Mariona Pinart1, Marta Benet2, Isabella Annesi-Maesano3, Andrea von Berg4, Dietrich Berdel4, Karin C L Carlsen5, Kai-Håkon Carlsen5, Carsten Bindslev-Jensen6, Esben Eller6, Maria P Fantini7, Jacopo Lenzi7, Ulrike Gehring8, Joachim Heinrich9, Cynthia Hohmann10, Jocelyne Just11, Thomas Keil12, Marjan Kerkhof13, Manolis Kogevinas14, Sibylle Koletzko15, Gerard H Koppelman16, Inger Kull17, Susanne Lau18, Erik Melén19, Isabelle Momas20, Daniela Porta21, Dirkje S Postma22, Fanny Rancière20, Henriette A Smit23, Renato T Stein24, Christina G Tischer9, Maties Torrent25, Magnus Wickman19, Alet H Wijga26, Jean Bousquet27, Jordi Sunyer1, Xavier Basagaña2, Stefano Guerra28, Judith Garcia-Aymerich2, Josep M Antó29. 1. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; CIBER Epidemiología y Salud Pública, Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. 2. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; CIBER Epidemiología y Salud Pública, Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. 3. EPAR U707 INSERM, Paris VI, Paris, France; EPAR UMR-S UPMC, Paris VI, Paris, France. 4. Marien-Hospital Wesel, Research Institute, Department of Pediatrics, Wesel, Germany. 5. Department of Paediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway. 6. Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark. 7. Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy. 8. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands. 9. Institute of Epidemiology I, Helmholtz Zentrum, Munich, Germany. 10. Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Berlin, Germany. 11. Groupe Hospitalier Trousseau-La Roche-Guyon, Centre de l'Asthme et des Allergies, APHP, Université Paris 6, Paris, France. 12. Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Berlin, Germany; Institute of Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany. 13. University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, Netherlands. 14. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; CIBER Epidemiología y Salud Pública, Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain; National School of Public Health, Athens, Greece. 15. Division of Pediatric Gastroenterology and Hepatology, Dr von Haunersches Kinderspital, Ludwig-Maximilians-University of Munich, Munich, Germany. 16. University of Groningen, University Medical Center Groningen, Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, Groningen, Netherlands. 17. Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Sach's Children's Hospital, Stockholm, Sweden. 18. Department of Pneumology and Immunology, Charité Campus Virchow, Berlin, Germany. 19. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Sach's Children's Hospital, Stockholm, Sweden. 20. Department of Public Health and Biostatistics, Paris Descartes University, EA 4064, Paris, France; Paris Municipal Department of Social Action, Childhood, and Health, Paris, France. 21. Department of Epidemiology, Lazio Regional Health Service, Rome, Italy. 22. University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, Netherlands. 23. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands. 24. School of Medicine, Pontifícia Universidade Católica RGS, Porto Alegre, Brazil. 25. CIBER Epidemiología y Salud Pública, Barcelona, Spain; Area de Salut de Menorca, IB-Salut, Spain. 26. Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands. 27. WHO Collaborating Center for Asthma and Rhinitis, Montpellier, France; University Hospital of Montpellier, Hôpital Arnaud de Villeneuve, Montpellier, France. 28. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; CIBER Epidemiología y Salud Pública, Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain; Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA. 29. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; CIBER Epidemiología y Salud Pública, Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. Electronic address: jmanto@creal.cat.
Abstract
BACKGROUND: Eczema, rhinitis, and asthma often coexist (comorbidity) in children, but the proportion of comorbidity not attributable to either chance or the role of IgE sensitisation is unknown. We assessed these factors in children aged 4-8 years. METHODS: In this prospective cohort study, we assessed children from 12 ongoing European birth cohort studies participating in MeDALL (Mechanisms of the Development of ALLergy). We recorded current eczema, rhinitis, and asthma from questionnaires and serum-specific IgE to six allergens. Comorbidity of eczema, rhinitis, and asthma was defined as coexistence of two or three diseases in the same child. We estimated relative and absolute excess comorbidity by comparing observed and expected occurrence of diseases at 4 years and 8 years. We did a longitudinal analysis using log-linear models of the relation between disease at age 4 years and comorbidity at age 8 years. FINDINGS: We assessed 16 147 children aged 4 years and 11 080 aged 8 years in cross-sectional analyses. The absolute excess of any comorbidity was 1·6% for children aged 4 years and 2·2% for children aged 8 years; 44% of the observed comorbidity at age 4 years and 50·0% at age 8 years was not a result of chance. Children with comorbidities at 4 years had an increased risk of having comorbidity at 8 years. The relative risk of any cormorbidity at age 8 years ranged from 36·2 (95% CI 26·8-48·8) for children with rhinitis and eczema at age 4 years to 63·5 (95% CI 51·7-78·1) for children with asthma, rhinitis, and eczema at age 4 years. We did longitudinal assessment of 10 107 children with data at both ages. Children with comorbidities at 4 years without IgE sensitisation had higher relative risks of comorbidity at 8 years than did children who were sensitised to IgE. For children without comorbidity at age 4 years, 38% of the comorbidity at age 8 years was attributable to the presence of IgE sensitisation at age 4 years. INTERPRETATION: Coexistence of eczema, rhinitis, and asthma in the same child is more common than expected by chance alone-both in the presence and absence of IgE sensitisation-suggesting that these diseases share causal mechanisms. Although IgE sensitisation is independently associated with excess comorbidity of eczema, rhinitis, and asthma, its presence accounted only for 38% of comorbidity, suggesting that IgE sensitisation can no longer be considered the dominant causal mechanism of comorbidity for these diseases.
BACKGROUND:Eczema, rhinitis, and asthma often coexist (comorbidity) in children, but the proportion of comorbidity not attributable to either chance or the role of IgE sensitisation is unknown. We assessed these factors in children aged 4-8 years. METHODS: In this prospective cohort study, we assessed children from 12 ongoing European birth cohort studies participating in MeDALL (Mechanisms of the Development of ALLergy). We recorded current eczema, rhinitis, and asthma from questionnaires and serum-specific IgE to six allergens. Comorbidity of eczema, rhinitis, and asthma was defined as coexistence of two or three diseases in the same child. We estimated relative and absolute excess comorbidity by comparing observed and expected occurrence of diseases at 4 years and 8 years. We did a longitudinal analysis using log-linear models of the relation between disease at age 4 years and comorbidity at age 8 years. FINDINGS: We assessed 16 147 children aged 4 years and 11 080 aged 8 years in cross-sectional analyses. The absolute excess of any comorbidity was 1·6% for children aged 4 years and 2·2% for children aged 8 years; 44% of the observed comorbidity at age 4 years and 50·0% at age 8 years was not a result of chance. Children with comorbidities at 4 years had an increased risk of having comorbidity at 8 years. The relative risk of any cormorbidity at age 8 years ranged from 36·2 (95% CI 26·8-48·8) for children with rhinitis and eczema at age 4 years to 63·5 (95% CI 51·7-78·1) for children with asthma, rhinitis, and eczema at age 4 years. We did longitudinal assessment of 10 107 children with data at both ages. Children with comorbidities at 4 years without IgE sensitisation had higher relative risks of comorbidity at 8 years than did children who were sensitised to IgE. For children without comorbidity at age 4 years, 38% of the comorbidity at age 8 years was attributable to the presence of IgE sensitisation at age 4 years. INTERPRETATION: Coexistence of eczema, rhinitis, and asthma in the same child is more common than expected by chance alone-both in the presence and absence of IgE sensitisation-suggesting that these diseases share causal mechanisms. Although IgE sensitisation is independently associated with excess comorbidity of eczema, rhinitis, and asthma, its presence accounted only for 38% of comorbidity, suggesting that IgE sensitisation can no longer be considered the dominant causal mechanism of comorbidity for these diseases.
Authors: Alvar Agustí; Josep Maria Antó; Charles Auffray; Ferran Barbé; Esther Barreiro; Jordi Dorca; Joan Escarrabill; Rosa Faner; Laura I Furlong; Judith Garcia-Aymerich; Joaquim Gea; Bertil Lindmark; Eduard Monsó; Vicente Plaza; Milo A Puhan; Josep Roca; Juan Ruiz-Manzano; Laura Sampietro-Colom; Ferran Sanz; Luis Serrano; James Sharpe; Oriol Sibila; Edwin K Silverman; Peter J Sterk; Jacob I Sznajder Journal: Am J Respir Crit Care Med Date: 2015-02-15 Impact factor: 21.405
Authors: Nikos Stratakis; Theano Roumeliotaki; Emily Oken; Ferran Ballester; Henrique Barros; Mikel Basterrechea; Sylvaine Cordier; Renate de Groot; Herman T den Dekker; Liesbeth Duijts; Merete Eggesbø; Maria Pia Fantini; Francesco Forastiere; Ulrike Gehring; Marij Gielen; Davide Gori; Eva Govarts; Hazel M Inskip; Nina Iszatt; Maria Jansen; Cecily Kelleher; John Mehegan; Carolina Moltó-Puigmartí; Monique Mommers; Andreia Oliveira; Sjurdur F Olsen; Fabienne Pelé; Costanza Pizzi; Daniela Porta; Lorenzo Richiardi; Sheryl L Rifas-Shiman; Sian M Robinson; Greet Schoeters; Marin Strøm; Jordi Sunyer; Carel Thijs; Martine Vrijheid; Tanja G M Vrijkotte; Alet H Wijga; Manolis Kogevinas; Maurice P Zeegers; Leda Chatzi Journal: Int J Epidemiol Date: 2017-10-01 Impact factor: 7.196
Authors: Daniel Aguilar; Nathanael Lemonnier; Gerard H Koppelman; Erik Melén; Baldo Oliva; Mariona Pinart; Stefano Guerra; Jean Bousquet; Josep M Anto Journal: PLoS One Date: 2019-11-06 Impact factor: 3.240
Authors: Brooks W Morgan; Trishul Siddharthan; Matthew R Grigsby; Suzanne L Pollard; Robert Kalyesubula; Robert A Wise; Bruce Kirenga; William Checkley Journal: J Allergy Clin Immunol Pract Date: 2018-02-01
Authors: Caroline Roduit; Remo Frei; Martin Depner; Anne M Karvonen; Harald Renz; Charlotte Braun-Fahrländer; Elisabeth Schmausser-Hechfellner; Juha Pekkanen; Josef Riedler; Jean-Charles Dalphin; Erika von Mutius; Roger Pascal Lauener; Anne Hyvärinen; Pirkka Kirjavainen; Sami Remes; Marjut Roponen; Marie-Laure Dalphin; Vincent Kaulek; Markus Ege; Jon Genuneit; Sabina Illi; Micahel Kabesch; Bianca Schaub; Petra Ina Pfefferle; Gert Doekes Journal: JAMA Pediatr Date: 2017-07-01 Impact factor: 16.193