European approach to therapy optimization in pediatric asthma A precision medicine strategy

Asthma is a heterogeneous disease with diverse inflammatory mechanisms and clinical presentations, necessitating a shift from a one-size-fits-all approach towards a precision medicine strategy. This thesis aims to enhance the phenotyping of moderate-to-severe pediatric asthma by identifying potential biomarkers and assessing risk factors to optimize management and treatment.
Part 1 provides an overview of pediatric asthma pathophysiology, highlighting recent advances in treatment and the role of biomarker discovery in phenotyping. The impact of emerging technologies, such as digital health tools and omics approaches, in improving precision medicine is also discussed.
Part 2 systematically reviews the influence of common risk factors on exhaled volatile organic compounds (VOCs) in obstructive pulmonary diseases, including asthma. Understanding these confounders is crucial for conducting breathomics-based studies.
Part 3 investigates pediatric asthma medication use and inhaler device types. The SysPharmPediA study reveals that uncontrolled asthma persists in some children despite adherence to guideline-based treatments. Additionally, ICS inhaler device types (metered-dose inhalers (MDIs) versus dry powder inhalers (DPIs)) are shown to be associated with altered saliva microbiome compositions, suggesting a potential link between inhaler device types and oral microbiome.
Part 4 explores blood inflammatory phenotypes using eosinophil and neutrophil counts in pediatric asthma. Four distinct inflammatory phenotypes (eosinophilic, neutrophilic, mixed, and paucigranulocytic) are identified, each associated with different asthma burdens and inflammatory mediator profiles. This phenotyping approach may help and guide the personalized treatment of pediatric asthma.
Part 5 integrates all the findings, addresses methodological challenges, and proposes future research directions. This thesis underscores the need for personalized treatment strategies in pediatric asthma to improve clinical outcomes and children's quality of life.