Our study found that eczema in early childhood was strongly associated with the development of asthma and rhinitis during the following 5-year period. Eczema was one of the strongest independent risk factors. Interestingly, when eczema was divided into subgroups, children with early onset of eczema, moderate to severe eczema, and persistence of eczema had the highest odds of developing asthma and rhinitis.
This population-based prospective study confirms that early eczema affects later development of asthma and rhinitis.
Although some previous prospective studies were not able to show an association between early childhood eczema and later development of asthma and rhinitis[6, 8], our findings are robust and in line with the study by Arshad et al. In addition, similar results regarding severity have been found in both Gustavsson’s and Ricci’s eczema cohorts[12, 13], which reported that eczematous children with high severity scores were at increased risk of developing asthma. To the best of our knowledge, our study is the first prospective cohort to show that early onset of eczema or persistent eczema increases the odds of later onset of asthma in both boys and girls, which is in contrast to a previous study that only showed a relationship in boys. Definitions of asthma and rhinitis are important for the interpretation of results. Our sensitivity analysis confirmed that the association between eczema and asthma/rhinitis remained when symptom-based criteria for asthma and rhinitis were used.
Possible explanations for the relationship between eczema and asthma and rhinitis
Evidence from several experimental studies has suggested that impaired epithelial function results in increased sensitization and IgE production. In humans, the theory of epicutaneous sensitization is supported by the observation that exposing atopic children to topical emollients containing peanut protein leads to an increased risk of airway peanut sensitization. Genetic factors, such as the common loss of function mutations within the filaggrin gene, are a risk factor for incident eczema and account for skin barrier dysfunction[23, 24]. Recently, it has been shown that filaggrin mutations affect asthma, which supports the hypothesis that impaired skin function acts as a gateway for allergens, increasing the risk of atopic airways diseases.
Advantages and limitations
A major advantage of our study was its prospective design, which made results less subject to recall bias and allowed assessment of temporal relationships. Our study had a large sample size compared with earlier studies[6, 8]. Our results should be less prone to selection and ascertainment bias because of its population-based design. We also had a high response rate and limited loss to follow-up. There were no differences between the analysed sample and drop-outs in health-related variables; therefore results might have been biased towards 1. A higher prevalence of socioeconomic risk factors in children leaving the study, while assuming that low socioeconomic status is a risk factor for the incidence of asthma, might have biased the results towards 1 as well. Therefore, our conclusions that eczema is associated with later onset of asthma and rhinitis would not change if all children had participated. The advantages of the study design and performance allow generalization of results.
Reporting of eczema by questionnaire might have advantages compared with assessment by physicians, because eczema can be intermittent. The term “itchy flexural rash in the last 12 months” has been shown to correlate well with diagnosis by a physician in a validation study performed in the UK on children aged 3–11 years. Sensitivity in this previous study was 84% and specificity was 93%. In addition, the ISAAC eczema questionnaire has been used for studies on pre-school children. Although questions for diagnosis have been validated for eczema in 4–11-year-olds and for asthma in children aged 1–6 years, the ISAAC questionnaire has not been validated for parental information regarding preschool children. However, we consider that it is unlikely that there was differential misclassification; random misclassification would mean that any bias in our estimates was towards null.
Currently, there is no clear definition of persistence of eczema, which is consistent as reported by Williams. Illi and Möhrenschlager considered eczema as persistent when signs of the disease were present at different points of time. In our study, persistence of eczema was defined as having had eczema at least three times. Therefore, the risk of including children with “short-term rashes only” might be low, but we cannot exclude the possibility that some children classified as having persistent eczema had longer symptom-free intervals. It would have been advantageous to assess the prevalence of eczema more often during the study period.
Based on the results of our study, further evidence is required to unravel the underlying mechanisms of eczema in early childhood leading to asthma. Although we confirmed a relationship between childhood eczema and incident asthma and rhinitis, the association between childhood eczema and later asthma and rhinitis might still be separate and sequential, but are otherwise unrelated in the background of an atopic phenotype. Because the relationship between childhood eczema and incident asthma and rhinitis was temporal, strong, and linear, our findings suggest that the relationship might be causal. In this regard, impaired skin function might hypothetically be one explanatory factor, and the effect of early and successful treatment of eczema should be explored regarding the incidence of asthma as one outcome measure[30, 31]. Further, it might be beneficial to estimate if objective measured sensitization (IgE) modifies or confounds the eczema/asthma relationship in future studies. Our study results have important implications for patient management since asthma can lead to high impairment and costs.