IV: Introduction
Asthma is a heterogeneous illness, characterized typically by persistent airway inflammation, history of respiratory symptoms such as shortness of breath, wheeze, chest tightness and cough which differ in severity over time along with variable restriction of expiratory airflow. The limiting airflow could later become persistent.1 The inflammatory pathway starts with the development of type 2 (Th2) T helper cells which are dependent on dendritic cells (antigen presenting cells) and certain cytokines such as IL-4 and IL-13.2 Additionally, airway epithelial cells and smooth muscle cells tend to play important roles in influencing or perpetuating the airway reaction to T helper type 2 cytokines.3
While the majority of asthmatic children have minor to severe disease and can be adequately controlled with standard medicines, a minority (around 5%) of children with asthma suffer from a severe uncontrolled disease that carrying a significant health and socio-burden, and requires additional but still limited treatment options.4 While asthma is already known to have large genetic component, several studies indicate that genotype variation contributes significantly to the heterogeneity of asthma phenotype and morbidity.5
Epithelial genes directly induced in asthma include the transmembrane protein 178 (TMEM178), which is a negative regulator of the nuclear factor of activated T-cells (NFAT). Inflammation caused by NFAT is known actor in asthma pathogenesis.6 Chloride pathway, calcium activated family member 1 (CLCA1) associated with mucus hyper-secretion,airway hyperreactivity, and hyper-eosinophilia in asthma7 serpin peptidase inhibitor, clade B, member 2 (SERPINB2) (also known as plasminogen activator inhibitor-2) which belongs the serpin class of proteases and functions to inhibiting plasminogen activation and promoting fibrin formation and deposition. In turn, Periostin (POSTN) which is an integrin ligand and extracellular matrix protein with function in cell adhesion, cell motility, and matrix remodeling.8 FKBP5 which is a hsp90 co-chaperone that control the sensitivity of glucocorticoid receptor (GR).9
Therefore, we aimed to study epithelial cell genes (TMEM178, FKBP5, CLCA1, SERPINB2 and Periostin) in childhood asthma and their utility in predicting asthma severity atopic status and level of control.