What makes preschool wheeze persist as childhood asthma? - Development of dynamic ribonucleic acid biomarkers for diagnosis and prognosis

Bakgrund:

Asthma is a complex disease with genetic and environmental contribution. No biomarkers exist that could accurately diagnose or prognose asthma, predict the outcome, monitor the progression or the effect of treatment. Our results suggest that childhood asthma patients and their subtypes can be distinguished by blood transcriptomics. Also, we could identify longitudinal epigenetic patterns in asthmatic children indicating activation of eosinophils and cytotoxic Tcells.

Målsättning:

We aim to characterize the viral, genetic and immunological factors for acute childhood asthma. We will also evaluate the importance of early airway infections and interaction between specific viruses, allergy, and genetic predisposition for the risk of persistent asthma. We hope to develop a molecular tool to complement the clinical diagnosis of asthma.

We aim to discover and adopt novel RNA-based biomarkers to diagnose asthma, monitor disease progression, predict its outcome and study treatment effects. Arbetsplan: 156 children (<4 yrs) with acute wheeze and 102 controls have been recruited at Astrid Lindgren Children´s Hospital. For cases, a revisit after 2-4 m is followed by annual visits until schoolage with biological

samples taken at each visit. Global methods will be used to identify genetic variants, gene expression profiles and epigenetic differences between the same children with acute wheeze and in remission, and healthy controls. Sequencing and microarrays will be used. In the same children longitudinal analysis of allergy and inflammatory markers are performed.

Betydelse:

We aim to classify children with acute wheeze based on the combination of clinical criteria, airway microbes, genetic and epigenetic profiles. If childhood asthma patients and their subtypes can be distinguished by blood transcriptomics this could result in a molecular diagnostic and prognostic tool to complement todays clinical diagnosis.We have identified biomarkers of gene expression profiles at acute wheeze that with high accuracy predicts asthma medication at school age. The biomarkers are also associated to lung function, but need independent verification.

Molecular pathways resulting in novel target for treatment of childhood asthma may even be identified. Respiratory infections are associated with asthma. Infectious agents are potential treatment targets and understanding their effect on asthma development is important. Increased knowledge, can improve treatment strategies.