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1. Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude

Author

Latha Kadalayil, Md. Zahangir Alam, Cory Haley White, Akram Ghantous, Esther Walton, Olena Gruzieva, Simon Kebede Merid, Ashish Kumar, Ritu P. Roy, Olivia Solomon, Karen Huen, Brenda Eskenazi, Peter Rzehak, Veit Grote, Jean-Paul Langhendries, Elvira Verduci, Natalia Ferre, Darek Gruszfeld, Lu Gao, Weihua Guan, Xuehuo Zeng, Enrique F. Schisterman, John F. Dou, Kelly M. Bakulski, Jason I. Feinberg, Munawar Hussain Soomro, Giancarlo Pesce, Nour Baiz, Elena Isaevska, Michelle Plusquin, Marina Vafeiadi, Theano Roumeliotaki, Sabine A. S. Langie, Arnout Standaert, Catherine Allard, Patrice Perron, Luigi Bouchard, Evelien R. van Meel, Janine F. Felix, Vincent W. V. Jaddoe, Paul D. Yousefi, Cecilia H. Ramlau-Hansen, Caroline L. Relton, Elmar W. Tobi, Anne P. Starling, Ivana V. Yang, Maria Llambrich, Gillian Santorelli, Johanna Lepeule, Lucas A. Salas, Mariona Bustamante, Susan L. Ewart, Hongmei Zhang, Wilfried Karmaus, Stefan Röder, Ana Claudia Zenclussen, Jianping Jin, Wenche Nystad, Christian M. Page, Maria Magnus, Dereje D. Jima, Cathrine Hoyo, Rachel L. Maguire, Tuomas Kvist, Darina Czamara, Katri Räikkönen, Tong Gong, Vilhelmina Ullemar, Sheryl L. Rifas-Shiman, Emily Oken, Catarina Almqvist, Robert Karlsson, Jari Lahti, Susan K. Murphy, Siri E. Håberg, Stephanie London, Gunda Herberth, Hasan Arshad, Jordi Sunyer, Regina Grazuleviciene, Dana Dabelea, Régine P. M. Steegers-Theunissen, Ellen A. Nohr, Thorkild I. A. Sørensen, Liesbeth Duijts, Marie-France Hivert, Vera Nelen, Maja Popovic, Manolis Kogevinas, Tim S. Nawrot, Zdenko Herceg, Isabella Annesi-Maesano, M. Daniele Fallin, Edwina Yeung, Carrie V. Breton, Berthold Koletzko, Nina Holland, Joseph L. Wiemels, Erik Melén, Gemma C. Sharp, Matt J. Silver, Faisal I. Rezwan, and John W. Holloway

Subjects
PACE, Meta-analysis, Birth season, DNA methylation, Differentially methylated regions (DMR), Latitude, Medicine, Genetics, QH426-470
Abstract

Abstract Background Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. Methods We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1–11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. Results We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values

Published
2023
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2. Maternal haemoglobin levels in pregnancy and child DNA methylation: a study in the pregnancy and childhood epigenetics consortium

Author

Justiina Ronkainen, Anni Heiskala, Florianne O.L. Vehmeijer, Estelle Lowry, Doretta Caramaschi, Guadalupe Estrada Gutierrez, Jonathan A. Heiss, Nadine Hummel, Elina Keikkala, Tuomas Kvist, Allison Kupsco, Phillip E. Melton, Giancarlo Pesce, Munawar H. Soomro, Marta Vives-Usano, Nour Baiz, Elisabeth Binder, Darina Czamara, Mònica Guxens, Sanna Mustaniemi, Stephanie J. London, Sebastian Rauschert, Marja Vääräsmäki, Martine Vrijheid, Anette-G. Ziegler, Isabella Annesi-Maesano, Mariona Bustamante, Rae-Chi Huang, Sandra Hummel, Allan C. Just, Eero Kajantie, Jari Lahti, Deborah Lawlor, Katri Räikkönen, Marjo-Riitta Järvelin, Janine F. Felix, and Sylvain Sebert

Subjects
maternal haemoglobin, dna methylation, developmental programming, pregnancy, Genetics, QH426-470
Abstract

Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.

Published
2022
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3. Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Author

Simon Kebede Merid, Alexei Novoloaca, Gemma C. Sharp, Leanne K. Küpers, Alvin T. Kho, Ritu Roy, Lu Gao, Isabella Annesi-Maesano, Pooja Jain, Michelle Plusquin, Manolis Kogevinas, Catherine Allard, Florianne O. Vehmeijer, Nabila Kazmi, Lucas A. Salas, Faisal I. Rezwan, Hongmei Zhang, Sylvain Sebert, Darina Czamara, Sheryl L. Rifas-Shiman, Phillip E. Melton, Debbie A. Lawlor, Göran Pershagen, Carrie V. Breton, Karen Huen, Nour Baiz, Luigi Gagliardi, Tim S. Nawrot, Eva Corpeleijn, Patrice Perron, Liesbeth Duijts, Ellen Aagaard Nohr, Mariona Bustamante, Susan L. Ewart, Wilfried Karmaus, Shanshan Zhao, Christian M. Page, Zdenko Herceg, Marjo-Riitta Jarvelin, Jari Lahti, Andrea A. Baccarelli, Denise Anderson, Priyadarshini Kachroo, Caroline L. Relton, Anna Bergström, Brenda Eskenazi, Munawar Hussain Soomro, Paolo Vineis, Harold Snieder, Luigi Bouchard, Vincent W. Jaddoe, Thorkild I. A. Sørensen, Martine Vrijheid, S. Hasan Arshad, John W. Holloway, Siri E. Håberg, Per Magnus, Terence Dwyer, Elisabeth B. Binder, Dawn L. DeMeo, Judith M. Vonk, John Newnham, Kelan G. Tantisira, Inger Kull, Joseph L. Wiemels, Barbara Heude, Jordi Sunyer, Wenche Nystad, Monica C. Munthe-Kaas, Katri Räikkönen, Emily Oken, Rae-Chi Huang, Scott T. Weiss, Josep Maria Antó, Jean Bousquet, Ashish Kumar, Cilla Söderhäll, Catarina Almqvist, Andres Cardenas, Olena Gruzieva, Cheng-Jian Xu, Sarah E. Reese, Juha Kere, Petter Brodin, Olivia Solomon, Matthias Wielscher, Nina Holland, Akram Ghantous, Marie-France Hivert, Janine F. Felix, Gerard H. Koppelman, Stephanie J. London, and Erik Melén

Subjects
Development, Epigenetics, Gestational age, Preterm birth, Transcriptomics, Medicine, Genetics, QH426-470
Abstract

Abstract Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P

Published
2020
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4. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Author

Guillaume Pouessel, Claire Claverie, Julien Labreuche, Jean-Marie Renaudin, Aimée Dorkenoo, Mireille Eb, Anne Moneret-Vautrin, Antoine Deschildre, Stephane Leteurtre, Linus Grabenhenrich, Margitta Worm, Sabine Dölle, Kathrin Scherer, Isidor Hutteger, Morten Christensen, Carsten Bindslev-Jensen, Charlotte Mortz, Esben Eller, Henrik Fomsgaard Kjaer, Leonor Carneiro-Leão, Jenny Badas, Alice Coimbra, Dikla Pivko Levy, Moshe Ben-Shoshan, Ayelet Rimon, Shira Benor, Nicolette J. T. Arends, Nikki Edelbroek, Hans de Groot, Joyce A. M. Emons, H. Kim A. Brand, Dirk Verhoeven, Leonieke N. van Veen, Nicolette W. de Jong, Geunwoong Noh, Eun Ha Jang, Mariona Pascal, Olga Dominguez, Mònica Piquer, Montserrat Alvaro, Rosa Jimenez-Feijoo, Jaime Lozano, Adriana Machinena, Maria del Mar Folqué, Maria Teresa Giner, Ana María Plaza, Paul Turner, Nandinee Patel, Marta Vazquez-Ortiz, Sarah Lindsley, Lucy Walker, Simon Rosenberg, Adriano Mari, Claudia Alessandri, Ivana Giangrieco, Lisa Tuppo, Chiara Rafaiani, Georg Mitterer, Michela Ciancamerla, Rosetta Ferrara, Maria Livia Bernardi, Danila Zennaro, Maurizio Tamburrini, Maria Antonetta Ciardiello, Christian Harwanegg, Antonio Fernandez, Regina Selb, Philippe Egenmann, Michelle Epstein, Karin Hoffmann-Sommergruber, Frits Koning, Martinus Lovik, E. N. Clare Mills, Javier Moreno, Henk van Loveren, Jean-Michel Wal, Susanne Diesner, Cornelia Bergmayr, Barbara Pfitzner, Vera Elisabeth Assmann, Philipp Starkl, David Endesfelder, Thomas Eiwegger, Zsolt Szepfalusi, Heinz Fehrenbach, Erika Jensen-Jarolim, Anton Hartmann, Isabella Pali-Schöll, Eva Untersmayr, Soren Wille, Peter Meyer, Caroline Klingebiel, Jonas Lidholm, Angelica Ehrenberg, Jonas Östling, Isabelle Cleach, Jean-Louis Mège, Joana Vitte, Roberta Aina, Pawel Dubiela, Sabine Pfeifer, Merima Bublin, Christian Radauer, Piotr Humeniuk, Stefan Kabasser, Riccardo Asero, Gador Bogas, Francisca Gomez, Paloma Campo, Maria Salas, Inmaculada Doña, Esther Barrionuevo, Maria Auxiliadora Guerrero, Cristobalina Mayorga, Ana Prieto, Domingo Barber, Maria Jose Torres, Annette Jamin, Andrea Wangorsch, Barbara Ballmer, Stefan Vieths, Stephan Scheurer, Danijela Apostolovic, Jelena Mihailovic, Maja Krstic, Maria Starkhammar, Tanja Cirkovic Velickovic, Carl Hamsten, Marianne van Hage, Francine C. van Erp, Edward F. Knol, Hannah M. Kansen, Bo Pontoppidan, Yolanda Meijer, Cornelis K. van der Ent, André C. Knulst, Rebekah Sayers, Helen Brown, Adnan Custovic, Angela Simpson, Claire Mills, Juliane Schulz, Network for Online Registration of Anaphylaxis (NORA), Jaap Akkerdaas, Muriel Totis, Annabelle Capt, Corinne Herouet-Guicheney, Ronald van Ree, Tushar Banerjee, Antima Banerjee, Mathilde Claude, Grégory Bouchaud, Roberta Lupi, Laure Castan, Olivier Tranquet, Sandra Denery-Papini, Marie Bodinier, Chantal Brossard, Rosella De Poi, Elisa Gritti, Emiliano De Dominicis, Bert Popping, Patrizia Polverino de Laureto, Kati Palosuo, Anna Kaarina Kukkonen, Anna Pelkonen, Mika Mäkelä, Nanju Alice Lee, Johanna Rost, Sridevi Muralidharan, Dianne Campbell, Sam Mehr, Catherine Nock, Joseph Baumert, Steve Taylor, Carla Mastrorilli, Salvatore Tripodi, Carlo Caffarelli, Serena Perna, Andrea Di Rienzo Businco, Ifigenia Sfika, Arianna Dondi, Annamaria Bianchi, Carlotta Povesi Dascola, Giampaolo Ricci, Francesca Cipriani, Nunzia Maiello, Michele Miraglia del Giudice, Tullio Frediani, Simone Frediani, Francesco Macrì, Chiara Pistoletti, Iride Dello Iacono, Maria Francesca Patria, Elena Varin, Diego Peroni, Pasquale Comberiati, Loredana Chini, Viviana Moschese, Sandra Lucarelli, Roberto Bernardini, Giuseppe Pingitore, Umberto Pelosi, Roberta Olcese, Matteo Moretti, Anastasia Cirisano, Diego Faggian, Alessandro Travaglini, Mario Plebani, Maria Carmen Verga, Mauro Calvani, Paolo Giordani, Paolo Maria Matricardi, Noe Ontiveros, Francisco Cabrera-Chavez, Julie Galand, Etienne Beaudouin, The Anaphylaxis Working Group of the French Allergology SocietyThe Anaphylaxis Working Group of the French Allergology Society, Florence Pineau, Shinobu Sakai, Kayoko Matsunaga, Reiko Teshima, Colette Larré, Sandra Denery, Sebastian Tschirner, Valérie Trendelenburg, Gabriele Schulz, Bodo Niggemann, Kirsten Beyer, Youcef Bouferkas, Younes Belabbas, Djamel Saidi, Omar Kheroua, Kamel Eddine El Mecherfi, Malika Guendouz, Abir Haddi, Hanane Kaddouri, Luis Amaral, Ana Pereira, Susana Rodrigues, Mareen Datema, Laurian Jongejan, Michael Clausen, Andre Knulst, Nikolaos Papadopoulos, Marek Kowalski, Frédéric de Blay, Aeilko Zwinderman, Karin Hoffman-Sommergruber, Barbara Ballmer-Weber, Montserrat Fernandez-Rivas, Shan Deng, Jia Yin, Charlotte Eisenmann, Maria Nassiri, Rabea Reinert, Johanna P. M. van der Valk, Roy Gerth van Wijk, Yvonne Vergouwe, Ewout W. Steyerberg, Marit Reitsma, Harry J. Wichers, Huub F. J. Savelkoul, Berber Vlieg-Boerstra, Anthony E. J. Dubois, Fabrícia Carolino, Ana Rodolfo, Josefina Cernadas, Dasha Roa-Medellín, Ana Rodriguez-Fernandez, Joaquín Navarro, Vicente Albendiz, María Luisa Baeza, Sonsoles Intente-Herrero, Andrea Mikkelsen, Kirsten Mehlig, Lauren Lissner, Linda Verrill, Stefano Luccioli, Jolanda van Bilsen, Frieke Kuper, André Wolterbeek, Tanja Rouhani Rankouhi, Lars Verschuren, Hilde Cnossen, Prescilla Jeurink, Johan Garssen, Léon Knippels, Jossie Garthoff, Geert Houben, Winfried Leeman, M. Eleonore Pettersson, Afke M. M. Schins, Gerard H. Koppelman, Boudewjin J. Kollen, Svitlana Zubchenko, Sarah Kuntz, Pablo Mérida, Montserrat Álvaro, Monica Piquer, Carmen Riggioni, Juan Heber Castellanos, Rosa Jimenez, Melanie Cap, Elodie Drumez, Stéphanie Lejeune, Caroline Thumerelle, Clémence Mordacq, Véronique Nève, Sonia Ricò, Margherita Varini, Rita Nocerino, Linda Cosenza, Antonio Amoroso, Margherita Di Costanzo, Carmen Di Scala, Giorgio Bedogni, Roberto Berni Canani, Paul J. Turner, Paloma Poza-Guedes, Ruperto González-Pérez, Inmaculada Sánchez-Machín, Victor Matheu-Delgado, Erik Wambre, Anne-Sofie Ballegaard, Charlotte Madsen, Juliane Gregersen, Katrine Lindholm Bøgh, Philippe Aubert, Michel Neunlist, Antoine Magnan, Daniel Lozano-Ojalvo, Alba Pablos-Tanarro, Leticia Pérez-Rodríguez, Elena Molina, Rosina López-Fandiño, Akila Rekima, Patricia Macchiaverni, Mathilde Turfkruyer, Sebastien Holvoet, Lénaïck Dupuis, Nour Baiz, Isabella Annesi-Maesano, Annick Mercenier, Sophie Nutten, Valérie Verhasselt, Ines Mrakovcic-Sutic, Srdan Banac, Ivana Sutic, Zdenka Baricev-Novakovic, Ingrid Sutic, Valentino Pavisic, Rosa Muñoz-Cano, Teodoríkez Jiménez-Rodríguez, Daniel Corbacho, Jordi Roca-Ferrer, Joan Bartra, Aleksandar Bulog, Vladimir Micovic, Lidia Markiewicz, Agata Szymkiewicz, Anna Szyc, Barbara Wróblewska, Bryan M. Harvey, Lucien F. Harthoorn, A. Wesley Burks, Georgios Rentzos, Anna-Lena Bramstång Björk, Ulf Bengtsson, Colin Barber, Chrystyna Kalicinsky, Christine Breynaert, Lieve Coorevits, Cornelia Jansen, Erna Van Hoeyveld, Kristin Verbeke, Anne-Marie Kochuyt, Rik Schrijvers, Diana Deleanu, Adriana Muntean, Maria Konstantakopoulou, Maria Pasioti, Anastasia Papadopoulou, Anna Iliopoulou, Nikolaos Mikos, Evangelia Kompoti, Eunice Dias de Castro, Borja Bartalomé, Kok Loong Ue, Elizabeth Griffiths, Stephen Till, Kate Grimshaw, Graham Roberts, Anna Selby, Indre Butiene, Jose Ignacio Larco, Ruta Dubakiene, Ana Fiandor, Alessandro Fiocchi, Nikos Papadopoulos, Sigurveig Sigurdardottir, Aline Sprikkelman, Anne-Fleur Schoemaker, Paraskevi Xepapadaki, Thomas Keil, Zizi Cojocariu, Beatriz Secades Barbado, Vasti Iancu, Esozia Arroabarren, Marta Goñi Esarte, Miren Arteaga, Mayra Coutinho Andrade, Denise Borges, Jorge Kalil, Pedro Giavina Bianchi, Rosana Camara Agondi, Rinkesh Kumar Gupta, Akanksha Sharma, Kriti Gupta, Mukul Das, Premendra Dwivedi, Rusudan Karseladze, Liana Jorjoliani, Lali Saginadze, Mariam Tskhakaia, Katia Basello, Gabriele Piuri, Attilio Francesco Speciani, Michela Carola Speciani, Carla Camerotto, Francesco Zinno, Olga Pakholchuk, Svitlana Nedelska, Stefano Pattini, Maria Teresa Costantino, Silvia Peveri, Danilo Villalta, Eleonora Savi, Andrea Costanzi, Vera A. Revyakina, Marina A. Kiseleva, Elena D. Kuvshinova, Inna A. Larkova, Anton A. Shekhetov, Diana Silva, André Moreira, José Plácido, Hanneke van der Kleij, Esther van Twuijver, Robbert Sutorius, Pieter-Jan de Kam, Jenny van Odijk, Helen Lindqvist, Elin Lustig, Amyra Ali Azamar Jácome, Karla Leversia Borjas Aguilar, Miguel García Domínguez, David Alejandro Mendoza Hernández, Cristiano Caruso, Cono Casale, Gian Lodovico Rapaccini, Antonino Romano, Italo De Vitis, Renata R. Cocco, Carolina Aranda, Marcia C. Mallozi, Jackeline F. Motta, Lilian Moraes, Antonio Pastorino, Nelson Rosario, Ekaterini Goudouris, Arnaldo Porto, Neusa F. Wandalsen, Emanuel Sarinho, Flavio Sano, Dirceu Solé, Constantinos Pitsios, Maria Petrodimopoulou, Ekaterini Papadopoulou, Maria Passioti, Meropi Kontogianni, Nino Adamia, Ekaterina Khaleva, Ana Prieto del Prado, George Du Toit, Edyta Krzych, Urszula Samolinska-Zawisza, Konrad Furmanczyk, Aneta Tomaszewska, Filip Raciborski, Agnieszka Lipiec, Piotr Samel-Kowalik, Artur Walkiewicz, Jacek Borowicz, Boleslaw Samolinski, Aimee Lou Nano, Marysia Recto, Maria Luisa Somoza, Natalia Blanca López, Diana Pérez Alzate, Francisco Javier Ruano, Maria Isabel Garcimartín, Elisa Haroun, Maria Vázquez de la Torre, Antonia Rojas, Montserrat López Onieva, Gabriela Canto, Alexandra Rodrigues, Andreia Forno, António Jorge Cabral, Rute Gonçalves, Ilya Vorozhko, Tatyana Sentsova, Olga Chernyak, Svetlana Denisova, Lidia Ilènko, Valery Muhortnich, Caroline Zimmermann, Alexander Rohrbach, Faisal R. Bakhsh, Kollen Boudewijn, Anne-Marie Oomkes-Pilon, Dorien Van Ginkle, Mira Šilar, Anja Jeverica, Tina Vesel, Tadej Avčin, Peter Korošec, Johanna van der Valk, Irene Berends, Nicolette Arends, Maurits van Maaren, Harry Wichers, Joyce Emons, Anthony Dubois, Nicolette de Jong, Oksana Matsyura, Lesya Besh, Chung-Hsiung Huang, Tong-Rong Jan, Gary Stiefel, Jean Tratt, Kerrie Kirk, Fabricia Carolino, Stefania Arasi, Lucia Caminiti, Giuseppe Crisafulli, Chiara Fiamingo, Jlenia Fresta, Giovanni Pajno, Ben Remington, Astrid Kruizinga, W. Marty Blom, Joost Westerhout, Sabina Bijlsma, Joe Baumert, Mark Blankestijn, Henny Otten, Rob Klemans, Anouska D. Michelsen-Huisman, Harmieke van Os-Medendorp, Astrid G. Kruizinga, Astrid Versluis, Gert van Duijn, H. Mary-Lene de Zeeuw-Brouwer, Jacqueline J. M. Castenmiller, Hub P. J. M. Noteborn, Geert F. Houben, Kristian Bravin, David Luyt, Bushra Javed, Phil Couch, Christopher Munro, Phil Padfield, Matt Sperrin, Aideen Byrne, Lizalet Oosthuizen, Carina Kelleher, Fiona Ward, Niamh Brosnan, Graham King, Eva Corbet, Josué Alejandro Huertas Guzmán, Montserrat Bosque García, Oscar Asensio, Laura Valdesoiro Navarrete, Helena Larramona, Xavier Domingo Miró, Katarzyna Pyrz, Moira Austin, Yanne Boloh, Philip Couch, Deirdre Galloway, Pilar Hernandez, Jonathan O’B. Hourihane, Fiona Kenna, Barbara Majkowska-Wojciechowska, Lynne Regent, Marina Themisb, Sabine Schnadt, Aida Semic-Jusufagic, Audrey Dunn Galvin, Tiina Kauppila, Mikael Kuitunen, Nikolaos A. Kitsioulis, Nikolaos Douladiris, Sofia Kostoudi, Ioanna Manolaraki, Dimitris Mitsias, Emmanouil Manousakis, Nikolaos G. Papadopoulos, Rebecca Knibb, Jennifer Hammond, Richard Cooke, Jaakko Yrjänä, Anna-Maija Hanni, Päivi Vähäsarja, Oona Mustonen, Teija Dunder, Petri Kulmala, Eva Lasa, Carmen D’Amelio, Sara Martínez, Alejandro Joral, Gabriel Gastaminza, Maria Jose Goikoetxea, David C. A. Candy, Marleen T. J. Van Ampting, Manon M. Oude Nijhuis, Assad M. Butt, Diego G. Peroni, Adam T. Fox, Jan Knol, Louise J. Michaelis, Ines Padua, Patricia Padrao, Pedro Moreira, Renata Barros, Hanan Sharif, Manzoor Ahmed, Nehad Gomaa, Joris Mens, Koen Smit, Frans Timmermans, Tomaž Poredoš, Anja Koren Jeverica, Marjeta Sedmak, Evgen Benedik, Meta Accetto, Mirjana Zupančič, Glauce Yonamine, Gustavo Soldateli, Bruna Aquilante, Antonio Carlos Pastorino, Cleonir Lui de Moraes Beck, Andrea Keiko Gushken, Mayra de Barros Dorna, Cristiane Nunes dos Santos, Ana Paula Moschione Castro, Abdulhadi Al-Qahtani, Rand Arnaout, Agha Rehan Khaliq, Rashid Amin, Farrukh Sheikh, Jorge Alvarez, Marta Anda, Miriam Palacios, Montserrat De Prada, Carmen Ponce, Bianca Balbino, Riccardo Sibilano, Thomas Marichal, Nicolas Gaudenzio, Hajime Karasuyama, Pierre Bruhns, Mindy Tsai, Laurent L. Reber, Stephen J. Galli, Ana Reis Ferreira, Josefina R. Cernadas, Aida del Campo García, Sara Pereiro Fernández, Nerea Sarmiento Carrera, Fernando Bandrés Sánchez-Cruz, José Ramón Fernández Lorenzo, Stephanie Claus, Claudia Pföhler, Franziska Ruëff, Regina Treudler, Mercedes Escarrer Jaume, Agustin Madroñero, Maria Teresa Guerra Perez, Juan Carlos Julia, Charlotte Hands Plovdiv, Lee Gethings, Jim Langridge, Karine Adel-Patient, Hervé Bernard, Ivona Barcievic-Jones, Raditsa Sokolova, Rumyana Yankova, Mariya Ivanovska, Marianna Murdjeva, Tatyana Popova, Svetlan Dermendzhiev, Martin Karjalainen, Ulrike Lehnigk, Duncan Brown, Julie C. Locklear, Julie Locklear, Ioana Maris, Jonathan Hourihane, Cristina Ornelas, Joana Caiado, Manuel Branco Ferreira, Manuel Pereira-Barbosa, Yolanda Puente, Juan Carlos Daza, Francisco Javier Monteseirin, Natalia Ukleja-Sokolowska, Ewa Gawronska-Ukleja, Magdalena Zbikowska-Gotz, Zbigniew Bartuzi, Lukasz Sokolowski, Aine Adams, Bernard Mahon, Karen English, Nelly Gourdon-Dubois, Laetitia Sellam, Bruno Pereira, Elodie Michaud, Khaled Messaoudi, Bertrand Evrard, Jean-Luc Fauquert, Francisca Palomares, Gador Gomez, Maria Jose Rodriguez, Luisa Galindo, Ana Molina, Lorella Paparo, Maurizio Mennini, Rosita Aitoro, Adam Wawrzeńczyk, Michał Przybyszewski, Anna Wawrzeńczyk, Hulya Ercan Sarıcoban, Meltem Ugras, Zerrin Yalvac, Bertine M. J. Flokstra-de Blok, J. L. van der Velde, Andrea Vereda, Clara Ippolito, Amaranta Traversa, Daniela Adriano, Daniela Manila Bianchi, Silvia Gallina, Lucia Decastelli, Melina Makatsori, Anne Miles, Sonja Posega Devetak, Iztok Devetak, Soraya Ainad Tabet, Jeanette Fisker Trandbohus, Pernille Winther, Hans-Jørgen Malling, Kirsten Skamstrup Hansen, Lene Heise Garvey, Chia-Chi Wang, Yin-Hua Cheng, Chun-Wei Tung, Mariola Dietrich, Ingo Marenholz, Birgit Kalb, Sarah Grosche, Katharina Blümchen, Rupert Schlags, Mareike Price, Sylke Rietz, Jorge Esparza-Gordillo, Susanne Lau, Young-Ae Lee, Ali Almontasheri, Mohammad Al Bahkali, Sahar Elshorbagi, Abdullah Alfhaid, Mashary Altamimi, Eman Madbouly, Hassan Al-Dhekri, Rand K. Arnaout, Maria Basagaña, Sira Miquel, Borja Bartolomé, Bettina Brix, Stefanie Rohwer, Sandra Brandhoff, Alena Berger, Waltraud Suer, Alf Weimann, Cristina Bueno, Laura Martín-Pedraza, Sara Abián, Pablo San Segundo-Acosta, Juan Carlos López-Rodríguez, Rodrigo Barderas, Eva Batanero, Javier Cuesta-Herranz, María Teresa Villalba, Magna Correia, Filipe Benito-Garcia, Cristina Arêde, Susana Piedade, Mário Morais-Almeida, James Hindley, Ross Yarham, Anna Kuklinska-Pijanka, David Gillick, Karine Patient, Martin D. Chapman, Katrine L. Bøgh, Ana Miranda, Eugénia Matos, Anna Sokolova, Huan Rao, Ivona Baricevic-Jones, Frances Smith, Wentong Xue, Helga Magnusdottir, Anna G. Vidarsdottir, Sigrun Lund, Anders Blom Jensen, Bjorn R. Ludviksson, Reyna Simon, Robert Elfont, Sean Bennett, Robert Voyksner, Maria de Lurdes Torre, Songül Yürek, Margaretha A. Faber, Annick Bastiaensen, Evelyne Mangodt, Athina van Gasse, Ine Decuyper, Vito Sabato, Margo M. Hagendorens, Chris H. Bridts, Luc S. De Clerck, Didier Ebo, Susanne Schwarz, Mandy Ziegert, Saskia Albroscheit, Christian Schwager, Skadi Kull, Jochen Behrends, Niels Röckendorf, Frauke Schocker, Andreas Frey, Arne Homann, Wolf-Meinhard Becker, Uta Jappe, Nesrine Zaabat, Sylvia Osscini, Chantal Agabriel, Benoît Sterling, Ania Carsin, Valérie Liabeuf, Monica Maćków, Alina Zbróg, Monica Bronkowska, Justine Courtois, Romy Gadisseur, Catherine Bertholet, Pierre Lukas, Etienne Cavalier, Philippe Delahaut, Birgit Quinting, Margareta Brandt Gertmo, Ewa Ternesten Hasseus, Vladyslava Barzylovych, Júlio Oliveira, Luis F. Ensina, Carolina S. Aranda, Leire Dopazo, Rebeca Lopez, Raquel Perez, Laura Santos-Diez, Agurtzane Bilbao, Juan Miguel Garcia, Ignacio García Núñez, María Ángeles Algaba Mármol, María José Barasona Villarejo, José Antonio Bácter Martos, Marina Suárez Vergara, José María Ignacio García, Agata Michalska, Grzegorz Sergiejko, Robert Zacniewski, Ileana-Maria Ghiordanescu, Cristina Deaconu, Mihaela Popescu, Roxana Silvia Bumbacea, Alkerta Ibranji, Elida Nikolla, Gjustina Loloci, Nanna Juel-Berg, Lau Fabricius Larsen, Lars Kjaergaard Poulsen, João Marcelino, Ricardo Prata, Ana Célia Costa, Fátima Duarte, Marta Neto, Jennifer Santos, Luís Câmara Pestana, Daniel Sampaio, Paola Minale, Paola Dignetti, Donatella Bignardi, Irena Nedelea, Florin-Dan Popescu, Mariana Vieru, Florin-Adrian Secureanu, Carmen Saviana Ganea, Miguel Vieira, José Pedro Moreira Silva, Timothy Watts, Sophia Watts, Marta Lomikovska, Marina Peredelskaya, Natalia Nenasheva, Ivana Filipovic, Zorica Zivkovic, Djordje Filipovic, Jennette Higgs, Amena Warner, and Carla Jones

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2017
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5. Discriminating severe seasonal allergic rhinitis. Results from a large nation-wide database.

Author

Davide Caimmi, Nour Baiz, Shreosi Sanyal, Soutrik Banerjee, Pascal Demoly, and Isabella Annesi-Maesano

Subjects
Medicine, Science
Abstract

Allergic rhinitis (AR) is a chronic disease affecting a large amount of the population. To optimize treatment and disease management, it is crucial to detect patients suffering from severe forms. Several tools have been used to classify patients according to severity: standardized questionnaires, visual analogue scales (VAS) and cluster analysis. The aim of this study was to evaluate the best method to stratify patients suffering from seasonal AR and to propose cut-offs to identify severe forms of the disease. In a multicenter French study (PollinAir), patients suffering from seasonal AR were assessed by a physician that completed a 17 items questionnaire and answered a self-assessment VAS. Five methods were evaluated to stratify patients according to AR severity: k-means clustering, agglomerative hierarchical clustering, Allergic Rhinitis Physician Score (ARPhyS), total symptoms score (TSS-17), and VAS. Fisher linear, quadratic discriminant analysis, non-parametric kernel density estimation methods were used to evaluate miss-classification of the patients and cross-validation was used to assess the validity of each scale. 28,109 patients were categorized into "mild", "moderate", and "severe", through the 5 different methods. The best discrimination was offered by the ARPhyS scale. With the ARPhyS scale, cut-offs at a score of 8-9 for mild to moderate and of 11-12 for moderate to severe symptoms were found. Score reliability was also acceptable (Cronbach's α coefficient: 0.626) for the ARPhyS scale, and excellent for the TSS-17 (0.864). The ARPhyS scale seems the best method to target patients with severe seasonal AR. In the present study, we highlighted optimal discrimination cut-offs. This tool could be implemented in daily practice to identify severe patients that need a specialized intervention.

Published
2018
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6. Prenatal Maternal Depression Related to Allergic Rhinoconjunctivitis in the first 5 Years of Life in Children of the EDEN Mother-Child Cohort Study

Author

Cailiang Zhou Ph.D., Gladys Ibanez Ph.D., Vincent Miramont Ph.D., Magali Steinecker Ph.D., Nour Baiz Ph.D., Soutrik Banerjee Ph.D., Jocelyne Just Ph.D., Isabella Annesi-Maesano Ph.D., and Julie Chastang Ph.D.

Subjects
Otorhinolaryngology, RF1-547, Immunologic diseases. Allergy, RC581-607
Abstract

Backgroud Evidence about the relationship between prenatal maternal depression and the development of childhood asthma and allergies in early life is scarce. We aimed to examine this relationship by using data set of EDEN mother-child cohort study. A total of 1139 children were followed-up until the age of 5 years. Methods Prenatal maternal depression was self-reported by using the Centre for Epidemiological Studies-Depression scale (CES-D) questionnaire and was classified into binary variable (maternal depression [CES-D score of≥16] and no maternal depression [CES-D score of

Published
2017
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7. Physical activity, sedentary behaviour, and childhood asthma: a European collaborative analysis

Author

Sibylle Koletzko, Jordi Sunyer, Liesbeth Duijts, Henrique Barros, Steve Turner, Jolanda M A Boer, Ville Peltola, Geertje W Dalmeijer, Mads Melbye, Johnny Ludvigsson, Ulrike Gehring, Marie Standl, Anna Bergstrom, Andrea von Berg, Guillermo Fernandez-Tardon, Hazel M Inskip, Judith Garcia-Aymerich, Tamara Schikowski, Graham Devereux, Berthold Koletzko, Claudia E Kuehni, Hanna Lagström, Veit Grote, Tanja G M Vrijkotte, John Mehegan, Virissa Lenters, Isabella Annesi-Maesano, Ferran Ballester, Peter Bager, Katharine C Pike, Cecily Kelleher, Carel Thijs, Monique Mommers, Sandra Ekström, Klaus Bønnelykke, Maties Torrent, Margreet W Harskamp-van Ginkel, Mikel Subiza-Pérez, Åshild Faresjö, Marianne Eijkemans, Anders Ulrik Eliasen, Nour Baïz, Ana Cristina Santos, Sara M Mensink-Bout, Claudia Flexeder, Merete Åse Eggesbø, Mónica López-Vicente, Gunda Herberth, Eva S L Pedersen, Maria Jansen, and Cornelis K van der Ent

Subjects
Medicine, Diseases of the respiratory system, RC705-779
Abstract

Objectives To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study.Design Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined.Setting Children aged 0–18 years from 26 European birth cohorts.Participants 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood.Main outcome measure Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity) at age 6–18 years.Results Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3–5 years was not associated with asthma at age 6–18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results.Conclusions Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood.

Published
2024
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8. Reply

Author

Patricia Macchiaverni, Nour Baiz, Akila Rekima, Isabella Annesi-Maesano, and Valerie Verhasselt

Subjects
Milk, Human, Risk Factors, Immunology, Pyroglyphidae, Respiratory Hypersensitivity, Immunology and Allergy, Animals, Humans, Female, Allergens, Child
Published
2018

9. Indoor Air Quality and Sources in Schools and Related Health Effects

Author

Isabella Annesi-Maesano, Nour Baiz, Soutrik Banerjee, Peter Rudnai, Solenne Rive, and null the SINPHONIE Group

Subjects
Adult, Adolescent, Health, Toxicology and Mutagenesis, Respiratory Tract Diseases, education, Air pollution, Toxicology, medicine.disease_cause, Young Adult, Indoor air quality, Air pollutants, Risk Factors, Adverse health effect, Environmental health, Hypersensitivity, medicine, Humans, Child, Air quality index, Respiratory health, Air Pollutants, Schools, Health consequences, business.industry, Attendance, Middle Aged, Faculty, Occupational Diseases, Air Pollution, Indoor, Child, Preschool, business
Abstract

Good indoor air quality in schools is important to provide a safe, healthy, productive, and comfortable environment for students, teachers, and other school staff. However, existing studies demonstrated that various air pollutants are found in classrooms, sometimes at elevated concentrations. Data also indicated that poor air quality may impact children's health, in particular respiratory health, attendance, and academic performance. Nevertheless, it should be noted that there are other adverse health effects that are less documented. Few data exist for teachers and other adults that work in schools. Allergic individuals seem to be at a higher risk for adverse respiratory health consequences. Air quality improvement represents an important measure for prevention of adverse health consequences in children and adults in schools.

Published
2013
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10. Symptom control and health‐related quality of life in allergic rhinitis with and without comorbid asthma: A multicentre European study

Author

Subhabrata Moitra, Marzia Simoni, Sandra Baldacci, Sara Maio, Anna Angino, Patrizia Silvi, Giovanni Viegi, Stefania La Grutta, Franco Ruggiero, Gianni Bedini, Francesca Natali, Lorenzo Cecchi, Uwe Berger, Maria Prentovic, Amir Gamil, Nour Baïz, Michel Thibaudon, Samuel Monnier, Davide Caimmi, Luciana K. Tanno, Pascal Demoly, Simone Orlandini, and Isabella Annesi‐Maesano

Subjects
allergy treatment, CARAT, food allergy, pollen, RHINASTHMA, rhinitis, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Allergic rhinitis (AR) is a major non‐communicable disease that affects the health‐related quality of life (HRQoL) of patients. However, data on HRQoL and symptom control in AR patients with comorbid asthma (AR + asthma) are lacking. Methods In this multicentre, cross‐sectional study, patients with AR were screened and administered questionnaires of demographic characteristics and health conditions (symptoms/diagnosis of AR and asthma, disease severity level, and allergic conditions). HRQoL was assessed using a modified version of the RHINASTHMA questionnaire (30, ‘not at all bothered’ ‐ 150 ‘very much bothered’) and symptom control was evaluated by a modified version of the Control of Allergic Rhinitis/Asthma Test (CARAT) (0, ‘no control’ ‐ 30, ‘very high control’). Results Out of 643 patients with AR, 500 (78%) had asthma as a comorbidity, and 54% had moderate‐severe intermittent AR, followed by moderate‐severe persistent AR (34%). Compared to the patients with AR alone, patients with AR + asthma had significantly higher RHINASTHMA (e.g., median RHINASTHMA‐total score 48.5 vs. 84, respectively) and a significantly lower CARAT score (median CARAT‐total score 23 vs. 16.5, respectively). Upon stratifying asthma based on severity, AR patients with severe persistent asthma had worse HRQoL and control than those with mild persistent asthma. The association was significantly higher among non‐obese participants compared to obese ones, with RHINASTHMA‐upper symptoms score but not with CARAT. Conclusions Our observation of poorer HRQoL and symptoms control in AR patients with comorbid asthma supports the importance of a comprehensive approach for the management of AR in case of a comorbid allergic condition.

Published
2023
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11. Maternal diet before and during pregnancy and risk of asthma and allergic rhinitis in children

Author

Nour Baïz, Jocelyne Just, Julie Chastang, Anne Forhan, Blandine de Lauzon-Guillain, Anne-Marie Magnier, Isabella Annesi-Maesano, and the EDEN Mother-Child Cohort Study Group

Subjects
Diet, Preconception, Pregnancy, Allergic diseases, Wheezing, Allergic rhinitis, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Consumption of certain foods during pregnancy has been shown to have beneficial effects on childhood asthma and allergic disease development and aggravation. However, most studies provide conflicting results and the relationships between maternal preconceptional diet and risks of childhood asthma and allergic disease have not previously been explored. The objective of this study was to assess maternal diet during the year before pregnancy and the last 3 months of pregnancy and investigate their associations with the risks of asthma, wheezing, allergic rhinitis and atopic dermatitis in young children. Methods The study sample consisted of 1140 mother–child pairs from the EDEN cohort. Mothers had responded to the food frequency questionnaires used to assess diet before and during pregnancy. Children were followed up using health questionnaires. The health outcomes studied were: asthma, wheezing, allergic rhinitis and atopic dermatitis by the age of 3 years. Results Using multivariable-adjusted logistic regression models, significant inverse associations were observed between cooked green vegetable consumption before pregnancy and childhood asthma; consumption of eggs and raw vegetables before and during pregnancy, consumption of grains before pregnancy, and consumption of cooked green vegetables during pregnancy and allergic rhinitis. For the first time, a significant positive association was found between meat intake during the preconceptional period and a risk of wheezing, allergic rhinitis and atopic dermatitis. Conclusions Based on our findings, preconceptional and prenatal maternal intake of certain type of food groups may be preventive against asthma, wheezing and allergic rhinitis, whereas higher maternal intake of meat before pregnancy may increase the risk of wheezing, allergic rhinitis and atopic dermatitis in young children.

Published
2019
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13. Postnatal Environmental Tobacco Smoke Exposure Related to Behavioral Problems in Children.

Author

Julie Chastang, Nour Baïz, Jean Sébastien Cadwallader, Sarah Robert, John L Dywer, Denis André Charpin, Denis Caillaud, Frédéric de Blay, Chantal Raherison, François Lavaud, and Isabella Annesi-Maesano

Subjects
Medicine, Science
Abstract

The purpose of this study was to examine the association between pre and post environmental tobacco smoke (ETS) exposure and behavioral problems in schoolchildren.In the cross-sectional 6 cities Study conducted in France, 5221 primary school children were investigated. Pre- and postnatal exposure to secondhand tobacco smoke at home was assessed using a parent questionnaire. Child's behavioral outcomes (emotional symptoms and conduct problems) were evaluated by the Strengths and Difficulties Questionnaire (SDQ) completed by the parents.ETS exposure during the postnatal period and during both pre- and postnatal periods was associated with behavioral problems in children. Abnormal emotional symptoms (internalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.72 (95% Confidence Interval (CI)= 1.36-2.17), whereas the OR was estimated to be 1.38 (95% CI= 1.12-1.69) in the case of postnatal exposure only. Abnormal conduct problems (externalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.94 (95% CI= 1.51-2.50), whereas the OR was estimated to be 1.47 (95% CI=1.17-1.84) in the case of postnatal exposure only. Effect estimates were adjusted for gender, study center, ethnic origin, child age, low parental education, current physician diagnosed asthma, siblings, preterm birth and single parenthood.Postnatal ETS exposure, alone or in association with prenatal exposure, increases the risk of behavioral problems in school-age children.

Published
2015
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14. Maternal complications and conditions in pregnancy and wheezing in early childhood: A combined analysis of 14 European birth cohorts

Author

Zugna, Daniela, Galassi, Claudia, Annesi-Maesano, Isabelle, Baiz, Nour, Barros, Henrique, Correia, Sofia, Di Gregori, Valentina, Duijts, Liesbeth, Forastiere, Francesco, Gascon, Mireia, Inskip, Hazel, Jaddoe, Vincent W. V., Fantini, Maria Pia, Larsen, Pernille Stemann, Andersen, Anne-Marie Nybo, John Penders, Petersen, Maria Skaalum, Porta, Daniela, Steuerwald, Ulrike, Sunyer, Jordi, Thijs, Carel, Vrijheid, Martine, Richiardi, Lorenzo, Rusconi, Franca, Daniela Zugna, Claudia Galassi, Isabelle Annesi-Maesano, Nour Baiz, Henrique Barro, Sofia Correia, Valentina Di Gregori, Liesbeth Duijt, Francesco Forastiere, Mireia Gascon, Hazel Inskip, Vincent W.V. Jaddoe, Maria Pia Fantini, Pernille Stemann Larsen, Anne-Marie Nybo Andersen, John Pender, Maria Skaalum Petersen, Daniela Porta, Ulrike Steuerwald, Jordi Sunyer, Carel Thij, Martine Vrijheid, and Lorenzo Richiardi and Franca Rusconi

Subjects
EPIDEMIOLOGY, INFANTS, WHEEZING
Abstract

Aims.We assessed the relationship of maternal complications including hypertensive disorders and diabetes in pregnancy, and pre-pregnancy body mass index (BMI) with wheezing symptoms in infants, combining data from birth cohorts participating in the CHICOS (Developing a Child Cohort Research Strategy for Europe) project. Methods. Eligible cohorts met the following criteria: recruitment from 1990 onwards, maternal complications recorded at any time during pregnancy, and wheezing recorded in the first 12-24 months of life. Associations of maternal complications and ever (≥ one episode), and recurrent (≥4 episodes) wheezing were assessed for each cohort, adjusting for maternal country of birth, education, asthma, smoking in pregnancy, parity, and age. Crude, adjusted and mutually adjusted risks ratios (aRR) were pooled using a random-effects meta-analysis. Results. The analysis included 93245 subjects. Ever wheezing ranged from 20 to 47 %, and recurrent wheezing from 3 to 14%. Pre-eclampsia and obesity (BMI≥ 30; ref: BMI: 18.5-24) were associated with an increased risk of ever wheezing (aRR, 1.09; 95% CI: 1.02, 1.17 and 1.12; 95% CI: 1.07, 1.18, respectively). Both estimates increased slightly for recurrent wheezing. Maternal pre-pregnancy overweight (BMI: 25-29) was associated with an increased risk of wheezing, both ever and recurrent (aRR: 1.09, 95% CI: 1.06, 1.11 and 1.20: 1.13, 1.26, respectively). Neither hypertension nor diabetes were found to be associated with ever or recurrent wheezing. Conclusions. Pre-pregnancy overweight, obesity and pre-eclampsia are associated with a slightly increased risk of wheezing in infants.

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