from DEFINE/CONFIRM were conducted to evaluate the effect of DMF in patients previously treated with interferon (IFN) beta. Methods Patients (age 18–55 years; Expanded Disability Status Scale score, 0–5.0) were randomized to receive DMF 240 mg BID or TID, placebo, or glatiramer acetate (CONFIRM only) for up to 2 years. Previous IFN users received at least 1 IFN treatment >3 months before randomization. Data for DMF 240 mg BID (approved dosing regimen) are reported. Findings In the integrated intention-to-treat population, 172 and 169 patients receiving DMF or placebo, respectively, had received ≥1 prior IFN. In this subgroup, significant reductions with DMF versus placebo were observed for the annualized relapse rate (rate ratio, 0.55 [95% CI, 0.40–0.77]), new/newly enlarging T2-hyperintense lesions (lesion mean ratio, 0.16 [95% CI, 0.09–0.29]), odds of having more gadolinium-enhancing lesions (odds ratio, 0.17 [95% CI, 0.07–0.44]), and new T1-hypointense lesions (lesion mean ratio, 0.25 [95% CI, 0.14–0.45]). Median Expanded Disability Status Scale scores remained stable during the study period. Adverse events associated with DMF included flushing and gastrointestinal events. Implications In this post hoc analysis in patients with previous IFN treatment, DMF demonstrated significant efficacy over 2 years versus placebo and an adverse event profile consistent with the overall population of DEFINE/CONFIRM. ClinicalTrials.gov identifiers: DEFINE, NCT00420212; and CONFIRM, NCT00451451.

Chronic obstructive pulmonary disease (COPD) has been identified as a risk factor for cardiovascular diseases such as myocardial infarction. The role of COPD in cerebrovascular disease is, however, less certain. Although earlier studies have suggested that the risk for stroke is also increased in COPD, more recent investigations have generated mixed results.The primary objective of our review was to quantify the magnitude of the association between COPD and stroke. We also sought to clarify the nature of the relationship between COPD and stroke by investigating whether the risk of stroke in COPD varies with age, sex, smoking history, and/or type of stroke and whether stroke risk is modified in particular COPD phenotypes.The MEDLINE and EMBASE databases were searched in May 2016 to identify articles that compared stroke outcomes in people with and without COPD. Studies were grouped by study design to distinguish those that reported prevalence of stroke (cross-sectional studies) from those that estimated incidence (cohort or case-control studies). In addition, studies were stratified according to study population characteristics, the nature of COPD case definitions, and adjustment for confounding (smoking). Heterogeneity was assessed using the IAlthough both prevalence and incidence of stroke are increased in people with COPD, the weight of evidence does not support the hypothesis that COPD is an independent risk factor for stroke. The possibility remains that COPD is causal in certain subsets of patients with COPD and for certain stroke subtypes.

BACKGROUND: Complaints of 'food allergy' are increasing. Standardized surveys of IgE sensitization to foods are still uncommon and multicountry surveys are rare. We have assessed IgE sensitization to food-associated allergens in different regions of Europe using a common protocol. METHODS: Participants from general populations aged 20-54 years in eight European centres (Zurich, Madrid, Utrecht, Lodz, Sophia, Athens, Reykjavik and Vilnius) were asked whether they had allergic symptoms associated with specific foods. Weighted samples of those with and without allergic symptoms then completed a longer questionnaire and donated serum for IgE analysis by ImmunoCAP for 24 foods, 6 aeroallergens and, by allergen microarray, for 48 individual food proteins. RESULTS: The prevalence of IgE sensitization to foods ranged from 23.6% to 6.6%. The least common IgE sensitizations were to fish (0.2%), milk (0.8%) and egg (0.9%), and the most common were to hazelnut (9.3%), peach (7.9%) and apple (6.5%). The order of prevalence of IgE sensitization against different foods was similar in each centre and correlated with the prevalence of the pollen-associated allergens Bet v 1 and Bet v 2 (r = 0.86). IgE sensitization to plant allergen components unrelated to pollen allergens was more evenly distributed and independent of pollen IgE sensitization (r = -0.10). The most common foods containing allergens not cross-reacting with pollens were sesame, shrimp and hazelnut. DISCUSSION: IgE sensitization to foods is common, but varies widely and is predominantly related to IgE sensitization to pollen allergens. IgE sensitization to food allergens not cross-reacting with pollens is rare and more evenly distributed.

Background: According to the community-based EuroPrevall surveys, prevalence of self-reported food allergy (FA) in adults across Europe ranges from 2% to 37% for any food and 1% to 19% for 24 selected foods. Objective: To determine the prevalence of probable FA (symptoms plus specific IgE-sensitization) and challenge-confirmed FA in European adults, along with symptoms and causative foods. Methods: In phase I of the EuroPrevall project, a screening questionnaire was sent to a random sample of the general adult population in 8 European centers. Phase II consisted of an extensive questionnaire on reactions to 24 preselected commonly implicated foods, and measurement of specific IgE levels. Multiple imputation was performed to estimate missing symptom and serology information for nonresponders. In the final phase, subjects with probable FA were invited for double-blind placebo-controlled food challenge. Results: Prevalence of probable FA in adults in Athens, Reykjavik, Utrecht, Lodz, Madrid, and Zurich was respectively 0.3%, 1.4%, 2.1%, 2.8%, 3.3%, and 5.6%. Oral allergy symptoms were reported most frequently (81.6%), followed by skin symptoms (38.2%) and rhinoconjunctivitis (29.5%). Hazelnut, peach, and apple were the most common causative foods in Lodz, Utrecht, and Zurich. Peach was also among the top 3 causative foods in Athens and Madrid. Shrimp and fish allergies were relatively common in Madrid and Reykjavik. Of the 55 food challenges performed, 72.8% were classified as positive. Conclusions: FA shows substantial geographical variation in prevalence and causative foods across Europe. Although probable FA is less common than self-reported FA, prevalence still reaches almost 6% in parts of Europe.

JC virus (JCV) is an opportunistic virus known to cause progressive multifocal leukoencephalopathy. Anti-JC virus (Anti-JCV) antibody prevalence in a large, geographically diverse, multi-national multiple sclerosis (MS) cohort was compared in a cross-sectional study. Overall, anti-JCV antibody prevalence was 57.6%. Anti-JCV antibody prevalence in MS patients ranged from approximately 47% to 68% across these countries: Norway, 47.4%; Denmark, 52.6%; Israel, 56.6%; France, 57.6%; Italy, 58.3%; Sweden, 59.0%; Germany, 59.1%; Austria, 66.7% and Turkey, 67.7%. Prevalence increased with age (from 49.5% in patients < 30 years of age to 66.5% in patients ≥ 60 years of age; p < 0.0001 comparing all age categories), was lower in females than in males (55.8% versus 61.9%; p < 0.0001) and was not affected by prior immunosuppressant or natalizumab use.

BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.

Objectives. We assessed the effects of indoor risk factors, including smoking, on different types of cough and on cough and wheeze in combination.Methods. Our sample was composed of 1232 men and women residing in a semirural area of Chile. We used a standardized questionnaire, sensitization to 8 allergens, and bronchial hyperresponsiveness to methacholine to assess cough and wheeze characteristics. Information was gathered on dampness, mold, ventilation, heating, housing quality, smoking, and environmental tobacco smoke exposure.Results. Most exposures were associated with cough alone or cough in combination with wheeze. Smoking, past smoking, and environmental tobacco smoke exposure were strongly associated with dry cough and wheeze. The use of coal for heating was associated with dry cough. Leaks, mold, and lack of kitchen ventilation were associated with cough and wheeze. Nocturnal cough and productive cough were associated with specific types of sensitization, but dry cough was not. Productive cough was associated with hyperresponsiveness to methacholine.Conclusions. Several different types of indoor exposures, including environmental tobacco smoke exposure, are important contributors to morbidity associated with cough and wheeze. A vigorous preventive strategy designed to lower exposures to indoor risk factors would lower rates of respiratory morbidity.

The present authors investigated whether wheezing is less common in children who consume more apples and other fruits. A population-based survey of 2,640 primary school children aged 5-10 yrs was carried out in Greenwich (South London, UK). Information about asthma symptoms and fruit consumption was obtained by means of a questionnaire. After controlling for potential confounding variables, eating bananas at least once a day (compared with less than once a month) was negatively associated with current wheeze (odds ratio 0.66; 95% confidence interval 0.44-1.00) and ever wheeze (0.69 (0.50-0.95)), but not with ever asthma (0.80 (0.56-1.14)). Drinking apple juice from concentrate at least once a day (compared with less than once a month) was also negatively associated with current wheeze (0.53 (0.34-0.83)), weakly associated with ever wheeze (0.74 (-0.54-1.02)), but not associated with ever asthma. Consumption of apples, other fruits and orange juice was not significantly associated with asthma symptoms. No association was found between eating fresh apples and asthma symptoms in the study population, but some evidence was found to suggest that a higher consumption of apple juice from concentrate and bananas may protect against wheezing in children.

Aim: Diet might modulate lung function decline. We assessed the relationship between baseline dietary intake and 13 year lung function decline in European adults. Methods: In 2000, adults from Norway, Germany and the UK, from the European Community Respiratory Health Survey (ECRHS) answered questions on respiratory health, and had the following spirometric measurements: Forced vital capacity (FVC), forced exhaled volume in 1 second (FEV1), from which the ratio FEV1/FVC, FEV1 below lower limit of normal (FEV1 Results: 733 individuals (mean age 43.5 ± 6.6 years at baseline) were included. A per-tertile increase in vitamin C intake was associated with a -3.74 mL/year lower decline in FEV1 (95% CI -7.29, -0.20). Per-tertile increase in pizza intake was associated with a more accelerated FEV1 and FVC decline (5.63 ml/year (95% CI 2.69, 8.57); 4.65mL/year (95% CI 0.88, 8.41) respectively). These associations remained statistically significant after controlling for multiple testing. In ex-smokers, a per-tertile increase in total fruit intake at baseline was associated with a lower decline in FEV1 (-4.91 mL/year (95% CI -9.68, -0.13) and FVC (-19.45 mL/year (95% CI-32.99, -5.91). Conclusion: Dietary intake of vitamin C and total fruit intake may slow down lung function decline in adults.

Background: Poor ventilatory function (VF) is a risk factor for general mortality. Cross-sectional evidence from this population 1 and from other studies shows that VF is associated with markers of cardiovascular disease (CVD). We investigated if VF was prospectively related to cardio-metabolic (CM) markers of CVD in young adults. Methods: In 2002, 998 adults aged 22-28 answered a health questionnaire and underwent spirometry (Forced vital capacity (FVC), forced exhaled volume in 1 second (FEV 1 ), the ratio FEV 1 /FVC, FEV 1 below lower limit of normal (FEV 1 1 /FVC Results: 766 (76.8%) individuals had valid data at follow-up. AO was negatively associated with FEV 1 and FVC at baseline (adjusted odds ratio (aOR) 0.42; 95% CI 0.21 to 0.84; and aOR 0.39; 95% CI 0.21 to 0.74, respectively). TG levels were negatively associated with FEV 1 at baseline (aOR 0.62; 95% CI 0.39 to 0.98). A higher risk of elevated HOMA-IR was observed in those with an FEV 1 Conclusion: Poor VF is prospectively related to several CM markers of CVD. The magnitude of these associations warrants investigation into the possible mechanisms. 1 Garcia-Larsen V et al . Ventilatory function and cardiovascular risk factors in young adults. BMC Pulm Med 2014; 14(1):206. doi: 10.1186/1471-2466-14-206.

Background: Diet might influence the risk of allergic diseases. Evidence from developing countries with high prevalence of childhood asthma is scant. Methods: Information on wheeze, rhinitis, and eczema was collected from 3209 children aged 6–7 years in 2005, who were taking part in the International Study on Asthma and Allergy in Children (ISAAC) in Colombia. Intake frequency of twelve food groups was assessed. Associations between each food group and current wheeze, rhino-conjunctivitis, and eczema were investigated with multiple logistic regressions, adjusting for potential confounders. Simes’ procedure was used to test for multiple comparisons. Results: 14.9% of children reported wheeze in the last 12 months, 16% rhino-conjunctivitis, and 22% eczema. Eczema was negatively associated with consumption of fresh fruits and pulses three or more times per week (adjusted Odds ratio (aOR): 0.64, 95% Confidence Interval (CI): 0.49 to 0.83, p value = 0.004, and aOR: 0.62, 95% CI: 0.47 to 0.80, p value &lt, 0.001, respectively). Current wheeze was negatively associated with intake of potatoes (aOR: 0.44, 95% CI: 0.31 to 0.62, p value = 0.005), whilst this outcome was positively associated with consumption of fast food (aOR: 1.76, 95% CI: 1.32 to 2.35, p value = 0.001). These associations remained statistically significant after controlling for multiple comparisons. Conclusions: A traditional diet might have a protective effect against eczema and wheeze in Colombian children, whilst intake of fast foods increases this risk.

Shrimp (7-25%) and crab (4-9%) were the most common food sensitizations in Chinese children, except in Hong Kong, where egg (17%) and milk (15%) sensitization was higher than that to shrimp (13%). In all other sites

BACKGROUND: It is unknown whether food allergy (FA) in an unselected population is comparable to those from an outpatient clinic population. OBJECTIVE: To discover if FA in a random sample from the Dutch community is comparable to that of outpatients. METHODS: This study was part of the Europrevall-project. A random sample of 6600 adults received a questionnaire. Those with symptoms to one of 24 defined priority foods were tested for sIgE. Participants with a positive case history and elevated sIgE were evaluated by double-blind placebo-controlled food challenge (DBPCFC). Outpatients with a suspicion of FA were evaluated by questionnaire, sIgE and DBPCFC. RESULTS: In the community, severe symptoms were reported less often than in outpatients (39.3% vs. 54.3%). Participants in the community were less commonly sensitized to any of the foods. When selecting only those with a probable FA (i.e. symptoms of priority food and elevation of sIgE to the respective food), no major differences were observed with respect to severity, causative foods, sensitization and DBPCFC between the groups. CONCLUSION: In the Netherlands, there are large differences in self-reported FA between community and outpatients. However, Dutch community and outpatients with a probable FA do not differ with respect to severity, causative foods, sensitization and DBPCFC-outcome.

Summary Background There are several reports showing that obese adults report more respiratory symptoms suggestive of asthma than those who are not obese. Objective To determine the association of body mass index with respiratory symptoms and atopy in young adults Method Information collected from 15 454 participants in the European Community Respiratory Health Survey, a multicentre cross-sectional survey of young adults, was analysed to determine the association of body mass index with respiratory symptoms and atopy. Results Men and women with a body mass index of greater than 30 were at an increased risk of wheeze with shortness of breath compared with those with a body mass of 20–24.99 (OR in men 1.85, 95% confidence interval 1.41–2.42; OR in women 2.03, 95% confidence interval 1.59–2.58). Similar associations were observed for other symptoms suggestive of asthma. Body mass index was not associated with ‘hayfever or nasal allergies’, specific IgE to house dust mite, grass or cat or with total IgE in men or women. Conclusion Reported associations of body mass index with symptoms suggestive of asthma are unlikely to be explained by a higher risk of atopy in the obese. Alternative explanations must be sought.

SummaryBackground Routine prophylaxis with replacement factor VIII (FVIII) – the standard of care for severe hemophilia A – often requires frequent intravenous infusions (three or four times weekly). An FVIII molecule with an extended half-life could reduce infusion frequency. The A-LONG study established the safety, efficacy and prolonged pharmacokinetics of recombinant FVIII Fc fusion protein (rFVIIIFc) in previously treated adolescents and adults with severe hemophilia A. Objective In this post hoc analysis, we investigated the relationship between subjects' prestudy (FVIII) and on-study (rFVIIIFc) regimens. Methods We analyzed two subgroups of subjects: prior prophylaxis and on-study individualized prophylaxis (n = 80), and prior episodic treatment and on-study weekly prophylaxis (n = 16). Subjects' prestudy dosing regimens and bleeding rates were compared with their final rFVIIIFc regimens and annualized bleeding rates (ABRs) in the last 3 months on-study. Dosing regimen simulations based on population pharmacokinetics models for rFVIII and rFVIIIFc were performed. Results As compared with their prestudy regimen, 79 of 80 (98.8%) subjects on individualized rFVIIIFc prophylaxis decreased their infusion frequency. Overall ABRs were low, with comparable factor consumption. Longer dosing intervals, including 5-day dosing, were associated with higher baseline von Willebrand factor antigen levels. Simulated dosing regimens predicted a greater proportion of subjects with steady-state FVIII activity trough levels of ≥ 1 IU dL−1 (1%) with rFVIIIFc than with equivalent rFVIII regimens. Conclusion These results suggest that patients on rFVIIIFc prophylaxis can reduce their infusion frequency as compared with their prior FVIII regimen while maintaining low bleeding rates, affording more patients trough levels of ≥ 1 IU dL−1 than with rFVIII products requiring more frequent dosing regimens.

Summary In the phase 3 B-LONG [Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Subjects with Haemophilia B] study, rFIXFc dosed every 1–2 weeks was safe and efficacious in previously treated subjects with haemophilia B. To date, there are no evaluations of transitioning from conventional to long-acting factor IX (FIX) prophylaxis. This post-hoc analysis of B-LONG subjects compared prophylaxis with other FIX products and rFIXFc. Pre- and on-study data were analysed to assess dosing regimen, weekly FIX consumption and annualized bleeding rates (ABRs). Population pharmacokinetics models were used to generate FIX activity profiles with rFIXFc and recombinant FIX prophylaxis. Thirty-nine subjects, previously treated prophylactically, were evaluated. Prior to study, most subjects (69·2%) received twice-weekly FIX infusions; on study, subjects infused rFIXFc once every 1–2 weeks with c. 30–50% reductions in weekly consumption. On-study estimated mean ABRs were lower than pre-study estimated mean ABRs. Models predicted that rFIXFc administered 50 iu/kg weekly and 100 iu/kg every 10 d would maintain steady-state FIX trough levels ≥1 iu/dl in 95·4% and 89·2% of subjects, respectively. These results indicate that patients receiving rFIXFc prophylaxis can markedly reduce infusion frequency and FIX consumption, have a greater likelihood of maintaining FIX activity >1 iu/dl and experience fewer bleeding episodes compared with prior FIX prophylaxis.

Low preparedness for food allergy as perceived by school staff: a EuroPrevall survey across Europe Thuy-My Le, MD, PhD*, Ischa Kummeling, PhD*, Danielle Dixon, MD, Laura Barreales Tolosa, MD, Barbara Ballmer-Weber, MD, Michael Clausen, MD, M. Hazel Gowland, BA, Barbara Majkowska-Wojciechowska, MD, Tihomir Mustakov, MD, Nikolaos G. Papadopoulos, MD, PhD, Andre C. Knulst, MD, PhD, James Potts, BSc, Rimantas Stukas, PhD, and Peter Burney, MD

BACKGROUND: The epidemiological surveys in children and adults of the EU-funded multidisciplinary Integrated Project EuroPrevall, launched in June 2005, were designed to estimate the currently unknown prevalence of food allergy and exposure to known or suspected risk factors for food allergy across Europe. We describe the protocol for the epidemiological surveys in children and adults. This protocol provides specific instructions on the sampling strategy, the use of questionnaires, and collection of blood samples for immunological analyses. METHODS: The surveys were performed as multi-centre, cross-sectional studies in general populations. Case-control studies were nested within these surveys. The studies in children aged 7-10 years and adults aged 20-54 years were undertaken in eight centres representing different social and climatic regions in Europe. RESULTS: After a community-based survey collecting basic information on adverse reactions to foods, all those stating they had experienced such reactions, as well as of a random sample of those stating 'no reactions' to foods, completed a detailed questionnaire on potential risks and exposures. Also a blood sample was taken to allow serological analysis to establish patterns of food and aeroallergen sensitization. We also included a questionnaire to schools on their preparedness for dealing with food allergy amongst pupils. Subjects reporting adverse reactions to foods and sensitized to the same food(s) were called in for a full clinical evaluation that included a double blind placebo controlled food challenge (DBPCFC), following a protocol which is described in detail elsewhere. CONCLUSIONS: The outcome of these studies will help to improve our understanding of several important aspects of food allergies in the European Community, providing for more well-informed policies and effective measures of disease prevention, diagnosis and management.