title: Comorbidity of eczema, rhinitis, and asthma in IgE-sensitised and non-IgE-sensitised children in MeDALL: a population-based cohort study.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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: 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.
authors: Mariona
authors: M
authors: Pinart
authors: 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.
authors: Marta
authors: M
authors: Benet
authors: EPAR U707 INSERM, Paris VI, Paris, France; EPAR UMR-S UPMC, Paris VI, Paris, France.
authors: Isabella
authors: I
authors: Annesi-Maesano
authors: Marien-Hospital Wesel, Research Institute, Department of Pediatrics, Wesel, Germany.
authors: Andrea
authors: A
authors: von Berg
authors: Marien-Hospital Wesel, Research Institute, Department of Pediatrics, Wesel, Germany.
authors: Dietrich
authors: D
authors: Berdel
authors: Department of Paediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors: Karin C L
authors: KC
authors: Carlsen
authors: Department of Paediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors: Kai-Håkon
authors: KH
authors: Carlsen
authors: Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
authors: Carsten
authors: C
authors: Bindslev-Jensen
authors: Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
authors: Esben
authors: E
authors: Eller
authors: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
authors: Maria P
authors: MP
authors: Fantini
authors: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
authors: Jacopo
authors: J
authors: Lenzi
authors: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands.
authors: Ulrike
authors: U
authors: Gehring
authors: Institute of Epidemiology I, Helmholtz Zentrum, Munich, Germany.
authors: Joachim
authors: J
authors: Heinrich
authors: Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors: Cynthia
authors: C
authors: Hohmann
authors: Groupe Hospitalier Trousseau-La Roche-Guyon, Centre de l'Asthme et des Allergies, APHP, Université Paris 6, Paris, France.
authors: Jocelyne
authors: J
authors: Just
authors: Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Berlin, Germany; Institute of Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.
authors: Thomas
authors: T
authors: Keil
authors: University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, Netherlands.
authors: Marjan
authors: M
authors: Kerkhof
authors: 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.
authors: Manolis
authors: M
authors: Kogevinas
authors: Division of Pediatric Gastroenterology and Hepatology, Dr von Haunersches Kinderspital, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: Sibylle
authors: S
authors: Koletzko
authors: University of Groningen, University Medical Center Groningen, Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, Groningen, Netherlands.
authors: Gerard H
authors: GH
authors: Koppelman
authors: 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.
authors: Inger
authors: I
authors: Kull
authors: Department of Pneumology and Immunology, Charité Campus Virchow, Berlin, Germany.
authors: Susanne
authors: S
authors: Lau
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Sach's Children's Hospital, Stockholm, Sweden.
authors: Erik
authors: E
authors: Melén
authors: Department of Public Health and Biostatistics, Paris Descartes University, EA 4064, Paris, France; Paris Municipal Department of Social Action, Childhood, and Health, Paris, France.
authors: Isabelle
authors: I
authors: Momas
authors: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors: Daniela
authors: D
authors: Porta
authors: University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, Netherlands.
authors: Dirkje S
authors: DS
authors: Postma
authors: Department of Public Health and Biostatistics, Paris Descartes University, EA 4064, Paris, France; Paris Municipal Department of Social Action, Childhood, and Health, Paris, France.
authors: Fanny
authors: F
authors: Rancière
authors: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
authors: Henriette A
authors: HA
authors: Smit
authors: School of Medicine, Pontifícia Universidade Católica RGS, Porto Alegre, Brazil.
authors: Renato T
authors: RT
authors: Stein
authors: Institute of Epidemiology I, Helmholtz Zentrum, Munich, Germany.
authors: Christina G
authors: CG
authors: Tischer
authors: CIBER Epidemiología y Salud Pública, Barcelona, Spain; Area de Salut de Menorca, IB-Salut, Spain.
authors: Maties
authors: M
authors: Torrent
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Sach's Children's Hospital, Stockholm, Sweden.
authors: Magnus
authors: M
authors: Wickman
authors: Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
authors: Alet H
authors: AH
authors: Wijga
authors: WHO Collaborating Center for Asthma and Rhinitis, Montpellier, France; University Hospital of Montpellier, Hôpital Arnaud de Villeneuve, Montpellier, France.
authors: Jean
authors: J
authors: Bousquet
authors: 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.
authors: Jordi
authors: J
authors: Sunyer
authors: 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.
authors: Xavier
authors: X
authors: Basagaña
authors: 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.
authors: Stefano
authors: S
authors: Guerra
authors: 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.
authors: Judith
authors: J
authors: Garcia-Aymerich
authors: 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.
authors: Josep M
authors: JM
authors: Antó
mesh_terms: D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D003430:Cross-Sectional Studies; D004485:Eczema / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007155:Immunologic Factors / Q000097:blood*; D016014:Linear Models; D008297:Male; D015995:Prevalence; D011446:Prospective Studies; D012220:Rhinitis / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology; D012306:Risk; D011795:Surveys and Questionnaires
chemical_list: D007155:Immunologic Factors; D007073:Immunoglobulin E