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1.  4th Pediatric Allergy and Asthma Meeting (PAAM) 
Yavuz, S. Tolga | Koc, Ozan | Gungor, Ali | Gok, Faysal | Hawley, Jessica | O’Brien, Christopher | Thomas, Matthew | Brodlie, Malcolm | Michaelis, Louise | Mota, Inês | Gaspar, Ângela | Piedade, Susana | Sampaio, Graça | Dias, José Geraldo | Paiva, Miguel | Morais-Almeida, Mário | Madureira, Cristina | Lopes, Tânia | Lopes, Susana | Almeida, Filipa | Sequeira, Alexandra | Carvalho, Fernanda | Oliveira, José | Gay-Crosier, Fabienne | Nenciu, Ioana-Valentina | Nita, Andreia Florina | Ulmeanu, Alexandru | Oraseanu, Dumitru | Zapucioiu, Carmen | Machinena, Adrianna | Sánchez, Olga Domínguez | Lozano, Montserrat Alvaro | Feijoo, Rosa Jiménez | Blasco, Jaime Lozano | Gibert, Mònica Piquer | Muñoz, Mª Teresa Giner | da Costa, Marcia Dias | Martín, Ana Maria Plaza | Yilmaz, Ebru Arik | Cavkaytar, Özlem | Buyuktiryaki, Betul | Soyer, Ozge | Sackesen, Cansin | Netting, Merryn | El-Merhibi, Adaweyah | Gold, Michael | Quinn, Patrick | Penttila, Irmeli | Makrides, Maria | Giavi, Stavroula | Muraro, Antonella | Lauener, Roger | Mercenier, Annick | Bersuch, Eugen | Montagner, Isabella M. | Passioti, Maria | Celegato, Nicolò | Summermatter, Selina | Nutten, Sophie | Bourdeau, Tristan | Vissers, Yvonne M. | Papadopoulos, Nikolaos G. | van der Kleij, Hanneke | Warmenhoven, Hans | van Ree, Ronald | Pieters, Raymond | Opstelten, Dirk Jan | van Schijndel, Hans | Smit, Joost | Fitzsimons, Roisin | Timms, Victoria | Du Toit, George | Kaya, Guven | Gulec, Mustafa | Saldir, Mehmet | Sener, Osman | Hassan, Nagwa | Shaaban, Hala | El-Hariri, Hazem | Mahfouz, Ahmed Kamel Inas E. | Gabor, Papp | Gabor, Biro | Csaba, Kovacs | Chawes, Bo | Bønnelykke, Klaus | Stokholm, Jakob | Heickendorff, Lene | Brix, Susanne | Rasmussen, Morten | Bisgaard, Hans | Hallas, Henrik Wegener | Arianto, Lambang | Pincus, Maike | Keil, Thomas | Reich, Andreas | Wahn, Ulrich | Lau, Susanne | Grabenhenrich, Linus | Fagerstedt, Sara | Hesla, Helena Marell | Johansson, Emelie | Rosenlund, Helen | Mie, Axel | Scheynius, Annika | Alm, Johan | Esparza-Gordillo, Jorge | Matanovic, Anja | Marenholz, Ingo | Bauerfeind, Anja | Rohde, Klaus | Nemat, Katja | Lee-Kirsch, Min-Ae | Nordenskjöld, Magnus | Winge, Marten C.G. | Krüger, Renate | Beyer, Kirsten | Kalb, Birgit | Niggemann, Bodo | Hübner, Norbert | Cordell, Heather J. | Bradley, Maria | Lee, Young-Ae | Gough, Hannah | Schramm, Dirk | Beschorner, John | Schuster, Antje | Bauer, Carl-Peter | Forster, Johannes | Zepp, Fred | Bergmann, Renate | Bergmann, Karl | Garcia, Filipe Benito | Santos, Natacha | Pité, Helena | Papadopoulou, Athina | Mermiri, Despina | Xatziagorou, Elpida | Tsanakas, Ioannis | Lampidi, Stavroula | Priftis, Kostas | Fuertes, Elaine | Markevych, Iana | Bowatte, Gayan | Gruzieva, Olena | Gehring, Ulrike | Becker, Allan | Berdel, Dietrich | Brauer, Michael | Carlsten, Chris | Hoffmann, Barbara | Kozyrskyj, Anita | Lodge, Caroline | Pershagen, Göran | Wijga, Alet | Joachim, Heinrich | Zivkovic, Zorica | Djuric-Filipovic, Ivana | Jocić-Stevanovic, Jasmina | Zivanovic, Snežana | Taka, Styliani | Kokkinou, Dimitra | Papakonstantinou, Aliki | Stefanopoulou, Panagiota | Georgountzou, Anastasia | Maggina, Paraskevi | Stamataki, Sofia | Papaevanggelou, Vassiliki | Andreakos, Evangelos | Gibert, Monica Piquer | Spera, Adriana Machinena | Deliu, Matea | Belgrave, Danielle | Simpson, Angela | Custovic, Adnan | Marques, João Gaspar | Carreiro-Martins, Pedro | Belo, Joana | Serranho, Sara | Peralta, Isabel | Neuparth, Nuno | Leiria-Pinto, Paula | Vazquez-Ortiz, Marta | Pascal, Mariona | Plaza, Ana Maria | Juan, Manel | Paparo, Lorella | Nocerino, Rita | Aitoro, Rosita | Langella, Ilaria | Amoroso, Antonio | Amoroso, Alessia | Di Scala, Carmen | Berni Canani, Roberto | Maity, Santanu | Rotiroti, Giuseppina | Gandhi, Minal | Jonsson, Karin | Ljung, Annika | Hesselmar, Bill | Adlerbert, Ingegerd | Brekke, Hilde | Johansen, Susanne | Wold, Agnes | Sandberg, Ann-Sofie | Nordlund, Björn | Lundholm, Cecilia | Ullemar, Villhelmina | van Hage, Marianne | Örtqvist, Anne | Almqvist, Catarina | Selby, Anna | Grimshaw, Kate | Clausen, Michael | Dubakiene, Ruta | Fiocchi, Alessandro | Kowalski, Marek | Papadopoulos, Nikos | Reche, Marta | Sigurdardottir, Sigurveig | Sprikkleman, Aline | Xepapadaki, Paraskevi | Mills, Clare | Roberts, Graham | Neto, Herberto Jose Chong | Wandalsen, Gustavo Falbo | Bianca, Ana Carolina Dela | Aranda, Carolina | Rosário, Nelson Augusto | Solé, Dirceu | Mallol, Javier | Marcos, Luis García | Banic, Ivana | Rijavec, Matija | Plavec, Davor | Korosec, Peter | Turkalj, Mirjana | Bozicevic, Alen | De Mieri, Maria | Hamburger, Matthias | Holley, Simone | Morris, Ruth | Mitchell, Frances | Knibb, Rebecca | Latter, Susan | Liossi, Christina | Hassan, Mostafa M. M. | Barman, Malin | Sandin, Anna | Posa, Daniela | Perna, Serena | Hoffmann, Ute | Chen, Kuan-Wei | Resch, Yvonne | Vrtala, Susanne | Valenta, Rudolf | Matricardi, Paolo Maria | Tsilochristou, Olympia | Rohrbach, Alexander | Cappella, Antonio | Hofmaier, Stephanie | Hatzler, Laura | D’Amelio, Raffaele | Björkander, Sophia | Johansson, Maria A. | Lasaviciute, Gintare | Sverremark-Ekström, Eva | Rüschendorf, Franz | Strachan, David P. | Spycher, Ben D. | Baurecht, Hansjörg | Margaritte-Jeannin, Patricia | Sääf, Annika | Kerkhof, Marjan | Ege, Markus | Baltic, Svetlana | Matheson, Melanie C. | Li, Jin | Michel, Sven | Ang, Wei Q. | McArdle, Wendy | Arnold, Andreas | Homuth, Georg | Demenais, Florence | Bouzigon, Emmanuelle | Söderhäll, Cilla | de Jongste, Johan C. | Postma, Dirkje S. | Braun-Fahrländer, Charlotte | Horak, Elisabeth | Ogorodova, Ludmila M. | Puzyrev, Valery P. | Bragina, Elena Yu | Hudson, Thomas J. | Morin, Charles | Duffy, David L. | Marks, Guy B. | Robertson, Colin F. | Montgomery, Grant W. | Musk, Bill | Thompson, Philip J. | Martin, Nicholas G. | James, Alan | Sleiman, Patrick | Toskala, Elina | Rodriguez, Elke | Fölster-Holst, Regina | Franke, Andre | Lieb, Wolfgang | Gieger, Christian | Heinzmann, Andrea | Rietschel, Ernst | Cichon, Sven | Nöthen, Markus M. | Pennell, Craig E. | Sly, Peter D. | Schmidt, Carsten O. | Schneider, Valentin | Heinig, Matthias | Holt, Patrick G. | Kabesch, Michael | Weidinger, Stefan | Hakonarson, Hakon | Ferreira, Manuel AR | Laprise, Catherine | Freidin, Maxim B | Genuneit, Jon | Koppelman, Gerard H | Melén, Erik | Dizier, Marie-Hélène | John Henderson, A. | Lee, Young Ae | González-Delgado, Purificacion | Caparrós, Esther | Clemente, Fernando | Cueva, Begoña | Moreno, Victoria M. | Carretero, Jose Luis | Fernández, Javier | Swan, Kate | Gopi, Mudiyur | Smith, Tim | Ramesh, Edara | Sadasivam, Arun | Arêde, Cristina | Borrego, Luís Miguel | Pires, Graça | Santa-Marta, Cristina | Brand, Stephanie | Stein, Karina | Heine, Holger | Kauth, Marion | Rolfsjord, Leif Bjarte | Bakkeheim, Egil | Skjerven, Håvard Ove | Carlsen, Kai-Håkon | Hunderi, Jon Olav | Berents, Teresa Løvold | Mowinckel, Petter | Lødrup Carlsen, Karin C. | Munzel, Ullrich | Berger, William | Valiente, Román | Vozmediano, Valvanera | Lukas, John C. | Rodríguez, Mónica | Guarnaccia, Sebastiano | Vitale, Luigi | Pluda, Ada | D’Agata, Emanuele | Colombo, Denise | Felici, Stefano | Gretter, Valeria | Facchetti, Susanna | Pecorelli, Gaia | Quecchia, Cristina | Guibas, George | Spandou, Evangelia | Megremis, Spyridon | West, Peter | Papadopoulos, Nikolaos | Rufo, João Cavaleiro | Madureira, Joana | Paciência, Inês | Aguiar, Lívia | Padrão, Patrícia | Pinto, Mariana | Delgado, Luís | Moreira, Pedro | Teixeira, João Paulo | Fernandes, Eduardo Oliveira | Moreira, André | Dominguez, Adriana Izquierdo | Valero, Antonio | Mullol, Joaquim | Del Cuvillo, Alfonso | Montoro, Javier | Jauregui, Ignacio | Bartra, Joan | Davila, Ignacio | Ferrer, Marta | Sastre, Joaquin | Martins, Catarina | Lima, Jorge | Leandro, Maria José | Nunes, Glória | Branco, Jorge Cunha | Trindade, Hélder | Borrego, Luis Miguel | Conkar, Secil | Kilic, Mehtap | Aygun, Canan | Sancak, Recep | Tagalaki, Eleni | Banos, Lambros | Vlachou, Anna | Giannoula, Fotini | Pavlakou, Marina | Kryoni, Maria | Makris, Kostas | Lazova, Snezhina | Petrova, Guergana | Miteva, Dimitrinka | Perenovska, Penka | Klyucharova, Aliya | Skorohodkina, Olesya | Koumaki, Dimitra | Manousaki, Alkisti | Agrapidi, Maria | Iatridou, Lida | Eruk, Omima | Myridakis, Konstantinos | Manousakis, Emmanouil | Koumaki, Vasiliki | Dimou, Maria | Ingemansson, Maria | Hedlin, Gunilla | Pastor, Nitida | de Boissieu, Delphine | Vanderhoof, Jon | Moore, Nancy | Maditz, Kaitlin | Mehdi, Adeli | Elhassan, Shaza | Beck, Carolin | Al-Hammadi, Ahmed | Maris, Ioana | O’Sullivan, Ronan | Hourihane, Jonathan | Raptis, George | DunnGalvin, Audrey | Greenhawt, Matthew | Venter, Carina | O’Regan, Evelyn | Cronin, Duncan | O’Reilly, Anna | Abdelaziz, Foued | Khelifi-Touhami, Dounia | Selim, Nihad | Khelifi-Touhami, Tahar | Merida, Pablo | Plaza, Ana Mª | Castellanos, Juan Heber | Lozano, Jaime | Dominguez, Olga | Piquer, Monica | Jimenez, Rosa | Giner, Mª Teresa | Kakleas, Konstantinos | Joishy, Manohar | Maskele, Wendmu | Jenkins, Huw R. | Escarrer, Mercedes | Madroñero, Agustín | Guerra, Maria Teresa | Julia, Juan Carlos | Cerda, Juan Carlos | Contreras, Javier | Tauler, Eulalia | Vidorreta, Maria Jesus | Rojo, Ana | Del Valle, Silvia | Flynn, Niamh | Foley, Gary | Harmon, Carol | Fitzsimons, John | Baynova, Krasimira | Del Robledo, Ávila Maria | Marina, Labella | Cortes, Aaron | Sciaraffia, Alicia | Castillo, Angela | Juel-Berg, Nanna | Hansen, Kirsten Skamstrup | Poulsen, Lars Kærgaard | Lazar, Adina | Aguiar, Rita | Lopes, Anabela | Paes, Maria J. | Santos, Amélia S. | Pereira-Barbosa, M. A. | Eke Gungor, Hatice | Uytun, Salih | Sahiner, Umit Murat | Altuner Torun, Yasemin | Zivanovic, Mirjana | Atanasković-Marković, Marina | Vesel, Tina | Nahtigal, Mihaela | Obermayer-Temlin, Andreja | Križnik, Eva Šoster | Maslar, Mirjana | Bizjak, Ruben | Tomšič-Matic, Marjeta | Posega-Devetak, Sonja | Skerbinjek-Kavalar, Maja | Predalič, Mateja | Avčin, Tadej | Pouessel, Guillaume | Beaudouin, Etienne | Moneret-Vautrin, Anne M. | Deschildre, Antoine | Viñas, Marta | Borja, Bartolomé | Hernández, Nora | Castillo, Mª José | Izquierdo, Adriana | Ibero, Marcel | Kocabas, Can Naci | Heming, Camille | Garrett, Emily | Blackstock, Adam | Chodhari, Rahul | Belohlavkova, Simona | Kopelentova, Eliska | Visek, Petr | Setinova, Ivana | Svarcova, Ivana | Sjölander, Sigrid | Nilsson, Nora | Berthold, Malin | Ekoff, Helena | Borres, Magnus | Nilsson, Caroline | González Domínguez, Loreto | Muñoz Archidona, Cristina | Moreira Jorge, Ana | Quevedo Teruel, Sergio | Bracamonte Bermejo, Teresa | Castillo Fernández, Miriam | Pineda de la Losa, Fernando | Echeverría Zudaire, Luis Ángel | Vrani, Olga | Mavroudi, Antigone | Fotoulaki, Maria | Emporiadou, Maria | Spiroglou, Kleomenis | Xinias, Ioannis | Sadreddini, Helyeh A. | Warnes, Mia | Traves, Donna | Kostić, Gordana | Filipovic, Đorđe | Sittisomwong, Sawapon | Sittisomwong, Siripong | Podolec, Zygmunt | Hartel, Marcin | Panek, Daria | Podolec-Rubiś, Magdalena | Banasik, Tomasz | Abbasi, Elham | Moghtaderi, Mozhgan | Sanneerappa, Phani | Deliu, Alina | Kutty, Moosa | Ramesh, Nagabathula | Sherkat, Roya | Sabri, Mohammad Reza | Dehghan, Bahar | Bigdelian, Hamid | Raeesi, Nahid | Afshar, Mino | Rahimi, Hamid | Klein, Christoph | Al-Jebouri, Mohemid | Svitich, Oxana A. | Zubacheva, Daria O. | Potemkin, Dmitrii A. | Gankovskaya, Ludmila V. | Zverev, Vitalii V. | OB Doyle, Elaine | Gallagher, Paul | Dewlett, Sherine | Man, Kin | Pocock, James | Gerrardhughes, Anna | Wasilewska, Jolanta | Kaczmarski, Maciej | Lebensztejn, Dariusz | Thuraisingham, Chandramani | Sinniah, Davendralingam | Chen, Yue | Mei, Xiaomei | Ozdogan, Sebnem | Karadeniz, Pinar | Ayyildiz-Emecen, Durdugul | Oncul, Ummuhan | Sari, Gizem | Cavdar, Sabanur | Farzan, Niloufar | Vijverberg, Susanne J. | Palmer, Colin J. | Tantisira, Kelan G. | Maitland-van der Zee, Anke-Hilse | Yavuzyilmaz, Fatma | Urganci, Nafiye | Usta, Merve | Hoxha, Mehmet | Basho, Maksim | Wandalsen, Gustavo F. | Monteiro, Fernanda | Lame, Blerta | Mesonjesi, Eris | Sherri, Arjeta | Ibranji, Alkerta | Gjati, Laert | Loloci, Gjustina | Bardhi, Ardii | Moghtaderi, Behnam | Farjadian, Shirin | Eghtedari, Dorna | Olaya, Manuela | Del Mar Vasquez, Laura | Ramirez, Luis Fernando | Serrano, Carlos Daniel | Usta Guc, Belgin | Asilsoy, Suna | Ozer, Fulya | Shopova, Sylvia | Papochieva, Vera | Loekmanwidjaja, Jessica | Mallozi, Márcia | Ratner, Paul | Soteres, Daniel | Novák, Zoltán | Yáñez, Anahí | Ildikó, Kiss | Kuna, Piotr | Tortajada, Miguel | Valiente, Román | Feuerhahn, Julia | Blome, Christine | Hadler, Meike | Karagiannis, Efstrathios | Langenbruch, Anna | Augustin, Matthias | Roux, Michel | Kakudo, Shinji | Zeldin, Robert K. | Sokolova, Anna | Silva, Tiago Milheiro | Zivanovic, Snezana S. | Cvetkovic, Vesna | Nikolic, Ivana | Zivanovic, Sonja J. | Saranac, Ljiljana | Nesterenko, Zoia | Radic, Snezana | Milenkovic, Branislava | Smiljanic, Spomenka | Micic-Stanijevic, Milka | Calovic, Olivera | Hofbauer, Anne Marie Bro | Agertoft, Lone | Everson, Lucy | Kearney, Jessica | Coppel, Jonny | Braithwaite, Simon | Christiansen, Elisabeth S. | Kjaer, Henrik Fomsgaard | Eller, Esben | Mørtz, Charlotte G. | Halken, Susanne | Román India, Cristina | Jiménez Jiménez, Juana | Echeverría Zudaire, Luis | O’Connor, Cathal | Kanti, Varvara | Lünnemann, Lena | Malise, Günther | Ludriksone, Laine | Stroux, Andrea | Henrich, Wolfgang | Abu-Dakn, Michael | Blume-Peytavi, Ulrike | Garcia Bartels, Natalie | Schario, Marianne | Stanley, Thorsten | Brandenbarg, Nicolien | Boardman, Alia | McGreevy, Gary | Rodger, Emily | Knight, Katherine | Taylor, Trisha | Scanlan, Gemma | Christoph, Grüber | van Stuivenberg, Margriet | Mosca, Fabio | Moro, Guido | Chirico, Gaetano | Braegger, Christian P. | Riedler, Joseph | Yavuz, Yalcin | Boehm, Günther | Arasi, Stefania | Crisafulli, Giuseppe | Caminiti, Lucia | Porcaro, Federica | Pajno, Giovanni Battista | Tanaka, Akane | Togawa, Yaei | Oida, Kumiko | Kambe, Naotomo | Arkwright, Peter | Amagai, Yosuke | Shimojo, Naoki | Sato, Yasunori | Mochizuki, Hiroyuki | Jang, Hyosun | Ishizaka, Saori | Matsuda, Hiroshi | Barlianto, Wisnu | Olivianto, Ery | Chandra Kusuma, H. M. S. | Mollica, Mariapia | Trinchese, Giovanna | Alfano, Elena | Amato, Francesco | Pirozzi, Claudio | Calignano, Antonio | Meli, Rosaria | Rossberg, Siri | Gerhold, Kerstin | Zimmermann, Kurt | Zaino, Mohammad | Geske, Thomas | Hamelmann, Eckard | Bogovic, Sarah | van den Berg, Jochem | Janssen, Chantal | Claver, Angela | Martin-Muñoz, Mª Flor | Martorell, C. | Belver, M. T. | Alonso Lebrero, E. | Zapatero, L. | Fuentes, V. | Piqué, M. | Plaza, A. | Muñoz, C. | Blasco, Cristina | Villa, B. | Gómez, C. | Nevot, S. | García, J. M. | Echeverria, L. | DeWitt, Brenda | Holloway, Judith | Hodge, Donald | Ludman, Sian | Jafari-Mamaghani, Merhdad | Ebling, Rosemary | Fox, Adam T. | Lack, Gideon | Lovén Björkman, Sofia | Ballardini, Natalia | Basu, Supriyo | Hallet, Jenny | Srinivas, Jyothi | Stringer, Hazel | Jay, Nicola | Fonseca, Paula | Vieira, Clara | Mastrorilli, Carla | Caffarelli, Carlo | Asero, Riccardo | Tripodi, Salvatore | Dondi, Arianna | Ricci, Gianpaolo | Povesi Dascola, Carlotta | Calamelli, Elisabetta | Cipriani, Francesca | Di Rienzo Businco, Andrea | Bianchi, Annamaria | Candelotti, Paolo | Frediani, Tullio | Verga, Carmen | Korovessi, Paraskevi | Tiliakou, Skevi | Tavoulari, Evaggelia | Moraiti, Kalliopi-Maria | Tee, Wan Jean | Deiratany, Samir | Seedhoo, Raymond | McNamara, Roisin | Okafor, Ike | Khaleva, Ekaterina | Novic, Gennady | Bychkova, Natalia | Abd Al-Aziz, Amany | Fatouh, Amany | Motawie, Ayat | Bostany, Eman El | Ibrahim, Amr | Andonova, Sylvia | Savov, Alexey | Zoto, Maria | Kyriakakou, Marialena | Vassilopoulou, Mariza | Balaska, Athina | Kostaridou, Stavroula | Wartna, Jorien | Bohnen, Arthur M. | Elshout, Gijs | Pols, David H. J. | Bindels, Patrick J. E. | Seys, Sven F. | Dilissen, Ellen | Van der Eycken, Sarah | Schelpe, An-Sofie | Marijsse, Gudrun | Troosters, Thierry | Vanbelle, Vincent | Aertgeerts, Sven | Ceuppens, Jan L. | Dupont, Lieven J. | Peers, Koen | Bullens, Dominique M. | Lokas, Sandra Bulat | Zivkovic, Jelena | Nogalo, Boro | Kobal, Iva Mrkic | Oliveira, Georgeta | Pike, Katharine | Melo, Alda | Amélia, Tomás | Cidrais Rodrigues, José Carlos | Serrano, Cristina | Lopes dos Santos, José Manuel | Lopes, Carla | Schauer, Uwe | Bergmann, Karl-Christian | Moral, Luis | Toral, Teresa | Marco, Nuria | Avilés, Beléns García | Fuentes, Mª Jesús | Garde, Jesús | Montahud, Cristina | Perona, Javier | Forniés, Mª José | Arroabarren, Esozia | Anda, Marta | Sanz, Maria Luisa | Lizaso, Maria Teresa | Arregui, Candida | May, Sara | Hartz, Martha | Joshi, Avni | Park, Miguel A. | Posega Devetak, Sonja | Koren Jeverica, Anja | Castro, Leonor | Gouveia, Carolina | Marques, Ana Carvalho | Cabral, Antonio Jorge | Amaral, Luis | Carolino, Fabrícia | Castro, Eunice | Passos, Madalena | Cernadas, Josefina R. | Amaral, Luís | Dias de Castro, Eunice | Pineda, Fernando | Gomes, Armanda | Brough, Helen | Röhmel, Jobst | Schwarz, Carsten | Mehl, Anne | Stock, Philippe | Staab, Doris | Seib, Christine | Critchlow, Anita | Barber, Alyson | Delavalle, Belen | Garriga, Teresa | Vilá, Blanca | Astolfi, Annalisa | Di Chiara, Costanza | Neri, Iria | Patrizi, Annalisa | Neskorodova, Katerina | Kudryavtseva, Asya | Alvarez, Jorge | Palacios, Miriam | Martinez-Merino, Marta | Vaquero, Ibone
Clinical and Translational Allergy  2016;6(Suppl 1):1-60.
Table of contents
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: Miscellaneous (PP48–PP58)
PP48 Surveillance study on safety of SLIT in pediatric population
Ivana Djuric-Filipovic, Zorica Zivkovic, Snežana Zivanovic, Gordana Kostić, Đorđe Filipovic
PP49 Efficacy and safety of mixed mite subcutaneous immunotherapy among allergic rhinitis patients in the Northeastern Thailand
Sawapon Sittisomwong, Siripong Sittisomwong
PP50 Effect of inhaled beclomethasone or placebo on brain stem activity in a patient chronically treated with steroids: preliminary report
Zygmunt Podolec, Marcin Hartel, Daria Panek, Magdalena Podolec-Rubiś, Tomasz Banasik
PP51 Sensitisation to aeroallergens in patients with allergic rhinitis, asthma and atopic dermatitis in Shiraz, Southwestern Iran
Elham Abbasi, Mozhgan Moghtaderi
PP52 Referring a child for allergy test: how appropriate are we?
Phani Sanneerappa, Alina Deliu, Moosa Kutty, Nagabathula Ramesh
PP53 EBV lymphoproliferative disease and cardiac lymphoma in a STK4 deficient patient
Roya Sherkat, Mohammad Reza Sabri, Bahar Dehghan, Hamid Bigdelian, Nahid Raeesi, Mino Afshar, Hamid Rahimi, Christoph Klein
PP54 A case study: the effect of massive honeybees attack on various body parameters atopic girl including allergy
Mohemid Al-Jebouri
PP55 The role of TLR9, NLRP3 and proIL-1β in activation of antiviral innate immunity
Oxana A. Svitich, Daria O. Zubacheva, Dmitrii A. Potemkin, Ludmila V. Gankovskaya, Vitalii V. Zverev
PP56 Overnight pulse oximetry, as a screening tool to diagnose obstructive sleep apnoea. How effective is it?
Phani Sanneerappa, Elaine OB Doyle, Paul Gallagher, Nagabathula Ramesh
PP57 The presentation and management of acute urticaria and allergic reactions in children in a multi-ethnic, inner city Emergency Department (ED)
Sherine Dewlett, Kin Man, Minal Gandhi, James Pocock, Anna Gerrardhughes
PP58 Food allergens responsible for delayed-type sensitisation in atopy patch test in children diagnosed with autism spectrum disorder
Jolanta Wasilewska, Maciej Kaczmarski, Dariusz Lebensztejn
POSTER VIEWING SESSION 4: Asthma—Rhinitis (PP59–PP87)
PP59 Systematic review of incense as a trigger factor for asthma
Chandramani Thuraisingham, Davendralingam Sinniah
PP60 Increased risks of mood and anxiety disorders in children with asthma
Yue Chen, Xiaomei Mei
PP61
PP62 Asthma Control Test (ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) association in children
Sebnem Ozdogan, Pinar Karadeniz, Durdugul Ayyildiz-Emecen, Ummuhan Oncul
PP63 Seasonal and gender variations in vitamin D levels in children with asthma and its association with pulmonary function tests
Sebnem Ozdogan, Gizem Sari, Sabanur Cavdar
PP64 Defining treatment response in childhood asthma: rationale and design of the Pharmacogenomics in the Childhood Asthma (PiCA) consortium
Niloufar Farzan, Susanne J. Vijverberg, Colin J. Palmer, Kelan G. Tantisira, Anke-Hilseon Maitland-van der Zee behalf of the PiCA consortium
PP65 Prevalence of asthma and allergic disease in patients with inflammatory disease compared to celiac disease
Fatma Yavuzyilmaz, Sebnem Ozdogan, Nafiye Urganci, Merve Usta
PP66 A severe case with cystic fibrosis (CF) asthma
Mehmet Hoxha, Maksim Basho
PP67 Severe asthma exacerbation complicated with pneumothorax in a child with uncontrolled asthma due to poor treatment compliance
Ioana Valentina Nenciu, Andreia Florina Nita, Adina Lazar, Alexandru Ulmeanu, Carmen Zapucioiu, Dumitru Oraseanu
PP68 Evaluation of the Pediatric Quality of Life inventory (PedsQL) asthma module among low income asthmatic children and adolescents in Sao Paolo, Brazil
Gustavo F. Wandalsen, Fernanda Monteiro, Dirceu Solé
PP69 Early initiation of specific immunotherapy in asthma patients leads to higher benefits
Blerta Lame, Eris Mesonjesi, Arjeta Sherri
PP70 Treatment resistant asthma and rhinosinusitis with recurrent pulmonary infections. Is it primary ciliary dyskinesia?
Alkerta Ibranji, Laert Gjati, Gjustina Loloci, Ardii Bardhi
PP71 The comparison of sensitisation to animal allergens in children- and adult- onset patients with asthma
Behnam Moghtaderi, Shirin Farjadian, Dorna Eghtedari
PP72 Characterisation of children less than five years with wheezing episodes in Cali, Colombia
Manuela Olaya, Laura Del Mar Vasquez, Luis Fernando Ramirez, Carlos Daniel Serrano
PP73 Evaluation of the patients with recurrent croup
Belgin Usta Guc, Suna Asilsoy, Fulya Ozer
PP74 Obesity in adolescence compromising the asthma control
Guergana Petrova, Sylvia Shopova, Vera Papochieva, Snezhina Lazova, Dimitrinka Miteva, Penka Perenovska
PP75 Sleep behavior in children with persistent allergic rhinitis
Gustavo F. Wandalsen, Jessica Loekmanwidjaja, Márcia Mallozi, Dirceu Solé
PP76 Randomised trial of the safety of MP29-02* compared with fluticasone propionate nasal spray in children aged ≥4 years to <12 years with allergic rhinitis
William Berger, Ulrich Wahn, Paul Ratner, Daniel Soteres
PP77 Safety and tolerability evaluation of bilastine 10 mg in children from 2 to 11 years of age with allergic rhinoconjunctivitis or urticaria
Zoltán Novák, Anahí Yáñez, Kiss Ildikó, Piotr Kuna, Miguel Tortajada, Román Valiente, the Bilastine Pediatric Safety Study Group
PP78 Sensitisation to Alternaria alternata: Is it a risk factor for severe rhinitis?
Susana Lopes, Filipa Almeida, Tânia Lopes, Cristina Madureira, José Oliveira, Fernanda Carvalho
PP79 Validation of the Patient Benefit Index (PBI) for the assessment of patient-related outcomes in allergic rhinitis in children
Julia Feuerhahn, Christine Blome, Meike Hadler, Efstrathios Karagiannis, Anna Langenbruch, Matthias Augustin
PP80 Efficacy of sublingual tablet of house dust mite allergen extracts in adolescents with house dust mite-associated allergic rhinitis
Michel Roux, Shinji Kakudo, Efstrathios Karagiannis, Robert K. Zeldin
PP81 Lung function improvement in a child treated with omalizumab for bronchial asthma
Anna Sokolova, Tiago Milheiro Silva
PP82 How to treat a child suffering from asthma, allergic rhinitis, allergy to peanuts and diabetes at the same time?
Snezana S. Zivanovic, Vesna Cvetkovic, Ivana Nikolic, Sonja J. Zivanovic
PP83 Nitric oxide in exhaled air in the relationship of the degree of sensitisation to aeroallergens
Snezana S. Zivanovic, Ljiljana Saranac, Ivana Nikolic, Sonja J. Zivanovic, Zorica Zivkovic
PP84 Clinical basis of diagnostic errors in pediatric asthma
Zoia Nesterenko
PP85
PP86 Childhood asthma control in Serbia and organised Asthma Educational Intervention (AEI)
Snezana Radic, Branislava Milenkovic, Spomenka Smiljanic, Milka Micic-Stanijevic, Olivera Calovic
PP87 Experience from a group of adolescents with severe allergic asthma treated with Omalizumab
Anne Marie Bro Hofbauer, Lone Agertoft
THEMATIC POSTER SESSION 1: Prevention and Treatment—Epidemiology (TP01–TP18)
TP01 A cost effective primary school asthma education program: pilot study from inner London schools
Lucy Everson, Jessica Kearney, Jonny Coppel, Simon Braithwaite, Rahul Chodhari
TP02 The prevalence of allergic diseases among 14–15 years old adolescents in two Danish birth cohorts 14 years apart
Elisabeth S. Christiansen, Henrik Fomsgaard Kjaer, Esben Eller, Charlotte G. Mørtz, Susanne Halken
TP03 Does pattern of sensitisation to phleum pratense change with age? Is it different in children with allergic rhinitis or asthma?
Cristina Román India, Ana Moreira Jorge, Loreto González Domínguez, Cristina Muñoz Archidona, Sergio Quevedo Teruel, Teresa Bracamonte Bermejo, Juana Jiménez Jiménez, Luis Echeverría Zudaire
TP04 Practicalities of prevention of peanut allergy: modelling a national response to LEAP
Cathal O’Connor, Jonathan Hourihane
TP05 Comparison of the influence of sunflower seed oil and skin care lotion on the skin barrier function of newborns: a randomised controlled trial
Varvara Kanti, Lena Lünnemann, Günther Malise, Laine Ludriksone, Andrea Stroux, Wolfgang Henrich, Michael Abu-Dakn, Ulrike Blume-Peytavi, Natalie Garcia Bartels
TP06 The effect of daily skin care on skin barrier properties in infants with dry skin and risk for atopic dermatitis
Varvara Kanti, Lena Lünnemann, Laine Ludriksone, Marianne Schario, Andrea Stroux, Ulrike Blume-Peytavi, Natalie Garcia Bartels
TP07 Change in sum total aeroallergen skin prick test wheal diameters at 6 months predicts which children will respond to subcutaneous immunotherapy by three years
Thorsten Stanley, Nicolien Brandenbarg
TP08 Are mobile apps regarding adrenaline auto-injectors accessed by adolescents for support and education in the community?
Alia Boardman, Gary McGreevy, Emily Rodger, Katherine Knight, Victoria Timms, Trisha Taylor, Gemma Scanlan, Roisin Fitzsimons
TP09
TP10 Prevention of early atopic dermatitis among low-atopy-risk infants by immunoactive prebiotics is not sustained after the first year of life
Grüber Christoph, Ulrich Wahn, Margriet van Stuivenberg, Fabio Mosca, Guido Moro, Gaetano Chirico, Christian P. Braegger, Joseph Riedler, Yalcin Yavuz, Günther Boehm
TP11
TP12
TP13 Treatment with Omalizumab in a 16-year-old Caucasian girl with refractory solar urticaria
Stefania Arasi, Giuseppe Crisafulli, Lucia Caminiti, Federica Porcaro, Giovanni Battista Pajno
TP14 Ultra-pure soft water ameliorates skin conditions of adult and child patients with atopic dermatitis
Akane Tanaka, Yaei Togawa, Kumiko Oida, Naotomo Kambe, Peter Arkwright, Yosuke Amagai, Naoki Shimojo, Yasunori Sato, Hiroyuki Mochizuki, Hyosun Jang, Saori Ishizaka, Hiroshi Matsuda
TP15 Potential adjuvant effect of immunomodulator to improve specific immunotherapy in asthmatic child
Wisnu Barlianto, Ery Olivianto, H. M. S. Chandra Kusuma
TP16 How can Component Resolved Diagnosis (CRD) influence in Specific Immunotherapy (SIT) prescription, in a Spanish children population
Ana Moreira Jorge, Cristina Román India, Loreto González Domínguez, Cristina Muñoz Archidona, Juana Jiménez Jiménez, Teresa Bracamonte Bermejo, Sergio Quevedo Teruel, Luis Echeverría Zudaire
TP17 Mitochondrial dysfunction in food allergy: effects of L. rhamnosus GG in a mice model of peanut allergy
Rosita Aitoro, Mariapia Mollica, Roberto Berni Canani, Giovanna Trinchese, Elena Alfano, Antonio Amoroso, Lorella Paparo, Francesco Amato, Claudio Pirozzi, Antonio Calignano, Rosaria Meli
TP18 Prediction of atopic diseases in childhood: elevated blood eosinophils in infancy in a high risk birth cohort
Siri Rossberg, Kerstin Gerhold, Kurt Zimmermann, Mohammad Zaino, Thomas Geske, Eckard Hamelmann, Susanne Lau
THEMATIC POSTER SESSION 2: Food allergy—Anaphylaxis (TP19–TP38)
TP19
TP20
TP21 Double-blind provocation tests in non-IgE mediated cow’s milk allergy and the occurrence of placebo reactions
Sarah Bogovic, Jochem van den Berg, Chantal Janssen
TP22 Gradual introduction of baked egg (BE) in egg allergic patients under 2 years old
Angela Claver
TP23 Randomised controlled trial of SOTI with raw hen’s egg in children with persistent egg allergy I: safety and efficacy of daily vs. weekly protocols of induction
Mª Flor Martin-Muñoz, C. Martorell, M. T. Belver, E. Alonso Lebrero, L. Zapatero, V. Fuentes, M. Piqué, A. Plaza, C. Muñoz, A. Martorell, Cristina Blasco, B. Villa, C. Gómez, S. Nevot, J. M. García, L. Echeverria
TP24 Randomised controlled trial of SOTI with raw hen’s egg in children with persistent egg allergy II: a randomised controlled trial to study a safer, more effective and easy to perform maintenance (daily vs. every two days) pattern of egg SOTI
Mª Flor Martin-Muñoz, C. Martorell, M. T. Belver, E. Alonso Lebrero, L. Zapatero, V. Fuentes, M. Piqué, A. Plaza, C. Muñoz, A. Martorell, Cristina Blasco, B. Villa, C. Gómez, S. Nevot, J. M. García, L. Echeverria
TP25 Determining the safety of baked egg home reintroduction for children with mild egg allergy
Brenda DeWitt, Judith Holloway, Donald Hodge
TP26 Demographics, investigations and patterns of sensitisation in children with oral allergy syndrome in a London Teaching Hospital
Sian Ludman, Merhdad Jafari-Mamaghani, Rosemary Ebling, Adam T. Fox, Gideon Lack, George Du Toit
TP27 Airborne peanut challenge in children: allergic reactions are rare
Sofia Lovén Björkman, Caroline Nilsson, Natalia Ballardini
TP28 The nutty question on Pediatric Wards: to be or “nut” to be?
Supriyo Basu, Jenny Hallet, Jyothi Srinivas
TP29
TP30
TP31 Allergy education in nursery schools
Hazel Stringer, Nicola Jay
TP32 Food allergy in the first year of life
Tânia Lopes, Cristina Madureira, Filipa Almeida, Susana Lopes, Paula Fonseca, Clara Vieira, Fernanda Carvalho
TP33 Prevalence and geographic distribution of oral allergy syndrome in Italian children: a multicenter study
Carla Mastrorilli, Carlo Caffarelli, Riccardo Asero, Salvatore Tripodi, Arianna Dondi, Gianpaolo Ricci, Carlotta Povesi Dascola, Elisabetta Calamelli, Francesca Cipriani, Andrea Di Rienzo Businco, Annamaria Bianchi, Paolo Candelotti, Tullio Frediani, Carmen Verga, Paolo Maria Matricardi
TP34 Are common standardised allergen extracts used in skin test enough in the diagnosis of nuts allergy?
Cristina Muñoz Archidona, Loreto González Domínguez, Ana Moreira Jorge, Sergio Quevedo Teruel, Teresa Bracamonte Bermejo, Miriam Castillo Fernández, Fernando Pineda de la Losa, Luis Ángel Echeverría Zudaire
TP35 Evaluation of IgE sensitisation in children with allergic proctocolitis and its relationship to atopic dermatitis
Despina Mermiri, Paraskevi Korovessi, Skevi Tiliakou, Evaggelia Tavoulari, Kalliopi-Maria Moraiti, Fotini Giannoula, Athina Papadopoulou
TP36 Food allergy in children: are we managing them appropriately in the Emergency Department?
Wan Jean Tee, Samir Deiratany, Raymond Seedhoo, Roisin McNamara, Ike Okafor
TP37 Importance of oil body associated allergenic proteins in nuts suspected allergy children
Loreto González Domínguez, Ana Moreira Jorge, Cristina Muñoz Archidona, Teresa Bracamonte Bermejo, Sergio Quevedo Teruel, Fernando Pineda de la Losa, Miriam Castillo Fernández, Luis Ángel Echeverría Zudaire
TP38 Practical application of basophil activation test in children with food allergy
Ekaterina Khaleva, Gennady Novic, Natalia Bychkova
THEMATIC POSTER SESSION 3: Asthma (TP39–TP57)
TP39 Effect of corticosteroid therapy upon serum magnesium level in chronic asthmatic children
Amany Abd Al-Aziz, Amany Fatouh, Ayat Motawie, Eman El Bostany, Amr Ibrahim
TP40 ADAM33 in Bulgarian children with asthma
Guergana Petrova, Dimitrinka Miteva, Snezhina Lazova, Penka Perenovska, Sylvia Andonova, Alexey Savov
TP41
TP42 The impact of vitamin D serum levels in asthma and allergic rhinitis
Maria Zoto, Marialena Kyriakakou, Paraskevi Xepapadaki, Nikolaos G. Papadopoulos
TP43 Life-threatening, first reported, paradoxical bronchospasm after nebulised Salbutamol in a 10 year old child
Paraskevi Korovessi, Mariza Vassilopoulou, Athina Balaska, Lambros Banos, Stavroula Kostaridou, Despina Mermiri
TP44
TP45 Asthma symptoms in children with treatment for allergic rhinoconjunctivitis
Jorien Wartna, Arthur M. Bohnen, Gijs Elshout, David H. J. Pols, Patrick J. E. Bindels
Erasmus MC, Rotterdam, The Netherlands
TP46 Atopy increased the risk of developing exercise-induced bronchoconstriction in young athletes
Sven F. Seys; Ellen Dilissen, Sarah Van der Eycken, An-Sofie Schelpe, Gudrun Marijsse, Thierry Troosters, Vincent Vanbelle, Sven Aertgeerts, Jan L. Ceuppens, Lieven J. Dupont, Koen Peers, Dominique M. Bullens
TP47 The effect of higher BMI on risk for asthma and treatment outcome in overweight and obese children
Ivana Banic, Sandra Bulat Lokas, Jelena Zivkovic, Boro Nogalo, Iva Mrkic Kobal, Davor Plavec, Mirjana Turkalj
TP48
TP49
TP50
TP51
TP52 The impact of a multidisciplinary project intended to change the culture of nebulisers towards pressurised metered dose inhalers
Georgeta Oliveira, Katharine Pike, Alda Melo, Tomás Amélia, José Carlos Cidrais Rodrigues, Cristina Serrano, José Manuel Lopes dos Santos, Carla Lopes
TP53
TP54
TP55
TP56 Increased asthma control in patients with severe persistent allergic asthma after 12 month of nightly temperature controlled laminar airflow (TLA)
Eckard Hamelmann, Uwe Schauer, Karl-Christian Bergmann
TP57
THEMATIC POSTER SESSION 4: Drug allergy—Dermatology (TP58–TP77)
TP58 Should we proceed directly to provocation challenges to diagnose drug allergy? Our experience says yes
Luis Moral, Teresa Toral, Nuria Marco, Beléns García Avilés, Mª Jesús Fuentes, Jesús Garde, Cristina Montahud, Javier Perona, Mª José Forniés
TP59 Anaphylaxis to 13-valent pneumococcal vaccine
Esozia Arroabarren, Marta Anda, Maria Luisa Sanz, Maria Teresa Lizaso, Candida Arregui
TP60 Intrapartum antibiotic exposure for treatment of group B streptococcus was not associated with the development of penicillin allergy in children
Sara May, Martha Hartz, Avni Joshi, Miguel A. Park
TP61 Evaluation of suspected drug hypersensitivity reactions in 169 children referred to the General Hospital
Sonja Posega Devetak, Tina Vesel, Anja Koren Jeverica, Tadej Avčin
TP62 Drug provocation testing: experience of a tertiary hospital
Leonor Castro, Carolina Gouveia, Ana Carvalho Marques, Antonio Jorge Cabral
TP63 Perioperative anaphylaxis: a growing concern in pediatric population
Luis Amaral, Fabrícia Carolino, Eunice Castro, Madalena Passos, Josefina R. Cernadas
TP64 Raising awareness of hypersensitivity to non-steroidal anti-inflammatory drugs in the pediatric age
Fabrícia Carolino, Luís Amaral, Eunice Dias de Castro, Josefina R. Cernadas
TP65 Perioperative anaphylaxis in young children: how to confirm the suspicion
Josefina R. Cernadas, Fabrícia Carolino, Luís Amaral, Fernando Pineda, Armanda Gomes
TP66 A case study of a child suspected to be penicillin allergic-digging deeper
Katherine Knight, Roisin Fitzsimons, Helen Brough
TP67 Prevalence, characteristics and risk factors of hypersensitivity reactions to antibiotics in patients with cystic fibrosis
Jobst Röhmel, Carsten Schwarz, Anne Mehl, Philippe Stock, Doris Staab
TP68 Antibiotic drug hypersensitivity in cystic fibrosis: A pilot study using cellular allergy tests for diagnostics
Jobst Röhmel, Carsten Schwarz, Christine Seib, Doris Staab, Philippe Stock
TP69 Oral antibiotics challenges in children
Anita Critchlow, Alyson Barber, Nicola Jay
TP70 Hypersensitivity reaction to vancomycin: a new successful desensitization protocol
Belen Delavalle, Teresa Garriga, Blanca Vilá, Cristina Blasco
TP71
TP72 Clinical phenotypes according to FLG gene loss of function mutations in children with atopic dermatitis
Francesca Cipriani, Annalisa Astolfi, Costanza Di Chiara, Elisabetta Calamelli, Iria Neri, Annalisa Patrizi, Gianpaolo Ricci
TP73
TP74 Urticaria in children: clinical and epidemiological features
Katerina Neskorodova, Asya Kudryavtseva
TP75
TP76 Acute urticaria at the Pediatrics Emergency Department: is it allergy?
Esozia Arroabarren, Jorge Alvarez, Marta Anda, Miriam Palacios, Marta Martinez-Merino, Ibone Vaquero
TP77
doi:10.1186/s13601-016-0117-8
PMCID: PMC5123301
2.  Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease 
BMC Pulmonary Medicine  2016;16:146.
Background
Reduced lung function in patients with chronic obstructive pulmonary disease (COPD) is likely due to both environmental and genetic factors. We report here a targeted high-throughput DNA sequencing approach to identify new and previously known genetic variants in a set of candidate genes for COPD.
Methods
Exons in 22 genes implicated in lung development as well as 61 genes and 10 genomic regions previously associated with COPD were sequenced using individual DNA samples from 68 cases with moderate or severe COPD and 66 controls matched for age, gender and smoking. Cases and controls were selected from the Obstructive Lung Disease in Northern Sweden (OLIN) studies.
Results
In total, 37 genetic variants showed association with COPD (p < 0.05, uncorrected). Several variants previously discovered to be associated with COPD from genetic genome-wide analysis studies were replicated using our sample. Two high-risk variants were followed-up for functional characterization in a large eQTL mapping study of 1,111 human lung specimens. The C allele of a synonymous variant, rs8040868, predicting a p.(S45=) in the gene for cholinergic receptor nicotinic alpha 3 (CHRNA3) was associated with COPD (p = 8.8 x 10−3). This association remained (p = 0.003 and OR = 1.4, 95 % CI 1.1-1.7) when analysing all available cases and controls in OLIN (n = 1,534). The rs8040868 variant is in linkage disequilibrium with rs16969968 previously associated with COPD and altered expression of the CHRNA5 gene. A follow-up analysis for detection of expression quantitative trait loci revealed that rs8040868-C was found to be significantly associated with a decreased expression of the nearby gene cholinergic receptor, nicotinic, alpha 5 (CHRNA5) in lung tissue.
Conclusion
Our data replicate previous result suggesting CHRNA5 as a candidate gene for COPD and rs8040868 as a risk variant for the development of COPD in the Swedish population.
Electronic supplementary material
The online version of this article (doi:10.1186/s12890-016-0309-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12890-016-0309-y
PMCID: PMC5106844  PMID: 27835950
COPD; Sequencing; eQTL; Association; Lung development; CHRNA5
3.  Individualized prediction of lung-function decline in chronic obstructive pulmonary disease 
Background:
The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV1) in current smokers with mild-to-moderate COPD.
Methods:
Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV1 values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations.
Results:
We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV1 2.75 L) to create the individualized prediction equations. There was significant between-individual variability in the rate of FEV1 decline, with the interval for the annual rate of decline that contained 95% of individuals being −124 to −15 mL/yr for smokers and −83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets.
Interpretation:
A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD.
Trial registration:
Lung Health Study — ClinicalTrials.gov, no. NCT00000568; Pan-Canadian Early Detection of Lung Cancer Study — ClinicalTrials.gov, no. NCT00751660
doi:10.1503/cmaj.151483
PMCID: PMC5047815  PMID: 27486205
4.  Protocadherin-1 Localization and Cell-Adhesion Function in Airway Epithelial Cells in Asthma 
PLoS ONE  2016;11(10):e0163967.
Background
The asthma gene PCDH1 encodes Protocadherin-1, a putative adhesion molecule of unknown function expressed in the airway epithelium. Here, we characterize the localization, differential expression, homotypic adhesion specificity and function of PCDH1 in airway epithelial cells in asthma.
Methods
We performed confocal fluorescence microscopy to determine subcellular localization of PCDH1 in 16HBE cells and primary bronchial epithelial cells (PBECs) grown at air-liquid interface. Next, to compare PCDH1 expression and localization in asthma and controls we performed qRT-PCR and fluorescence microscopy in PBECs and immunohistochemistry on airway wall biopsies. We examined homotypic adhesion specificity of HEK293T clones overexpressing fluorescently tagged-PCDH1 isoforms. Finally, to evaluate the role for PCDH1 in epithelial barrier formation and repair, we performed siRNA knockdown-studies and measured epithelial resistance.
Results
PCDH1 localized to the cell membrane at cell-cell contact sites, baso-lateral to adherens junctions, with increasing expression during epithelial differentiation. No differences in gene expression or localization of PCDH1 isoforms expressing the extracellular domain were observed in either PBECs or airway wall biopsies between asthma patients and controls. Overexpression of PCDH1 mediated homotypic interaction, whereas downregulation of PCDH1 reduced epithelial barrier formation, and impaired repair after wounding.
Conclusions
In conclusion, PCDH1 is localized to the cell membrane of bronchial epithelial cells baso-lateral to the adherens junction. Expression of PCDH1 is not reduced nor delocalized in asthma even though PCDH1 contributes to homotypic adhesion, epithelial barrier formation and repair.
doi:10.1371/journal.pone.0163967
PMCID: PMC5049773  PMID: 27701444
6.  Molecular mechanisms underlying variations in lung function: a systems genetics analysis 
The Lancet. Respiratory medicine  2015;3(10):782-795.
Summary
Background
Lung function measures reflect the physiological state of the lung, and are essential to the diagnosis of chronic obstructive pulmonary disease (COPD). The SpiroMeta-CHARGE consortium undertook the largest genome-wide association study (GWAS) so far (n=48 201) for forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC) in the general population. The lung expression quantitative trait loci (eQTLs) study mapped the genetic architecture of gene expression in lung tissue from 1111 individuals. We used a systems genetics approach to identify single nucleotide polymorphisms (SNPs) associated with lung function that act as eQTLs and change the level of expression of their target genes in lung tissue; termed eSNPs.
Methods
The SpiroMeta-CHARGE GWAS results were integrated with lung eQTLs to map eSNPs and the genes and pathways underlying the associations in lung tissue. For comparison, a similar analysis was done in peripheral blood. The lung mRNA expression levels of the eSNP-regulated genes were tested for associations with lung function measures in 727 individuals. Additional analyses identified the pleiotropic effects of eSNPs from the published GWAS catalogue, and mapped enrichment in regulatory regions from the ENCODE project. Finally, the Connectivity Map database was used to identify potential therapeutics in silico that could reverse the COPD lung tissue gene signature.
Findings
SNPs associated with lung function measures were more likely to be eQTLs and vice versa. The integration mapped the specific genes underlying the GWAS signals in lung tissue. The eSNP-regulated genes were enriched for developmental and inflammatory pathways; by comparison, SNPs associated with lung function that were eQTLs in blood, but not in lung, were only involved in inflammatory pathways. Lung function eSNPs were enriched for regulatory elements and were over-represented among genes showing differential expression during fetal lung development. An mRNA gene expression signature for COPD was identified in lung tissue and compared with the Connectivity Map. This in-silico drug repurposing approach suggested several compounds that reverse the COPD gene expression signature, including a nicotine receptor antagonist. These findings represent novel therapeutic pathways for COPD.
Interpretation
The system genetics approach identified lung tissue genes driving the variation in lung function and susceptibility to COPD. The identification of these genes and the pathways in which they are enriched is essential to understand the pathophysiology of airway obstruction and to identify novel therapeutic targets and biomarkers for COPD, including drugs that reverse the COPD gene signature in silico.
Funding
The research reported in this article was not specifically funded by any agency. See Acknowledgments for a full list of funders of the lung eQTL study and the Spiro-Meta CHARGE GWAS.
doi:10.1016/S2213-2600(15)00380-X
PMCID: PMC5021067  PMID: 26404118
7.  Atopy and Inhaled Corticosteroid Use Associate with Fewer IL-17+ Cells in Asthmatic Airways 
PLoS ONE  2016;11(8):e0161433.
Background
Interleukin (IL)-17 plays a critical role in numerous immune and inflammatory responses and was recently suggested to contribute to the pathogenesis of nonatopic (non-eosinophil/neutrophil-dominant) asthma. We aimed to compare expression of IL-17 in bronchial airways between atopic and nonatopic asthmatics, with/without inhaled corticosteroid (ICS) use and to identify its major cellular source.
Methods
Bronchial biopsies from 114 patients with mild-to-moderate asthma were investigated: 33 nonatopic, 63 non-corticosteroid users, 90 nonsmokers. IL-17 expression was correlated with atopy and inflammatory cell counts (EPX, NP57, CD3, CD4, CD8, CD20, CD68), taking ICS use and smoking into account. Multiple linear regression analyses were used to determine the independent factors as well as the most relevant inflammatory cells contributing to IL-17 expression. Double immunostainings were performed to confirm the major cellular source of IL-17.
Results
In non-ICS users, nonatopic asthmatics had more IL-17+ cells in the airway wall than atopic asthmatics. In both atopic and nonatopic asthmatics, ICS use was associated with lower numbers of IL-17+ cells, independent of smoking. The number of IL-17+ cells was associated with the number of neutrophils (B: 0.26, 95% CI: 0.17–0.35) and eosinophils (B: 0.18, 95% CI: 0.07–0.29). The majority of IL-17+ cells were neutrophils, as confirmed by double immunostaining.
Conclusions
We show for the first time that atopy and ICS use are associated with lower numbers of IL-17+ cells in asthmatic airways. Importantly, IL-17+ cells were mostly neutrophils which conflicts with the paradigm that lymphocytes (Th17) are the main source of IL-17.
doi:10.1371/journal.pone.0161433
PMCID: PMC4994949  PMID: 27552197
8.  Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease 
Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina (San Diego, CA) Human660W-Quad BeadChip on European Americans with COPD from the Lung Health Study. Linear regression models with correlated meta-analyses, including data from baseline (n = 2,814) and Year 5 (n = 2,657), were used to test for common genetic variants associated with airway responsiveness. Genotypic imputation was performed using reference 1000 Genomes Project data. Expression quantitative trait loci (eQTL) analyses in lung tissues were assessed for the top 10 markers identified, and immunohistochemistry assays assessed protein staining for SGCD and MYH15. Four genes were identified within the top 10 associations with airway responsiveness. Markers on chromosome 9p21.2 flanked by LINGO2 met a predetermined threshold of genome-wide significance (P < 9.57 × 10−8). Markers on chromosomes 3q13.1 (flanked by MYH15), 5q33 (SGCD), and 6q21 (PDSS2) yielded suggestive evidence of association (9.57 × 10−8 < P ≤ 4.6 × 10−6). Gene expression studies in lung tissue showed single nucleotide polymorphisms on chromosomes 5 and 3 to act as eQTL for SGCD (P = 2.57 × 10−9) and MYH15 (P = 1.62 × 10−6), respectively. Immunohistochemistry confirmed localization of SGCD protein to airway smooth muscle and vessels and MYH15 to airway epithelium, vascular endothelium, and inflammatory cells. We identified novel loci associated with airway responsiveness in a GWAS among smokers with COPD. Risk alleles on chromosomes 5 and 3 acted as eQTLs for SGCD and MYH15 messenger RNA, and these proteins were expressed in lung cells relevant to the development of airway responsiveness.
doi:10.1165/rcmb.2014-0198OC
PMCID: PMC4566043  PMID: 25514360
COPD; airway reactivity; bronchial responsiveness; eQTL; δ-sarcoglycan
10.  Meta-analysis of genome-wide association studies identifies 10 loci influencing allergic sensitization 
Nature genetics  2013;45(8):902-906.
Allergen-specific IgE (allergic sensitization) plays a central role in the pathogenesis of allergic disease. We performed the first large-scale genome wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up the top SNP from 26 loci in 6,114 affected individuals and 9,920 controls. We increased the number of susceptibility loci with genome-wide significant association to allergic sensitization from three to 10, including SNPs in or near TLR6, C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2 and HLA-B. All the top-SNPs were associated with allergic symptoms in an independent study. Risk variants at these 10 loci were estimated to account for at least 25% of allergic sensitization and allergic rhinitis. Understanding the molecular mechanisms underlying these associations may provide novel insight into the etiology of allergic disease.
doi:10.1038/ng.2694
PMCID: PMC4922420  PMID: 23817571
11.  ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults 
Background
The clinical response to inhaled corticosteroids (ICS) is associated with single nucleotide polymorphisms (SNPs) in various genes. This study aimed to relate variations in genes in the steroid pathway and asthma susceptibility genes to exacerbations in children and young adults treated with ICS.
Methods
We performed a meta-analysis of three cohort studies: PACMAN (n=357, age: 4-12 years, the Netherlands), BREATHE (n=820, age: 3-22 years, UK) and PAGES (n=391, age: 2-16 years, UK). Seventeen genes were selected based on a role in the glucocorticoid signaling pathway or a reported association with asthma. Two outcome parameters were used to reflect exacerbations: hospital visits and oral corticosteroid (OCS) use in the previous year. The most significant associations were tested in three independent validation cohorts; the CAMP (clinical trial, n=172, age:5-12 years, USA), GALA II (n=745, age:8-21, USA) and PASS cohorts (n=391, age:5-18, UK) to test the robustness of the findings. Finally, all results were meta-analyzed.
Results
Two SNPs in ST13 (rs138335 and rs138337), but not in the other genes, were associated at a nominal level with an increased risk of exacerbations in asthmatics using ICS in the three cohorts studied. In a meta-analysis of all six studies, ST13 rs138335 remained associated with an increased risk of asthma-related hospital visits and OCS use in the previous year,; OR=1.22 (p=0.013) and OR=1.22 (p=0.0017) respectively.
Conclusion and clinical relevance
A novel susceptibility gene, ST13, coding for a co-chaperone of the glucocorticoid receptor, is associated with exacerbations in asthmatic children and young adults despite their ICS use. Genetic variation in the glucocorticoid signaling pathway may contribute to the interindividual variability in clinical response to ICS treatment in children and young adults.
doi:10.1111/cea.12492
PMCID: PMC4461653  PMID: 25616159
Childhood asthma; corticosteroids; exacerbations; pharmacogenomics; ST13
12.  Multi-ethnic genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis 
Paternoster, Lavinia | Standl, Marie | Waage, Johannes | Baurecht, Hansjörg | Hotze, Melanie | Strachan, David P | Curtin, John A | Bønnelykke, Klaus | Tian, Chao | Takahashi, Atsushi | Esparza-Gordillo, Jorge | Alves, Alexessander Couto | Thyssen, Jacob P | den Dekker, Herman T | Ferreira, Manuel A | Altmaier, Elisabeth | Sleiman, Patrick MA | Xiao, Feng Li | Gonzalez, Juan R | Marenholz, Ingo | Kalb, Birgit | Yanes, Maria Pino | Xu, Cheng-Jian | Carstensen, Lisbeth | Groen-Blokhuis, Maria M | Venturini, Cristina | Pennell, Craig E | Barton, Sheila J | Levin, Albert M | Curjuric, Ivan | Bustamante, Mariona | Kreiner-Møller, Eskil | Lockett, Gabrielle A | Bacelis, Jonas | Bunyavanich, Supinda | Myers, Rachel A | Matanovic, Anja | Kumar, Ashish | Tung, Joyce Y | Hirota, Tomomitsu | Kubo, Michiaki | McArdle, Wendy L | Henderson, A J | Kemp, John P | Zheng, Jie | Smith, George Davey | Rüschendorf, Franz | Bauerfeind, Anja | Lee-Kirsch, Min Ae | Arnold, Andreas | Homuth, Georg | Schmidt, Carsten O | Mangold, Elisabeth | Cichon, Sven | Keil, Thomas | Rodríguez, Elke | Peters, Annette | Franke, Andre | Lieb, Wolfgang | Novak, Natalija | Fölster-Holst, Regina | Horikoshi, Momoko | Pekkanen, Juha | Sebert, Sylvain | Husemoen, Lise L | Grarup, Niels | de Jongste, Johan C | Rivadeneira, Fernando | Hofman, Albert | Jaddoe, Vincent WV | Pasmans, Suzanne GMA | Elbert, Niels J | Uitterlinden, André G | Marks, Guy B | Thompson, Philip J | Matheson, Melanie C | Robertson, Colin F | Ried, Janina S | Li, Jin | Zuo, Xian Bo | Zheng, Xiao Dong | Yin, Xian Yong | Sun, Liang Dan | McAleer, Maeve A | O'Regan, Grainne M | Fahy, Caoimhe MR | Campbell, Linda E | Macek, Milan | Kurek, Michael | Hu, Donglei | Eng, Celeste | Postma, Dirkje S | Feenstra, Bjarke | Geller, Frank | Hottenga, Jouke Jan | Middeldorp, Christel M | Hysi, Pirro | Bataille, Veronique | Spector, Tim | Tiesler, Carla MT | Thiering, Elisabeth | Pahukasahasram, Badri | Yang, James J | Imboden, Medea | Huntsman, Scott | Vilor-Tejedor, Natàlia | Relton, Caroline L | Myhre, Ronny | Nystad, Wenche | Custovic, Adnan | Weiss, Scott T | Meyers, Deborah A | Söderhäll, Cilla | Melén, Erik | Ober, Carole | Raby, Benjamin A | Simpson, Angela | Jacobsson, Bo | Holloway, John W | Bisgaard, Hans | Sunyer, Jordi | Hensch, Nicole M Probst | Williams, L Keoki | Godfrey, Keith M | Wang, Carol A | Boomsma, Dorret I | Melbye, Mads | Koppelman, Gerard H | Jarvis, Deborah | McLean, WH Irwin | Irvine, Alan D | Zhang, Xue Jun | Hakonarson, Hakon | Gieger, Christian | Burchard, Esteban G | Martin, Nicholas G | Duijts, Liesbeth | Linneberg, Allan | Jarvelin, Marjo-Riitta | Noethen, Markus M | Lau, Susanne | Hübner, Norbert | Lee, Young-Ae | Tamari, Mayumi | Hinds, David A | Glass, Daniel | Brown, Sara J | Heinrich, Joachim | Evans, David M | Weidinger, Stephan
Nature genetics  2015;47(12):1449-1456.
Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified 10 novel risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with novel secondary signals at 4 of these). Notably, the new loci include candidate genes with roles in regulation of innate host defenses and T-cell function, underscoring the important contribution of (auto-)immune mechanisms to atopic dermatitis pathogenesis.
doi:10.1038/ng.3424
PMCID: PMC4753676  PMID: 26482879
13.  Effectiveness of initiating extrafine-particle versus fine-particle inhaled corticosteroids as asthma therapy in the Netherlands 
Background
Most randomised clinical trials typically exclude a significant proportion of asthma patients, including those at higher risk of adverse events, with comorbidities, obesity, poor inhaler technique and adherence, or smokers. However, these patients might differentially benefit from extrafine-particle inhaled corticosteroids (ICS). This matched cohort, database study, compared the effectiveness of extrafine-particle with fine-particle ICS in a real-life population initiating ICS therapy in the Netherlands.
Methods
Data were from the Pharmo Database Network, comprising pharmacy and hospital discharge records, representative of 20 % of the Dutch population. The study population included patients aged 12 − 60, with a General Practice-recorded diagnosis for asthma (International Classification of Primary Care code R96), when available, ≥2 prescriptions for asthma therapy at any time in their recorded history, and receiving first prescription of ICS therapy as either extrafine-particle (ciclesonide or hydrofluoroalkane beclomethasone dipropionate [BDP]) or fine-particle ICS (fluticasone propionate or non-extrafine-particle-BDP). Patients were matched (1:1) on relevant demographic and clinical characteristics over 1-year baseline. Primary outcomes were severe exacerbation rates, risk domain asthma control and overall asthma control during the year following first ICS prescription. Secondary outcomes, treatment stability and being prescribed higher versus lower category of short-acting β2 agonists (SABA) dose, were compared over a 1-year outcome period using conditional logistic regression models.
Results
Following matching, 1399 patients were selected in each treatment cohort (median age: 43 years; males: 34 %). Median (interquartile range) initial ICS doses (fluticasone-equivalents in μg) were 160 (160 − 320) for extrafine-particle versus 500 (250 − 500) for fine-particle ICS (p < 0.001). Following adjustment for residual confounders, matched patients prescribed extrafine-particle ICS had significantly lower rates of exacerbations (adjusted rate ratio [95 % CI], 0.59 [0.47–0.73]), and significantly higher odds of achieving asthma control and treatment stability in the year following initiation than those prescribed fine-particle ICS, and this occurred at lower prescribed doses. Patients prescribed extrafine-particle ICS had lower odds of being prescribed higher doses of SABA (0.50 [0.44–0.57]).
Conclusion
In this historical, matched study, extrafine-particle ICS was associated with better odds of asthma control than fine-particle ICS in patients prescribed their first ICS therapy in the Netherlands. Of importance, this was reached at significantly lower prescribed dose.
Electronic supplementary material
The online version of this article (doi:10.1186/s12890-016-0234-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12890-016-0234-0
PMCID: PMC4869182  PMID: 27184175
Asthma; Effectiveness; Extrafine-particle; Fine-particle; Inhaled corticosteroids
14.  Urokinase plasminogen activator receptor polymorphisms and airway remodelling in asthma 
The European Respiratory Journal  2016;47(5):1568-1571.
In the past decade, several asthma genes have been identified [1]; however, the key challenge is to determine how these genetic changes contribute to the underlying lung biology. We identified the urokinase plasminogen activator receptor (PLAUR) as an asthma susceptibility gene by positional cloning [2]. We showed that the same single nucleotide polymorphisms (SNPs) were associated with soluble PLAUR levels in blood, airway hyperresponsiveness (AHR) and accelerated lung function decline in asthma; a clinical feature linked to airway wall remodelling [2]. Therefore, we hypothesised that PLAUR may contribute to structural changes in asthma via increased levels of the membrane bound or soluble receptor. We subsequently showed that PLAUR levels were elevated in the airway epithelium of asthma patients and that PLAUR has a role in epithelial repair responses [3]. The aim of the current study was to 1) test for association between PLAUR SNPs and markers of airway remodelling using bronchial biopsies from asthma patients; and 2) test for association between SNPs and staining for PLAUR in airway tissue.
PLAUR polymorphisms and levels are associated with markers of airway remodelling in lung biopsies of asthma patients http://ow.ly/X5Srl
doi:10.1183/13993003.01571-2015
PMCID: PMC4851936  PMID: 26869673
15.  Advanced glycation endproducts and their receptor in different body compartments in COPD 
Respiratory Research  2016;17:46.
Background
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by chronic airway inflammation and emphysema, and is caused by exposure to noxious particles or gases, e.g. cigarette smoke. Smoking and oxidative stress lead to accelerated formation and accumulation of advanced glycation end products (AGEs), causing local tissue damage either directly or by binding the receptor for AGEs (RAGE). This study assessed the association of AGEs or RAGE in plasma, sputum, bronchial biopsies and skin with COPD and lung function, and their variance between these body compartments.
Methods
Healthy smoking and never-smoking controls (n = 191) and COPD patients (n = 97, GOLD stage I-IV) were included. Autofluorescence (SAF) was measured in the skin, AGEs (pentosidine, CML and CEL) and sRAGE in blood and sputum by ELISA, and in bronchial biopsies by immunohistochemistry. eQTL analysis was performed in bronchial biopsies.
Results
COPD patients showed higher SAF values and lower plasma sRAGE levels compared to controls and these values associated with decreased lung function (p <0.001; adjusting for relevant covariates). Lower plasma sRAGE levels significantly and independently predicted higher SAF values (p < 0.001). One SNP (rs2071278) was identified within a region of 50 kB flanking the AGER gene, which was associated with the gene and protein expression levels of AGER and another SNP (rs2071278) which was associated with the accumulation of AGEs in the skin.
Conclusion
In COPD, AGEs accumulate differentially in body compartments, i.e. they accumulate in the skin, but not in plasma, sputum and bronchial biopsies. The association between lower sRAGE and higher SAF levels supports the hypothesis that the protective mechanism of sRAGE as a decoy-receptor is impaired in COPD.
Electronic supplementary material
The online version of this article (doi:10.1186/s12931-016-0363-2) contains supplementary material, which is available to authorized users.
doi:10.1186/s12931-016-0363-2
PMCID: PMC4847335  PMID: 27117828
COPD; RAGE; Advanged glycation end-products; sRAGE
17.  Asthma–COPD Overlap. Clinical Relevance of Genomic Signatures of Type 2 Inflammation in Chronic Obstructive Pulmonary Disease 
Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids.
Objectives: To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features.
Methods: We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89).
Measurements and Main Results: The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD.
Conclusions: These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and “asthma-like” features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma.
doi:10.1164/rccm.201408-1458OC
PMCID: PMC4407484  PMID: 25611785
chronic obstructive pulmonary disease; gene expression profiling; biological markers
18.  Early response to inhaled bronchodilators and corticosteroids as a predictor of 12-month treatment responder status and COPD exacerbations 
Background
Early treatment response markers, for example, improvement in forced expiratory volume in 1 second (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score, may help clinicians to better manage patients with chronic obstructive pulmonary disease (COPD). We investigated the prevalence of clinically important improvements in FEV1 and SGRQ scores after 2-month budesonide/formoterol or formoterol treatment and whether such improvements predict subsequent improvements and exacerbation rates.
Methods
This post hoc analysis is based on data from three double-blind, randomized studies in patients with moderate-to-very-severe COPD receiving twice-daily budesonide/formoterol or formoterol alone for 6 or 12 months. Prebronchodilator FEV1 and SGRQ total score were measured before treatment and at 2 and 12 months; COPD exacerbation rates were measured during months 2–12. Responders were defined by ≥100 mL improvement in prebronchodilator FEV1 and ≥4-point decrease in SGRQ total score.
Results
Overall, 2,331 and 1,799 patients were included in the 0–2- and 0–12-month responder analyses, respectively, and 2,360 patients in the 2–12-month exacerbation rate analysis. At 2 months, 35.1% of patients were FEV1 responders and 44.3% were SGRQ responders. The probability of response was significantly greater with budesonide/formoterol than with formoterol or placebo for both parameters. Two-month responders had a greater chance of 12-month response than 2-month nonresponders for both FEV1 (odds ratio, 5.57; 95% confidence interval, 4.14–7.50) and SGRQ (odds ratio, 3.87; 95% confidence interval, 2.83–5.31). Two-month response in FEV1 (P<0.001), but not SGRQ (P=0.11), was associated with greater reductions in exacerbation risk.
Conclusion
Early FEV1 and SGRQ treatment responses relate to their changes at 12 months. FEV1 response, but not SGRQ response, at 2 months predicts the risk of a future COPD exacerbation in some, but not all patients. This is potentially useful in clinical practice, although more sensitive and specific markers of favorable treatment response are required.
doi:10.2147/COPD.S93303
PMCID: PMC4772946  PMID: 26952309
anti-inflammatories; bronchodilator effect; chronic obstructive pulmonary disease; predictors; risk assessment; risk factors
19.  Ambient air pollution, lung function and airway responsiveness in children with asthma 
Background
Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthma are lacking.
Objective
To investigate pollution effects in a longitudinal asthma study and effect modification by controller medications.
Methods
We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide (NO2) and sulfur dioxide (SO2) levels in 1,003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to zip/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and FVC %predicted, FEV1/FVC and PC20, adjusting for seasonality and confounders.
Results
Same-day and 1-week average CO levels were negatively associated with post-bronchodilator %predicted FEV1 (change(95%CI) per IQR: −0.33(−0.49, −0.16), −0.41(−0.62, −0.21), respectively) and FVC (−0.19(−0.25, −0.07), −0.25(−0.43, −0.07)). Longer-term four-month averages of CO were negatively associated with prebronchodilator %predicted FEV1 and FVC (−0.36(−0.62, −0.10), −0.21(−0.42, −0.01)). Four-month averaged CO and ozone levels were negatively associated with FEV1/FVC (p<0.05). Increased four-month average NO2 levels were associated with reduced post-bronchodilator FEV1 and FVC %predicted. Long-term exposures to SO2 were associated with reduced PC20 (%change(95%CI) per IQR:-6(-11,-1.5)). Treatment augmented the negative short-term CO effect on PC20.
Conclusions
Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications may not protect but worsens the CO effects on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.
doi:10.1016/j.jaci.2015.05.028
PMCID: PMC4742428  PMID: 26187234
asthma; ambient air pollution; airway hyperresponsiveness; inhaled corticosteroids; lung function
20.  Association of Forced Vital Capacity with the Developmental Gene NCOR2 
PLoS ONE  2016;11(2):e0147388.
Background
Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes.
Methods
Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 children (ALSPAC). Associations were considered replicated if the replication p-value survived Bonferroni correction (p<0.002; 0.05/25), with a nominal p-value considered as suggestive evidence. For SNPs with evidence of replication, effects on the expression levels of nearby genes in lung tissue were tested in 1,111 lung samples (Lung eQTL consortium), with further functional investigation performed using public epigenomic profiling data (ENCODE).
Results
NCOR2-rs12708369 showed strong replication in children (p = 0.0002), with replication unavailable in adults due to low imputation quality. This intronic variant is in a strong transcriptional enhancer element in lung fibroblasts, but its eQTL effects could not be tested due to low imputation quality in the eQTL dataset. SERPINE2-rs6754561 replicated at nominal level in both adults (p = 0.036) and children (p = 0.045), while WNT16-rs2707469 replicated at nominal level only in adults (p = 0.026). The eQTL analyses showed association of WNT16-rs2707469 with expression levels of the nearby gene CPED1. We found no statistically significant eQTL effects for SERPINE2-rs6754561.
Conclusions
We have identified a new gene, NCOR2, in the retinoic acid signalling pathway pointing to a role of vitamin A metabolism in the regulation of FVC. Our findings also support SERPINE2, a COPD gene with weak previous evidence of association with FVC, and suggest WNT16 as a further promising candidate.
doi:10.1371/journal.pone.0147388
PMCID: PMC4737618  PMID: 26836265
21.  Elemental Constituents of Particulate Matter and Newborn’s Size in Eight European Cohorts 
Environmental Health Perspectives  2015;124(1):141-150.
Background
The health effects of suspended particulate matter (PM) may depend on its chemical composition. Associations between maternal exposure to chemical constituents of PM and newborn’s size have been little examined.
Objective
We aimed to investigate the associations of exposure to elemental constituents of PM with term low birth weight (LBW; weight < 2,500 g among births after 37 weeks of gestation), mean birth weight, and head circumference, relying on standardized fine-scale exposure assessment and with extensive control for potential confounders.
Methods
We pooled data from eight European cohorts comprising 34,923 singleton births in 1994–2008. Annual average concentrations of elemental constituents of PM ≤ 2.5 and ≤ 10 μm (PM2.5 and PM10) at maternal home addresses during pregnancy were estimated using land-use regression models. Adjusted associations between each birth measurement and concentrations of eight elements (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) were calculated using random-effects regression on pooled data.
Results
A 200-ng/m3 increase in sulfur in PM2.5 was associated with an increased risk of LBW (adjusted odds ratio = 1.36; 95% confidence interval: 1.17, 1.58). Increased nickel and zinc in PM2.5 concentrations were also associated with an increased risk of LBW. Head circumference was reduced at higher exposure to all elements except potassium. All associations with sulfur were most robust to adjustment for PM2.5 mass concentration. All results were similar for PM10.
Conclusion
Sulfur, reflecting secondary combustion particles in this study, may adversely affect LBW and head circumference, independently of particle mass.
Citation
Pedersen M, Gehring U, Beelen R, Wang M, Giorgis-Allemand L, Andersen AM, Basagaña X, Bernard C, Cirach M, Forastiere F, de Hoogh K, Gražulevičienė R, Gruzieva O, Hoek G, Jedynska A, Klümper C, Kooter IM, Krämer U, Kukkonen J, Porta D, Postma DS, Raaschou-Nielsen O, van Rossem L, Sunyer J, Sørensen M, Tsai MY, Vrijkotte TG, Wilhelm M, Nieuwenhuijsen MJ, Pershagen G, Brunekreef B, Kogevinas M, Slama R. 2016. Elemental constituents of particulate matter and newborn’s size in eight European cohorts. Environ Health Perspect 124:141–150; http://dx.doi.org/10.1289/ehp.1409546
doi:10.1289/ehp.1409546
PMCID: PMC4710606  PMID: 26046983
22.  Dissecting genetics for chronic mucus hypersecretion in smokers with and without COPD 
Background
Smoking is a notorious risk factor for chronic mucus hypersecretion (CMH). CMH frequently occurs in Chronic Obstructive Pulmonary Disease (COPD). The question arises whether the same single nucleotide polymorphisms (SNPs) are related to CMH in smokers with and without COPD.
Methods
We performed two genome wide association studies on CMH under an additive genetic model in male heavy smokers (≥20 pack-years) with COPD (n=849, 39.9% CMH) and without COPD (n=1,348, 25.4% CMH), followed by replication and meta-analysis in comparable populations, and assessment of the functional relevance of significantly associated SNPs.
Results
GWA analysis on CMH in COPD and non-COPD yielded no genome wide significance after replication. In COPD, our top SNP (rs10461985, p=5.43×10−5) was located in the GDNF-antisense gene that is functionally associated with the GDNF gene. Expression of GDNF in bronchial biopsies of COPD patients was significantly associated with CMH (p=0.007). In non-COPD, 4 SNPs had a p-value <10−5 in the meta-analysis, including a SNP (rs4863687) in the MAML3 gene, the T-allele showing modest association with CMH (p=7.57×10−6, OR=1.48) and with significantly increased MAML3 expression in lung tissue (p=2.59×10−12).
Conclusions
Our data suggest the potential for differential genetic backgrounds of CMH in individuals with and without COPD.
doi:10.1183/09031936.00093314
PMCID: PMC4498483  PMID: 25234806
23.  Prediction of Long-Term Benefits of Inhaled Steroids by Phenotypic Markers in Moderate-to-Severe COPD: A Randomized Controlled Trial 
PLoS ONE  2015;10(12):e0143793.
Background
The decline in lung function can be reduced by long-term inhaled corticosteroid (ICS) treatment in subsets of patients with chronic obstructive pulmonary disease (COPD). We aimed to identify which clinical, physiological and non-invasive inflammatory characteristics predict the benefits of ICS on lung function decline in COPD.
Methods
Analysis was performed in 50 steroid-naive compliant patients with moderate to severe COPD (postbronchodilator forced expiratory volume in one second (FEV1), 30–80% of predicted, compatible with GOLD stages II-III), age 45–75 years, >10 packyears smoking and without asthma. Patients were treated with fluticasone propionate (500 μg bid) or placebo for 2.5 years. Postbronchodilator FEV1, dyspnea and health status were measured every 3 months; lung volumes, airway hyperresponsiveness (PC20), and induced sputum at 0, 6 and 30 months. A linear mixed effect model was used for analysis of this hypothesis generating study.
Results
Significant predictors of attenuated FEV1-decline by fluticasone treatment compared to placebo were: fewer packyears smoking, preserved diffusion capacity, limited hyperinflation and lower inflammatory cell counts in induced sputum (p<0.04).
Conclusions
Long-term benefits of ICS on lung function decline in patients with moderate-to-severe COPD are most pronounced in patients with fewer packyears, and less severe emphysema and inflammation. These data generate novel hypotheses on phenotype-driven therapy in COPD.
Trial Registration
ClinicalTrials.gov NCT00158847
doi:10.1371/journal.pone.0143793
PMCID: PMC4699453  PMID: 26659582
24.  Meta-analysis identifies seven susceptibility loci involved in the atopic march 
Marenholz, Ingo | Esparza-Gordillo, Jorge | Rüschendorf, Franz | Bauerfeind, Anja | Strachan, David P. | Spycher, Ben D. | Baurecht, Hansjörg | Margaritte-Jeannin, Patricia | Sääf, Annika | Kerkhof, Marjan | Ege, Markus | Baltic, Svetlana | Matheson, Melanie C. | Li, Jin | Michel, Sven | Ang, Wei Q. | McArdle, Wendy | Arnold, Andreas | Homuth, Georg | Demenais, Florence | Bouzigon, Emmanuelle | Söderhäll, Cilla | Pershagen, Göran | de Jongste, Johan C. | Postma, Dirkje S. | Braun-Fahrländer, Charlotte | Horak, Elisabeth | Ogorodova, Ludmila M. | Puzyrev, Valery P. | Bragina, Elena Yu | Hudson, Thomas J. | Morin, Charles | Duffy, David L. | Marks, Guy B. | Robertson, Colin F. | Montgomery, Grant W. | Musk, Bill | Thompson, Philip J. | Martin, Nicholas G. | James, Alan | Sleiman, Patrick | Toskala, Elina | Rodriguez, Elke | Fölster-Holst, Regina | Franke, Andre | Lieb, Wolfgang | Gieger, Christian | Heinzmann, Andrea | Rietschel, Ernst | Keil, Thomas | Cichon, Sven | Nöthen, Markus M. | Pennell, Craig E. | Sly, Peter D. | Schmidt, Carsten O. | Matanovic, Anja | Schneider, Valentin | Heinig, Matthias | Hübner, Norbert | Holt, Patrick G. | Lau, Susanne | Kabesch, Michael | Weidinger, Stefan | Hakonarson, Hakon | Ferreira, Manuel A. R. | Laprise, Catherine | Freidin, Maxim B. | Genuneit, Jon | Koppelman, Gerard H. | Melén, Erik | Dizier, Marie- Hélène | Henderson, A John | Lee, Young Ae
Nature Communications  2015;6:8804.
Eczema often precedes the development of asthma in a disease course called the ‘atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10−8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10−9). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.
The development of asthma following eczema is known as the atopic march. Here the authors conduct a GWAS on affected children and identify two novel loci associated with the disease phenotype.
doi:10.1038/ncomms9804
PMCID: PMC4667629  PMID: 26542096
25.  Susceptibility loci for lung cancer are associated with mRNA levels of nearby genes in the lung 
Carcinogenesis  2014;35(12):2653-2659.
Summary
This study extends the functional meaning of lung cancer susceptibility loci to gene expression in the lung and suggests that the risk alleles on 15q25 and 6p21 mediate their effect by regulating the expression levels of CHRNA5 and APOM, respectively.
Recent studies identified three genetic loci reproducibly associated with lung cancer in populations of European ancestry, namely 15q25, 5p15 and 6p21. The goals of this study are first to confirm whether these loci are associated with lung cancer in a French Canadian population and second to identify disease-associated single nucleotide polymorphisms (SNPs) influencing messenger RNA (mRNA) expression levels of genes in the lung, that is expression quantitative trait loci (eQTLs). SNPs were genotyped in 420 patients undergoing lung cancer surgery and compared with 3151 controls of European ancestry. Genome-wide gene expression levels in non-tumor lung tissues of the same 420 patients were also measured to identify eQTLs. Significant eQTLs were then followed-up in two replication sets (n = 339 and 363). SNPs found in the three susceptibility loci were associated with lung cancer in the French Canadian population. Strong eQTLs were found on chromosome 15q25 with the expression levels of CHRNA5 (P = 2.23 × 10− 22 with rs12907966). The CHRNA5-rs12907966 eQTL was convincingly validated in the two replication sets (P = 3.46 × 10− 16 and 2.01 × 10− 15). On 6p21, a trend was observed for rs3131379 to be associated with the expression of APOM (P = 3.58 × 10− 4) and validated in the replication sets (P = 1.11 × 10− 8 and 6.84 × 10− 4). On 5p15, no significant eQTLs were found. This study confirmed that chromosomes 15q25, 5p15 and 6p21 harbored susceptibility loci for lung cancer in French Canadians. Most importantly, this study suggests that the risk alleles at 15q25 and 6p21 may mediate their effect by regulating the mRNA expression levels of CHRNA5 and APOM in the lung.
doi:10.1093/carcin/bgu184
PMCID: PMC4247514  PMID: 25187487

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