Protective and risk factors for childhood asthma in observational birth cohorts : the role of vitamin D and allergic rhinitis

Summary
Background: Asthma is an inflammatory disease of the airways of the lung. There has been an increase in the prevalence of asthma and other allergic diseases over the past decades and, due to its high prevalence, it is of major public health concern. The reasons for this increase are still largely unknown, but interactions between various types of environmental exposures in populations with different genetic backgrounds have been proposed. Complicating matters, childhood asthma is not one disease but rather a syndrome characterised by several distinct wheezing phenotypes, rendering research even more challenging. The best way to research risk and protective factors is with birth cohorts that follow children from birth over the first years of their life, allowing temporal sequence of exposure and the development of asthma or allergic diseases to be analysed.
Aim: The aim of the present thesis was to achieve an overview of birth cohorts on asthma and allergic diseases; to investigate potential risk and potential protective factors for the development of asthma in childhood; and to determine whether a tool to help monitor children with respiratory diseases throughout their life would be necessary and helpful.
Methods: The overview of birth cohorts was achieved with a systematic PubMed search of all existing birth cohorts on asthma and allergic diseases. Vitamin D was investigated as a potential protective factor within the Protection against Allergy-Study in Rural Environments (PASTURE) birth cohort, which is an ongoing observational birth cohort on the development of allergic diseases in 5 European countries. Over 1,100 pregnant women were enrolled and their offspring is being followed up to the age of 6 years.
Allergic rhinitis was investigated as a potential risk factor within the German Multicentre Atopy (MAS) study which is another observational birth cohort on the development of atopic diseases in early childhood in five German cities. Over 1,300 children were followed from birth to the age of 13 years.
Lung function reference equations were developed using data from the LuftiBus project, (Germany, Switzerland, Austria, Finland and France)which is a mobile bus equipped with flow-sensing spirometers that tours the greater Zurich (Switzerland) area and offers spirometry measurements to the general population. Spirometry data are recorded electronically along with data on basic health and lifestyle information.
Results: An overview of birth cohorts on asthma and allergic diseases with special emphasis on risk and protective factors is presented.
Within the PASTURE cohort, vitamin D supplementation during pregnancy was shown to increase cord blood mRNA levels of Immunoglobulin-Like Transcripts (ILT)3 and ILT4, which are two inhibitory receptors on tolerogenic dendritic cells. This finding may point towards an early induction of tolerogenic immune responses by maternal vitamin D intake, potentially influencing the prenatal immune system and possibly the development of atopic diseases.
Within the MAS cohort, allergic rhinitis in preschool children was shown to be a predictor for subsequent wheezing onset. Preschool children with rhinitis might thus benefit from early assessment of allergic sensitization to identify the children at high risk of wheezing.
Within the LuftiBus project, the lung function data allowed the development of spirometry reference equations for a central European population between 8 and 90 years of age that can be implemented in a wide range of clinical settings.
Conclusion: During the last decades many risk and protective factors for the development of asthma were identified but only a few have enough evidence to issue population based recommendations. As protective factor, vitamin D supplementation during pregnancy may influence the prenatal immune system and play a role in the development of atopic diseases. As risk factor, allergic rhinitis was found to be a precursor for subsequent wheezing onset. Both factors can be influenced and prospective studies are needed to determine whether they may change the prevalence of asthma and other allergic diseases. The spirometry reference equations developed are a useful tool for clinicians working in central Europe and following patients over years. As they spans across all ages they are practical to track disease progression from childhood to adulthood and assess effectiveness of therapy over time.
The PhD thesis allowed a few more insights to be added to the complex entity of respiratory diseases in childhood, helping to understand risk and protective factors. The spirometry tool developed may help clinicians monitor children with respiratory diseases throughout their life.
In the years to come, more research is needed to determine whether the protective and risk factors studied can be influenced and whether their alteration has any effect on the incidence of asthma.