Primary recovery of hyaluronic acid produced in Streptococcus equi subsp. zooepidemicus using PEG-citrate aqueous two-phase systems

Given its biocompatibility, rheological, and physiological properties, hyaluronic acid (HA) has become a biomaterial of increasing interest with multiple applications in medicine and cosmetics. In recent decades, microbial fermentations have become an important source for the industrial production of HA. However, due to its final applications, microbial HA must undergo critical and long purification processes to ensure clinical and cosmetic grade purity. Aqueous two-phase systems (ATPS) have proven to be an efficient technique for the primary recovery of high-value biomolecules. Nevertheless, their implementation in HA downstream processing has been practically unexplored. In this work, polyethylene glycol (PEG)–citrate ATPS were used for the first time for the primary recovery of HA produced with an engineered strain of Streptococcus equi subsp. zooepidemicus. The effects of PEG molecular weight (MW), tie-line length (TLL), volume ratio (VR), and sample load on HA recovery and purity were studied with a clarified fermentation broth as feed material. HA was recovered in the salt-rich bottom phase, and its recovery increased when a PEG MW of 8000 g mol−1 was used. Lower VR values (0.38) favoured HA recovery, whereas purity was enhanced by a high VR (3.50). Meanwhile, sample load had a negative impact on both recovery and purity. The ATPS with the best performance was PEG 8000 g mol−1, TLL 43% (w/w), and VR 3.50, showing 79.4% HA recovery and 74.5% purity. This study demonstrated for the first time the potential of PEG–citrate ATPS as an effective primary recovery strategy for the downstream process of microbial HA

Grupo español de cirugía torácica asistida por videoimagen: método, auditoría y resultados iniciales de una cohorte nacional prospectiva de pacientes tratados con resecciones anatómicas del pulmón

Introduction: our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). Methods: we conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for '90-day mortality' and 'Grade IIIb-V complications'. Results: the series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). Conclusions: more than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030

Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

BACKGROUND: Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. FINDINGS: Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9-3·0) for men and 3·5 years (3·4-3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78-0·92) and 1·2 years (1·1-1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. INTERPRETATION: Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. FUNDING: Bill & Melinda Gates Foundation

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries : an analysis from the Global Burden of Disease Study 2016

Background The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2.5th percentile estimated between 1990 and 2030, and 100 as the 97.5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. Findings Globally, the median health-related SDG index was 56.7 (IQR 31.9-66.8) in 2016 and country-level performance markedly varied, with Singapore (86.8, 95% uncertainty interval 84.6-88.9), Iceland (86.0, 84.1-87.6), and Sweden (85.6, 81.8-87.8) having the highest levels in 2016 and Afghanistan (10.9, 9.6-11.9), the Central African Republic (11.0, 8.8-13.8), and Somalia (11.3, 9.5-13.1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. Interpretation GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations. Copyright The Authors. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 4.0 license.Peer reviewe

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

International audienceLife-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

4Th Pediatric Allergy And Asthma Meeting (Paam)

WORKSHOP 4: Challenging clinical scenarios (CS01–CS06), CS01 Bullous lesions in two children: solitary mastocytoma, S. Tolga Yavuz, Ozan Koc, Ali Gungor, Faysal Gok, CS02 Multi-System Allergy (MSA) of cystic fibrosis: our institutional experience, Jessica Hawley, Christopher O’Brien, Matthew Thomas, Malcolm Brodlie, Louise Michaelis, CS03 Cold urticaria in pediatric age: an invisible cause for severe reactions, Inês Mota, Ângela Gaspar, Susana Piedade, Graça Sampaio, José Geraldo Dias, Miguel Paiva, Mário Morais-Almeida, CS04 Angioedema with C1 inhibitor deficiency in a girl: a challenge diagnosis, Cristina Madureira, Tânia Lopes, Susana Lopes, Filipa Almeida, Alexandra Sequeira, Fernanda Carvalho, José Oliveira, CS05 A child with unusual multiple organ allergy disease: what is the primer?, Fabienne Gay-Crosier, CS06 A case of uncontrolled asthma in a 6-year-old patient, Ioana-Valentina Nenciu, Andreia Florina Nita, Alexandru Ulmeanu, Dumitru Oraseanu, Carmen Zapucioiu, ORAL ABSTRACT SESSION 1: Food allergy (OP01–OP06), OP01 Food protein-induced enterocolitis syndrome: oral food challenge outcomes for tolerance evaluation in a Pediatric Hospital, Adrianna Machinena, Olga Domínguez Sánchez, Montserrat Alvaro Lozano, Rosa Jimenez Feijoo, Jaime Lozano Blasco, Mònica Piquer Gibert, Mª Teresa Giner Muñoz, Marcia Dias da Costa, Ana Maria Plaza Martín, OP02 Characteristics of infants with food protein-induced enterocolitis syndrome and allergic proctocolitis, Ebru Arik Yilmaz, Özlem Cavkaytar, Betul Buyuktiryaki, Ozge Soyer, Cansin Sackesen, OP03 The clinical and immunological outcomes after consumption of baked egg by 1–5 year old egg allergic children: results of a randomised controlled trial, MerrynNetting, Adaweyah El-Merhibi, Michael Gold, PatrickQuinn, IrmeliPenttila, Maria Makrides, OP04 Oral immunotherapy for treatment of egg allergy using low allergenic, hydrolysed egg, Stavroula Giavi, Antonella Muraro, Roger Lauener, Annick Mercenier, Eugen Bersuch, Isabella M. Montagner, Maria Passioti, Nicolò Celegato, Selina Summermatter, Sophie Nutten, Tristan Bourdeau, Yvonne M. Vissers, Nikolaos G. Papadopoulos, OP05 Chemical modification of a peanut extract results in an increased safety profile while maintaining efficacy, Hanneke van der Kleij, Hans Warmenhoven, Ronald van Ree, Raymond Pieters, Dirk Jan Opstelten, Hans van Schijndel, Joost Smit, OP06 Administration of the yellow fever vaccine in egg allergic children, Roisin Fitzsimons, Victoria Timms, George Du Toit, ORAL ABSTRACT SESSION 2: Asthma (OP07–OP12), OP07 Previous exacerbation is the most important risk factor for future exacerbations in school-age children with asthma, S. Tolga Yavuz, Guven Kaya, Mustafa Gulec, Mehmet Saldir, Osman Sener, Faysal Gok, OP08 Comparative study of degree of severity and laboratory changes between asthmatic children using different acupuncture modalities, Nagwa Hassan, Hala Shaaban, Hazem El-Hariri, Ahmed Kamel Inas E. Mahfouz, OP09 The concentration of exhaled carbon monoxide in asthmatic children with different controlled stadium, Papp Gabor, Biro Gabor, Kovacs Csaba, OP10 Effect of vitamin D3 supplementation during pregnancy on risk of persistent wheeze in the offspring: a randomised clinical trial, Bo Chawes, Klaus Bønnelykke, Jakob Stokholm, Lene Heickendorff, Susanne Brix, Morten Rasmussen, Hans Bisgaard, OP11 Lung function development in childhood, Henrik Wegener Hallas, Bo Chawes, Lambang Arianto, Hans Bisgaard, OP12 Is the effect of maternal and paternal asthma different in female and male children before puberty?, Maike Pincus, Thomas Keil, Andreas Reich, Ulrich Wahn, Susanne Lau, Linus Grabenhenrich, ORAL ABSTRACT SESSION 3: Epidemiology—genetics (OP13–OP18), OP13 Lifestyle is associated with incidence and category of allergen sensitisation: the ALADDIN birth cohort, Sara Fagerstedt, Helena Marell Hesla, Emelie Johansson, Helen Rosenlund, Axel Mie, Annika Scheynius, Johan Alm, OP15 Maternal filaggrin mutations increase the risk of atopic dermatitis in children: an effect independent of mutation inheritance, Jorge Esparza-Gordillo, Anja Matanovic, Ingo Marenholz, Anja Bauerfeind, Klaus Rohde, Katja Nemat, Min-Ae Lee-Kirsch, Magnus Nordenskjöld, Marten C. G. Winge, Thomas Keil, Renate Krüger, Susanne Lau, Kirsten Beyer, Birgit Kalb, Bodo Niggemann, Norbert Hübner, Heather J. Cordell, Maria Bradley, Young-Ae Lee, OP16 Allergic multimorbidity of asthma, rhinitis and eczema in the first 2 decades of the German MAS birth cohort, Thomas Keil, Hannah Gough, Linus Grabenhenrich, Dirk Schramm, Andreas Reich, John Beschorner, Antje Schuster, Carl-Peter Bauer, Johannes Forster, Fred Zepp, Young-Ae Lee, Renate Bergmann, Karl Bergmann, Ulrich Wahn, Susanne Lau, OP17 Childhood anaphylaxis: a growing concern, Filipe Benito Garcia, Inês Mota, Susana Piedade, Ângela Gaspar, Natacha Santos, Helena Pité, Mário Morais-Almeida, OP18 Indoor exposure to molds and dampness in infancy and its association to persistent atopic dermatitis in school age. Results from the Greek ISAAC II study, Athina Papadopoulou, Despina Mermiri, Elpida Xatziagorou, Ioannis Tsanakas, Stavroula Lampidi, Kostas Priftis, ORAL ABSTRACT SESSION 4: Pediatric rhinitis—immunotherapy (OP19–OP24), OP19 Associations between residential greenness and childhood allergic rhinitis and aeroallergen sensitisation in seven birth cohorts, Elaine Fuertes, Iana Markevych, Gayan Bowatte, Olena Gruzieva, Ulrike Gehring, Allan Becker, Dietrich Berdel, Michael Brauer, Chris Carlsten, Barbara Hoffmann, Anita Kozyrskyj, Caroline Lodge, Göran Pershagen, Alet Wijga, Heinrich Joachim, OP20 Full symptom control in pediatric patients with allergic rhinitis and asthma: results of a 2-year sublingual allergen immunotherapy study, Zorica Zivkovic, Ivana Djuric-Filipovic, Jasmina Jocić-Stevanovic, Snežana Zivanovic, OP21 Nasal epithelium of different ages of atopic subjects present increased levels of oxidative stress and increased cell cytotoxicity upon rhinovirus infection, Styliani Taka, Dimitra Kokkinou, Aliki Papakonstantinou, Panagiota Stefanopoulou, Anastasia Georgountzou, Paraskevi Maggina, Sofia Stamataki, Vassiliki Papaevanggelou, Evangelos Andreakos, Nikolaos G. Papadopoulos, OP22 Cluster subcutaneous immunotherapy schedule: tolerability profile in children, Monica Piquer Gibert, Montserrat Alvaro Lozano, Jaime Lozano Blasco, Olga Domínguez Sánchez, Rosa Jiménez Feijoo, Marcia Dias da Costa, Mª Teresa Giner Muñoz, Adriana Machinena Spera, Ana Maria Plaza Martín, OP23 Rhinitis as a risk factor for asthma severity in 11-year old children: population-based cohort study, Matea Deliu, Danielle Belgrave, Angela Simpson, Adnan Custovic, OP24 The Global Lung Function Initiative equations in airway obstruction evaluation of asthmatic children, João Gaspar Marques, Pedro Carreiro-Martins, Joana Belo, Sara Serranho, Isabel Peralta, Nuno Neuparth, Paula Leiria-Pinto, POSTER DISCUSSION SESSION 1: Food allergy (PD01–PD05), PD01 Allergen-specific humoral and cellular responses in children who fail egg oral immunotherapy due to allergic reactions, Marta Vazquez-Ortiz, Mariona Pascal, Ana Maria Plaza, Manel Juan, PD02 FoxP3 epigenetic features in children with cow milk allergy, Lorella Paparo, Rita Nocerino, Rosita Aitoro, Ilaria Langella, Antonio Amoroso, Alessia Amoroso, Carmen Di Scala, Roberto Berni Canani, PD04 Combined milk and egg allergy in early childhood: let them eat cake?, Santanu Maity, Giuseppina Rotiroti, Minal Gandhi, PD05 Introduction of complementary foods in relation to allergy and gut microbiota in farm and non-farm children, Karin Jonsson, Annika Ljung, Bill Hesselmar, Ingegerd Adlerbert, Hilde Brekke, Susanne Johansen, Agnes Wold, Ann-Sofie Sandberg, POSTER DISCUSSION SESSION 2: Asthma and wheeze (PD06–PD16), PD06 The association between asthma and exhaled nitric oxide is influenced by genetics and sensitisation, Björn Nordlund, Cecilia Lundholm, Villhelmina Ullemar, Marianne van Hage, Anne Örtqvist, Catarina Almqvist, PD09 Prevalence patterns of infant wheeze across Europe, Anna Selby, Kate Grimshaw, Thomas Keil, Linus Grabenhenrich, Michael Clausen, Ruta Dubakiene, Alessandro Fiocchi, Marek Kowalski, Nikos Papadopoulos, Marta Reche, Sigurveig Sigurdardottir, Aline Sprikkleman, Paraskevi Xepapadaki, Clare Mills, Kirsten Beyer, Graham Roberts, PD10 Epidemiologic changes in recurrent wheezing infants, Herberto Jose Chong Neto, Gustavo Falbo Wandalsen, Ana Carolina Dela Bianca, Carolina Aranda, Nelson Augusto Rosário, Dirceu Solé, Javier Mallol, Luis García Marcos, PD13 A single nucleotide polymorphism in the GLCCI1 gene is associated with response to asthma treatment in children, IvanaBanic, Matija Rijavec, Davor Plavec, Peter Korosec, Mirjana Turkalj, PD14 Pollen induced asthma: Could small molecules in pollen exacerbate the protein-mediated allergic response?, Alen Bozicevic, Maria De Mieri, Matthias Hamburger, PD15 A qualitative study to understand how we can empower teenagers to better self-manage their asthma, Simone Holley, Ruth Morris, Frances Mitchell, Rebecca Knibb, Susan Latter, Christina Liossi, Graham Roberts, PD16 Polymorphism of endothelial nitric oxide synthase (eNOS) gene among Egyptian children with bronchial asthma, Mostafa M. M. Hassan, POSTER DISCUSSION SESSION 3: Mechanisms—Epidemiology (PD17–PD21), PD17 Pregnancy outcomes in relation to development of allergy in a Swedish birth cohort, Malin Barman, Anna Sandin, Agnes Wold, Ann-Sofie Sandberg, PD18 Evolution of the IgE response to house dust mite molecules in childhood, Daniela Posa, Serena Perna, Carl-Peter Bauer, Ute Hoffmann, Johannes Forster, Fred Zepp, Antje Schuster, Ulrich Wahn, Thomas Keil, Susanne Lau, Kuan-Wei Chen, Yvonne Resch, Susanne Vrtala, Rudolf Valenta, Paolo Maria Matricardi, PD19 Antibody recognition of nsLTP-molecules as antigens but not as allergens in the German-MAS birth cohort, Olympia Tsilochristou, Alexander Rohrbach, Antonio Cappella, Stephanie Hofmaier, Laura Hatzler, Carl-Peter Bauer, Ute Hoffmann, Johannes Forster, Fred Zepp, Antje Schuster, RaffaeleD’Amelio, Ulrich Wahn, Thomas Keil, Susanne Lau, Paolo Maria Matricardi, PD20 Early life colonization with Lactobacilli and Staphylococcus aureus oppositely associates with the maturation and activation of FOXP3+ CD4 T-cells, Sophia Björkander, Maria A. Johansson, Gintare Lasaviciute, Eva Sverremark-Ekström, PD21 Genome-wide meta-analysis identifies 7 susceptibility loci involved in the atopic march, Ingo Marenholz, Jorge Esparza-Gordillo, Franz Rüschendorf, Anja Bauerfeind, David P. Strachan, Ben D. Spycher, Hansjörg Baurecht, Patricia Margaritte-Jeannin, Annika Sääf, Marjan Kerkhof, Markus Ege, Svetlana Baltic, Melanie C Matheson, Jin Li, Sven Michel, Wei Q. Ang, Wendy McArdle, Andreas Arnold, Georg Homuth, Florence Demenais, Emmanuelle Bouzigon, Cilla Söderhäll, Göran Pershagen, Johan C. de Jongste, Dirkje S Postma, Charlotte Braun-Fahrländer, Elisabeth Horak, Ludmila M. Ogorodova, Valery P. Puzyrev, Elena Yu Bragina, Thomas J Hudson, Charles Morin, David L Duffy, Guy B Marks, Colin F Robertson, Grant W Montgomery, Bill Musk, Philip J Thompson, Nicholas G. Martin, Alan James, Patrick Sleiman, Elina Toskala, Elke Rodriguez, Regina Fölster-Holst, Andre Franke, Wolfgang Lieb, Christian Gieger, Andrea Heinzmann, Ernst Rietschel, Thomas Keil, Sven Cichon, Markus M Nöthen, Craig E Pennell, Peter D Sly, Carsten O Schmidt, Anja Matanovic, Valentin Schneider, Matthias Heinig, Norbert Hübner, Patrick G. Holt, Susanne Lau, Michael Kabesch, Stefan Weidinger, Hakon Hakonarson, Manuel AR Ferreira, Catherine Laprise, Maxim B. Freidin, Jon Genuneit, Gerard H Koppelman, Erik Melén, Marie-Hélène Dizier, A. John Henderson, Young Ae Lee, POSTER DISCUSSION SESSION 4: Food allergy—Anaphylaxis (PD22–PD26), PD22 Atopy patch test in food protein induced enterocolitis caused by solid food, Purificacion González-Delgado, Esther Caparrós, Fernando Clemente, Begoña Cueva, Victoria M. Moreno, Jose Luis Carretero, Javier Fernández, PD23 Watermelon allergy: a novel presentation, Kate Swan, George Du Toit, PD24 A pilot study evaluating the usefulness of a guideline template for managing milk allergy in primary care, Mudiyur Gopi, Tim Smith, Edara Ramesh, Arun Sadasivam, PD26 Efficacy and safety of cow’s milk oral immunotherapy protocol, Inês Mota, Filipe Benito Garcia, Susana Piedade, Angela Gaspar, Graça Sampaio, Cristina Arêde, Luís Miguel Borrego, Graça Pires, Cristina Santa-Marta, Mário Morais-Almeida, POSTER DISCUSSION SESSION 5: Prevention and treatment—Allergy (PD27–PD36), PD27 Allergy-protection by the lactic acid bacterium Lactococcus lactis G121: mode-of-action as revealed in a murine model of experimental allergy, Stephanie Brand, Karina Stein, Holger Heine, Marion Kauth, PD29 The relationship between quality of life and morning salivary cortisol after acute bronchiolitis in infancy, Leif Bjarte Rolfsjord, Egil Bakkeheim, Johan Alm, Håvard Ove Skjerven, Kai-Håkon Carlsen, Jon Olav Hunderi, Teresa Løvold Berents, Petter Mowinckel, Karin C. Lødrup Carlsen, PD30 Randomised trial of the efficacy of MP29-02* compared with fluticasone propionate nasal spray in children aged ≥6 years to <12 years with allergic rhinitis, Ulrich Wahn, Ullrich Munzel, William Berger, PD31 10 mg of oral bilastine in 2 to 11 years old children has similar exposure to the adult therapeutic dose (20 mg), Ulrich Wahn, Román Valiente, Valvanera Vozmediano, John C. Lukas, Mónica Rodríguez, PD33 Daily symptoms, nocturnal symptoms, activity limitations and reliever therapies during the three steps of IOEASMA programme: a comparison, Sebastiano Guarnaccia, Luigi Vitale, Ada Pluda, Emanuele D’Agata, Denise Colombo, Stefano Felici, Valeria Gretter, Susanna Facchetti, Gaia Pecorelli, Cristina Quecchia, PD34 Sensitisation to an inert aeroallergen in weaning rats and longstanding disease, in a sensitisation-tolerant and easily tolerisable rodent strain, George Guibas, Evangelia Spandou, Spyridon Megremis, Peter West, Nikolaos Papadopoulos, PD35 Bacterial and fungi exposure in school and allergic sensitisation in children, João Cavaleiro Rufo, Joana Madureira, Inês Paciência, Lívia Aguiar, Patrícia Padrão, Mariana Pinto, Luís Delgado, Pedro Moreira, João Paulo Teixeira, Eduardo Oliveira Fernandes, André Moreira, PD36 Comparative study of allergy rhinitis between two populations: children vs. adults, Adriana Izquierdo Dominguez, Antonio Valero, Joaquim Mullol, Alfonso Del Cuvillo, Javier Montoro, Ignacio Jauregui, Joan Bartra, Ignacio Davila, Marta Ferrer, Joaquin Sastre, POSTER VIEWING SESSION 1: Inflammation—Genetics—Immunology—Dermatology (PP01–PP09), PP01 Immune profile in late pregnancy: immunological markers in atopic asthmaticwomen as risk factors for atopy in the progeny, Catarina Martins, Jorge Lima, Maria José Leandro, Glória Nunes, Jorge Cunha Branco, Hélder Trindade, Luis Miguel Borrego, PP02 The impact of neonatal sepsis on development of allergic diseases, Secil Conkar, Mehtap Kilic, Canan Aygun, Recep Sancak, PP03 Clinical overview of selective IgE deficiency in childhood, Athina Papadopoulou, Eleni Tagalaki, Lambros Banos, Anna Vlachou, Fotini Giannoula, Despina Mermiri, PP04 Inverse relationship between serum 25(ΟΗ) vitamin D3 and total IgE in children and adolescence, Athina Papadopoulou, Stavroula Lampidi, Marina Pavlakou, Maria Kryoni, Kostas Makris, PP05, PP06, PP07 Asthma control questionnaire and specific IgE in children, Snezhina Lazova, Guergana Petrova, Dimitrinka Miteva, Penka Perenovska, PP08 Features of chronic urticaria of adolescents, Aliya Klyucharova, Olesya Skorohodkina, PP09 Cutaneous mastocytosis in children: a clinical analysis of 8 cases in Greece, Dimitra Koumaki, Alkisti Manousaki, Maria Agrapidi, Lida Iatridou, Omima Eruk, Konstantinos Myridakis, Emmanouil Manousakis, Vasiliki Koumaki, POSTER VIEWING SESSION 2: Food allergy—Anaphylaxis (PP10–PP47), PP10 Prognostic factors in egg allergy, Maria Dimou, Maria Ingemansson, Gunilla Hedlin, PP11 Evaluation of the efficacy of an amino acid-based formula in infants who are intolerant to extensively hydrolysed protein formula, Nitida Pastor, Delphine de Boissieu, Jon Vanderhoof, Nancy Moore, Kaitlin Maditz, PP12 Anaphylaxis and epinephrine auto-injector use: a survey of pediatric trainees, Adeli Mehdi, Shaza Elhassan, Carolin Beck, Ahmed Al-Hammadi, PP13 Anaphylaxis in children: acute management in the Emergency Department, Ioana Maris, Ronan O’Sullivan, Jonathan Hourihane,, PP14 Understanding Cumbrian schools preparedness in managing children at risk of anaphylaxis in order to provide training and support which will create healthy and safe environments for children with allergies, George Raptis, Louise Michaelis, PP15 A new valid and reliable parent and child questionnaire to measure the impact of food protein enterocolitis syndrome on children: the FPIES Quality of Life Questionnaire (FPIESQL), Parent and Child Short Form, Audrey DunnGalvin, Matthew Greenhawt, Carina Venter, Jonathan Hourihane, PP16 An in-depth case study investigation of the experiences of teenagers and young adults in growing up and living with food allergy with emphasis on coping, management and risk, support, and social and self-identity, Evelyn O’Regan, Duncan Cronin, Jonathan Hourihane, Anna O’Reilly, Audrey DunnGalvin, PP17 Cow’s milk protein allergy in Constantine. A retrospective study of 62 cases between 1996 and 2013, Foued Abdelaziz, Dounia Khelifi-Touhami, Nihad Selim, Tahar Khelifi-Touhami, PP18, PP19 Cow’s milk and egg oral immunotherapy in children older than 5 years, Pablo Merida, Ana Mª Plaza, Juan Heber Castellanos, Adrianna Machinena, Montserrat Alvaro Lozano, Jaime Lozano, Olga Dominguez, Monica Piquer, Rosa Jimenez, Mª Teresa Giner, PP20 Professionals’ awareness of management of Cow’s Milk Protein Allergy (CMPA) in North Wales Hospitals, Konstantinos Kakleas, Manohar Joishy, Wendmu Maskele, Huw R. Jenkins, PP21, PP22 Anaphylaxis: the great unknown for teachers. Presentation of a protocol for schools, Mercedes Escarrer, Agustín Madroñero, Maria Teresa Guerra, Juan Carlos Julia, Juan Carlos Cerda, Javier Contreras, Eulalia Tauler, Maria Jesus Vidorreta, Ana Rojo, Silvia Del Valle, PP23 Challenges facing children with food allergies and their parents in out of school activity sectors, Niamh Flynn, PP24 A review of food challenges at a Regional Irish Centre, Gary Foley, Carol Harmon, John Fitzsimons, PP25 The use of epinephrine in infants with anaphylaxis, Krasimira Baynova, Ávila Maria Del Robledo, Labella Marina, PP26, PP27, PP28 Mother’s psychological state predicts the expression of symptoms in food allergic children, Aaron Cortes, Alicia Sciaraffia, Angela Castillo, PP29 The correlation between sIgE towards tree nuts and birch pollen in a Danish Pediatric Allergy Clinic, Nanna Juel-Berg, Kirsten Skamstrup Hansen, Lars Kærgaard Poulsen, PP30 Food allergy in children: evaluation of parents’ use of online social media, Andreia Florina Nita, Ioana Valentina Nenciu, Adina Lazar, Dumitru Oraseanu, PP31 The impact of food allergy on quality of life: FAQLQ questionnaire, Rita Aguiar, Anabela Lopes, Maria J. Paes, Amélia S. Santos, M. A. Pereira-Barbosa, PP32 An unexpected cause of anaphylaxis: potato, Hatice Eke Gungor, Salih Uytun, Umit Murat Sahiner, Yasemin Altuner Torun, PP33 Is it clinical phenotype of allergic diseases determined by sensitisation to food?, Mirjana Zivanovic, Marina Atanasković-Marković, PP34, PP35 Prescribing adrenaline auto-injectors in children in 2014: the data from regional pediatricians, Tina Vesel, Mihaela Nahtigal, Andreja Obermayer-Temlin, Eva Šoster Križnik, Mirjana Maslar, Ruben Bizjak, Marjeta Tomšič-Matic, Sonja Posega-Devetak, Maja Skerbinjek-Kavalar, Mateja Predalič, Tadej Avčin, PP36 Who should have an adrenaline autoinjector? Adherence to the European and French guidelines among 121 allergists from the Allergy Vigilance Network, Guillaume Pouessel, Etienne Beaudouin, Anne M. Moneret-Vautrin, Antoine Deschildre, Allergy Vigilance Network, PP37 Anaphylaxis by Anacardium Occidentale, Marta Viñas, Bartolomé Borja, Nora Hernández, Mª José Castillo, Adriana Izquierdo, Marcel Ibero, PP38 Anaphylaxis with honey in a child, S. Tolga Yavuz, Ali Gungor, Betul Buyuktiryaki, Ozan Koc, Can Naci Kocabas, Faysal Gok, PP39 Evaluation of courses adopted to children on prevention, recognition and management of anaphylaxis, Tina Vesel, Mihaela Nahtigal, PP40 Symptomatic dust mites and shrimp allergy: three pediatric case reports, Filipa Almeida, Susana Lopes, Cristina Madureira, Tânia Lopes, Fernanda Carvalho, PP41 Poor identification rates of nuts by high risk individuals: a call for improved education and support for families, Camille Heming, Emily Garrett, Adam Blackstock, Santanu Maity, Rahul Chodhari, PP42 DAFALL: database of food allergies in the Czech Republic, Simona Belohlavkova, Eliska Kopelentova, Petr Visek, Ivana Setinova, Ivana Svarcova, PP43 Serological cross-reactivity between grass and wheat is not only caused by profilins and CCDs, Sigrid Sjölander, Nora Nilsson, Malin Berthold, Helena Ekoff, Gunilla Hedlin, Magnus Borres, Caroline Nilsson, PP44 Oil body associated proteins in children with nuts allergy. Allergens to consider in IgE-mediated nuts allergy, Loreto González Domínguez, Cristina Muñoz Archidona, Ana Moreira Jorge, Sergio Quevedo Teruel, Teresa Bracamonte Bermejo, Miriam Castillo Fernández, Fernando Pineda de la Losa, Luis Ángel Echeverría Zudaire, PP45, PP46 Protective effect of helicobacter pylori infection against food allergy in children, Olga Vrani, Antigone Mavroudi, Maria Fotoulaki, Maria Emporiadou, Kleomenis Spiroglou, Ioannis Xinias, PP47 Anaphylaxis pathway: A road tryp-tase to success?, Helyeh A. Sadreddini, Mia Warnes, Donna Traves, POSTER VIEWING SESSION 3: Miscell

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124·1 million DALYs [95% UI 111·2 million to 137·0 million]), high systolic blood pressure (122·2 million DALYs [110·3 million to 133·3 million], and low birthweight and short gestation (83·0 million DALYs [78·3 million to 87·7 million]), and for women, were high systolic blood pressure (89·9 million DALYs [80·9 million to 98·2 million]), high body-mass index (64·8 million DALYs [44·4 million to 87·6 million]), and high fasting plasma glucose (63·8 million DALYs [53·2 million to 76·3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9·3% (6·9–11·6) decline in deaths and a 10·8% (8·3–13·1) decrease in DALYs at the global level, while population ageing accounts for 14·9% (12·7–17·5) of deaths and 6·2% (3·9–8·7) of DALYs, and population growth for 12·4% (10·1–14·9) of deaths and 12·4% (10·1–14·9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27·3% (24·9–29·7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Funding The Bill & Melinda Gates Foundation, Bloomberg Philanthropies