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A TRranslational approach to Identify Biomarkers for Asthma and Lung function impairment

Periodic Reporting for period 2 - TRIBAL (A TRranslational approach to Identify Biomarkers for Asthma and Lung function impairment)

Reporting period: 2019-06-01 to 2020-11-30

Persistence of childhood asthma into adult life is associated with lung function impairment and increased risk of chronic obstructive pulmonary disease, COPD. Evidence is now emerging that adult diseases, like COPD, may have their origin early in life. However, there are no established biomarkers that can accurately monitor asthma progression or predict development of COPD in adults, and the role of early life exposures and events has yet to be defined. Although tobacco smoking is known to cause respiratory disease, robust studies on associations in young adults are still sparse.

COPD is estimated by the WHO to become the 3rd leading cause of death by 2030. The estimated costs for our society are immense, let alone impaired quality of life and suffering for affected individuals. In TRIBAL I will address the time point during childhood when disease processes were initiated with the ultimate goal to enable preventive efforts as early as possible and guide research on drug development for asthma and COPD.
During the first TRIBAL scientific reporting period, we have as planned, had a major focus on data collection. TRIBAL is based on the BAMSE birth cohort study established in 1994 and by June 2019, we had completed the 24-year study follow-up. Out of 4,089 original study participants more than 3,000 (75%) answered an extensive electronic questionnaire focusing on chronic respiratory disease symptoms, non-communicable diseases, life-style factors and environmental exposures. In addition, participants have completed the clinical follow-up including advanced lung function measurements, blood sampling and nasal epithelial cell brushing as outlined for the TRIBAL project. In parallel with TRIBAL data collection, data cleaning, database management and quality control activities have been undertaken in order to prepare the 24-year follow-up data for analyses.

Our new TRIBAL results on chronic respiratory disease in young adults provides robust evidence that early life exposures (air pollution, tobacco smoke) and lung insults (pneumonia or viral bronchitis) do matter for respiratory health in young adults and that classic “smokers’ diseases” such as chronic bronchitis and irreversible lung function impairments are not uncommon in this age group. Our results show that prevention of these conditions would be possible with targeted efforts.

Experimental analyses are now commencing in TRIBAL to unravel underlying disease mechanism for respiratory diseases in young adults, with the overall aim to provide new knowledge that may guide drug development and intervention programs.
TRIBAL is truly a translational research project that accommodates both inter and cross disciplinary research efforts. Our proposed advanced immune phenotype analyses are unprecedented in sample size and research focus, and the same applies to metabolomic profiling of historial biospeciemens from early childhood. Also for the deep clinical phenotyping, multiple breath washout (MBW) measurements in around 2000 subjects is unprecedented in terms of sample size and research questions in point. As such, at the end of the project I expect that we will have contributed significantly with knowledge to guide clinical follow-up programs of children at risk of chronic respiratory disease, as well as identified mechanisms and key disease drivers that will allow for targeted pharmaceutical or life-style intervention efforts.

Thanks to TRIBAL and the BAMSE24-year data collection, we found ourselves in a unique positive for COVID-19 studies on young adults. Therefore, we have now launched a specific BAMSE COVID-19 follow up that firmly builds on TRIBAL data and achievements. In this new project, we propose a new measurement wave with serological analyses of SARS-Cov-2 immunity, clinical COVID-19 follow-up, risk factor assessment, elucidations of underlying genetic and immunologic factors, and new lung function tests to evaluate long-term pulmonary effects.