Clinical and Inflammatory Correlates of Fractional Exhaled Nitric Oxide in Turkish Children and Adolescents with Asthma: Exploratory Analysis of the FCER2 rs2228137 Polymorphism

Background/Objectives: Fractional exhaled nitric oxide (FeNO) is a noninvasive biomarker of eosinophilic airway inflammation in asthma, but data on its clinical correlates in Turkish children and adolescents are limited. This study aimed to determine which clinical and inflammatory characteristics were independently associated with FeNO and, as a secondary exploratory objective, to assess whether the FCER2 rs2228137 (R62W) polymorphism is associated with FeNO and related clinical features. Methods: In this cross-sectional study of 100 children and adolescents aged 6–18 years with asthma receiving inhaled corticosteroid/long-acting beta-agonist therapy at a tertiary center in Istanbul, Türkiye, FeNO, spirometry, skin prick testing, peripheral blood eosinophil percentage, total IgE, and Asthma Control Questionnaire (ACQ) score were measured. Genotyping of rs2228137 was performed by SNaPshot multiplex assay and confirmed by Sanger sequencing. The primary inferential analysis was a multivariable linear regression of ln-transformed FeNO with age, sex and BMI z-score as prespecified baseline covariates; analyses by American Thoracic Society (ATS) FeNO categories were descriptive, and genotype was examined as a covariable in adjusted regression models. Results: In the primary multivariable analysis (n = 98; R2 = 0.42), blood eosinophil percentage (β = 0.082, 95% CI 0.039–0.124; p < 0.001) and ACQ score (β = 0.264, 95% CI 0.135–0.394; p < 0.001) were independently associated with ln(FeNO), as was age (β = 0.074, 95% CI 0.013–0.134; p = 0.02), whereas total IgE and aeroallergen sensitization were not independently associated with FeNO. Descriptive analyses across clinically defined ATS FeNO categories showed gradients consistent with a greater type 2 inflammatory burden and poorer symptom control at higher FeNO levels. In exploratory analyses with the rs2228137 genotype entered as a covariable in the adjusted models, no genotype–phenotype association was statistically significant across the examined models (FeNO, FEV1, eosinophil percentage, total IgE, skin prick test positivity, uncontrolled asthma); this prespecified secondary analysis was statistically underpowered, particularly for the TT genotype (n = 5). Conclusions: FeNO is a useful adjunctive biomarker of type 2 airway inflammation and symptom control in Turkish children and adolescents with asthma, whereas the exploratory FCER2 rs2228137 analysis did not reveal genotype–phenotype associations; given the small subgroup sizes, these findings should be regarded as hypothesis-generating.