Language and Cognitive Performance in Children with Well-Controlled Asthma: Associations with Serum pNF-H and...

Background/Objectives: Childhood asthma is increasingly viewed as a systemic condition that may also affect neurodevelopmental processes. We examined language and cognitive performance and their associations with serum biomarkers of neuroinflammation, neuroaxonal integrity and synaptic function in school-aged children with clinically well-controlled asthma. Methods: In this cross-sectional study, 67 children (33 with asthma and 34 healthy controls) underwent the Wechsler Intelligence Scale for Children-Revised (WISC-R), the Turkish Nonword Repetition Test (TAST), the Turkish School-Age Language Development Test (TODİL), sleep and psychosocial scales, and audiometric screening. Serum interleukin-4 (IL-4), IL-13, C-X-C motif chemokine ligand 13 (CXCL13), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), chitinase-3-like protein-1 (YKL-40/CHI3L1), triggering receptor expressed on myeloid cells 2 (TREM2), monocyte chemoattractant protein-1 (MCP-1), synaptosomal-associated protein 25 (SNAP-25), neurogranin, and phosphorylated neurofilament heavy chain (pNF-H) were measured using enzyme-linked immunosorbent assay (ELISA). Groups were compared with Mann-Whitney U and chi-square/Fisher tests and with age- and sex-adjusted regression using HC3 robust standard errors, with Benjamini-Hochberg (BH) false-discovery-rate (FDR) correction within predefined outcome families; within the asthma group, biomarkers were related to language and cognitive outcomes in exploratory multiple regression. Results: Serum pNF-H was higher in the asthma group (p = 0.001; pFDR = 0.012), remained higher after age and sex adjustment (p = 0.002), and was robust to outlier handling. Neurogranin was higher in the unadjusted comparison (p = 0.012), marginal after panel-level FDR (pFDR = 0.065), and significant after adjustment (p = 0.003). Several WISC-R indices, most clearly full-scale IQ, were lower in the asthma group, favoring controls. Within the asthma group, neurogranin was positively associated with WISC-R vocabulary and picture completion and TODIL organizing. Conclusions: Even in well-controlled asthma, specific language and cognitive domains may differ from those of healthy peers, alongside higher peripheral biomarkers related to neuroaxonal and synaptic processes. These findings are exploratory and require confirmation in larger, longitudinal samples.