Abstract
BACKGROUND: This study aims to determine the relationship between tobacco use, inhalation injury, and ARDS in burn-injured adults. METHODS: This study was an observational cohort of 2,485 primary burn admissions to a referral burn center between January 1, 2008 and March 15, 2015. Subjects were evaluated by methods used to account for mediation and traditional approaches (multivariable logistic regression and propensity score analysis). Mediation analysis examined both the (1) indirect effect of tobacco use via inhalation injury as the mediator on ARDS development and (2) the direct effect of tobacco use alone on ARDS development. RESULTS: ARDS development occurred in 6.8% (n = 170) of the cohort. Inhalation injury occurred in 5.0% (n = 125) of the cohort, and ARDS developed in 48.8% (n = 83) of the subjects with inhalation injury. Tobacco use was 2-fold more common in subjects with ARDS. In the mediated model, the direct effect of tobacco use on ARDS, including interaction between tobacco use and inhalation injury, was not significant (odds ratio [OR] 1.63, 95% CI 0.91-2.92, P = .10). However, the indirect effect of tobacco use via inhalation injury as the mediator was significant (OR 1.61, 95% CI 1.25-2.07, P < .001), and the proportion of the total effect of tobacco use operating through the mediator was 55.6%. In the non-mediation models (multivariable logistic regression and propensity score analysis), which controlled for inhalation injury and other covariables, the OR for the association between tobacco use and ARDS was 1.84 (95% CI 1.22-2.81, P < .001) and 1.69 (95% CI 1.04-2.75, P = .03), respectively. CONCLUSIONS: In mediation analysis, inhalation injury was the overwhelming predictor for ARDS development, whereas tobacco use has its strongest effect indirectly through inhalation injury. Patients with at least moderate inhalation injury are at greatest risk for ARDS development despite baseline risk factors like tobacco use.