Numerous studies have examined the association between pharmacogenetic effects and the response to inhaled corticosteroids (ICS) in patients with asthma. In fact, several single nucleotide polymorphisms of a number of candidate genes have been identified that might influence the clinical response to ICS in children with asthma. Their direct or indirect effects depend on their role in the inflammatory process in asthma or the anti-inflammatory action of corticosteroids, respectively. Among the genes identified, variants in T-box 21 (TBX21) and Fc fragment of IgE receptor II (FCER2) contribute indirectly to the variability in the response to ICS by altering the inflammatory mechanisms in asthma, while other genes such as corticotropin releasing hormone receptor 1 (CRHR1), nuclear receptor subfamily 3 group C member 1 (NR3C1), stress induced phosphoprotein 1 (STIP1), dual specificity phosphatase 1 (DUSP1), glucocorticoid induced 1 (GLCCI1), histone deacetylase 1 (HDAC), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and vascular endothelial growth factors (VEGF) directly affect this variability through the anti-inflammatory mechanisms of ICS. The results to date indicate various potential genetic factors associated with the response to ICS, which could be utilized to predict the individual therapeutic response of children with asthma to ICS. Clinical trials are underway and their results are greatly anticipated. Further pharmacogenetic studies are needed to fully understand the effects of genetic variation on the response to ICS in children with asthma.

In children with asthma, the responsiveness of inhaled corticosteroids (ICS) is depended on asthma endotype and phenotype. This study aimed to describe the clinical and biological characteristics, and its correlation with polymorphism of rs28364072 in FCER2 of asthmatic children. This work aimed to study the correlation between fractional concentration of exhaled nitric oxide (FENO) level and rs28364072 polymorphism of FCER2 gene with ICS responsiveness and disease control in children with asthma. This study was a prospective and descriptive study. All clinical characteristics, FENO, blood eosinophil counts (BEC), skin prick test (SPT), total IgE, asthma control test, and FCER2 gene polymorphism were performed for each patient. One hundred and seven asthmatic children who were over 5 years old (9.2 ± 2.6), were included. Patients with FENO > 20 ppb had higher percentage of positive SPT, total IgE level, and BEC (89.2 vs 80.0%, 851.1 vs 656.9 UI ml−1, and 785 ± 576 G L−1 vs 425 ± 364 G L−1; respectively). Among them, there were 54.2% of homozygous TT, 36.4% of heterozygous TC, and 9.4% of homozygous CC of rs28364072 polymorphism in FCER2. The percentage of patients with controlled asthma was increasing after 1 month and 3 months (47.1% and 58.8%; respectively). During the study, the ICS was decreasing as indicated by asthma control (348 ± 118 mcg at 1st month vs 329 ± 119 mcg at 3rd month; p < 0.05). CC genotype had the lowest level of increasing FEV1 compared to that in genotype TC and TT (8.4% vs 8.7% and 27.1%; p > 0.05 and p < 0.05; respectively). The percentage of polymorphism in rs28364072 of FCER2 was significant higher in patients with controlled asthma compared to uncontrolled asthma. Asthmatic children with high FENO and rs28364072 polymorphism in FCER2 gene are good responders to ICS; however, asthmatic children with homozygous variant CC of rs28364072 are poorly responsive to ICS.

IntroductionFractional exhaled nitric oxide (FENO) is a biomarker of airway inflammation in asthma. The measurement of FENO is utilized to assist in the diagnosis and treatment of children with asthma, especially for those treated with inhaled corticosteroids.ObjectivesThe aims of this study were to evaluate the correlations between FENO and atopic status, blood eosinophil levels, FCER2 mutation, and asthma control in Vietnamese children.Subjects and methodsThis was a prospective and descriptive study approved by the local Ethical Board. All children with uncontrolled asthma, seen in the National Hospital of Pediatrics (Hanoi, Vietnam), were included. Exhaled breath FENO, blood eosinophils, skin prick test, total IgE, asthma control test (ACT), and FCER2 gene polymorphism were performed at inclusion. They were followed up at 3 months to evaluate clinical status, FENO levels, and ACT.ResultsForty-two children with uncontrolled asthma with a mean age of 10±3 years (6–16 years) were included. The male/female ratio was 2.5/1. The mean FENO levels were 26±25 ppb. FENO was significantly higher in patients with a positive skin prick test for respiratory allergens (P<0.05). FENO was significantly correlated with blood eosinophil levels (r=0.5217; P=0.0004). Five of the 32 subjects (15.6%) had a mutation of FCER2 gene (rs28364072 SNP). In this group, the levels of FENO were highest (37±10 ppb; P<0.05). The levels of FENO were significantly decreased after 3 months of treatment (17±8 ppb vs 26±25 ppb; P<0.05). Significant correlations between inhaled corticosteroid doses and FENO levels occurred at 1 and 3 months (r=0.415, P=0.007; r=0.396, P=0.010; respectively). There were no correlations between FENO levels, ACT, and daily use of salbutamol. After 3 months, asthma remained uncontrolled in 22.2% of children.ConclusionThe measurement of FENO levels is a useful and feasible tool to predict clinical, biological, and asthma control in Vietnamese children.