Single cell genomics of asthma remission
Asthma is a worldwide problem, with an estimated 300 million affected individuals. The prevalence of asthma is highest between 10 and 25 years and gradually decreases at higher age, with remission rates of asthma becoming higher. In adulthood average remission rates of asthma are approximate 2% per year, with a higher chance to become in remission with an earlier onset of asthma, less severe airway obstruction, more severe bronchial hyperresponsiveness, and cessation of smoking. Studies on asthma remission have often been hampered by important variation in criteria for definition of asthma remission. Clinical remission was defined as the absence of asthma symptoms and no use of asthma medication. Complete remission of asthma was defined as the absence of asthma symptoms, no use of asthma medication, normal lung function and no bronchial hyperresponsiveness. In a longitudinal study by Vonk et al. Thorax 2004; 59:925-929 it was found that clinical remission occurred in 30% and complete remission in 22% of all cases.
We still have minimal understanding of the cellular and molecular mechanisms that determine whether or not asthma persists or undergoes apparent spontaneous resolution. Further research in clinical studies is essential for the identification of new therapies. The aim of the current project is to determine the underlying cell-type specific gene expression patterns involved in remission of asthma by single cell transcriptomic profiling of CD4+ T Lymphocytes and eosinophils (and potentially B cells, ILC2 and bronchial epithelial cells) from 4 patient groups for whom biopsy, genetic and phenotypic data will become available.
High-throughput, high resolution single cell transcriptomic profiling of the immune cell populations in the blood and airway walls will provide unprecendented insights into the cellular immune pathways involved in asthma and its remission, and are expected to lead to novel diagnostic and therapeutic targets in asthma and its remission.