Periodic Reporting for period 4 - TRIBAL (A TRranslational approach to Identify Biomarkers for Asthma and Lung function impairment)
Reporting period: 2022-06-01 to 2024-02-29
Persistence of childhood asthma into adult life is associated with lung function impairment and increased risk of chronic obstructive pulmonary disease, COPD. 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. 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.
The overall aim was to identify and extensively phenotype young adults with persistent asthma and pre-stage COPD by detailed lung function assessment and to identify biomarkers for asthma and lung function impairment.
The overall aim was to identify and extensively phenotype young adults with persistent asthma and pre-stage COPD by detailed lung function assessment and to identify biomarkers for asthma and lung function impairment.
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.
Clinical evaluation of asthma subjects has been performed with longitudinal approaches to evaluate asthma from birth to adulthood to identify those with a persistent asthma phenotype. Importantly, the persistent asthma trajectory group showed more signs of type 2 inflammation than the adolescent-onset trajectory group, and our results highlight the need of identifying patients with adolescent asthma to optimize care, because they suffer the same lack of asthma control as those with persistent asthma. Our immune profiling of asthma subjects revealed distinct cellular phenotypes in overweight/obese individuals with asthma, and targeted proteomics analyses revealed strong associations with biomarkers such as CC16 and CK with persistent asthma.
Identification of subjects with pre-stage COPD and chronic airway disease have resulted in several important findings: Chronic bronchitis is rather common at this young age (5.5%), with active smoking, air pollution exposure and a short period of breastfeeding as significant risk factors. The prevalence of airflow limitation is also rather common (7.2%), whereas lung function impairment corresponding to a COPD diagnosis (i.e. chronic airflow limitation) was, as expected, less common (2%). Several indicators of early life airway infections and respiratory disease as well as environmental exposures (air pollutants in particular) were risk factors associated with COPD according to lung function at this young age. Lung function trajectories from childhood to adulthood have been particularly evaluated with novel findings in relation to lung function catch-up and growth failure. Protein biomarkers linked to impaired lung function have also been identified. Very importantly, improved air quality leads to better lung function growth, which sends a very important message to policy makers.
Clinical evaluation of asthma subjects has been performed with longitudinal approaches to evaluate asthma from birth to adulthood to identify those with a persistent asthma phenotype. Importantly, the persistent asthma trajectory group showed more signs of type 2 inflammation than the adolescent-onset trajectory group, and our results highlight the need of identifying patients with adolescent asthma to optimize care, because they suffer the same lack of asthma control as those with persistent asthma. Our immune profiling of asthma subjects revealed distinct cellular phenotypes in overweight/obese individuals with asthma, and targeted proteomics analyses revealed strong associations with biomarkers such as CC16 and CK with persistent asthma.
Identification of subjects with pre-stage COPD and chronic airway disease have resulted in several important findings: Chronic bronchitis is rather common at this young age (5.5%), with active smoking, air pollution exposure and a short period of breastfeeding as significant risk factors. The prevalence of airflow limitation is also rather common (7.2%), whereas lung function impairment corresponding to a COPD diagnosis (i.e. chronic airflow limitation) was, as expected, less common (2%). Several indicators of early life airway infections and respiratory disease as well as environmental exposures (air pollutants in particular) were risk factors associated with COPD according to lung function at this young age. Lung function trajectories from childhood to adulthood have been particularly evaluated with novel findings in relation to lung function catch-up and growth failure. Protein biomarkers linked to impaired lung function have also been identified. Very importantly, improved air quality leads to better lung function growth, which sends a very important message to policy makers.
TRIBAL is truly a translational research project that accommodates both inter and cross disciplinary research efforts. Our advanced immune phenotype analyses are unprecedented in sample size and research focus, and the same applies to biomarker profiling of historial biospeciemens from early childhood. Also for the deep clinical phenotyping, advanced lung function measurements in around 2000 subjects is unique in terms of sample size and research questions in point.
The three main findings - beyond state of the art - were:
1) Impaired lung function occur at all ages – from childhood to adulthood – and several risk factors are now identified that allow for prevention of chronic respiratory disease (Wang et al, Thorax 2021 and ERJ 2021). KI press-release from 2021 here: https://www.eurekalert.org/news-releases/591892
2. Lung function levels typically track with age in most people, but both lung function catch-up and growth failure may occur during childhood and adolescence (Wang et al, AJRCCM 2023). Improved air quality (i.e. lower air pollution levels) leads to improved lung function in children (Yu et al, ERJ 2023). KI press release here: https://news.ki.se/childrens-lung-capacity-improved-in-cleaner-air
3. A new web-tool launched for monitoring lung function growth and decline (Melén et al, Lancet 2024). https://news.ki.se/innovative-digital-tool-enables-monitoring-of-lung-function-over-time-0
The three main findings - beyond state of the art - were:
1) Impaired lung function occur at all ages – from childhood to adulthood – and several risk factors are now identified that allow for prevention of chronic respiratory disease (Wang et al, Thorax 2021 and ERJ 2021). KI press-release from 2021 here: https://www.eurekalert.org/news-releases/591892
2. Lung function levels typically track with age in most people, but both lung function catch-up and growth failure may occur during childhood and adolescence (Wang et al, AJRCCM 2023). Improved air quality (i.e. lower air pollution levels) leads to improved lung function in children (Yu et al, ERJ 2023). KI press release here: https://news.ki.se/childrens-lung-capacity-improved-in-cleaner-air
3. A new web-tool launched for monitoring lung function growth and decline (Melén et al, Lancet 2024). https://news.ki.se/innovative-digital-tool-enables-monitoring-of-lung-function-over-time-0