Precision medicine to diagnose asthma in preschool children: comparison of clinical scores, lung function, biomarkers, and genetic tests

Asthma is an umbrella term for several phenotypes and endotypes. It most frequently begins before the age of 6, with significant morbidity and decline in lung function occurring among all pediatric age groups. A delay in the diagnosis of asthma in preschoolers is associated with more severe exacerbations. One problem clinicians face is how to diagnose asthma early in its course; epidemiological phenotypes (i.e., transient, persistent, late-onset, and mid-childhood remitting wheeze) can only be ascertained retrospectively, and clinical phenotypes (e.g., episodic viral and multi-trigger wheeze) suffer from high variability and no relation with underlying pathological airway markers. International guidelines recommend that lung function tests and biomarkers be performed before diagnosing asthma in children under 5 years old. However, spirometry and airway resistance measures are typically normal in most preschoolers with asthma, and blood eosinophil counts, the most reliable biomarker for inhaled corticosteroid therapy, vary widely over time. Clinical predictive indices can help in predicting and diagnosing asthma in preschoolers. At least eight clinical predictive indices have been published, and four have been validated (API, PIAMA, APT, and PARS). Here, we will review the challenges of diagnosing asthma in the preschool age, the utility of several clinical indices, and the usefulness of incorporating biomarkers such as volatile organic components, exhaled breath condensate, and gene expression. Finally, we will discuss existing gaps and future directions for research in the field.