Airway mucus gel plays a vital role in maintaining the integrity of mucosal epithelia and protecting respiratory health. Such defensive mechanism stems primarily from a constant clearance of mucus-entrapped inhaled pathogens and particulates by mucociliary transport. The success in removing mucus-entrapped harmful substances relies heavily on proper mucus rheology. It is well established that hydration is the single most important determinant of mucus rheological properties. In a healthy condition, the body precisely controls the degree of mucus hydration through modulating physiological parameters of various ionic concentrations in the nascent microenvironment which bathe the mucus. On the contrary, inadequate mucus hydration and abnormal mucus hypersecretion seem to be the major causal factors underlying pathological states involving the accumulation of highly viscous mucus plugs, obstructive airflow, chronic infection and inflammation. These symptoms are characteristic of pulmonary diseases including, but not limited to, chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis (CF). My research focused on the mechanisms of how (i) environmental and (ii) physiological factors affect mucus secretion and rheological properties. My first project tested whether titanium dioxide nanoparticles (TiO₂ NPs), a common air pollutant that constitutes airborne particulate matter, can induce mucin hypersecretion from airway epithelial cells via a Ca²⁺-mediated pathway. Aside from being an airborne pollutant, many engineered NPs are utilized in the nanoindustry and have acquired secondary surface modifications. The question of functionalized NPs with surface charges being able to alter mucus rheological properties is the focal point of the second project. The third study aimed at understanding how physiological parameters involving bicarbonate ion concentrations regulate mucus rheological characteristics. Abnormal bicarbonate levels in humans have recently been suggested to instigate a devastating Caucasian disease, cystic fibrosis. A more in-depth comprehension of how both environmental and physiological factors disturb mucus rheology and over-secretion facilitate the design of future therapies to counteract the concomitant pathologies.