Articles
Comorbidity of eczema, rhinitis, and asthma in IgE-sensitised and non-IgE-sensitised children in MeDALL: a population-based cohort study

https://doi.org/10.1016/S2213-2600(13)70277-7Get rights and content

Summary

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.

Funding

EU Seventh Framework Programme.

Introduction

Although widely acknowledged, coexisting disorders in patients with chronic diseases (comorbidity) are still underexplored.1 The coexistence of several diseases in the same person could be a result of chance, selection bias, or causation.2 If chance and bias can be excluded, the remaining excess comorbidity can be ascribed to causal relationships between the coexisting diseases. A network topology-based approach assessing the connections between pairs of diseases (comorbidity) and enzyme-encoding genes has been proposed to gain insight into the shared pathophysiology of coexisting diseases.3 Better understanding of how common risk factors interact with shared pathophysiological pathways affecting comorbidity could inform prevention and treatment of common chronic diseases.1 The prevalence of allergy-related diseases such as eczema, rhinitis, and asthma has reached epidemic proportions in high-income countries.4 An important feature of this rise is that these diseases coexist in many children5—termed allergic or atopic comorbidity. For example, in the ISAAC study,6 almost 15% of asthmatic children aged 6–7 years and 40% of those aged 13–14 years also had allergic rhinitis.6 A study of 3778 pairs of 7-year-old children matched to their siblings suggests that eczema in infancy might cause hay fever in patients with asthma.7 A unifying hypothesis—the atopic march—states that atopic disorders progress sequentially, from eczema in infants to rhinitis and asthma in children, suggesting that atopy could be a common link8 although the evidence that allergic comorbidity is more common in IgE-sensitised children9, 10 has not been confirmed by other studies.11 However, no previous studies have assessed how much of the comorbidity of eczema, rhinitis, and asthma is attributable to chance or to causal determinants,2 which could have led to erroneous assumptions about allergic comorbidity. A better understanding of comorbidity of eczema, rhinitis, and asthma could help to improve prediction and care of such diseases during childhood. Several predictive indices have been proposed for childhood asthma, but none have been developed for comorbidity of asthma, eczema, and rhinitis. Yet, early treatment is paramount to minimise symptoms and increase quality of life.

As part of the Mechanisms of the Development of ALLergy (MeDALL) project,12, 13 we used data from a large network of birth cohorts in Europe to assess the excess comorbidity of eczema, rhinitis, and asthma in children aged 4 years and 8 years, and the role of IgE-mediated sensitisation. We postulated that comorbidity will be more common than would be expected if these diseases were independent.

Section snippets

Study design and participants

This study is based on information and samples obtained from 12 longitudinal birth cohorts in eight European countries (Denmark, France, Germany, Italy, Netherlands, Norway, Spain, Sweden).12 AMICS–Menorca,14 BAMSE,5 DARC,9 ECA,15 GINIplus,16 LISAplus,17 MAS,18 and PIAMA19 recruited children between 1990 and 1998, whereas EDEN,20 Paris,21 ROBBIC–Rome,22 and ROBBIC–Bologna22 included children from 2003 to 2006. Most studies recruited unselected population-based birth cohorts. Five cohorts

Results

The study population consisted of 16 147 children aged 4 years (mean 46·1 months, SD 5·4) and 11 080 aged 8 years (mean 106·5, SD 12·1), of whom 10 107 had information available at both ages (figure 1, table 1). Generally, excluded children with missing data at ages 4 years and 8 years tended to be older, of medium or low socioeconomic status, and with higher parental smoking than participants (table 1). At both ages, excluded children were also less likely to be sensitised to IgE than were

Discussion

We have shown that eczema, rhinitis, and asthma coexist in the same children both at age 4 and 8 years more often than would have been expected if these diseases were independent and that the presence of comorbidity at age 4 years is a strong determinant of comorbidity at age 8 years, suggesting the existence of causal relationships between these diseases. To our knowledge, this study is the first to show that excess comorbidity of eczema, rhinitis, and asthma is present in children both with

References (53)

  • NA Leonardi et al.

    Validation of the Asthma Predictive Index and comparison with simpler clinical prediction rules

    J Allergy Clin Immunol

    (2011)
  • JM Valderas et al.

    Defining comorbidity: implications for understanding health and health services

    Ann Fam Med

    (2009)
  • D-S Lee et al.

    The implications of human metabolic network topology for disease comorbidity

    Proc Natl Acad Sci USA

    (2008)
  • W Eder et al.

    The asthma epidemic

    N Engl J Med

    (2006)
  • N Ballardini et al.

    Development and comorbidity of eczema, asthma and rhinitis to age 12: data from the BAMSE birth cohort

    Allergy

    (2012)
  • D Strachan et al.

    Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC)

    Pediatr Allergy Immunol

    (1997)
  • HF Kjaer et al.

    The prevalence of allergic diseases in an unselected group of 6-year-old children. The DARC birth cohort study

    Pediatr Allergy Immunol

    (2008)
  • BLK Chawes et al.

    Children with allergic and nonallergic rhinitis have a similar risk of asthma

    J Allergy Clin Immunol

    (2010)
  • J Bousquet et al.

    MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine

    Allergy

    (2011)
  • J Sunyer et al.

    Early exposure to dichlorodiphenyldichloroethylene, breastfeeding and asthma at age six

    Clin Exp Allergy

    (2006)
  • KC Lødrup Carlsen

    The environment and childhood asthma (ECA) study in Oslo: ECA-1 and ECA-2

    Pediatr Allergy Immunol

    (2002)
  • AV Berg et al.

    Impact of early feeding on childhood eczema: development after nutritional intervention compared with the natural course—the GINIplus study up to the age of 6 years

    Clin Exp Allergy

    (2010)
  • A Zutavern et al.

    Timing of solid food introduction in relation to eczema, asthma, allergic rhinitis, and food and inhalant sensitization at the age of 6 years: results from the prospective birth cohort study LISA

    Pediatrics

    (2008)
  • RL Bergmann et al.

    Atopic diseases in infancy. The German multicenter atopy study (MAS-90)

    Pediatr Allergy Immunol

    (1994)
  • AH Wijga et al.

    Cohort profile: the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort

    Int J Epidemiol

    (2013)
  • P Drouillet et al.

    Maternal fatty acid intake and fetal growth: evidence for an association in overweight women. The ‘EDEN mother-child’ cohort (study of pre- and early postnatal determinants of the child's development and health)

    Br J Nutr

    (2009)
  • Cited by (0)

    Contributed equally

    View full text