The airway epithelial barrier (AEB) is a dynamic interface that maintains respiratory homeostasis. Complex networks of epithelial cells, intercellular junctions, and immune constituents support the structural and functional integrity of the AEB. This review synthesizes how the respiratory exposome components disrupt AEB physiology by compromising junctional integrity, triggering oxidative stress, and inducing inflammation. The review further analyzes how these perturbations lead to maladaptive responses in chronic respiratory diseases (CRDs) and the effectiveness of emerging biologics targeting epithelial-derived alarmins in treating CRDs. By integrating exposome science with epithelial physiology, we provide a unified framework for understanding environmental impacts on airway health.