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Deviation in pulmonary surfactant structure–function activity can impair airway patency and lead to respiratory disorders. This novel study aims to evaluate the influence cigarette/e-cigarette vapour has on model surfactant films located within a simulated pulmonary environment using a lung biosimulator. Chromatographic analysis confirmed that nicotine levels were consistent with the sampling regimen employed. On exposure to smoke vapour, Langmuir isotherms exhibited condensed character and a significant reduction in maximum surface pressure was noted in all cases. Langmuir isocycles, reflective of the human breathing cycle, demonstrated condensed character on smoke vapour delivery. A reduction in the maximum surface pressure was clear only in the case of cigarette vapour application. The components of cigarette vapour can cause oxidative damage to pulmonary surfactant and impair recycling. Neutral nicotine molecules can weaken the structure of the monolayer and cause destabilisation. A protective effect was evident in the case of repeated surfactant compression – relaxation cycles (i.e. the ability to reduce the surface tension term was impaired less), demonstrating a likely innate biological defensive mechanism of the lung. E-cigarette vapour appeared to have a reduced impact on surfactant performance, which may hold value in harm reduction over the longer term