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