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Project - The PASTURE/ EFRAIM cohort study design

The EFRAIM project is the continuation of the assessment of the PASTURE birth cohort. In addition the EFRAIM project comprises further analysis of blood and environmental samples collected from the cohorts between birth and today, as well as more data analysis.

PASTURE is a birth cohort of children born to farm and non-farm women from rural areas across Europe. Five study centres in Austria, Germany, Finland, France and Switzerland enrolled over 1,000 children. The presence of asthma and allergic illnesses was assessed in the parents before their child’s birth and in the children at birth, at age 2 and 12 months. Particular attention was given to environmental microbial and dietary exposure as well as to the child’s maturing immune response early in life. In addition genetic factors were taken into account. 

In part supported by the FORALLVENT EU-project, and in part by the 5 field centres own funding, the contact to the cohorts was maintained by follow up questionnaire assessments at age 1.5, two, three, four and five years. Furthermore, environmental samples for microbial and dietary determinants were collected. Maturation of the immune system was again investigated in blood samples collected at age 4.5 years. 

EFRAIM is the continuation of follow up of the PASTURE birth cohort until age 6. The assessment includes a comprehensive questionnaire on health and environmental exposures. A clinical examination comprises the assessment of the prevalence of atopic dermatitis. Comparable to a routine clinical assessment a lung function test determines respiratory parameters. Concentrations of exhaled nitric oxide are measured to identify inflammatory airway responses in the cohort children. Atopic sensitization is determined as the presence of specific serum IgE antibodies against common inhalant and food allergens. Investigations on the development of the innate and adaptive immune response continue in blood samples of the 6 year olds. These measures include the assessment of gene expression of receptors for the recognition of microbial molecules, the investigation of the differentiation and function of immunologically active blood cells and the assessment of molecules stimulating and modulating the adaptive immune response. Moreover, environmental samples are collected again for the follow up of microbial and dietary exposures in the cohort.

 

Many PASTURE samples, which had been collected before age 6 have not yet been analysed. The EFRAIM project provides financial resources for the continuation of this work. Early life factors are particularly addressed such as putatively protective factors in breast milk and serum markers of the antioxidant vitamins E and D. Serum levels of ω3- and ω6- polyunsaturated fatty acids and their ratio will be determined and will be related to allergic outcomes. Mucosal barrier function will be measured by different direct and indirect markers. Relevant qualitative and quantitative microbial exposure will be assessed by fingerprinting of faecal, cow’s milk and house dust samples collected in the first years of life. Epigenetic phenomena will be analysed in blood samples taken at different time points.

The availability of large numbers of consecutive samples covering immune responses on different levels (receptors, RNA, signalling and modulating proteins, regulating cytokines, immunologically active cells) and genetic information in the five rural birth cohorts allows dissecting the maturation of the immune system under well defined environmental conditions in utero up to school age as shown schematically in the figure below.

 To meet the challenge of this large study, a consortium of experts of several European countries accumulates and shares expertise in the fields of immunology, genetics, microbiology, epidemiology, paediatrics, dust analysis, statistics, milk sciences and vaccine development. The consortium provides laboratory facilities of high standards and up to date methodology.