Trans-generational and life-course perspective on environmental and life-style factors in relation to asthma, allergy and COPD

Every fifth child in Norway has asthma and one in ten adults suffers from COPD. COPD is estimated to be the third most common cause of death worldwide by 2030. The Shanghai Declaration 2011 calls for early life prevention of non-communicable diseases. We are investigating the relation of smoking, obesity and microbial environment with asthma and COPD over generations and over the life span; to assess the relative importance of exposure before conception and at different stages of life. In order to meet this aim the RHINESSA generation study (www.rhinessa.net) uses the large population based cohorts ECRHS and RHINE that have been followed with extensive characterization over 20 years, and investigate their offspring and parents in the study centres where that is feasible ?ten study centres in Northern Europe, Spain and Australia. The third follow-up of RHINE is complete in all study centres (n=13500), as is the third follow-up of the ECRHS study (n=7040). Data from both studies are cleaned and available for analyses. The RHINESSA web-based study has data for about 9000 offspring from all study centres; these data are cleaned and available for analysis. Clinical investigation of offspring is complete in some study centres including Bergen, and a test dataset ready for analysis. A recent publication showed that father's smoking and occupational welding prior to conception was related to almost doubled asthma risk in his children, and that father's smoking debut in early puberty was related to tripled asthma risk in his children. We also found that paternal grandmother?s smoking increased asthma risk, and results suggesting that father?s exposure in utero modified effects of father?s own smoking with regard to asthma in his future offspring. We are currently investigating this in another setting and preliminary results appear to confirm these findings. This research is novel and has most important implications ?public health planners need to account for the concept that the environment of young men may be of great importance for the health of their future children. Another important publication showed that early life/preconception environment influenced decline in lung function ? a measure reflecting lung ageing. Thus, not only lung function level and growth of the lungs appear to be partly determined early in life, but also the continuous process of lung ageing, decades later. Our analysis showed that early life factors were related to accelerated lung function decline particularly among persons who smoked. Thus, early life development might possibly impact lung function decline decades later by influencing susceptibility to adult insults like smoking. We recently published supporting evidence on interplay between maternal smoking in early life and own smoking in adulthood based on analysis of another study. A paper we published last year suggested that early life disadvantage increased susceptibility to occupational exposure to cleaning agents. This line of research is most important in order to understand how transgenerational and early life factors may impact on lung health through the life-span, and also has public health implications with regard to identification of vulnerable groups in which intervention may be particularly useful. Further, we have published a paper showing how asthma in adulthood was related to growing up in urban/rural environments, most likely reflecting impact of early life microbial environment on subsequent asthma, an area we are exploring further with measurements of microbiome. We have also published supportive research on various environmental exposures and various lung health outcomes, as well as studies validating tools needed for further inter/transgenerational research.

Background: Every fifth child in Oslo has asthma and one in ten adults suffers from COPD. COPD is estimated to be the third most common cause of death worldwide by 2030. In response, Europe 2020 and WHO invite to action against the threat of the global in crease in chronic diseases. The WUN Shanghai Declaration of May 2011 calls for early life prevention of non-communicable diseases. The impact of two main public health risks, smoking and obesity, on asthma/COPD is not clear. Smoking is a strong risk for C OPD, but it neither explains all COPD nor the large variation in lung function. There is limited understanding of the role of obesity in these diseases; asthma risk increases with obesity but end-stage COPD is related to under-nutrition. Research on feta l programming and epigenetic changes warrants a life-course and even trans-generational perspective. Novel data suggests that also the airway and gut microbiome may have impact on onset and progression of immunological diseases. Objective: To investigate the relation of smoking, obesity and microbiome with asthma and COPD over 3 generations and over the life span; to assess the relative importance of exposure before conception and at different stages of life. Methods: Offsprings (n=30000) of participants of the ECRHS/RHINE studies and the Bergen COPD Cohort will be investigated by questionnaire and biospecimens in ten centers, 9000 of these by clinical investigation. The grandparents will be investigated with questionnaire and registry data. Feasibility: This is a unique study, based on the successful ECRHS/RHINE with extensive data on index subjects, established infrastructure, world-leading researcher networks and excellent registry data. Impact: For policy makers, a basis for health education and effi cient preventive strategies. In clinical medicine, targeted guidelines on smoking and dietary intervention. For the scientific community, new insight in microbiota, life-course and trans-generational mechanisms