Allergic March of Asthma Eczema and Rhinitis

Mariona Pinart, PhD CREAL-Centre for Research in Environmental Epidemiology ISGlobal alliance Parc de Recerca Biomèdica de Barcelona Doctor Aiguader, 88 | 08003 Interveiw with:
Mariona Pinart, PhD
CREAL-Centre for Research in Environmental Epidemiology
ISGlobal alliance
Doctor Aiguader, 88 | 08003 Barcelona What are the main findings of the study?

Answer: The study examined 23.434 children at 4 and 8 years from 12 ongoing European population-based birth cohort studies that recorded information on current eczema, rhinitis, and asthma from questionnaires and serum-specific IgE to six allergens. We wanted to assess how often eczema, rhinitis and asthma coexist in the same children (comorbidity) and whether the occurrence of comorbidities was due to causality or casualty and finally we wanted to examine whether the occurrence of comorbidity was modified by IgE sensitization.

We found that comorbidity affects about 4% of children aged 4–8 years and that about 50% of this comorbidity is due to causality, suggesting that these diseases share common pathophysiological mechanisms. In addition, we found that children comorbidity at age 4 are 30 to 60 times more likely to have comorbidity at age 8 years, suggesting that the presence of comorbidity at age 4 years is a strong determinant of comorbidity at age 8 years. Even children with one single disease are also at high risk of developing comorbidity by age 8 years. Interestingly, we found that not only comorbidity is present in children both sensitized and not sensitized to IgE but also that only 38% of incident comorbidity at age 8 years is explained by the presence of IgE sensitization at age 4 years. Were any of the findings unexpected?

Answer:  Evidence supports that the atopic march is a useful paradigm to describe the sequential progression of eczema, rhinitis and asthma suggesting that atopy (IgE sensitization) could be the underlying mechanism linking these diseases to each other. Unexpectedly, we found that the tendency of these diseases to overlap is stronger in children without IgE sensitization and that incident comorbidity is not fully explained by IgE sensitization, suggesting that IgE sensitization can no longer be considered the dominant causal mechanism of the coexistence for these diseases. What should clinicians and patients take away from your report?

Answer:  First, comorbidity is more often observed than it would have been expected by chance, which means that comorbidity is a substantial public health problem and second, those children with one disease at age 4 years are 4-7 times more likely to develop comorbidity by age 8 years regardless of IgE sensitization, suggesting that clinicians have new evidence to support the design and implementation of health-care strategies for the management of comorbidity. What recommendations do you have for future research as a result of this study?

Answer:  Further research is needed to unravel the role of IgE sensitization as well as the other non-IgE-related underlying mechanisms linking these diseases to each other and that are therefore causally related to comorbidity. In this regard, our study is one the studies conducted in the EU-funded MeDALL (Mechanisms of the Development of Allergy) project which aims to generate novel knowledge on  the mechanism of initiation of allergy from early childhood to young adulthood. We are currently conducting other studies examining the inter-relationships between these diseases using other statistical approaches. Other on-going experimental studies on epigenetics, proteomics and transcriptomics within the frame of MeDALL may unravel the contribution of IgE sensitization to the development of allergic comorbidty as well as other pathophysiological mechanisms causally related to comorbidity, improve diagnostic and control strategies and ultimately may discover new targets for therapy.


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

Mariona Pinart PhD,Marta Benet BStat,Isabella Annesi-Maesano DSc,Andrea von Berg MD,Prof Dietrich Berdel MD,Prof Karin C L Carlsen MD,Prof Kai-Håkon Carlsen MD,Prof Carsten Bindslev-Jensen MD,Esben Eller PhD,Maria P Fantini MD,Jacopo Lenzi BStat,Ulrike Gehring PhD,Joachim Heinrich PhD,Cynthia Hohmann Dipl Psych,Prof Jocelyne Just MD,Thomas Keil MD,Marjan Kerkhof PhD,Prof Manolis Kogevinas MD,Prof Sibylle Koletzko MD,Prof Gerard H Koppelman MD,Inger Kull PhD,Prof Susanne Lau MD,Erik Melén MD,Prof Isabelle Momas PhD,Daniela Porta MSc,Prof Dirkje S Postma PhD,Fanny Rancière PhD,Prof Henriette A Smit PhD,Renato T Stein MD,Christina G Tischer PhD,Maties Torrent PhD,Prof Magnus Wickman MD,Alet H Wijga PhD,Prof Jean Bousquet MD,Prof Jordi Sunyer MD,Xavier Basagaña PhD,Stefano Guerra MD,Judith Garcia-Aymerich PhD,Prof Josep M Antó MD
The Lancet Respiratory Medicine – 14 January 2014
DOI: 10.1016/S2213-2600(13)70277-7