Status: Funded - Open
The early life metabolome in the origins of childhood asthma and allergy
Bo Chawes, M.D., Ph.D.
BACKGROUND: Childhood asthma and allergy presumably arise from gene-diet-microbe interactions during pregnancy and early infancy causing immune deregulation and subsequent chronic inflammation. The underlying biological pathways from low-grade inflammation to clinical disease presentation are however poorly understood.
GAP: We propose to investigate whether early life metabolic dysregulation is an intermediate step leading from low-grade inflammation to clinical disease penetrance.
HYPOTHESIS: Programming of childhood asthma and allergy disease is likely reflected in early metabolic changes leading to disease penetrance. Metabonomics may provide early biomarkers of disease development and disease control.
METHODS: The study is a translational research program bridging high quality clinical birth cohort data and an extensive biobank with unique laboratory and systems biology analytical expertise in metabonomics. Subjects comprise children of (1) COPSAC2000 (N=411) and COPSAC2010 (N=700), two ongoing clinical birth cohorts followed closely at visits to our research unit for development of asthma and allergy from birth till age 7yrs; and (2) COPSACregistry (N=1500), a case-control register-based cohort of children hospitalized for asthma and matched controls. Metabolic profiling will be performed in (1) COPSAC2000 (1600 serum and 1600 urine samples from ages ½, 1½, 4 and 6yrs), (2) COPSAC2010 (1400 serum and 1400 urine samples from ages ½ and 1½ yrs), and (3) COPSACregistry (1500 amnion fluid samples and 1500 dry blood spots).
IMPACT: Identification of metabolic phenotypes early in life prior to disease onset will improve our understanding of underlying disease mechanisms and may provide a biomarker of disease progression and control with the ultimate goal of improved prevention, diagnosis and treatment of childhood asthma and allergy.