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.