Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent ( = 21) vs. no persistent ( = 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g., , , , and ) and inhibiting apoptosis (e.g., higher mRNA expression of , , , and lower of , , ). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components (, ), involved in ECM remodeling (), neovascularization (, ), nerve functioning (, ), oxidative stress adaptation (, ), epigenetic modifications (, ), and the innate immune response (, ). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling.