Several theories have been presented to explain how e-cigarettes can cause lung disease. Mouse studies have demonstrated that lipids accumulate in the lung macrophages of mice exposed to e-cigarettes. The build-up has been traced to the breakdown of pulmonary surfactant; a lipid-rich compound produced by the lungs. This information has led to one theory that vaping damages the cells that line the airways which help maintain surfactant levels. Which one of the criteria for judging causality best corresponds to the scenario.

1. Strength of association
2. Dose-response
3. Biologic plausibility
4. Temporality