The nasal airway is lined by basal, ciliated and secretory epithelial cells similar to bronchial airway epithelium . As such, the nasal airway provides a readily accessible counterpart to the bronchial airway and may represent much of the pathology present in the asthmatic bronchial airway. Supporting this was a study of roughly 2300 genes expression in nasal and bronchial airway brushings, which revealed a close association between these 2 airway sites . In another study, differences in epithelial gene expression between the upper and lower airway epithelium largely disappear in patients with allergic rhinitis, with or without asthma .
The decision to perform our research on upper rather than the lower airway epithelium was inspired by its non-invasive sampling, which is more suitable in young children. It assists recruiting true pulmonary disease-free controls, which is not easy in researches using bronchoscopic specimen . It also allows patients with severe or uncontrolled asthma to be investigated without discontinuing their long-term inhaled corticosteroid asthma therapy, as nasal deposition can be considered negligible with the tools used in this study .
In the current study, TMEM178 relative gene expression levels showed significant down-regulation in asthmatic children when compared with control. In addition, TMEM178 expression levels decreased significantly with severity of asthma progression. Consistent with our results, Patel et al.  stated that TMEM178 expression decreases with the increase in asthma severity giving the known role of TMEM178 as a negative regulator of nuclear factor of activated T cells (NFAT). They hypothesized that TMEM178 plays a significant role in NFAT-induced severe asthma inflammation.
To estimate the performance characteristics of TMEM178 expression (2−ΔCt) for asthma severity prediction, the best cutoff point for 2−ΔCt of the expressed gene and the responsiveness (sensitivity and specificity) were analyzed, to our knowledge, for the first time. The expression of TMEM178 had a strong potential to predict different degrees of asthma severity .
In the present study, relative gene expression levels of CLCA1, SERPINB2 and periostin showed statistically significant up-regulation in epithelial airway cells of children with asthma, when compared with controls. Regarding asthma severity, relative gene expression levels of CLCA1, SERPINB2 and periostin showed no statistically significant differences between different groups. These results run in accordance with Mertens et al.  who stated that inflammation of allergic airways in asthma was characterized by signature of an airway epithelial gene consisting of periostin, CLCA1 and SERPINB2; this gene signature is suggested as a method for classification of asthma cases into phenotypes Th2-high and Th2-low. In another study, CLCA1, serpinB2 and periostin were up-regulated in asthmatics compared to healthy controls .
Sterk and Lutter  found that gene expression for IL13, periostin and CLCA1 were significantly up-regulated in asthmatic patients compared with control subjects. Additionally, greater expressions (up-regulation) of the IL-13 response gene signature (CLCA1, periostin and SERPINB2) were found in severe asthmatics compared to healthy controls .
CLCA1 was part of the CLCA (calcium-activated chloride channel regulator) family and performs an important role in the formation of goblet cell mucus from the respiratory tract epithelium. CLCA1 is also a main regulator for innate immune responses, in addition to regulation of mucus secretion. The secreted form of CLCA1 can serve as a signaling ligand that activates monocytes and alveolar macrophages in a dose-dependent manner, increase the levels of pro-inflammatory cytokines and chemokines (IL-1β, IL-6, IL-8 and TNF-α), and promote infiltration of inflammatory cells into the pulmonary epithelium and propria lamina. Accordingly, hCLCA1 in humans and its ortholog mCLCA1 in mice are suggested as a biomarker of inflammatory airway diseases (IAD) .
SERPINB2 is a protein coding gene which suppresses a serine protease and inhibits plasminogen activators and promotes formation of fibrin . Indeed, SERPINB2 gene expression that occurs during T helper type 2 cell allergic inflammation contributes to goblet cell metaplasia of airway epithelium and can modify epithelial-mesenchymal signaling, resulting in increased sub epithelial fibrosis . The overall impact is airway inflammation and bronchial hyper-responsiveness and epithelial remodeling, which are the main features of asthma .
Periostin is an IL-4 and IL-13 mediated extracellular matrix protein in epithelial airway cells and lung fibroblasts . In airway biopsies, the immunolocalization of periostin to the sub-epithelial zone indicates that it is basolaterally secreted into the underlying matrix. Periostin may interact with matrix proteins from this position to promote cell motility or epithelial–mesenchymal signaling that generate airway remodeling .
Herein, FKBP5 expression was increased in asthmatic children compared to control, however; the difference did not reach the border line of statistical significance. Likewise, FKBP5 showed no statistical variation between different asthma severity groups. In contrast, Singhania et al.  reported that FKBP5 was more pronounced in severe asthma compared to healthy controls. In the present study, the asthmatic children were not on nasal or systemic steroids that induce FKBP5 expression, which explain this discrepancy.
Steroids cause expressions of FKBP5 by activating glucocorticoid receptor elements . In addition, studies in vitro have shown that FKBP5 reduces the hormone binding affinity and decreases the amount of activated glucocorticoid receptor translocation to the cell nucleus . In an in vitro bioassay the expression FKBP5 mRNA in the peripheral blood was used to assess human corticosteroids sensitivity. Furthermore, FKBP5 was also reported as a biomarker for glucocorticoid responsiveness and as a possible glucocorticoid resistant asthma mediator .
Regarding to atopic status, relative gene expression levels of CLCA1, SERPINB2 and periostin were significantly up-regulated in atopic asthma than non-atopic, while there were no statistically significant differences between atopic and non-atopic asthma regarding both TMEM178 and FKBP51 expression levels. In line with our findings, a previous study reported that SERPINB2 gene expression can serve as a back-up marker of Th2-driven inflammation in respiratory epithelial cells, which is considered as the main mechanism of atopic asthma pathogenesis .
Two major researches have highlighted apparently conflicting opinions on the association between periostin with eosinophilia. An observational analysis showed periostin would be a better predictor of inflammation of eosinophil in the airway , while another cross-sectional study  revealed that a strong correlation between blood eosinophils and sputum eosinophils was discovered, but the interaction between serum periostin and eosinophils in sputum was not demonstrated. The most likely clarification for these obvious variations is that the former study investigated the periostin sensitivity and specificity to identify airway eosinophilia using a composite score rather than specifically comparing the relationship between blood periostin and a sputum eosinophil count, as performed in the later study. This indicates that blood periostin may provide additional value as a diagnostic tool of Th2 inflammation, but is not directly comparable with either blood or sputum eosinophilia. Such discrepancy in the calculation of biomarkers in various studies further highlights the heterogeneity and complexity of airway inflammation and the possible need of measuring several biomarkers in conjunction with one another to accurately try and determine a phenotype.
A cluster analysis reported 70 genes expression that distinguished Th2-high and Th2-low subjects, including IL13, IL5, periostin, CLCA1, and SERPINB2. Compared with Th2-low subjects, Th2-high individuals were more likely to be atopic and have elevated eosinophil counts. They stated that both atopy status and eosinophilic blood levels were closely related to Th2-high pattern of nasal gene expression, regardless of asthma status. These findings indicate that Th2 activation of atopic or systemically allergic airway is a part of the physiological foundation of asthma. Identifying of Th2-high subjects on the basis of nasal brushings is possible and may have a huge effect on both biomedical and clinical research .