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Understanding the mystery of the crying infant

Pediatric Research volume 97, pages 1433–1434 (2025)Cite this article

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Until the 19th century fever was considered to be a singular disease, but gradually through careful observation, the development of tools to measure and analyse, and advances in the knowledge of physiology and microbiology, this perception changed.1 Understanding the features of fever (e.g. age, pattern, duration) in association with physical symptoms (e.g. cough, vomiting) and stigmata (e.g. rash) allowed clinicians to recognise the expressed phenotype of disease and eventually to create an evidence base for diagnosis supported by investigation if required.

Many conditions that started as monolithic entities have, over time, been recognised as heterogeneous groups, with the original description becoming an umbrella term for several sub-phenotypes. Add to this the further recognition of endotypes (underlying pathological mechanisms) and genotypes (genetic determinants) and the complexity of disease expands significantly. Childhood asthma is a notable example of this evolution. While initially defined by the finding of intermittent, reversible wheeze, there are now multiple asthma phenotypes and the diversity continues to unfold.2 Phenotypes might be recognised through the separation of distinct clinical features or investigations however sometimes they can only be seen in retrospect, being difficult to predict at the time of presentation. Understanding asthma phenotypes and endotypes has been crucial for the application of personalised medicine. It helps in tailoring treatment based on the patient’s specific inflammatory profile or response pattern. For instance, understanding pathways of allergy and inflammation in asthma has led to biologic therapies (e.g., mepolizumab, dupilumab) that are effective for certain endotypes but which may not benefit others.2,3

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Authors and Affiliations

  1. Children’s Health Ireland at Temple St, Dublin 1, Ireland

    Jonathan Clarke & John J. Fitzsimons

  2. Department of Paediatrics, RCSI, Dublin, Ireland

    John J. Fitzsimons

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  1. Jonathan Clarke
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  2. John J. Fitzsimons
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Correspondence to John J. Fitzsimons.

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Clarke, J., Fitzsimons, J.J. Understanding the mystery of the crying infant. Pediatr Res 97, 1433–1434 (2025). https://doi.org/10.1038/s41390-024-03724-0

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