Capability Investment Strategy to Enable JPL Future Space Missions

The Jet Propulsion Laboratory (JPL) formulates and conducts deep space missions for NASA (the National Aeronautics and Space Administration). The Chief Technologist of JPL has responsibility for strategic planning of the laboratory's advanced technology program to assure that the required technological capabilities to enable future missions are ready as needed. The responsibilities include development of a Strategic Plan (Antonsson, E., 2005). As part of the planning effort, a structured approach to technology prioritization, based upon the work of the START (Strategic Assessment of Risk and Technology) (Weisbin, C.R., 2004) team, was developed. The purpose of this paper is to describe this approach and present its current status relative to the JPL technology investment

START Analysis for ESAS Capability Needs Prioritization

START is a tool to optimize research and development primarily for NASA missions. It was developed within the Strategic Systems Technology Program Office, a division of the Office of the Chief Technologist at NASA's Jet Propulsion Laboratory. START is capable of quantifying and comparing the risks, costs, and potential returns of technologies that are candidates for funding. START can be enormously helpful both in selecting technologies for development -- within the constraints of budget, schedule, and other resources -- and in monitoring their progress. START's methods are applicable to everything from individual tasks to multiple projects comprising entire programs of investigation. They can address virtually any technology assessment and capability prioritization issue. In this report, START is used to analyze the capability needs using data from NASA's Exploration Systems Architecture Study (ESAS)

Technology Assessment in Support of the Presidential Vision for Space Exploration

This document is a viewgraph presentation that contains: (1) pictorial description of lunar context, (2) Definition of base case, (3) Optimization results, (4) Effects of cost uncertainties for base case and different assumed annual budget levels and (5) Effects of temporal optimization

Diacylglycerol kinase promotes actin cytoskeleton remodeling and mechanical forces at the B cell immune synapse

International audienceDiacylglycerol kinases (DGKs) limit antigen receptor signaling in immune cells by consuming the second messenger diacylglycerol (DAG) to generate phosphatidic acid (PA). Here, we showed that DGK promotes lymphocyte function-associated antigen 1 (LFA-1)-mediated adhesion and F-actin generation at the immune synapse of B cells with antigen-presenting cells (APCs), mostly in a PA-dependent manner. Measurement of single-cell mechanical force generation indicated that DGK-deficient B cells exerted lower forces at the immune synapse than did wild-type B cells. Nonmuscle myosin activation and translocation of the microtubule-organizing center (MTOC) to the immune synapse were also impaired in DGK-deficient B cells. These functional defects correlated with the decreased ability of B cells to present antigen and activate T cells in vitro. The in vivo germinal center response of DGK-deficient B cells was also reduced compared with that of wild-type B cells, indicating that loss of DGK in B cells impaired T cell help. Together, our data suggest that DGK shapes B cell responses by regulating actin remodeling, force generation, and antigen uptake-related events at the immune synapse. Hence, an appropriate balance in the amounts of DAG and PA is required for optimal B cell function

PP08 / PP09 / PP11

Três Trabalho

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics

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. 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Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

Background Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. Methods PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. Findings Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. Interpretation Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p