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Atopic phenotypes and their implication in the atopic march.

Adnan Custovic1, Darije Custovic2, Blazenka Kljaić Bukvić3,4,5

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Summary

The traditional "atopic march" concept of sequential eczema, asthma, and allergic rhinitis development is challenged. Data-driven analysis suggests a multimorbidity framework better explains the co-occurrence of these allergic conditions.

Keywords:
allergic rhinitisallergic sensitizationasthmaatopic marcheczemamachine learningpersonalized medicine

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Area of Science:

  • Allergy and Immunology
  • Pediatric Allergy
  • Computational Biology

Background:

  • Eczema, allergic rhinitis, and asthma are considered atopic diseases with complex, multifactorial origins.
  • The "atopic march" hypothesis posits a sequential development: eczema in infancy, followed by asthma, then allergic rhinitis.
  • This linear progression model may not fully represent the heterogeneity of allergic disease phenotypes.

Purpose of the Study:

  • To review evidence on the multimorbidity of eczema, asthma, and rhinitis.
  • To evaluate the implications of data-driven analyses on the atopic march concept.
  • To explore alternative frameworks for understanding the co-occurrence of these allergic conditions.

Main Methods:

  • Literature search of PubMed and Web of Science for peer-reviewed articles up to July 2020.
  • Application of a Bayesian machine learning framework to birth cohort phenotypic data.
  • Analysis of data to assess the validity of the atopic march hypothesis.

Main Results:

  • Bayesian machine learning analysis of rich phenotypic data from birth cohorts revealed significant heterogeneity.
  • The postulated linear progression of symptoms (atopic march) does not adequately capture the diverse allergic phenotypes.
  • Eczema, wheeze, and rhinitis co-occur more frequently than expected by chance.

Conclusions:

  • The relationship between eczema, asthma, and rhinitis is better understood through a multimorbidity framework, not a strict atopic march sequence.
  • Co-occurrence of these conditions does not imply a specific, progressive, or causal relationship.
  • A single mechanism, like allergic sensitization, is unlikely to underpin all multimorbidity manifestations of these allergic diseases.