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INTRODUCTION There is a paucity of studies on e-cigarette use among adults with chronic lung disease. In the present study, we aimed to assess whether psychosocial or cognitive factors elucidate the relationship between chronic lung disease (CLD) and susceptibility to e-cigarette use and whether the relationship between CLD and e-cigarette use is conditional on the presence of respiratory symptoms. METHODS We recruited adults aged ≥18 years in Alabama with CLD from university medical clinics (n=140) and individuals without CLD (n=123 as a reference group). Information on sociodemographics, susceptibility to e-cigarette use, psychosocial factors, and cognitive factors were collected. Mediation analysis was used to assess whether the psychosocial factors or cognitive factors explained the association between CLD and susceptibility to using e-cigarettes, and moderation analysis was conducted to determine if respiratory factors would change the association between CLD and susceptibility to e-cigarette use. RESULTS Psychosocial factors (stress, depression, anxiety) and e-cigarette positive expectancy were notably high among individuals with CLD. Having CLD was associated with a lower likelihood of susceptibility to e-cigarette use. Higher levels of stress, being a smoker, boredom, taste/sensorimotor manipulation, and social facilitation were associated with higher odds of susceptibility to using e-cigarettes among individuals with CLD. Mediation analysis indicated a statistically significant indirect effect of CLD on the susceptibility to using e-cigarettes through stress and boredom reduction. We did not find a statistically significant interaction between CLD and respiratory symptoms affecting susceptibility to using e-cigarettes. CONCLUSIONS Individuals with CLD often exhibit stress, depression, and a positive view of e-cigarettes but are generally less inclined to use them. Stress, smoking habits, boredom, taste, and social influence can increase their susceptibility to e-cigarette use. Our findings call for further exploration to evaluate the temporal relationship between CLD status, psychosocial factors, cognitive factors, and susceptibility to using e-cigarettes. [ABSTRACT FROM AUTHOR]